# AMR release; corpus: bio; section: test; number of AMRs: 500 (generated on Mon Mar 14, 2016 at 21:45:05)
# ::id a_pmid_2234_3622.60 ::date 2015-05-28T07:09:27 ::annotator SDL-AMR-09 ::preferred
# ::snt Combined treatment of selumetinib and standard of care agents results in enhanced anti-tumour efficacy
# ::save-date Mon Jul 27, 2015 ::file a_pmid_2234_3622_60.txt
(r / result-01
:ARG1 (a / and
:op1 (t / treat-04
:ARG2 (a3 / and
:op1 (s2 / small-molecule :name (n / name :op1 "selumetinib"))
:op2 (s / standard
:mod (a2 / agent
:mod (c / care-03))))
:ARG3-of (c2 / combine-01)))
:ARG2 (e / efficacy
:ARG1-of (e2 / enhance-01)
:mod (c3 / counter-01
:ARG1 (t2 / tumor))))
# ::id a_pmid_2234_3622.61 ::date 2015-05-28T15:47:00 ::annotator SDL-AMR-09 ::preferred
# ::snt Mechanistic biomarker studies of the effects of selumetinib in human tumour xenograft models have shown that, in addition to pERK1/2 downregulation, a sustained exposure to the agent results in an increase in downstream apoptotic signalling and a decrease in cell cycle progression (Davies et al, 2007).
# ::save-date Mon Dec 21, 2015 ::file a_pmid_2234_3622_61.txt
(s / show-01
:ARG0 (s2 / study-01
:ARG1 (a / affect-01
:ARG0 (s3 / small-molecule :name (n3 / name :op1 "selumetinib"))
:ARG1 (m2 / model
:mod (x / xenograft
:mod (t / tumor))
:mod (h / human)))
:mod (b / biomarker
:mod (m / mechanistic)))
:ARG1 (r / result-01
:ARG1 (e / expose-01
:ARG2 s3
:ARG1-of (s4 / sustain-01))
:ARG2 (a7 / and
:op1 (d2 / downregulate-01
:ARG1 (e2 / enzyme :name (n / name :op1 "ERK1/2")
:ARG3-of (p / phosphorylate-01)))
:op2 (i / increase-01
:ARG1 (s5 / signal-07
:mod (a5 / apoptosis)
:location (d4 / downstream)))
:op3 (d3 / decrease-01
:ARG1 (p2 / progress-01
:ARG1 (c / cycle-02
:ARG1 (c2 / cell))))))
:ARG1-of (d5 / describe-01
:ARG0 (p5 / publication-91
:ARG0 (a3 / and
:op1 (p3 / person :name (n2 / name :op1 "Davies"))
:op2 (p4 / person
:mod (o / other)))
:time (d / date-entity :year 2007))))
# ::id a_pmid_2234_3622.62 ::date 2015-05-29T11:36:12 ::annotator SDL-AMR-09 ::preferred
# ::snt Furthermore, a chronic dosing schedule of selumetinib (25 mg kg–1 per bid for 14 doses) in HCT-116 xenografts increased the levels of the pro-apoptotic BH3 protein Bim-EL (∼4-fold increase) compared with no change with the level of this protein following a shorter dosing period (three doses) (Figure 1).
# ::save-date Wed Jan 13, 2016 ::file a_pmid_2234_3622_62.txt
(a / and
:op2 (i / increase-01
:ARG0 (s / schedule-01
:ARG1 (d2 / dose-01 :quant 14
:ARG2 (s2 / small-molecule :name (n4 / name :op1 "selumetinib")
:quant (c4 / concentration-quantity :quant 25
:unit (m / milligram-per-kilogram)))
:mod (c / chronic)
:frequency (r / rate-entity-91
:ARG1 2
:ARG2 (t / temporal-quantity :quant 1
:unit (d5 / day)))))
:ARG1 (l / level
:quant-of (p / protein :name (n2 / name :op1 "Bim-EL")
:ARG0-of (f / favor-01
:ARG1 (a2 / apoptosis))
:ARG1-of (i2 / include-91
:ARG2 (p4 / protein-family :name (n3 / name :op1 "BH3")))))
:ARG4 (p2 / product-of :op1 4)
:compared-to (c2 / change-01 :polarity -
:ARG1 (l2 / level
:quant-of p)
:ARG1-of (f3 / follow-01
:ARG2 (p3 / period
:time-of (d3 / dose-01)
:ARG1-of (s3 / short-07
:degree (m2 / more))
:ARG1-of (m3 / mean-01
:ARG3 (d4 / dose-01 :quant 3)))))
:location (x / xenograft
:mod (c3 / cell-line :name (n / name :op1 "HCT-116"))))
:ARG1-of (d / describe-01
:ARG0 (f2 / figure :mod 1)))
# ::id a_pmid_2234_3622.63 ::date 2015-05-28T15:50:33 ::annotator SDL-AMR-09 ::preferred
# ::snt In order to exploit the apoptotic threshold of selumetinib, we wanted to study the effects of combining it with agents known to induce the apoptotic cascade to drive tumour growth inhibition and/or cell death.
# ::save-date Tue Dec 22, 2015 ::file a_pmid_2234_3622_63.txt
(w / want-01
:ARG0 (w2 / we)
:ARG1 (s / study-01
:ARG0 w2
:ARG1 (a / affect-01
:ARG0 (c / combine-01
:ARG1 s2
:ARG2 (a2 / agent
:ARG0-of (i / induce-01
:ARG2 (c2 / cascade
:mod a3)
:purpose (d / drive-02
:ARG0 a2
:ARG1 (a4 / and-or
:op1 (i2 / inhibit-01
:ARG1 (g / grow-01
:ARG1 (t2 / tumor)))
:op2 (d2 / die-01
:ARG1 (c3 / cell))))
:ARG1-of (k / know-01))))))
:purpose (e / exploit-01
:ARG0 w2
:ARG1 (t / threshold
:poss (s2 / small-molecule :name (n / name :op1 "selumetinib"))
:mod (a3 / apoptosis))))
# ::id a_pmid_2234_3622.64 ::date 2015-05-28T15:56:00 ::annotator SDL-AMR-09 ::preferred
# ::snt The effects of selumetinib in combination with a number of key standard of care agents were tested pre-clinically in human tumour xenograft models and resulted in enhanced anti-tumour activity.
# ::save-date Mon Dec 21, 2015 ::file a_pmid_2234_3622_64.txt
(a / and
:op1 (t / test-01
:ARG1 (a2 / affect-01
:ARG0 (s / small-molecule :name (n2 / name :op1 "selumetinib"))
:ARG1-of (c / combine-01
:ARG2 (s2 / standard
:ARG1-of (k / key-02)
:mod (a4 / agent
:mod (c3 / care-03)
:quant (n / number)))))
:time (b / before
:op1 (c2 / clinic))
:location (m / model
:mod (x / xenograft
:mod (t2 / tumor))
:mod (h / human)))
:op2 (r / result-01
:ARG1 a2
:ARG2 (a3 / activity-06
:ARG1-of (e / enhance-01)
:ARG0-of (c4 / counter-01
:ARG1 t2))))
# ::id a_pmid_2234_3622.65 ::date 2015-05-28T15:59:44 ::annotator SDL-AMR-09 ::preferred
# ::snt A number of compounds including the DNA-alkylating agent TMZ and the anti-mitotic drug docetaxel resulted in a greatly enhanced tumour growth inhibition compared with monotherapies (Table 1 and supplementary Table 1).
# ::save-date Tue Jan 19, 2016 ::file a_pmid_2234_3622_65.txt
(r / result-01
:ARG1 (c2 / compound
:ARG2-of (i3 / include-91
:ARG1 (a3 / and
:op1 (a4 / agent
:ARG0-of (a / alkylate-01
:ARG1 (n / nucleic-acid :wiki "DNA" :name (n5 / name :op1 "DNA")))
:ARG1-of (m3 / mean-01
:ARG2 (s3 / small-molecule :name (n3 / name :op1 "TMZ"))))
:op2 (s2 / small-molecule :name (n4 / name :op1 "docetaxel")
:ARG0-of (c3 / counter-01
:ARG1 (m2 / mitosis)))))
:quant (n2 / number))
:ARG2 (i / inhibit-01
:ARG1 (g / grow-01
:ARG1 (t / tumor))
:ARG1-of (e / enhance-01
:ARG3 (g2 / great)
:compared-to (m / monotherapy)))
:ARG1-of (d / describe-01
:ARG0 (a2 / and
:op1 (t2 / table :mod 1)
:op2 (t3 / table :mod 1
:ARG2-of (s / supplement-01)))))
# ::id a_pmid_2234_3622.66 ::date 2015-05-28T15:47:43 ::annotator SDL-AMR-09 ::preferred
# ::snt However, combining selumetinib with gemcitabine did not enhance the anti-tumour activity of the individual agents (supplementary Table 1).
# ::save-date Mon Dec 21, 2015 ::file a_pmid_2234_3622_66.txt
(c / contrast-01
:ARG2 (e / enhance-01 :polarity -
:ARG0 (c2 / combine-01
:ARG1 (s2 / small-molecule :name (n / name :op1 "selumetinib"))
:ARG2 (s3 / small-molecule :name (n2 / name :op1 "gemcitabine")))
:ARG1 (a / activity-06
:ARG0 (a2 / agent
:mod (i / individual))
:ARG0-of (c3 / counter-01
:ARG1 (t2 / tumor))))
:ARG1-of (d / describe-01
:ARG0 (t / table :mod 1
:ARG2-of (s / supplement-01))))
# ::id a_pmid_2234_3622.67 ::date 2015-05-28T15:50:05 ::annotator SDL-AMR-09 ::preferred
# ::snt The data presented here suggests that when selumetinib is combined, with either TMZ or docetaxel, the resulting anti-tumour phenotypes maybe due to mechanistic interactions between the two compounds.
# ::save-date Sun Dec 20, 2015 ::file a_pmid_2234_3622_67.txt
(s / suggest-01
:ARG0 (d / data
:ARG1-of (p2 / present-01
:medium (h / here)))
:ARG1 (p3 / possible-01
:ARG1 (c2 / cause-01
:ARG0 (i / interact-01
:ARG0 s2
:ARG1 o
:ARG2 (m / mechanistic))
:ARG1 (p / phenotype
:ARG2-of (r / result-01)
:ARG0-of (c3 / counter-01
:ARG1 (t2 / tumor))))
:time (c / combine-01
:ARG1 (s2 / small-molecule :name (n2 / name :op1 "selumetinib"))
:ARG2 (o / or
:op1 (s4 / small-molecule :name (n3 / name :op1 "TMZ"))
:op2 (s3 / small-molecule :name (n / name :op1 "docetaxel"))))))
# ::id a_pmid_2234_3622.68 ::date 2015-05-28T16:03:06 ::annotator SDL-AMR-09 ::preferred
# ::snt Selumetinib in combination with TMZ enhances DNA damage
# ::save-date Tue Jun 9, 2015 ::file a_pmid_2234_3622_68.txt
(e / enhance-01
:ARG0 (c / combine-01
:ARG1 (s / small-molecule :name (n / name :op1 "selumetinib"))
:ARG2 (s2 / small-molecule :name (n2 / name :op1 "TMZ")))
:ARG1 (d / damage-01
:ARG0 c
:ARG1 (n3 / nucleic-acid :wiki "DNA" :name (n4 / name :op1 "DNA"))))
# ::id a_pmid_2234_3622.69 ::date 2015-05-28T16:04:17 ::annotator SDL-AMR-09 ::preferred
# ::snt The combination of selumetinib and TMZ in the SW-620 human tumour xenograft model resulted in a significantly enhanced anti-tumour efficacy (103.5% inhibition; P<0.0005), compared with selumetinib (52% inhibition; P<0.0005) and TMZ (88% inhibition; P<0.0005) alone (Figure 2A).
# ::save-date Mon Dec 21, 2015 ::file a_pmid_2234_3622_69.txt
(r / result-01
:ARG1 (c2 / combine-01
:ARG1 s2
:ARG2 s3
:location (c3 / cell-line :name (n / name :op1 "SW-620")
:mod (x / xenograft
:mod (t3 / tumor
:mod (h / human)))))
:ARG2 (e / efficacy
:ARG0-of (c / counter-01
:ARG1 t3)
:ARG1-of (e2 / enhance-01
:ARG1-of (s / significant-02))
:ARG1-of (m5 / mean-01
:ARG2 (a3 / and
:op1 (i3 / inhibit-01
:degree (p / percentage-entity :value 103.5))
:op2 (s4 / statistical-test-91
:ARG2 (l / less-than :op1 0.0005)))))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "2A"))
:compared-to (a / and
:op1 (s2 / small-molecule :name (n2 / name :op1 "selumetinib")
:ARG0-of (i / inhibit-01
:degree (p2 / percentage-entity :value 52))
:mod s4)
:op2 (s3 / small-molecule :name (n3 / name :op1 "TMZ")
:ARG0-of (i2 / inhibit-01
:degree (p3 / percentage-entity :value 88))
:mod s4)
:mod (a2 / alone)))
# ::id a_pmid_2234_3622.70 ::date 2015-05-29T11:05:55 ::annotator SDL-AMR-09 ::preferred
# ::snt At the end of the dosing period, the monotherapy and combination treatment groups were left to observe the growth rate following the cessation of dosing (animals in the control group had to be killed due to tumour size).
# ::save-date Mon Jul 27, 2015 ::file a_pmid_2234_3622_70.txt
(l / leave-17
:ARG1 (a / and
:op1 (g / group
:ARG1-of (t / treat-04
:ARG2 (m / monotherapy)))
:op2 (g2 / group
:mod (t2 / treat-04
:ARG1-of (c / combine-01))))
:time (e / end-01
:ARG1 (p / period
:time-of (d / dose-01)))
:purpose (o / observe-01
:ARG1 (r / rate
:mod (g3 / grow-01)
:ARG1-of (f / follow-01
:ARG2 (c2 / cease-01
:ARG1 d
:ARG1-of (m2 / mean-01
:ARG2 (o2 / obligate-01
:ARG1 (k / kill-01
:ARG1 (a2 / animal
:part-of (g4 / group
:mod (c4 / control))))
:ARG1-of (c3 / cause-01
:ARG0 (s / size
:poss (t3 / tumor))))))))))
# ::id a_pmid_2234_3622.71 ::date 2015-05-28T22:00:08 ::annotator SDL-AMR-09 ::preferred
# ::snt In the selumetinib and TMZ monotherapy-treated groups, tumour growth progressed rapidly once compound treatment had been removed.
# ::save-date Tue Jun 9, 2015 ::file a_pmid_2234_3622_71.txt
(p / progress-01
:ARG1 (g / grow-01
:ARG1 (t / tumor))
:manner (r / rapid)
:ARG1-of (c / cause-01
:ARG0 (r2 / remove-01
:ARG1 (t2 / treat-04
:ARG2 (c2 / compound))))
:location (a / and
:op1 (g2 / group
:ARG1-of (t3 / treat-04
:ARG2 (s / small-molecule :name (n / name :op1 "selumetinib")
:mod (m2 / monotherapy))))
:op2 (g3 / group
:ARG1-of (t4 / treat-04
:ARG2 (s2 / small-molecule :name (n2 / name :op1 "TMZ")
:mod m2)))))
# ::id a_pmid_2234_3622.72 ::date 2015-05-28T22:03:28 ::annotator SDL-AMR-09 ::preferred
# ::snt In contrast, the start of tumour growth in the combination group was delayed for approximately 24 days from the start of the experiment compared with 15 days in the TMZ alone group.
# ::save-date Tue Jun 9, 2015 ::file a_pmid_2234_3622_72.txt
(c / contrast-01
:ARG2 (d3 / delay-01
:ARG1 (s / start-01
:ARG1 (g / grow-01
:ARG1 (t3 / tumor)
:location (g2 / group
:mod (c2 / combine-01))))
:ARG2 (a / approximately
:op1 (t / temporal-quantity :quant 24
:unit (d / day)))
:compared-to (d4 / delay-01
:ARG2 (t2 / temporal-quantity :quant 15
:unit (d2 / day))
:location (g4 / group
:mod (s5 / small-molecule :name (n / name :op1 "TMZ")
:mod (a2 / alone))))
:time (s4 / start-01
:ARG1 (e / experiment-01))))
# ::id a_pmid_2234_3622.73 ::date 2015-05-29T11:48:06 ::annotator SDL-AMR-09 ::preferred
# ::snt In order to investigate potential mechanisms, to explain the enhanced combination effect with TMZ, we used the growth inhibition data generated from our anti-tumour studies to guide our pharmacodynamic sampling times (Figure 2A).
# ::save-date Tue Jun 9, 2015 ::file a_pmid_2234_3622_73.txt
(u / use-01
:ARG0 (w / we)
:ARG1 (d / data
:topic (i / inhibit-01
:ARG1 (g / grow-01))
:ARG1-of (g2 / generate-01
:ARG2 (s / study-01
:ARG0 w
:ARG0-of (c2 / counter-01
:ARG1 (t3 / tumor)))))
:ARG2 (g3 / guide-01
:ARG0 d
:ARG1 (t / time
:time-of (s2 / sample-01
:ARG0 w
:mod (p / pharmacodynamic))))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod "2A"))
:purpose (a / and
:op1 (i2 / investigate-01
:ARG0 w
:ARG1 (m / mechanism
:mod (p2 / potential)))
:op2 (e / explain-01
:ARG0 w
:ARG1 (a2 / affect-01
:ARG0 (c / combine-01
:ARG2 (s3 / small-molecule :name (n / name :op1 "TMZ")))
:ARG1-of (e2 / enhance-01)))))
# ::id a_pmid_2234_3622.74 ::date 2015-05-29T11:56:18 ::annotator SDL-AMR-09 ::preferred
# ::snt Samples were collected at the end of the TMZ dosing (PD1), when the TMZ and combination groups growth rate started to diverge (PD2), at the end of selumetinib dosing (PD3) and at the end of the re-growth period (PD4) (Figure 2A; white arrows on graph).
# ::save-date Sun Dec 20, 2015 ::file a_pmid_2234_3622_74.txt
(c / collect-01
:ARG1 (t5 / thing
:ARG1-of (s / sample-01))
:ARG1-of (d2 / describe-01
:ARG0 (a / and
:op1 (f / figure :mod "2A")
:op2 (a2 / arrow
:ARG1-of (w / white-03)
:location (g2 / graph))))
:time (a6 / and
:op1 (e / end-01
:ARG1 (d / dose-01
:ARG2 (s4 / small-molecule :name (n6 / name :op1 "TMZ")))
:ARG1-of (l / label-01
:ARG2 (t2 / thing :name (n / name :op1 "PD1"))))
:op2 (s2 / start-01
:ARG1 (d4 / diverge-01
:ARG0 (r / rate
:mod (g6 / grow-01
:ARG1 (g / group
:mod s4)))
:ARG1 (r2 / rate
:mod (g7 / grow-01
:ARG1 (g8 / group
:mod (c2 / combine-01)))))
:ARG1-of (l2 / label-01
:ARG2 (t3 / thing :name (n4 / name :op1 "PD2"))))
:op3 (e2 / end-01
:ARG1 (d3 / dose-01
:ARG2 (s3 / small-molecule :name (n5 / name :op1 "selumetinib")))
:ARG1-of (l3 / label-01
:ARG2 (t4 / thing :name (n3 / name :op1 "PD3"))))
:op4 (e3 / end-01
:ARG1 (g3 / grow-01
:mod (a4 / again))
:ARG1-of (l4 / label-01
:ARG2 (t / thing :name (n2 / name :op1 "PD4"))))))
# ::id a_pmid_2234_3622.75 ::date 2015-05-29T12:07:22 ::annotator SDL-AMR-09 ::preferred
# ::snt IHC analysis and histological scoring was performed on all the tissues collected to examine, selumetinib effects (pERK1/2), DNA damage (γH2A.X), apoptosis (cleaved caspase 3) and the cell cycle (pHH3) (scoring data not shown).
# ::save-date Sun Jan 17, 2016 ::file a_pmid_2234_3622_75.txt
(p / perform-02
:ARG1 (a5 / and
:op1 (a6 / analyze-01
:mod (i / immunohistochemistry))
:op2 (s2 / score-01
:ARG3 (h / histology)))
:location (t / tissue
:mod (a7 / all)
:ARG1-of (c3 / collect-01
:purpose (a4 / and
:op1 (e / examine-01
:ARG1 (a3 / affect-01
:ARG0 (s / small-molecule
:name (n5 / name :op1 "selumetinib"))
:ARG2 (e2 / enzyme
:name (n / name :op1 "ERK1/2")
:ARG3-of (p2 / phosphorylate-01))))
:op2 (e3 / examine-01
:ARG1 (d / damage-01
:ARG1 (n7 / nucleic-acid :wiki "DNA"
:name (n8 / name :op1 "DNA")))
:instrument (p5 / protein
:name (n2 / name :op1 "γH2A.X")))
:op3 (e4 / examine-01
:ARG1 (a2 / apoptosis)
:instrument (p6 / protein
:name (n3 / name :op1 "Cleaved" :op2 "Caspase" :op3 3)))
:op4 (e5 / examine-01
:ARG1 (c / cycle-02
:ARG1 (c2 / cell))
:instrument (p4 / protein
:name (n4 / name :op1 "HH3")
:ARG3-of (p3 / phosphorylate-01))))))
:ARG1-of (s3 / show-01 :polarity -
:ARG0 (d3 / data
:mod (s4 / score-01))))
# ::id a_pmid_2234_3622.76 ::date 2015-05-29T13:21:18 ::annotator SDL-AMR-09 ::preferred
# ::snt The sampling timepoint, which gave us the greatest insight into the mechanistic effects of these agents was that taken when we started to see the TMZ and combination groups diverge (PD2).
# ::save-date Sun Dec 20, 2015 ::file a_pmid_2234_3622_76.txt
(t3 / timepoint
:mod (t5 / thing :name (n / name :op1 "PD2"))
:ARG1-of (t4 / take-01
:ARG0 w
:time (s3 / start-01
:ARG0 w
:ARG1 (s2 / see-01
:ARG0 w
:ARG1 (d / diverge-01
:ARG0 (g4 / group
:mod (s4 / small-molecule :name (n2 / name :op1 "TMZ")))
:ARG1 (g3 / group
:mod (c / combine-01)
:ARG1-of (m3 / mean-01))))))
:domain (t / timepoint
:time-of (s / sample-01)
:ARG0-of (g2 / give-01
:ARG1 (i / insight
:mod (g / great
:degree (m / most))
:topic (a / affect-01
:ARG0 (a2 / agent
:mod (t2 / this))
:mod (m2 / mechanistic)))
:ARG2 (w / we))))
# ::id a_pmid_2234_3622.77 ::date 2015-05-29T13:30:43 ::annotator SDL-AMR-09 ::preferred
# ::snt As expected, in response to selumetinib or TMZ alone we saw changes in the mechanistic biomarkers pERK1/2 (decrease) and γH2A.X (increase), respectively, and a reduction in mitotic cells as shown by pHH3 in the selumetinib group compared with an increase in the TMZ tissues (Figure 2B).
# ::save-date Mon Jun 22, 2015 ::file a_pmid_2234_3622_77.txt
(r2 / respond-01
:ARG1 (o / or
:op1 (s2 / small-molecule :name (n4 / name :op1 "selumetinib"))
:op2 (s4 / small-molecule :name (n5 / name :op1 "TMZ"))
:mod (a / alone))
:ARG2 (s3 / see-01
:ARG0 w
:ARG1 (a3 / and
:op1 (c / change-01
:ARG1 (b2 / biomarker
:mod (m3 / mechanistic)
:ARG1-of (m5 / mean-01
:ARG2 (a4 / and
:op1 (e2 / enzyme :name (n / name :op1 "ERK1/2")
:ARG1-of (d / decrease-01)
:ARG3-of p2)
:op2 (p3 / protein :name (n2 / name :op1 "γH2A.X")
:mod m3
:ARG1-of (i / increase-01))))))
:op2 (r / reduce-01
:ARG1 (c2 / cell
:mod (m4 / mitosis))
:ARG1-of (s / show-01
:ARG0 (p / protein :name (n3 / name :op1 "HH3")
:ARG3-of (p2 / phosphorylate-01))
:location (g / group
:mod s2))
:compared-to (i2 / increase-01
:ARG1 (t2 / tissue
:mod s4))))
:ARG1-of (e / expect-01
:ARG0 (w / we))))
# ::id a_pmid_2234_3622.78 ::date 2015-05-28T22:04:00 ::annotator SDL-AMR-09 ::preferred
# ::snt Level of the apoptotic marker, cleaved caspase 3, was comparable in the combination group compared with the TMZ monotherapy (Figure 2B).
# ::save-date Tue Jun 9, 2015 ::file a_pmid_2234_3622_78.txt
(p / possible-01
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "2B"))
:ARG1 (c / compare-01
:ARG1 (l / level
:degree-of (m / marker :name (n / name :op1 "cleaved" :op2 "caspase" :op3 "3")
:mod (a / apoptosis))
:location (g / group
:mod (c2 / combine-01)))
:ARG2 (m2 / monotherapy
:mod (s / small-molecule :name (n2 / name :op1 "TMZ")))))
# ::id a_pmid_2234_3622.79 ::date 2015-05-28T22:07:33 ::annotator SDL-AMR-09 ::preferred
# ::snt However, in the combination group we observed a greatly enhanced upregulation of γH2A.X compared with the TMZ group alone, suggesting that when selumetinib and TMZ are combined DNA damage is enhanced (Figure 2B).
# ::save-date Tue Jun 9, 2015 ::file a_pmid_2234_3622_79.txt
(c / contrast-01
:ARG2 (o / observe-01
:ARG0 (w / we)
:ARG1 (u / upregulate-01
:ARG1 (p / protein :name (n / name :op1 "γH2A.X"))
:location (g / group
:mod (c2 / combine-01))
:ARG1-of (e / enhance-01
:ARG3 (g2 / great)
:compared-to (g3 / group
:mod (s3 / small-molecule :name (n3 / name :op1 "TMZ")
:mod (a2 / alone))))
:ARG0-of (s / suggest-01
:ARG1 (e2 / enhance-01
:ARG1 (d / damage-01
:ARG1 (n4 / nucleic-acid :wiki "DNA" :name (n5 / name :op1 "DNA")))
:time (c3 / combine-01
:ARG1 (s2 / small-molecule :name (n2 / name :op1 "selumetinib"))
:ARG2 s3)))))
:ARG1-of (d3 / describe-01
:ARG0 (f / figure :mod "2B")))
# ::id a_pmid_2234_3622.80 ::date 2015-05-29T08:39:59 ::annotator SDL-AMR-09 ::preferred
# ::snt Selumetinib is efficacious in combination with docetaxel when dosed concurrently or following docetaxel
# ::save-date Mon Jul 27, 2015 ::file a_pmid_2234_3622_80.txt
(e / efficacious
:time (o / or
:op1 (d / dose-01
:ARG1 (a / and
:op1 s3
:op2 s2)
:ARG1-of (c2 / concurrent-02))
:op2 (f / follow-01
:ARG1 s3
:ARG2 s2))
:domain (s3 / small-molecule :name (n2 / name :op1 "selumetinib")
:ARG1-of (c / combine-01
:ARG2 (s2 / small-molecule :name (n / name :op1 "docetaxel")))))
# ::id a_pmid_2234_3622.81 ::date 2015-05-29T08:46:53 ::annotator SDL-AMR-09 ::preferred
# ::snt Continuous, concurrent combinations of selumetinib and docetaxel resulted in significant anti-tumour effects in several models (Table 1 and Figure 3A).
# ::save-date Mon Jul 27, 2015 ::file a_pmid_2234_3622_81.txt
(r / result-01
:ARG1 (c / combine-01
:ARG1 (s / small-molecule :name (n / name :op1 "selumetinib"))
:ARG2 (s4 / small-molecule :name (n2 / name :op1 "docetaxel"))
:ARG1-of (c2 / concurrent-02)
:ARG1-of (c3 / continue-01))
:ARG2 (a / affect-01
:ARG2 (c4 / counter-01
:ARG0 (t / tumor))
:location (m / model
:quant (s2 / several))
:ARG1-of (s3 / significant-02))
:ARG1-of (d2 / describe-01
:ARG0 (a2 / and
:op1 (t2 / table :mod 1)
:op2 (f / figure :mod "3A"))))
# ::id a_pmid_2234_3622.82 ::date 2015-05-29T08:54:24 ::annotator SDL-AMR-09 ::preferred
# ::snt However, we were interested to explore the effect of dose sequencing on the anti-tumour efficacy of these two agents as administration of selumetinib and docetaxel as monotherapies results in distinct cell cycle phenotypes; a G1 or mitotic arrest, respectively.
# ::save-date Tue Jan 19, 2016 ::file a_pmid_2234_3622_82.txt
(c / contrast-01
:ARG2 (c2 / cause-01
:ARG0 (r / result-01
:ARG1 (a3 / administer-01
:ARG1 (a4 / and
:op1 (s2 / small-molecule :name (n2 / name :op1 "selumetinib"))
:op2 (s3 / small-molecule :name (n3 / name :op1 "docetaxel")))
:manner (m / monotherapy))
:ARG2 (p / phenotype
:mod (c4 / cycle-02
:ARG1 (c5 / cell)
:mod (d2 / distinct))
:ARG1-of (m5 / mean-01
:ARG2 (a5 / and
:op2 (a6 / arrest-02
:time (e3 / event :name (n / name :op1 "G1")))
:op3 (a7 / arrest-02
:time (m2 / mitosis))))))
:ARG1 (i / interest-01
:ARG1 (w / we)
:ARG2 (e / explore-01
:ARG0 w
:ARG1 (a / affect-01
:ARG0 (s / sequence-01
:ARG1 (d / dose-01))
:ARG1 (e2 / efficacy
:poss (a2 / agent :quant 2
:mod (t2 / this)
:ARG1-of (m4 / mean-01
:ARG2 a4)
:ARG0-of (c3 / counter-01
:ARG1 (t / tumor)))))))))
# ::id a_pmid_2234_3622.83 ::date 2015-05-29T11:05:20 ::annotator SDL-AMR-09 ::preferred
# ::snt Two schedules were designed in which mice bearing HCT-116 CRC tumours were treated with either a single dose of docetaxel (15 mg kg–1) followed 24 h later by selumetinib (25 mg kg–1 per bid) for 7 days (schedule 1) or selumetinib was administered as above for 7 days followed 24 h later with docetaxel (schedule 2) (Figure 3B).
# ::save-date Sun Jan 17, 2016 ::file a_pmid_2234_3622_83.txt
(d2 / design-01
:ARG1 (s / schedule :quant 2)
:ARG3 (o / or
:op1 (t2 / treat-04
:ARG1 (m2 / mouse
:ARG0-of (b / bear-01
:ARG1 (t3 / tumor
:mod (c / cell-line :name (n / name :op1 "HCT-116")
:mod (d4 / disease :name (n4 / name :op1 "CRC"))))))
:ARG2 (s5 / small-molecule :name (n3 / name :op1 "docetaxel")
:ARG2-of (d5 / dose-01
:ARG1-of (s2 / single-02))
:ARG2-of (f2 / follow-01
:ARG1 (d6 / dose-01
:ARG2 (s3 / small-molecule :name (n2 / name :op1 "selumetinib")
:quant (c3 / concentration-quantity :quant 25
:unit m3))
:duration (t / temporal-quantity :quant 7
:unit (d / day))
:frequency (r / rate-entity-91
:ARG1 2
:ARG2 (t5 / temporal-quantity :quant 1
:unit d)))
:time (l / late
:op1 (t4 / temporal-quantity :quant 24
:unit (h / hour))
:degree (m / more)))
:quant (c2 / concentration-quantity :quant 15
:unit (m3 / milligram-per-kilogram))))
:op2 (a / administer-01
:ARG1 s3
:duration t
:ARG2-of (f3 / follow-01
:ARG1 (a3 / administer-01
:ARG1 s5)
:time l)
:mod t2))
:ARG1-of (d3 / describe-01
:ARG0 (f / figure :mod "3B")))
# ::id a_pmid_2234_3622.84 ::date 2015-05-29T12:36:05 ::annotator SDL-AMR-09 ::preferred
# ::snt As monotherapies, docetaxel and selumetinib resulted in 77% (P<0.0005) and 50% (P<0.005) tumour growth inhibition, respectively (Figure 3C).
# ::save-date Mon Dec 21, 2015 ::file a_pmid_2234_3622_84.txt
(r / result-01
:ARG1 (a / and
:op1 (s2 / small-molecule :name (n2 / name :op1 "docetaxel"))
:op2 (s / small-molecule :name (n / name :op1 "selumetinib"))
:mod (m / monotherapy))
:ARG2 (a2 / and
:op1 (i / inhibit-01
:ARG1 (g / grow-01
:ARG1 (t / tumor)
:mod (p / percentage-entity :value 77))
:ARG1-of (s3 / statistical-test-91
:ARG2 (l / less-than :op1 0.0005)))
:op2 (i2 / inhibit-01
:ARG1 (g2 / grow-01
:ARG1 t
:mod (p2 / percentage-entity :value 50))
:ARG1-of (s4 / statistical-test-91
:ARG2 (l2 / less-than :op1 0.005))))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "3C")))
# ::id a_pmid_2234_3622.85 ::date 2015-05-29T12:40:17 ::annotator SDL-AMR-09 ::preferred
# ::snt Interestingly, in the two combination schedules docetaxel administered before selumetinib (schedule 1) resulted in a 110% (P<0.0005) compared with 61% (P<0.005) tumour growth inhibition when docetaxel was administered after selumetinib (schedule 2).
# ::save-date Sun Jan 3, 2016 ::file a_pmid_2234_3622_85.txt
(r / result-01
:ARG1 (a / administer-01
:ARG1 (s5 / small-molecule :name (n / name :op1 "docetaxel"))
:time (b / before
:op1 (a2 / administer-01
:ARG1 (s / small-molecule :name (n2 / name :op1 "selumetinib")))
:ARG1-of (m / mean-01
:ARG2 (s3 / schedule :mod 1))))
:ARG2 (i3 / inhibit-01
:degree (p / percentage-entity :value 110)
:compared-to (i / inhibit-01
:ARG1 (g / grow-01
:ARG1 (t / tumor))
:degree (p2 / percentage-entity :value 61)
:time (a3 / administer-01
:ARG1 s5
:time (a4 / after
:op1 s)
:ARG1-of (m4 / mean-01
:ARG2 (s4 / schedule :mod 2))))
:ARG1-of (s6 / statistical-test-91
:ARG2 (l2 / less-than :op1 0.0005)))
:ARG0-of (i2 / interest-01)
:condition (s2 / schedule :quant 2
:mod (c / combine-01)))
# ::id a_pmid_2234_3622.86 ::date 2015-05-28T22:12:42 ::annotator SDL-AMR-09 ::preferred
# ::snt These results suggest that selumetinib could enhance the efficacy of docetaxel when administered in the sequence of docetaxel followed by selumetinib.
# ::save-date Tue Jun 9, 2015 ::file a_pmid_2234_3622_86.txt
(s / suggest-01
:ARG0 (t / thing
:ARG2-of (r / result-01)
:mod (t2 / this))
:ARG1 (p / possible-01
:ARG1 (e / enhance-01
:ARG0 (s3 / small-molecule :name (n2 / name :op1 "selumetinib"))
:ARG1 (e2 / efficacy
:poss (s4 / small-molecule :name (n / name :op1 "docetaxel")))
:condition (a / administrate-01
:manner (s2 / sequence
:poss s4
:mod (f / follow-01
:ARG1 s3
:ARG2 s4))))))
# ::id a_pmid_2234_3622.87 ::date 2015-05-28T22:16:07 ::annotator SDL-AMR-09 ::preferred
# ::snt The sequence dependency of selumetinib when combined with docetaxel enhances apoptotic cell death
# ::save-date Tue Jun 9, 2015 ::file a_pmid_2234_3622_87.txt
(e / enhance-01
:ARG0 (d / depend-01
:ARG0 (s2 / small-molecule :name (n / name :op1 "selumetinib")
:ARG1-of (c / combine-01
:ARG2 (s3 / small-molecule :name (n2 / name :op1 "docetaxel"))))
:ARG1 (s / sequence))
:ARG1 (d2 / die-01
:ARG1 (c2 / cell)
:mod (a / apoptosis)))
# ::id a_pmid_2234_3622.88 ::date 2015-05-29T08:38:19 ::annotator SDL-AMR-09 ::preferred
# ::snt In order to determine the mechanism of action in the scheduling studies with docetaxel, a series of tumour tissue samples were taken at different time points following exposure to the two dosing regimens (Figure 4Ai and Bi).
# ::save-date Mon Jul 27, 2015 ::file a_pmid_2234_3622_88.txt
(s / sample-01
:ARG1 (t2 / tissue
:mod (t3 / tumor))
:time (p / point
:mod (t / time)
:ARG1-of (d4 / differ-02))
:ARG1-of (f / follow-01
:ARG2 (e / expose-01
:ARG2 (r2 / regimen :quant 2
:ARG0-of (d / dose-01))))
:ARG1-of (d2 / describe-01
:ARG0 (a / and
:op1 (f2 / figure :mod "4Ai")
:op2 (f3 / figure :mod "4Bi")))
:quant (s2 / series)
:purpose (d3 / determine-01
:ARG1 (m / mechanism
:mod (a2 / act-02)
:purpose (s3 / study-01
:ARG1 (s5 / small-molecule :name (n / name :op1 "docetaxel"))
:ARG1-of (s4 / schedule-01)))))
# ::id a_pmid_2234_3622.89 ::date 2015-05-29T09:40:00 ::annotator SDL-AMR-09 ::preferred
# ::snt To assess the cell cycle mechanistic effects the mitotic marker pHH3 was quantitated.
# ::save-date Tue Jan 19, 2016 ::file a_pmid_2234_3622_89.txt
(q / quantitate-01
:ARG1 (m / marker
:mod (m2 / mitosis)
:ARG1-of (m4 / mean-01
:ARG2 (p / protein :name (n / name :op1 "HH3")
:ARG1-of (p2 / phosphorylate-01))))
:purpose (a / assess-01
:ARG1 (a2 / affect-01
:ARG1 (c / cycle-02
:ARG1 (c2 / cell))
:mod (m3 / mechanistic))))
# ::id a_pmid_2234_3622.90 ::date 2015-05-29T09:44:56 ::annotator SDL-AMR-09 ::preferred
# ::snt In the sequence when docetaxel was administered before selumetinib, increased levels of pHH3 were observed at the early timepoints (PD1 & PD2) (2.7- and 2.3-fold change, respectively; P<0.0005).
# ::save-date Mon Dec 21, 2015 ::file a_pmid_2234_3622_90.txt
(o / observe-01
:ARG1 (l / level
:ARG1-of (i / increase-01
:ARG1-of (s4 / statistical-test-91
:ARG2 (l2 / less-than :op1 0.0005)))
:quant-of (p4 / protein :name (n / name :op1 "HH3")
:ARG3-of (p5 / phosphorylate-01)))
:time (t / timepoint
:mod (e / early))
:location (s / sequence
:mod (a / administer-01
:ARG1 (s3 / small-molecule :name (n5 / name :op1 "docetaxel"))
:time (b2 / before
:op1 (a2 / administer-01
:ARG1 (s2 / small-molecule :name (n4 / name :op1 "selumetinib"))))))
:ARG1-of (m2 / mean-01
:ARG2 (a3 / and
:op1 (t2 / thing :name (n2 / name :op1 "PD1"))
:op2 (t3 / thing :name (n3 / name :op1 "PD2"))))
:ARG1-of (m3 / mean-01
:ARG2 (a5 / and
:op1 (c / change-01
:ARG2 (p2 / product-of :op1 2.7))
:op2 (c2 / change-01
:ARG2 (p3 / product-of :op1 2.3)))))
# ::id a_pmid_2234_3622.91 ::date 2015-05-29T12:26:53 ::annotator SDL-AMR-09 ::preferred
# ::snt In schedule 2, pHH3 levels were seen to increase following docetaxel (PD7) (3.4-fold; P<0.0005) (Figure 4Aii and 4Bii).
# ::save-date Mon Dec 21, 2015 ::file a_pmid_2234_3622_91.txt
(s / see-01
:ARG1 (i / increase-01
:ARG1 (l / level
:quant-of (p3 / protein :name (n2 / name :op1 "HH3")
:ARG3-of (p4 / phosphorylate-01)))
:ARG2 (p / product-of :op1 3.4)
:ARG1-of (f / follow-01
:ARG2 (s2 / small-molecule :name (n3 / name :op1 "docetaxel")))
:ARG1-of (s4 / statistical-test-91
:ARG2 (l2 / less-than :op1 0.0005)))
:ARG1-of (d2 / describe-01
:ARG0 (a / and
:op1 (f2 / figure :mod "4Aii")
:op2 (f3 / figure :mod "4Bii")))
:condition (s3 / schedule :mod 2)
:ARG1-of (m3 / mean-01
:ARG2 (t / thing :name (n / name :op1 "PD7"))))
# ::id a_pmid_2234_3622.92 ::date 2015-05-29T12:35:08 ::annotator SDL-AMR-09 ::preferred
# ::snt When selumetinib was administered alone levels of pHH3 decreased at several measurement points compared with controls (PD2 P<0.0005; PD4 P<0.005; PD5 P<0.0005; PD6 P<0.0005) consistent with the inhibition of the MEK/ERK pathway resulting in a G1/S arrest.
# ::save-date Sun Jan 3, 2016 ::file a_pmid_2234_3622_92.txt
(d / decrease-01
:ARG1 (l / level
:quant-of (p7 / protein :name (n3 / name :op1 "HH3")
:ARG3-of (p8 / phosphorylate-01)))
:time (a / administer-01
:ARG1 (s / small-molecule :name (n8 / name :op1 "selumetinib")
:mod (a3 / alone)))
:time (p2 / point
:quant (s2 / several)
:mod (m3 / measure-01)
:ARG1-of (m4 / mean-01
:ARG2 (a4 / and
:op1 (t / thing :name (n4 / name :op1 "PD2"))
:op2 (t2 / thing :name (n5 / name :op1 "PD4"))
:op3 (t4 / thing :name (n6 / name :op1 "PD5"))
:op4 (t5 / thing :name (n7 / name :op1 "PD6")))))
:compared-to (c / control)
:ARG1-of (c2 / consistent-01
:ARG2 (i / inhibit-01
:ARG1 (p / pathway :name (n / name :op1 "MEK/ERK"))
:ARG1-of (r / result-01
:ARG2 (a2 / arrest-02
:time (e / event :name (n2 / name :op1 "G1/S"))))))
:ARG1-of (s3 / statistical-test-91
:ARG2 (l2 / less-than :op1 0.0005)))
# ::id a_pmid_2234_3622.93 ::date 2015-05-29T13:41:36 ::annotator SDL-AMR-09 ::preferred
# ::snt Interestingly, in both sequences in the combination there is a reduction in pHH3 compared with the docetaxel alone group at that timepoint (PD2 and PD7) (3.8- and 2.5-fold change, respectively; P<0.0005).
# ::save-date Mon Dec 21, 2015 ::file a_pmid_2234_3622_93.txt
(r / reduce-01
:ARG1 (p4 / protein :name (n / name :op1 "HH3")
:ARG3-of (p5 / phosphorylate-01))
:ARG0-of (i / interest-01)
:location (s / sequence
:mod (b / both)
:mod (c / combine-01))
:compared-to (g / group
:mod (s2 / small-molecule :name (n4 / name :op1 "docetaxel")
:mod (a / alone)))
:time (t / timepoint
:mod (t2 / that)
:ARG1-of (m2 / mean-01
:ARG2 (a2 / and
:op1 (t3 / thing :name (n2 / name :op1 "PD2"))
:op2 (t4 / thing :name (n3 / name :op1 "PD7")))))
:ARG1-of (m5 / mean-01
:ARG2 (a3 / and
:op1 (c2 / change-01
:ARG2 (p / product-of :op1 3.8))
:op2 (c3 / change-01
:ARG2 (p2 / product-of :op1 2.5))))
:ARG1-of (s3 / statistical-test-91
:ARG2 (l / less-than :op1 0.0005)))
# ::id a_pmid_2234_3622.94 ::date 2015-05-29T14:26:40 ::annotator SDL-AMR-09 ::preferred
# ::snt Levels of the apoptotic marker cleaved caspase 3, in tumour tissue taken from the docetaxel followed by selumetinib group, increased in this combination group (16.8-fold change from the control; P<0.0005) compared with the single agents alone (3.5- and 2.4-fold change for docetaxel and selumetinib, respectively) (Figure 4Aiii PD2).
# ::save-date Mon Jan 4, 2016 ::file a_pmid_2234_3622_94.txt
(i / increase-01
:ARG1 (l / level
:quant-of (m / marker :name (n / name :op1 "cleaved" :op2 "caspase" :op3 "3")
:mod (a3 / apoptosis)
:location (t / tissue
:source (t2 / tumor)
:ARG1-of (t3 / take-01
:ARG2 (g / group
:mod (s3 / small-molecule :name (n2 / name :op1 "docetaxel"))
:ARG2-of (f2 / follow-01
:ARG1 (g2 / group
:mod (s2 / small-molecule :name (n3 / name :op1 "selumetinib")))))))))
:ARG4 (a4 / and
:op1 (c / change-01
:ARG1 (c2 / control)
:ARG2 (p2 / product-of :op1 16.8)))
:compared-to (a / agent
:ARG1-of (s / single-02)
:mod (a2 / alone)
:ARG1-of (m2 / mean-01
:ARG2 (a5 / and
:op1 (c3 / change-01
:ARG0 s3
:ARG2 (p3 / product-of :op1 3.5))
:op2 (c4 / change-01
:ARG0 s2
:ARG2 (p4 / product-of :op1 2.4)))))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "4AiiiPD2"))
:location g
:ARG1-of (s4 / statistical-test-91
:ARG2 (l2 / less-than :op1 0.0005)))
# ::id a_pmid_2234_3622.95 ::date 2015-05-29T12:08:32 ::annotator SDL-AMR-09 ::preferred
# ::snt In comparison, tumour tissue analysed in the same study after the chronic dosing schedule of selumetinib did not demonstrate an increase in cleaved caspase 3 levels in the combination group when compared with the single agents alone.
# ::save-date Sun Jan 17, 2016 ::file a_pmid_2234_3622_95.txt
(c / compare-01
:ARG1 (d / demonstrate-01 :polarity -
:ARG0 (t / tissue
:source (t2 / tumor)
:ARG1-of (a3 / analyze-01
:ARG0 (s2 / study-01
:ARG1-of (s3 / same-01)
:time (a4 / after
:op1 (s4 / schedule-01
:ARG1 (d2 / dose-01
:ARG2 (s5 / small-molecule :name (n2 / name :op1 "selumetinib"))
:mod (c4 / chronic)))))))
:ARG1 (i / increase-01
:ARG1 (l / level
:location (g / group
:mod (c2 / combine-01))
:quant-of (p / protein :name (n / name :op1 "cleaved" :op2 "caspase" :op3 "3"))))
:time (c3 / compare-01
:ARG2 (a / agent
:ARG1-of (s / single-02))
:mod (a2 / alone))))
# ::id a_pmid_2234_3622.96 ::date 2015-05-29T09:45:32 ::annotator SDL-AMR-09 ::preferred
# ::snt When selumetinib was dosed before docetaxel an increase in cleaved caspase 3 was not observed in the combination group at any of the sampling timepoints compared with at least one of the monotherapies (Figure 4Biii).
# ::save-date Wed Mar 9, 2016 ::file a_pmid_2234_3622_96.txt
(o / observe-01 :polarity -
:ARG1 (i / increase-01
:ARG1 (p / protein :name (n / name :op1 "cleaved" :op2 "caspase" :op3 "3"))
:compared-to (m2 / monotherapy
:quant (a / at-least :op1 1)
:ARG1-of (i2 / include-91
:ARG2 (m3 / monotherapy))))
:time (d / dose-01
:ARG2 (s / small-molecule :name (n3 / name :op1 "selumetinib"))
:time (b / before
:op1 (d2 / dose-01
:ARG2 (s3 / small-molecule :name (n2 / name :op1 "docetaxel")))))
:location (g / group
:mod (c / combine-01))
:time (t / timepoint
:time-of (s2 / sample-01))
:ARG1-of (d4 / describe-01
:ARG0 (f / figure :mod "4Biii")))
# ::id a_pmid_2234_3622.97 ::date 2015-06-02T09:01:36 ::annotator SDL-AMR-09 ::preferred
# ::snt Representative IHC images from PD2 highlights the increase in pHH3 following docetaxel exposure and the increase in cleaved caspase 3 in the docetaxel followed by selumetinib group (Figure 4C).
# ::save-date Sun Jan 17, 2016 ::file a_pmid_2234_3622_97.txt
(h / highlight-01
:ARG0 (i / image
:ARG0-of (r / represent-01)
:source (t2 / thing :name (n7 / name :op1 "PD2"))
:mod (i4 / immunohistochemistry))
:ARG1 (a / and
:op1 (i2 / increase-01
:ARG1 (p / protein :name (n2 / name :op1 "HH3")
:ARG3-of (p3 / phosphorylate-01))
:ARG1-of (f / follow-01
:ARG2 (e / expose-01
:ARG1 p
:ARG2 (s / small-molecule :name (n3 / name :op1 "docetaxel")))))
:op2 (i3 / increase-01
:ARG1 (p2 / protein :name (n4 / name :op1 "caspase" :op2 "3")
:ARG1-of (c / cleave-01))
:location (g / group
:mod (s2 / small-molecule :name (n5 / name :op1 "docetaxel")
:ARG2-of (f3 / follow-01
:ARG1 (s3 / small-molecule :name (n6 / name :op1 "selumetinib")))))))
:ARG1-of (d / describe-01
:ARG0 (f2 / figure :mod "4C")))
# ::id a_pmid_2234_3622.98 ::date 2015-06-02T09:44:05 ::annotator SDL-AMR-09 ::preferred
# ::snt The data presented here suggests that the combination efficacy effect seen when docetaxel was dosed before selumetinib was due to an increase in apoptosis.
# ::save-date Thu Jun 11, 2015 ::file a_pmid_2234_3622_98.txt
(s / suggest-01
:ARG0 (d / data
:ARG1-of (p / present-01
:location (h / here)))
:ARG1 (c / cause-01
:ARG0 (i / increase-01
:ARG1 (a / apoptosis))
:ARG1 (a2 / affect-01
:ARG0 (e / efficient-01
:ARG1 (c2 / combine-01))
:ARG1-of (s2 / see-01
:time (d2 / dose-01
:ARG2 (s3 / small-molecule :name (n / name :op1 "docetaxel"))
:time (b / before
:op1 (d3 / dose-01
:ARG2 (s4 / small-molecule :name (n2 / name :op1 "selumetinib")))))))))
# ::id a_pmid_2234_3622.99 ::date 2015-06-02T10:16:19 ::annotator SDL-AMR-09 ::preferred
# ::snt Sequence scheduling of selumetinib and the Aurora B kinase inhibitor, barasertib (AZD1152), results in tumour regression and increased cell death
# ::save-date Sun Jun 14, 2015 ::file a_pmid_2234_3622_99.txt
(r / result-01
:ARG1 (s / schedule-01
:ARG1 (a2 / and
:op1 (s2 / small-molecule :name (n / name :op1 "selumetinib"))
:op2 (s3 / small-molecule :name (n2 / name :op1 "barasertib")
:ARG0-of (i2 / inhibit-01
:ARG1 (k / kinase :name (n3 / name :op1 "Aurora" :op2 "B")))))
:manner (s4 / sequence))
:ARG2 (a / and
:op1 (r2 / regress-01
:ARG1 (t / tumor))
:op2 (d / die-01
:ARG1 (c / cell)
:ARG1-of (i / increase-01))))
# ::id a_pmid_2234_3622.100 ::date 2015-06-02T10:32:21 ::annotator SDL-AMR-09 ::preferred
# ::snt The dose-scheduling effects of combining selumetinib and docetaxel lead us to investigate the sequence dependency of selumetinib combined with another mitotic targeting agent, the Aurora B kinase inhibitor, barasertib (AZD1152) (16).
# ::save-date Mon Jun 15, 2015 ::file a_pmid_2234_3622_100.txt
(l / lead-03
:ARG0 (a / affect-01
:ARG0 (c / combine-01
:ARG1 (s / small-molecule :name (n / name :op1 "selumetinib"))
:ARG2 (s2 / small-molecule :name (n2 / name :op1 "docetaxel")))
:ARG1 (s6 / schedule-01
:ARG1 (d2 / dose-01)))
:ARG1 (w / we)
:ARG2 (i / investigate-01
:ARG0 w
:ARG1 (d / depend-01
:ARG0 (s3 / small-molecule :name (n3 / name :op1 "selumetinib")
:ARG1-of (c2 / combine-01
:ARG2 (a2 / agent
:ARG0-of (t / target-01
:ARG1 (m / mitosis))
:ARG1-of (m2 / mean-01
:ARG2 (s5 / small-molecule :name (n5 / name :op1 "barasertib")
:ARG0-of (i3 / inhibit-01
:ARG1 (k / kinase :name (n4 / name :op1 "Aurora" :op2 "B")))))
:mod (a3 / another))))
:ARG1 (s4 / sequence)))
:ARG1-of (d3 / describe-01
:ARG0 (p / publication
:ARG1-of (c3 / cite-01
:ARG2 16))))
# ::id a_pmid_2234_3622.101 ::date 2015-06-02T10:49:07 ::annotator SDL-AMR-09 ::preferred
# ::snt We designed two regimes in which barasertib was dosed at 150 mg kg–1 per qd for 2 consecutive days through a mini-pump (MP) with a 24 h gap followed by selumetinib 25 mg kg–1 per bid for 14 consecutive days (schedule 1) or the reverse of this schedule where barasertib was dosed following selumetinib treatment (schedule 2) (Figure 5A).
# ::save-date Wed Mar 9, 2016 ::file a_pmid_2234_3622_101.txt
(d7 / design-01
:ARG0 (w / we)
:ARG1 (r4 / regime :quant 2
:consist-of (o / or
:op1 (d / dose-01
:ARG2 (a / and
:op1 (s / small-molecule :quant 150 :name (n / name :op1 "barasertib")
:quant (c2 / concentration-quantity :quant 150
:ARG1-of (r / rate-entity-91
:ARG2 (t / temporal-quantity :quant 24
:unit (h / hour)))
:unit (m2 / milligram-per-kilogram))))
:duration (t2 / temporal-quantity :quant 2
:unit (d3 / day
:mod (c / consecutive)))
:instrument (p / pump
:mod (m3 / mini))
:manner (g / gap
:duration (t3 / temporal-quantity :quant 24
:unit h))
:ARG2-of (f / follow-01
:ARG1 (d5 / dose-01
:ARG1 (s2 / small-molecule :name (n2 / name :op1 "selumetinib")
:quant (c3 / concentration-quantity :quant 25
:ARG1-of (r2 / rate-entity-91
:ARG2 (t4 / temporal-quantity :quant 12
:unit h))
:unit (m / milligram-per-kilogram)))
:duration (t5 / temporal-quantity :quant 14
:unit d3)))
:ARG1-of (m9 / mean-01
:ARG2 (s5 / schedule :mod 1)))
:op2 (d6 / dose-01
:ARG1 (s3 / small-molecule :name (n3 / name :op1 "barasertib"))
:ARG2-of (f2 / follow-01
:ARG1 (t6 / treat-03
:ARG3 (s4 / small-molecule :name (n4 / name :op1 "selumetinib"))))
:ARG1-of (d8 / describe-01
:ARG0 (f3 / figure :mod "5A"))
:ARG1-of (m10 / mean-01
:ARG2 (s6 / schedule :mod 2))
:ARG1-of (r3 / reverse-01
:ARG2 d)))))
# ::id a_pmid_2234_3622.102 ::date 2015-06-02T14:53:51 ::annotator SDL-AMR-09 ::preferred
# ::snt The CaLu-6 NSCLC human tumour xenograft model was used in this study as previous experience with both agents allowed us to select appropriate dose levels in order to investigate these schedules (Davies et al, 2007; Wilkinson et al, 2007).
# ::save-date Mon Dec 21, 2015 ::file a_pmid_2234_3622_102.txt
(u / use-01
:ARG1 (m / model
:mod (x2 / xenograft :name (n / name :op1 "CaLu-6")
:mod (t / tumor
:mod (h / human)
:mod (d / disease :name (n2 / name :op1 "NSCLC")))))
:ARG2 (t2 / thing
:ARG1-of (s / study-01)
:mod (t3 / this))
:ARG1-of (c2 / cause-01
:ARG0 (a / allow-01
:ARG0 (e / experience-01
:ARG0 w
:ARG1 (a2 / agent
:mod (b / both))
:time (p7 / previous))
:ARG1 (s2 / select-01
:ARG0 (w / we)
:ARG1 (l / level
:quant-of (d2 / dose-01
:ARG1-of (a3 / appropriate-02)))
:ARG3 (i / investigate-01
:ARG0 w
:ARG1 (s3 / schedule
:mod t3)))))
:ARG1-of (d3 / describe-01
:ARG0 (a4 / and
:op1 (p / publication-91
:ARG0 (a5 / and
:op1 (p2 / person :name (n3 / name :op1 "Davies"))
:op2 (p3 / person
:mod (o / other)))
:time (d4 / date-entity :year 2007))
:op2 (p4 / publication-91
:ARG0 (a6 / and
:op1 (p5 / person :name (n4 / name :op1 "Wilkinson"))
:op2 p3)
:time d4))))
# ::id a_pmid_2234_3622.103 ::date 2015-06-02T15:30:10 ::annotator SDL-AMR-09 ::preferred
# ::snt Selumetinib and barasertib alone resulted in 57% (P<0.005) and 95% (P<0.0005) tumour growth inhibition compared with the vehicle-treated controls at day 21 after the start of dosing.
# ::save-date Tue Dec 15, 2015 ::file a_pmid_2234_3622_103.txt
(a3 / and
:op1 (r / result-01
:ARG1 (s / small-molecule :name (n / name :op1 "selumetinib")
:mod (a / alone)
:ARG1-of (c / compare-01
:ARG2 (c3 / control
:ARG1-of (t2 / treat-04
:ARG2 (v / vehicle)))))
:ARG2 (i / inhibit-01
:ARG1 (g / grow-01
:ARG1 (t / tumor))
:quant (p / percentage-entity :value 57)
:time (a2 / after
:op1 (s2 / start-01
:ARG1 (d / dose-01))
:quant (t3 / temporal-quantity :quant 21
:unit (d2 / day)))
:ARG1-of (s4 / statistical-test-91
:ARG2 (l / less-than :op1 0.005))))
:op2 (r2 / result-01
:ARG1 (s3 / small-molecule :name (n2 / name :op1 "barasertib")
:mod a
:ARG1-of c)
:ARG2 (i2 / inhibit-01
:ARG1 g
:quant (p2 / percentage-entity :value 95)
:time a2
:ARG1-of (s5 / statistical-test-91
:ARG2 (l2 / less-than :op1 0.0005)))))
# ::id a_pmid_2234_3622.104 ::date 2015-06-02T15:31:49 ::annotator SDL-AMR-09 ::preferred
# ::snt In comparison when selumetinib was dosed before barasertib the anti-tumour efficacy was 74% (P<0.0005) in contrast to 106% (P<0.0005) observed when selumetinib was dosed following barasertib.
# ::save-date Sun Jan 3, 2016 ::file a_pmid_2234_3622_104.txt
(e3 / efficient-01
:ARG1 (d / dose-01
:ARG1 (s / small-molecule :name (n / name :op1 "selumetinib"))
:time (b / before
:op1 (d2 / dose-01
:ARG1 (s2 / small-molecule :name (n2 / name :op1 "barasertib")))))
:ARG2 (o / oppose-01
:ARG1 (t / tumor))
:ARG1-of (c / contrast-01
:ARG2 (e2 / efficient-01
:quant (p3 / percentage-entity :value 106)
:ARG1-of (o2 / observe-01
:time (d3 / dose-01
:ARG1 s
:ARG1-of (f / follow-01
:ARG2 s2)))
:ARG1-of (s4 / statistical-test-91
:ARG2 l)))
:ARG1-of (c2 / compare-01)
:quant (p / percentage-entity :value 74)
:ARG1-of (s3 / statistical-test-91
:ARG2 (l / less-than :op1 0.0005)))
# ::id a_pmid_2234_3622.105 ::date 2015-06-02T15:34:02 ::annotator SDL-AMR-09 ::preferred
# ::snt At 21 days after the start of dosing the control, animals had to be culled due to tumour size; however, the monotherapy and combination-treated groups were kept on study for a further 14 days.
# ::save-date Mon Dec 21, 2015 ::file a_pmid_2234_3622_105.txt
(m / multi-sentence
:snt1 (o / obligate-01
:ARG2 (c / cull-01
:ARG1 (a / animal)
:ARG1-of (c2 / cause-01
:ARG0 (s / size-01
:ARG1 (t / tumor)))
:time (a2 / after
:op1 (s2 / start-01
:ARG1 (d / dose-01
:ARG1 (c3 / control)))
:quant (t2 / temporal-quantity :quant 21
:unit (d2 / day)))))
:snt2 (h / have-concession-91
:ARG2 (k / keep-01
:ARG1 (a3 / and
:op1 (g / group
:mod (m2 / monotherapy))
:op2 (g2 / group
:ARG1-of (t3 / treat-04
:ARG2 (c5 / combine-01)))
:ARG1-of (s3 / study-01))
:duration (t5 / temporal-quantity :quant 14
:mod (f / further)
:unit d2))))
# ::id a_pmid_2234_3622.106 ::date 2015-06-02T16:10:24 ::annotator SDL-AMR-09 ::preferred
# ::snt During this time, the tumours in the monotherapy and schedule 2 groups started to re-grow.
# ::save-date Thu Jun 11, 2015 ::file a_pmid_2234_3622_106.txt
(s / start-01
:ARG0 (t / tumor
:source (a / and
:op1 (g / group
:mod (m / monotherapy))
:op2 (g2 / group
:mod (s2 / schedule :mod 2))))
:ARG1 (g3 / grow-01
:ARG1 t
:mod (a2 / again))
:time (t3 / time
:mod (t4 / this)))
# ::id a_pmid_2234_3622.107 ::date 2015-06-03T13:18:28 ::annotator SDL-AMR-09 ::preferred
# ::snt Interestingly, the tumours in the group where barasertib was administered before selumetinib (schedule 1) tumour re-growth was delayed (Figure 5B).
# ::save-date Thu Jun 11, 2015 ::file a_pmid_2234_3622_107.txt
(d / delay-01
:ARG1 (g / grow-01
:ARG1 (t / tumor
:source (g2 / group
:ARG2-of (a / administer-01
:ARG1 (s / small-molecule :name (n / name :op1 "barasertib"))
:time (b / before
:op1 (a2 / administer-01
:ARG1 (s2 / small-molecule :name (n2 / name :op1 "selumetinib"))))
:ARG2-of (m / mean-01
:ARG1 (s3 / schedule :mod 1))))))
:mod (i / interesting)
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod "5B")))
# ::id a_pmid_2234_3622.108 ::date 2015-06-03T13:52:34 ::annotator SDL-AMR-09 ::preferred
# ::snt In order to investigate this further, we performed pharmacodynamic analysis on tumour tissue.
# ::save-date Tue Jul 28, 2015 ::file a_pmid_2234_3622_108.txt
(p / perform-02
:ARG0 (w / we)
:ARG1 (a / analyze-01
:ARG0 w
:ARG1 (t / tissue
:mod (t2 / tumor))
:mod (p2 / pharmacodynamic))
:purpose (i / investigate-01
:ARG0 w
:ARG1 (t3 / this)
:degree (f / further)))
# ::id a_pmid_2234_3622.109 ::date 2015-06-03T14:03:40 ::annotator SDL-AMR-09 ::preferred
# ::snt In schedule 1 we analysed tumour tissue at 24 h after the end of the barasertib infusion (PD1) and at the end of the selumetinib-dosing period (PD2) (Figure 5A).
# ::save-date Sun Jan 3, 2016 ::file a_pmid_2234_3622_109.txt
(a / analyze-01
:ARG0 (w / we)
:ARG1 (t / tissue
:mod (t2 / tumor))
:time (a2 / after
:op1 (e / end-01
:ARG1 (i / infuse-01
:ARG1 (s / small-molecule :name (n / name :op1 "barasertib"))))
:quant (t3 / temporal-quantity :quant 24
:unit (h / hour)))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod "5A"))
:location (s3 / schedule :mod 1)
:time (a5 / and
:op1 (a3 / after
:op1 (e3 / end-01
:ARG1 (p2 / period
:duration-of (i2 / infuse-01
:ARG2 (s4 / small-molecule :name (n3 / name :op1 "barasertib"))
:ARG1-of (d3 / describe-01
:ARG2 (s5 / string-entity :value "PD1"))))))
:op2 (a4 / after
:op1 (e2 / end-01
:ARG1 (p / period
:duration-of (d / dose-01
:ARG2 (s2 / small-molecule :name (n2 / name :op1 "selumetinib")))
:ARG1-of (d4 / describe-01
:ARG2 (s6 / string-entity :value "PD2")))))))
# ::id a_pmid_2234_3622.110 ::date 2015-06-03T14:17:55 ::annotator SDL-AMR-09 ::preferred
# ::snt In schedule 2, tumours were harvested 24 h after the end of the barasertib infusion at the end of the study (PD3) (Figure 5A).
# ::save-date Sun Jan 3, 2016 ::file a_pmid_2234_3622_110.txt
(h / harvest-01
:ARG1 (t / tumor)
:time (a / and
:op1 (a2 / after
:op1 (e / end-01
:ARG1 (i / infuse-01
:ARG1 (s / small-molecule :name (n / name :op1 "barasertib")))))
:op2 (a3 / after
:op1 (e2 / end-01
:ARG1 (t2 / thing
:ARG1-of (s2 / study-01))))
:quant (t3 / temporal-quantity :quant 24
:unit (h2 / hour)))
:location (s3 / schedule :mod 2)
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "5A"))
:ARG1-of (d2 / describe-01
:ARG2 (s4 / string-entity :value "PD3")))
# ::id a_pmid_2234_3622.111 ::date 2015-06-03T14:23:05 ::annotator SDL-AMR-09 ::preferred
# ::snt Using flow cytometry we assessed tissues for polyploidy and demonstrated that compared with the vehicle-treated control group, barasertib-treated tumours resulted in increased polyploidy (1.7-fold change; P<0.05) in the PD1 samples consistent with the mechanism of this agent (Figure 5C) (Wilkinson et al, 2007).
# ::save-date Sun Dec 20, 2015 ::file a_pmid_2234_3622_111.txt
(a / and
:op1 (a2 / assess-01
:ARG0 (w / we)
:ARG1 (t / tissue)
:ARG2 (p / polyploidy))
:op2 (d / demonstrate-01
:ARG0 w
:ARG1 (r / result-01
:ARG1 (t2 / tumor
:ARG1-of (t3 / treat-04
:ARG2 (s / small-molecule :name (n / name :op1 "barasertib")))
:ARG1-of (c3 / compare-01
:ARG2 (g / group
:ARG0-of (c4 / control-01)
:ARG1-of (t6 / treat-03
:ARG2 (v / vehicle)))))
:ARG2 (p2 / polyploidy
:ARG1-of (i / increase-01
:ARG2 (p3 / product-of :op1 1.7)
:ARG2-of (m / mean-01
:ARG1 (c / change-01
:ARG1 p2))
:source (s2 / sample-01
:ARG2 (t4 / thing :name (n2 / name :op1 "PD1")))
:ARG1-of (c2 / consistent-01
:ARG2 (m2 / mechanism
:poss (a3 / agent
:mod (t5 / this))))
:ARG1-of (s3 / statistical-test-91
:ARG2 (l / less-than :op1 0.05))))))
:ARG2-of (u / use-01
:ARG0 w
:ARG1 (c5 / cytometry
:mod (f / flow)))
:ARG1-of (d2 / describe-01
:ARG0 (f2 / figure :mod "5C"))
:ARG1-of (d3 / describe-01
:ARG0 (p4 / publication-91
:ARG0 (a4 / and
:op1 (p5 / person :name (n3 / name :op1 "Wilkinson"))
:op2 (p6 / person
:mod (o / other)))
:time (d4 / date-entity :year 2007))))
# ::id a_pmid_2234_3622.112 ::date 2015-06-03T15:03:40 ::annotator SDL-AMR-09 ::preferred
# ::snt In the same experiment, we monitored the population of sub G1 cells in these groups.
# ::save-date Mon Jun 15, 2015 ::file a_pmid_2234_3622_112.txt
(m / monitor-01
:ARG0 (w / we)
:ARG1 (p / population
:consist-of (c / cell-line :name (n / name :op1 "sub" :op2 "G1")))
:location (g / group
:mod (t / this))
:medium (e / experiment-01
:ARG1-of (s / same-01)))
# ::id a_pmid_2234_3622.113 ::date 2015-06-03T15:23:12 ::annotator SDL-AMR-09 ::preferred
# ::snt At the end of the dosing period in schedule 1 (PD2), there was a significant increase (3.5-fold change; P<0.0005) in the sub G1 population in the combination compared with the vehicle-treated controls and selumetinib monotherapy (Figure 5Cii).
# ::save-date Sun Jan 3, 2016 ::file a_pmid_2234_3622_113.txt
(i / increase-01
:ARG1 (p / population
:consist-of (c / cell-line :name (n / name :op1 "sub" :op2 "G1"))
:ARG1-of (c3 / combine-01))
:ARG2 (p2 / product-of :op1 3.5
:ARG2-of (c2 / change-01))
:ARG1-of (s / significant-02)
:ARG2-of (m / mean-01)
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "5Cii"))
:ARG1-of (c4 / compare-01
:ARG2 (a / and
:op1 (c5 / control
:ARG1-of (t / treat-04
:ARG2 (v / vehicle)))
:op2 (m2 / monotherapy
:mod (s2 / small-molecule :name (n2 / name :op1 "selumetinib")))))
:time (a2 / after
:op1 (e / end-01
:ARG1 (p4 / period
:duration-of (d2 / dose-01)
:ARG1-of (d3 / describe-01
:ARG2 (s5 / string-entity :value "PD2"))
:time (s3 / schedule :mod 1))))
:ARG1-of (s4 / statistical-test-91
:ARG2 (l / less-than :op1 0.0005)))
# ::id a_pmid_2234_3622.114 ::date 2015-06-03T15:48:09 ::annotator SDL-AMR-09 ::preferred
# ::snt In comparison, the sub G1 populations in schedule 2 (PD3) were increased ∼2-fold in both the monotherapy and combination groups (Figure 5Dii).
# ::save-date Sun Jan 3, 2016 ::file a_pmid_2234_3622_114.txt
(i / increase-01
:ARG1 (p / population
:consist-of (c2 / cell-line :name (n / name :op1 "sub" :op2 "G1")))
:ARG2 (a2 / approximately
:op1 (p2 / product-of :op1 2))
:time (s / schedule :mod 2
:ARG1-of (d2 / describe-01
:ARG2 (s2 / string-entity :value "PD3")))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "5Dii"))
:ARG1-of (c / compare-01)
:location (a / and
:op1 (g / group
:mod (m / monotherapy))
:op2 (g2 / group
:ARG3-of (c3 / combine-01))))
# ::id a_pmid_2234_3622.115 ::date 2015-06-03T16:00:12 ::annotator SDL-AMR-09 ::preferred
# ::snt These results suggest that the sustained anti-tumour effect and regression observed when barasertib is scheduled before selumetinib is likely to be due to an avoidance of cell cycle-mediated antagonism which allowed an increase in cell death.
# ::save-date Mon Dec 21, 2015 ::file a_pmid_2234_3622_115.txt
(s / suggest-01
:ARG0 (t / thing
:ARG2-of (r / result-01)
:mod (t2 / this))
:ARG1 (l / likely-01
:ARG1 (c / cause-01
:ARG0 (a / avoid-01
:ARG1 (a2 / antagonize-02
:ARG1-of (m / mediate-01
:ARG0 (c2 / cycle-02
:ARG1 (c3 / cell)))
:ARG0-of (a3 / allow-01
:ARG1 (i / increase-01
:ARG1 (d / die-01
:ARG1 (c4 / cell))))))
:ARG1 (a4 / and
:op1 (a5 / affect-01
:ARG2 (o / oppose-01
:ARG1 (t3 / tumor))
:ARG1-of (s6 / sustain-01))
:op2 (r2 / regress-01)
:ARG1-of (o2 / observe-01
:time (s2 / schedule-01
:ARG1 (s3 / small-molecule :name (n / name :op1 "barasertib"))
:ARG3 (b / before
:op1 (s4 / schedule-01
:ARG1 (s5 / small-molecule :name (n2 / name :op1 "selumetinib"))))))))))
# ::id bel_pmid_1002_9589.23800 ::date 2015-04-02T02:24:15 ::annotator SDL-AMR-09 ::preferred
# ::snt We present a model in which activation of the MAPK cascade signals via c-fos/c-jun family members to activate alpha 2 integrin gene expression.
# ::save-date Sun Jan 3, 2016 ::file bel_pmid_1002_9589_23800.txt
(p2 / present-01
:ARG0 (w / we)
:ARG1 (m / model
:location-of (s / signal-07
:ARG0 (a / activate-01
:ARG1 (p / pathway :name (n / name :op1 "MAPK")))
:instrument (m2 / member
:ARG1-of (i / include-91
:ARG2 (a2 / and
:op1 (p3 / protein-family :name (n2 / name :op1 "c-fos"))
:op2 (p4 / protein-family :name (n3 / name :op1 "c-jun")))))
:purpose (a3 / activate-01
:ARG0 a
:ARG1 (e / express-03
:ARG1 (g / gene :name (n4 / name :op1 "alpha" :op2 "2" :op3 "integrin")))))))
# ::id bel_pmid_1002_9589.23888 ::date 2015-04-02T02:33:06 ::annotator SDL-AMR-09 ::preferred
# ::snt In addition, constitutive activation of the pathway via expression of the constitutively active mutants of MAPKK1 or MAPKK2 induced the expression of the platelet/megakaryocytic-specific genes alpha IIb and eta 3 .
# ::save-date Sat Jan 2, 2016 ::file bel_pmid_1002_9589_23888.txt
(a / and
:op2 (i / induce-01
:ARG0 (a2 / activate-01
:ARG1 (p / pathway)
:mod (c / constitutive)
:manner (e / express-03
:ARG2 (o / or
:op1 (e2 / enzyme :name (n / name :op1 "MAPKK1"))
:op2 (e3 / enzyme :name (n2 / name :op1 "MAPKK2"))
:ARG1-of (m2 / mutate-01)
:ARG0-of (a3 / activity-06
:mod c))))
:ARG2 (e4 / express-03
:ARG1 (a5 / and
:op1 (g / gene :name (n3 / name :op1 "alpha" :op2 "IIb"))
:op2 (g2 / gene :name (n4 / name :op1 "beta3"))
:ARG1-of (s / specific-02
:ARG2 (c3 / cell :name (n5 / name :op1 "platelet")
:source (c4 / cell :name (n6 / name :op1 "megakaryocyte"))))))))
# ::id bel_pmid_1008_0909.21272 ::date 2015-04-02T02:47:09 ::annotator SDL-AMR-09 ::preferred
# ::snt Using these methods, we found that JAK2 was essential for signal transduction but that loss of TYK2 made no appreciable difference in tyrosine phosphorylation of downstream molecules, including Mpl, STAT3, and Shc (33).....In fact, tyrosine phosphorylation of STATs and DNA binding assays seem to be almost interchangeable measures of transcriptional activity.
# ::save-date Tue Jan 19, 2016 ::file bel_pmid_1008_0909_21272.txt
(m / multi-sentence
:snt1 (f / find-01
:ARG0 (w / we)
:ARG1 (c / contrast-01
:ARG1 (e / essential
:domain (e2 / enzyme :name (n / name :op1 "JAK2"))
:purpose (t / transduce-01
:ARG1 (s / signal-07)))
:ARG2 (m2 / make-01
:ARG0 (l / lose-02
:ARG1 (e3 / enzyme :name (n2 / name :op1 "TYK2")))
:ARG1 (d / difference
:ARG1-of (a / appreciate-03
:ARG1-of (p9 / possible-01 :polarity -)))
:ARG3 (p / phosphorylate-01
:ARG1 (a2 / amino-acid :name (n3 / name :op1 "tyrosine")
:part-of (m5 / molecule
:location (d2 / downstream)
:ARG2-of (i / include-01
:ARG1 (a3 / and
:op1 (p2 / protein :name (n4 / name :op1 "Mpl"))
:op2 (p3 / protein :name (n5 / name :op1 "STAT3"))
:op3 (p4 / protein :name (n6 / name :op1 "Shc")))))))))
:ARG1-of (d3 / describe-01
:ARG0 (p5 / publication
:ARG1-of (c2 / cite-01
:ARG2 33)))
:manner (u / use-01
:ARG1 (m3 / method
:mod (t2 / this))))
:snt2 (s3 / seem-01
:ARG1 (a4 / and
:op1 (p6 / phosphorylate-01
:ARG1 (a5 / amino-acid :name (n7 / name :op1 "tyrosine")
:part-of (p7 / protein :name (n8 / name :op1 "STAT"))))
:op2 (a6 / assay-01
:ARG1 (b / bind-01
:ARG1 (n9 / nucleic-acid :wiki "DNA" :name (n10 / name :op1 "DNA"))))
:ARG2-of (m4 / measure-01
:ARG1 (a7 / activity-06
:ARG1 (t3 / transcribe-01))
:ARG1-of (i3 / interchange-01
:mod (a8 / almost)
:ARG1-of (p8 / possible-01))))
:mod (i2 / in-fact)))
# ::id bel_pmid_1008_0909.24618 ::date 2015-04-02T03:25:22 ::annotator SDL-AMR-09 ::preferred
# ::snt It has been difficult to interpret the physiologic role of STAT signaling in megakaryocyte development. In multiple cell lines it was reported that TPO induced activation of both STAT3 and STAT5 (5A and 5B) (26, 28?30, 37, 38)....However, when purified murine megakaryocyte extracts were examined, we found that STAT3 was much more pronounced in both tyrosine phosphorylation and DNA binding activity than STAT5 (32)
# ::save-date Mon Dec 21, 2015 ::file bel_pmid_1008_0909_24618.txt
(m / multi-sentence
:snt1 (d / difficult
:domain (i / interpret-01
:ARG1 (r / role
:mod (p2 / physiologic)
:poss (s / signal-07
:ARG0 (p3 / protein :name (n / name :op1 "STAT")))
:purpose (d2 / develop-02
:ARG1 (c / cell :name (n2 / name :op1 "megakaryocyte"))))))
:snt2 (r2 / report-01
:ARG1 (i2 / induce-01
:ARG0 (p4 / protein :name (n3 / name :op1 "TPO"))
:ARG2 (a / activate-01
:ARG1 (a2 / and
:op1 (p5 / protein :name (n4 / name :op1 "STAT3"))
:op2 (p6 / protein :name (n5 / name :op1 "STAT5"))
:mod (b / both))))
:ARG1-of (d3 / describe-01
:ARG0 (a3 / and
:op1 (f / figure :mod "5A")
:op2 (f2 / figure :mod "5B")
:op3 (p7 / publication
:ARG1-of (c2 / cite-01
:ARG2 (a4 / and :op1 26 :op2 28 :op3 30 :op4 37 :op5 38)))))
:location (c5 / cell-line
:quant (m5 / multiple)))
:snt3 (c6 / contrast-01
:ARG2 (f3 / find-01
:ARG0 (w / we)
:ARG1 (p / pronounced-02
:ARG1 (p9 / protein :name (n6 / name :op1 "STAT3"))
:degree (m2 / more
:quant (m3 / much))
:condition (a5 / and
:op1 (p10 / phosphorylate-01
:ARG1 (a6 / amino-acid :name (n7 / name :op1 "tyrosine")))
:op2 (a7 / activity-06
:ARG1 (b2 / bind-01
:ARG1 (n9 / nucleic-acid :wiki "DNA" :name (n10 / name :op1 "DNA"))))
:mod (b3 / both))
:compared-to (p11 / protein :name (n8 / name :op1 "STAT5")))
:time (e / examine-01
:ARG1 (t / thing
:ARG1-of (e2 / extract-01
:ARG2 (m6 / megakaryocyte
:mod (m4 / murine))
:ARG1-of (p13 / purify-01)))))
:ARG1-of (d5 / describe-01
:ARG0 (p12 / publication
:ARG1-of (c3 / cite-01
:ARG2 32)))))
# ::id bel_pmid_1008_5062.23884 ::date 2015-04-02T03:42:42 ::annotator SDL-AMR-09 ::preferred
# ::snt Activation of MEK1 and MEK2 involves phosphorylation upon conserved serine residues (Ser-218 and Ser-222 on MEK1, Ser-222 and Ser-226 on MEK2
# ::save-date Tue Apr 21, 2015 ::file bel_pmid_1008_5062_23884.txt
(i / involve-01
:ARG0 (a2 / activate-01
:ARG1 (a3 / and
:op1 (e / enzyme :name (n2 / name :op1 "MEK1"))
:op2 (e2 / enzyme :name (n3 / name :op1 "MEK2"))))
:ARG1 (p2 / phosphorylate-01
:ARG1 (r / residue
:mod (a4 / amino-acid :name (n4 / name :op1 "serine"))
:ARG1-of (c / conserve-01)
:ARG1-of (m / mean-01
:ARG2 (a5 / and
:op1 (a6 / and
:op1 (a7 / amino-acid :mod 218 :name (n5 / name :op1 "serine"))
:op2 (a8 / amino-acid :mod 222 :name (n6 / name :op1 "serine"))
:part-of e)
:op2 (a9 / and
:op1 (a10 / amino-acid :mod 222 :name (n7 / name :op1 "serine"))
:op2 (a11 / amino-acid :mod 226 :name (n8 / name :op1 "serine"))
:part-of e2))))))
# ::id bel_pmid_1019_4465.17324 ::date 2015-04-02T03:29:34 ::annotator SDL-AMR-09 ::preferred
# ::snt c-Cbl is tyrosine-phosphorylated, binds to Fyn upon insulin stimulation, and is translocated to small invaginations of the plasma membrane, called caveolae, after insulin stimulation
# ::save-date Mon Jan 4, 2016 ::file bel_pmid_1019_4465_17324.txt
(a / and
:op1 (p / phosphorylate-01
:ARG1 (a2 / amino-acid :name (n2 / name :op1 "tyrosine")
:part-of (p3 / protein :name (n / name :op1 "c-Cbl"))))
:op2 (b / bind-01
:ARG1 p3
:ARG2 (e / enzyme :name (n3 / name :op1 "Fyn"))
:condition (s / stimulate-01
:ARG2 (p4 / protein :name (n4 / name :op1 "insulin"))))
:op3 (t / translocate-01
:ARG1 p3
:ARG2 (i / invaginate-01
:ARG1 (m / membrane
:mod (p2 / plasma)
:ARG1-of (c / call-01
:ARG2 (c2 / caveolae)))
:mod (s2 / small))
:time (a3 / after
:op1 s)))
# ::id bel_pmid_1019_4465.17346 ::date 2015-04-02T05:27:43 ::annotator SDL-AMR-09 ::preferred
# ::snt Insulin and IGF-1 stimulation also promote association between IRS-1 and aVb3 integrin (vitronectin receptor)
# ::save-date Mon Jan 4, 2016 ::file bel_pmid_1019_4465_17346.txt
(p / promote-01
:ARG0 (s / stimulate-01
:ARG1 (a2 / and
:op1 (p6 / protein :name (n5 / name :op1 "insulin"))
:op2 (p3 / protein :name (n2 / name :op1 "IGF-1"))))
:ARG1 (a3 / associate-01
:ARG0 a2
:ARG1 (p2 / protein :name (n3 / name :op1 "IRS-1"))
:ARG2 (p5 / protein :name (n6 / name :op1 "aVb3" :op2 "integrin")
:ARG1-of (d / describe-01
:ARG2 (r / receptor
:mod (p4 / protein :name (n / name :op1 "vitronectin"))))))
:mod (a / also))
# ::id bel_pmid_1019_4465.17828 ::date 2015-04-02T05:34:18 ::annotator SDL-AMR-09 ::preferred
# ::snt Thiazolidinediones (TZDs), the class of insulin sensitizers that act through the nuclear receptor PPAR-g, increase CAP expression levels and c-Cbl phosphorylation significantly in adipocytes (54), possibly contributing to their insulin sensitizing effect
# ::save-date Sun Jan 3, 2016 ::file bel_pmid_1019_4465_17828.txt
(i / increase-01
:ARG0 (t / thiazolidinedione
:mod (c / class
:mod (m / molecular-physical-entity
:ARG0-of (s / sensitize-01
:ARG1 (p2 / protein :name (n3 / name :op1 "insulin")))
:ARG0-of (a / act-01
:instrument (r / receptor :name (n2 / name :op1 "PPAR-g")
:mod (n / nucleus))))))
:ARG1 (a2 / and
:op1 (l / level
:degree-of (e / express-03
:ARG2 (p5 / protein :name (n6 / name :op1 "CAP"))))
:op2 (p3 / phosphorylate-01
:ARG1 (p6 / protein :name (n4 / name :op1 "c-Cbl"))))
:ARG2 (s2 / significant-02)
:location (c2 / cell :name (n5 / name :op1 "adipocyte"))
:ARG1-of (d / describe-01
:ARG0 (p4 / publication
:ARG1-of (c4 / cite-01
:ARG2 54)))
:ARG0-of (c3 / contribute-01
:ARG1 (a3 / affect-01
:ARG2 (s3 / sensitize-01
:ARG0 t
:ARG1 p2))
:ARG1-of (p / possible-01)))
# ::id bel_pmid_1019_4465.19902 ::date 2015-04-02T06:43:55 ::annotator SDL-AMR-09 ::preferred
# ::snt Interestingly, this NPXY sequence is also a receptor internalization motif found in many members of the tyrosine kinase receptor family, the low-density lipoprotein receptor (11-13), and the transferrin receptor (14), all of which are internalized in a ligand-dependent fashion.
# ::save-date Mon Jan 4, 2016 ::file bel_pmid_1019_4465_19902.txt
(m / motif
:ARG0-of (i / internalize-01
:ARG1 (r / receptor))
:domain (d / dna-sequence :name (n / name :op1 "NPXY")
:mod (t / this))
:ARG1-of (f2 / find-01
:location (m2 / member
:quant (m3 / many)
:ARG1-of (i2 / include-91
:ARG2 (p / protein-family :name (n2 / name :op1 "tyrosine" :op2 "kinase" :op3 "receptor")))
:ARG1-of (i4 / internalize-01
:manner (d4 / depend-01
:ARG1 (l / ligand)))
:example (a / and
:op1 (p2 / protein :name (n3 / name :op1 "low-density" :op2 "lipoprotein" :op3 "receptor")
:ARG1-of (d2 / describe-01
:ARG0 (p3 / publication
:ARG1-of (c / cite-01
:ARG2 (v / value-interval :op1 11 :op2 13)))))
:op2 (p4 / protein :name (n4 / name :op1 "transferrin" :op2 "receptor")
:ARG1-of (d3 / describe-01
:ARG0 (p5 / publication
:ARG1-of (c2 / cite-01
:ARG2 14)))))))
:ARG2-of (i3 / interest-01)
:mod (a2 / also))
# ::id bel_pmid_1019_4465.19968 ::date 2015-04-02T07:41:15 ::annotator SDL-AMR-09 ::preferred
# ::snt Csk has been reported to associate with IRS-1 through its SH2 domain and promote dephosphorylation of the focal adhesion kinase (FAK) in an insulin-dependent manner (56).
# ::save-date Sun Jan 17, 2016 ::file bel_pmid_1019_4465_19968.txt
(r / report-01
:ARG1 (a / and
:op1 (a2 / associate-01
:ARG1 (p6 / protein-segment :name (n6 / name :op1 "SH2" :op2 "domain")
:part-of (p / protein :name (n / name :op1 "Csk")))
:ARG2 (p2 / protein :name (n2 / name :op1 "IRS-1")))
:op2 (p3 / promote-01
:ARG0 p
:ARG1 (d2 / dephosphorylate-01
:ARG1 (e / enzyme :name (n4 / name :op1 "focal" :op2 "adhesion" :op3 "kinase"))
:manner (d4 / depend-01
:ARG1 (p7 / protein :name (n3 / name :op1 "insulin"))))))
:ARG1-of (d5 / describe-01
:ARG0 (p5 / publication
:ARG1-of (c / cite-01
:ARG2 56))))
# ::id bel_pmid_1019_4465.20030 ::date 2015-04-02T08:15:35 ::annotator SDL-AMR-09 ::preferred
# ::snt In smooth muscle cells, blocking ligand occupancy of aVb3 integrin reduces IGF-1-induced IRS-1 phosphorylation
# ::save-date Sun Dec 20, 2015 ::file bel_pmid_1019_4465_20030.txt
(r / reduce-01
:ARG0 (b / block-01
:ARG1 (o / occupy-01
:ARG0 (l / ligand)
:ARG1 (i2 / integrin :name (n / name :op1 "aVb3"))))
:ARG1 (p / phosphorylate-01
:ARG1 (p2 / protein :name (n2 / name :op1 "IRS-1"))
:ARG2-of (i / induce-01
:ARG0 (p3 / protein :name (n3 / name :op1 "IGF-1"))))
:location (c / cell
:mod (m / muscle
:ARG1-of (s / smooth-06))))
# ::id bel_pmid_1019_4465.20066 ::date 2015-04-02T08:27:14 ::annotator SDL-AMR-09 ::preferred
# ::snt Nck associates with IRS-1 (45), many different tyrosine kinases, several serine/threonine kinases through its SH2 domain, as well as Sos through its SH3 domains
# ::save-date Mon Jan 4, 2016 ::file bel_pmid_1019_4465_20066.txt
(a / associate-01
:ARG0 (p3 / protein-segment :name (n8 / name :op1 "SH2" :op2 "domain")
:part-of (p / protein :name (n / name :op1 "Nck")))
:ARG1 (a2 / and
:op1 (e / enzyme :name (n2 / name :op1 "tyrosine" :op2 "kinase")
:quant (m / many)
:ARG1-of (d / differ-02))
:op2 (o / or
:op1 (e2 / enzyme :name (n3 / name :op1 "serine" :op2 "kinase"))
:op2 (e3 / enzyme :name (n4 / name :op1 "threonine" :op2 "kinase"))
:quant (s / several))
:op3 (p4 / protein-segment :name (n9 / name :op1 "SH3" :op2 "domain")
:part-of (p2 / protein :name (n6 / name :op1 "Sos"))))
:ARG2 (p5 / protein :name (n5 / name :op1 "IRS-1"))
:ARG1-of (d2 / describe-01
:ARG0 (p6 / publication
:ARG1-of (c / cite-01
:ARG2 45))))
# ::id bel_pmid_1019_4465.21192 ::date 2015-04-02T14:26:15 ::annotator SDL-AMR-09 ::preferred
# ::snt Gab-1 is heavily phosphorylated by the epidermal growth factor receptor, but poorly by the insulin receptor
# ::save-date Sun Jan 17, 2016 ::file bel_pmid_1019_4465_21192.txt
(c / contrast-01
:ARG1 (p / phosphorylate-01
:ARG1 (p4 / protein :name (n2 / name :op1 "Gab-1"))
:ARG2 (e / enzyme :name (n / name :op1 "epidermal" :op2 "growth" :op3 "factor" :op4 "receptor"))
:degree (h2 / heavy))
:ARG2 (p2 / phosphorylate-01
:ARG1 p4
:ARG2 (r / receptor
:mod (p5 / protein :name (n3 / name :op1 "insulin")))
:degree (p3 / poor)))
# ::id bel_pmid_1019_4465.21226 ::date 2015-04-08T00:00:00 ::annotator SDL-AMR-09 ::preferred
# ::snt Recently, it was shown that Fyn is one of the kinases responsible for the phosphorylation of caveolin
# ::save-date Wed Apr 29, 2015 ::file bel_pmid_1019_4465_21226.txt
(s / show-01
:ARG1 (e / enzyme :name (n / name :op1 "Fyn")
:ARG1-of (i / include-91
:ARG2 (k / kinase
:ARG0-of (r / responsible-01
:ARG1 (p / phosphorylate-01
:ARG1 (p2 / protein :name (n2 / name :op1 "caveolin")))))))
:time (r2 / recent))
# ::id bel_pmid_1019_4465.21256 ::date 2015-04-13T13:37:33 ::annotator SDL-AMR-09 ::preferred
# ::snt It also contains an additional binding site located in the phosphorylated kinase activation loop of the insulin receptor but is only very slightly phosphorylated by insulin receptor.
# ::save-date Mon Jan 4, 2016 ::file bel_pmid_1019_4465_21256.txt
(h / have-concession-91
:ARG1 (c / contain-01
:ARG0 (i / it)
:ARG1 (p3 / protein-segment
:location (l2 / loop
:ARG0-of (a / activate-01
:ARG1 (k / kinase
:ARG3-of (p / phosphorylate-01)))
:poss (r2 / receptor
:mod (p4 / protein :name (n / name :op1 "insulin"))))
:mod (a2 / additional)
:ARG1-of (b / bind-01))
:mod (a3 / also))
:ARG2 (p2 / phosphorylate-01
:ARG1 i
:ARG2 r2
:degree (s2 / slight
:degree (v / very)
:mod (o / only))))
# ::id bel_pmid_1019_4465.22614 ::date 2015-04-04T09:13:52 ::annotator SDL-AMR-09 ::preferred
# ::snt Crk has been reported to associate with tyrosine-phosphorylated proteins, such as p130Cas and paxillin (42, 43), involved in the rearrangement of cytoskeletal components, through its SH2 domain.
# ::save-date Wed Apr 29, 2015 ::file bel_pmid_1019_4465_22614.txt
(r / report-01
:ARG1 (a / associate-01
:ARG1 (p / protein :name (n / name :op1 "Crk"))
:ARG2 (p2 / protein
:example (a3 / and
:op1 (p4 / protein :name (n3 / name :op1 "p130Cas"))
:op2 (p5 / protein :name (n4 / name :op1 "paxillin"))
:ARG1-of (d / describe-01
:ARG0 (p6 / publication
:ARG1-of (c / cite-01
:ARG2 (a4 / and :op1 42 :op2 43)))))
:part (a2 / amino-acid :name (n2 / name :op1 "tyrosine"))
:ARG1-of (p3 / phosphorylate-01)
:ARG1-of (i / involve-01
:ARG2 (r2 / rearrange-01
:ARG1 (c2 / component
:part-of (c3 / cytoskeleton)))
:instrument (p7 / protein-segment :name (n5 / name :op1 "SH2" :op2 "domain")
:part-of p)))))
# ::id bel_pmid_1019_4465.22706 ::date 2015-04-04T09:27:39 ::annotator SDL-AMR-09 ::preferred
# ::snt c-Cbl associated protein (CAP) that has three sequential SH3 domains is specifically expressed in insulin-responsive cell types and associates with both c- Cbl and the insulin receptor
# ::save-date Sun Jan 3, 2016 ::file bel_pmid_1019_4465_22706.txt
(a / and
:op1 (e / express-03
:ARG2 (p / protein :name (n / name :op1 "c-Cbl" :op2 "associated" :op3 "protein")
:ARG0-of (h / have-03
:ARG1 (p2 / protein-segment :quant 3 :name (n2 / name :op1 "SH3" :op2 "domain")
:mod (s / sequential))))
:ARG3 (t / type-03
:ARG1 (c / cell
:ARG0-of (r / responsive-02
:ARG1 (p4 / protein :name (n4 / name :op1 "insulin")))))
:ARG1-of (s2 / specific-02))
:op2 (a2 / associate-01
:ARG1 p
:ARG2 (a3 / and
:op1 (p3 / protein :name (n3 / name :op1 "c-Cbl"))
:op2 (r2 / receptor
:mod p4))))
# ::id bel_pmid_1019_4465.22914 ::date 2015-04-04T09:38:05 ::annotator SDL-AMR-09 ::preferred
# ::snt Recently, phosphorylated p62dok was demonstrated to associate with the GTPase-activating protein (GAP) for Ras.
# ::save-date Thu Jan 14, 2016 ::file bel_pmid_1019_4465_22914.txt
(d / demonstrate-01
:ARG1 (a / associate-01
:ARG1 (p / protein :name (n2 / name :op1 "p62dok")
:ARG3-of (p2 / phosphorylate-01))
:ARG2 (p3 / protein :name (n3 / name :op1 "GTPase-activating" :op2 "protein"))
:beneficiary (p4 / protein-family :name (n / name :op1 "Ras")))
:time (r / recent))
# ::id bel_pmid_1019_4465.23034 ::date 2015-04-04T09:42:59 ::annotator SDL-AMR-09 ::preferred
# ::snt In the case of insulin, it is unclear whether SHIP associates with IRS proteins or the insulin receptor, although a recent report has demonstrated SHIP association with IRS-2 in response to erythropoietin
# ::save-date Sun Jan 3, 2016 ::file bel_pmid_1019_4465_23034.txt
(h / have-concession-91
:ARG1 (e / exemplify-01
:ARG0 (p4 / protein :name (n / name :op1 "insulin"))
:ARG1 (c / clear-06 :polarity -
:ARG1 (a / associate-01 :mode interrogative
:ARG1 (p2 / protein :name (n3 / name :op1 "SHIP"))
:ARG2 (o / or
:op1 (p / protein :name (n2 / name :op1 "IRS"))
:op2 (r / receptor
:mod p4)))))
:ARG2 (d / demonstrate-01
:ARG0 (r2 / report
:time (r3 / recent))
:ARG1 (a2 / associate-01
:ARG1 p
:ARG2 (p3 / protein :name (n4 / name :op1 "IRS-2"))
:ARG2-of (r4 / respond-01
:ARG1 (e2 / erythropoietin)))))
# ::id bel_pmid_1019_4465.23202 ::date 2015-04-04T09:50:58 ::annotator SDL-AMR-09 ::preferred
# ::snt The SH2 domain of the adaptor protein Grb- 2 and the SH2 domain of the phosphotyrosine phosphatase SHP-2 bind other sequences, including pYVNI, pYIDL, and pYASI sequences (1).
# ::save-date Thu Apr 16, 2015 ::file bel_pmid_1019_4465_23202.txt
(b / bind-01
:ARG1 (a / and
:op1 (p7 / protein-segment :name (n8 / name :op1 "SH2" :op2 "domain")
:part-of (p / protein :name (n2 / name :op1 "Grb2")
:mod (a2 / adaptor)))
:op2 (p8 / protein-segment :name (n / name :op1 "SH2" :op2 "domain")
:part-of (p2 / protein :name (n4 / name :op1 "phosphotyrosine" :op2 "phosphatase" :op3 "SHP-2"))))
:ARG2 (s / sequence
:ARG2-of (i / include-91
:ARG1 (a3 / and
:op1 (p3 / protein-segment :name (n5 / name :op1 "pYVNI"))
:op2 (p4 / protein-segment :name (n6 / name :op1 "pYIDL"))
:op2 (p5 / protein-segment :name (n7 / name :op1 "pYASI"))))
:mod (o / other))
:ARG1-of (d3 / describe-01
:ARG0 (p6 / publication
:ARG1-of (c / cite-01
:ARG2 1))))
# ::id bel_pmid_1019_4465.23382 ::date 2015-04-05T02:57:06 ::annotator SDL-AMR-09 ::preferred
# ::snt Since an inhibitor against SERCA induces apoptosis in some cell lines (76), the IRS/SERCA complex might be involved in an insulin and IGF-1-dependent antiapoptotic effect.
# ::save-date Mon Jan 4, 2016 ::file bel_pmid_1019_4465_23382.txt
(c / cause-01
:ARG0 (i2 / induce-01
:ARG0 (m2 / molecular-physical-entity
:ARG0-of (i / inhibit-01
:ARG1 (p2 / protein :name (n / name :op1 "SERCA"))))
:ARG2 (a / apoptosis)
:ARG1-of (d / describe-01
:ARG0 (p3 / publication
:ARG1-of (c4 / cite-01
:ARG2 76)))
:location (c3 / cell-line
:mod (s / some)))
:ARG1 (p / possible-01
:ARG1 (i3 / involve-01
:ARG1 (m / macro-molecular-complex
:part (p4 / protein :name (n2 / name :op1 "IRS"))
:part p2)
:ARG2 (a2 / affect-01
:ARG2 (c2 / counter-01
:ARG1 (a5 / apoptosis))
:ARG0-of (d2 / depend-01
:ARG1 (a4 / and
:op1 (p5 / protein :name (n3 / name :op1 "insulin"))
:op2 (p6 / protein :name (n5 / name :op1 "IGF-1"))))))))
# ::id bel_pmid_1019_4465.23752 ::date 2015-04-05T03:09:42 ::annotator SDL-AMR-09 ::preferred
# ::snt Grb-IR is a recently discovered SH2 domain protein that may translocate from the cytosol to the plasma membrane and bind directly to the tyrosine-phosphorylated insulin receptor
# ::save-date Sun Jan 3, 2016 ::file bel_pmid_1019_4465_23752.txt
(p6 / protein
:part (p5 / protein-segment :name (n2 / name :op1 "SH2" :op2 "domain"))
:ARG1-of (d2 / discover-01
:time (r / recent))
:domain (p2 / protein :name (n / name :op1 "Grb-IR"))
:ARG1-of (t / translocate-01
:ARG2 (m / membrane
:mod (p3 / plasma))
:ARG3 (c / cytosol)
:ARG1-of (p / possible-01))
:ARG1-of (b / bind-01
:ARG2 (r2 / receptor
:mod (i / insulin
:ARG1-of (p4 / phosphorylate-01))
:part (a2 / amino-acid :name (n4 / name :op1 "tyrosine")))
:ARG1-of (d / direct-02)
:ARG1-of p))
# ::id bel_pmid_1019_4465.23766 ::date 2015-04-05T03:17:58 ::annotator SDL-AMR-09 ::preferred
# ::snt The physiological substrates for SHP- 2 are not known, but overexpression of SHP-2 modulates cell adhesion and migration, as well as insulin activation of the Ras/MAP-kinase pathway Several isoforms of 14-3-3 proteins (b, e, and z) have also been shown to associate with IRS-1, presumably through one of the several RXRXXpS motifs of IRS-1.
# ::save-date Wed Jun 24, 2015 ::file bel_pmid_1019_4465_23766.txt
(m3 / multi-sentence
:snt1 (c / contrast-01
:ARG1 (k / know-01 :polarity -
:ARG1 (s / substrate
:mod (p2 / physiology)
:topic (p3 / protein :name (n2 / name :op1 "SHP-2"))))
:ARG2 (a / and
:op1 (m / modulate-01
:ARG0 (o / overexpress-01
:ARG1 p3)
:ARG1 (a4 / and
:op1 (a2 / and
:op1 (a3 / adhere-01
:ARG1 (c2 / cell))
:op2 (m2 / migrate-01
:ARG0 c2))
:op2 (a5 / activate-01
:ARG0 (i3 / insulin)
:ARG1 (p4 / pathway :name (n3 / name :op1 "Ras/MAP-kinase")))))))
:snt2 (s2 / show-01
:ARG1 (a8 / associate-01
:ARG1 (i / isoform
:mod (p / protein :name (n / name :op1 "14-3-3"))
:ARG1-of (d / describe-01
:ARG2 (a7 / and
:op1 (p5 / protein :name (n4 / name :op1 "14-3-3β"))
:op2 (p8 / protein :name (n5 / name :op1 "14-3-3ε"))
:op3 (p9 / protein :name (n8 / name :op1 "14-3-3ζ"))))
:quant (s3 / several))
:ARG2 (p6 / protein :name (n6 / name :op1 "IRS-1"))
:instrument (m5 / motif
:ARG1-of (i2 / include-91
:ARG2 (m4 / motif :name (n7 / name :op1 "RXRXXpS")
:part-of p6))
:ARG1-of (p7 / presume-01)))
:mod (a6 / also)))
# ::id bel_pmid_1019_4465.23768 ::date 2015-04-05T03:52:27 ::annotator SDL-AMR-09 ::preferred
# ::snt TNF-a appears to impair insulin signaling by increasing serine phosphorylation of IRS-1. Serine-phosphorylated IRS-1 inhibits insulin receptor tyrosine kinase activity, which leads to impaired downstream signaling
# ::save-date Wed Jan 13, 2016 ::file bel_pmid_1019_4465_23768.txt
(m / multi-sentence
:snt1 (a2 / appear-02
:ARG1 (i / impair-01
:ARG0 (p2 / protein :name (n2 / name :op1 "TNF-a"))
:ARG1 (s / signal-07
:ARG1 (i5 / insulin))
:manner (i2 / increase-01
:ARG0 p2
:ARG1 (p3 / phosphorylate-01
:ARG1 (a / amino-acid :name (n / name :op1 "serine")
:part-of (p4 / protein :name (n4 / name :op1 "IRS-1")))))))
:snt2 (i3 / inhibit-01
:ARG0 (p6 / phosphorylate-01
:ARG1 (a4 / amino-acid :name (n6 / name :op1 "serine")
:part-of (p5 / protein :name (n3 / name :op1 "IRS-1"))))
:ARG1 (a3 / activity-06
:ARG0 (e / enzyme :name (n5 / name :op1 "receptor" :op2 "tyrosine" :op3 "kinase")
:mod (i6 / insulin)))
:ARG0-of (l / lead-03
:ARG2 (s2 / signal-07
:location (d / downstream)
:ARG1-of (i4 / impair-01)))))
# ::id bel_pmid_1019_4465.23770 ::date 2015-04-05T04:01:19 ::annotator SDL-AMR-09 ::preferred
# ::snt other SH2 proteins, such as Crk (adaptor), Nck (adaptor), Fyn (tyrosine kinase), and Csk (tyrosine kinase), bind to tyrosine residues on IRS proteins through their specific SH2 domains.
# ::save-date Sun Jan 17, 2016 ::file bel_pmid_1019_4465_23770.txt
(b / bind-01
:ARG1 (p / protein-segment :name (n / name :op1 "SH2" :op2 "domain")
:example (a / and
:op1 (p2 / protein :name (n2 / name :op1 "Crk")
:ARG1-of (d / describe-01
:ARG2 (a2 / adaptor)))
:op2 (p3 / protein :name (n3 / name :op1 "Nck")
:ARG1-of (d2 / describe-01
:ARG2 a2))
:op3 (e2 / enzyme :name (n4 / name :op1 "Fyn")
:ARG1-of (d3 / describe-01
:ARG2 (e / enzyme :name (n6 / name :op1 "tyrosine" :op2 "kinase"))))
:op4 (p5 / protein :name (n5 / name :op1 "Csk")
:ARG1-of (d4 / describe-01
:ARG2 e)))
:mod (o / other))
:ARG2 (r / residue
:mod (a4 / amino-acid :name (n7 / name :op1 "tyrosine"))
:part-of (p7 / protein-segment :name (n9 / name :op1 "SH2" :op2 "domain")
:part-of (p6 / protein :name (n8 / name :op1 "IRS"))
:ARG1-of (s / specific-02))))
# ::id bel_pmid_1019_4465.23772 ::date 2015-04-05T04:07:46 ::annotator SDL-AMR-09 ::preferred
# ::snt Fyn is not activated directly by the insulin receptor, but rather by interaction with IRS-1 (49) and another insulin receptor substrate, c-Cbl (50).
# ::save-date Sun Jan 17, 2016 ::file bel_pmid_1019_4465_23772.txt
(c3 / contrast-01
:ARG1 (a / activate-01 :polarity -
:ARG0 (r / receptor
:mod (i / insulin))
:ARG1 (e / enzyme :name (n2 / name :op1 "Fyn"))
:ARG1-of (d / direct-02))
:ARG2 (a2 / activate-01
:ARG0 (i2 / interact-01
:ARG0 e
:ARG1 (a3 / and
:op1 (p2 / protein :name (n3 / name :op1 "IRS-1")
:ARG1-of (d2 / describe-01
:ARG0 (p3 / publication
:ARG1-of (c / cite-01
:ARG2 49))))
:op2 (s / substrate
:mod (r2 / receptor
:mod i)
:ARG1-of (d3 / describe-01
:ARG0 (p4 / publication
:ARG1-of (c2 / cite-01
:ARG2 50)))
:ARG0-of (m / mean-01
:ARG1 (p5 / protein :name (n / name :op1 "c-Cbl")))
:mod (a4 / another))))
:ARG1 e))
# ::id bel_pmid_1019_4465.23788 ::date 2015-04-05T04:16:53 ::annotator SDL-AMR-09 ::preferred
# ::snt Recently, b1 integrins have also been reported to enhance IRS-1 phosphorylation and interaction, but not glucose transport, with downstream molecules such as PI3-kinase and Akt (74). These results suggest that integrins and insulin/IGF-1 receptor signaling pathways converge at an early point in the signaling cascade around the IRS proteins.
# ::save-date Sun Jan 17, 2016 ::file bel_pmid_1019_4465_23788.txt
(m / multi-sentence
:snt1 (r / report-01
:ARG1 (c / contrast-01
:ARG1 (e / enhance-01
:ARG0 (p12 / protein :name (n / name :op1 "b1" :op2 "integrin"))
:ARG1 (a / and
:op1 (p3 / phosphorylate-01
:ARG1 (p4 / protein :name (n2 / name :op1 "IRS-1")))
:op2 (i / interact-01
:ARG0 p4
:ARG1 (m2 / molecule
:mod (d / downstream)
:example (a2 / and
:op1 (e3 / enzyme :name (n4 / name :op1 "PI3-kinase"))
:op2 (e5 / enzyme :name (n5 / name :op1 "Akt")))))))
:ARG2 (e2 / enhance-01 :polarity -
:ARG0 (t2 / transport-01
:ARG1 (s4 / small-molecule :name (n3 / name :op1 "glucose")))
:ARG1 a))
:time (r2 / recent)
:ARG1-of (d2 / describe-01
:ARG0 (p6 / publication
:ARG1-of (c2 / cite-01
:ARG2 74)))
:mod (a5 / also))
:snt2 (s / suggest-01
:ARG0 (t3 / thing
:ARG2-of (r3 / result-01)
:mod (t / this))
:ARG1 (c3 / converge-01
:ARG0 (p10 / protein :name (n8 / name :op1 "integrin"))
:ARG1 (p9 / pathway :name (n6 / name :op1 "insulin/IGF-1" :op2 "receptor")
:ARG0-of (s3 / signal-07
:mod (r5 / receptor)))
:time (p7 / point
:mod (e4 / early)
:subevent-of (c4 / cascade
:subevent (s2 / signal-07)
:location (a4 / around
:op1 (p8 / protein :name (n7 / name :op1 "IRS"))))))))
# ::id bel_pmid_1019_4465.24722 ::date 2015-04-05T17:29:49 ::annotator SDL-AMR-09 ::preferred
# ::snt PC-1 is a membrane glycoprotein with ectonucleotide pyrophosphatase activity that seems to act as an intrinsic inhibitor of insulin receptor tyrosine kinase activity
# ::save-date Wed Jan 13, 2016 ::file bel_pmid_1019_4465_24722.txt
(g / glycoprotein
:mod (m / membrane)
:ARG0-of (h2 / have-03
:ARG1 (a / activity-06
:ARG0 (e / enzyme :name (n3 / name :op1 "ectonucleotide" :op2 "pyrophosphatase"))))
:ARG0-of (a2 / act-01
:ARG1 (i2 / inhibit-01
:ARG0 p2
:ARG1 (a3 / activity-06
:ARG0 (e2 / enzyme :name (n4 / name :op1 "receptor" :op2 "tyrosine" :op3 "kinase")
:mod (i / insulin)))
:mod (i3 / intrinsic))
:ARG1-of (s / seem-01))
:domain (p2 / protein :name (n2 / name :op1 "PC-1")))
# ::id bel_pmid_1019_4465.24724 ::date 2015-04-06T06:56:01 ::annotator SDL-AMR-09 ::preferred
# ::snt It has been reported that PC-1 overexpression in skeletal muscle of obese subjects explains downregulation of insulin receptor tyrosine phosphorylation
# ::save-date Wed Jan 13, 2016 ::file bel_pmid_1019_4465_24724.txt
(r / report-01
:ARG1 (e / explain-01
:ARG0 (o / overexpress-01
:ARG1 (p3 / protein :name (n / name :op1 "PC-1"))
:location (m / muscle
:mod (s / skeletal)
:part-of (s2 / subject
:mod (o2 / obese))))
:ARG1 (d / downregulate-01
:ARG1 (p / phosphorylate-01
:ARG1 (p2 / protein :name (n2 / name :op1 "insulin" :op2 "receptor" :op3 "tyrosine"))))))
# ::id bel_pmid_1022_8560.5928 ::date 2015-04-06T07:02:33 ::annotator SDL-AMR-09 ::preferred
# ::snt Inhibition of MEK1 also led to reduced expression of alpha-enolase, phosphoglycerate kinase, elongation factor 2 and heterogeneous nuclear ribonucleoprotein A3, the latter two being detected as truncated proteins.
# ::save-date Wed Apr 29, 2015 ::file bel_pmid_1022_8560_5928.txt
(l / lead-03
:ARG0 (i / inhibit-01
:ARG1 (e / enzyme :name (n / name :op1 "MEK1")))
:ARG2 (e2 / express-03
:ARG1 (a / and
:op1 (e3 / enzyme :name (n2 / name :op1 "alpha-enolase"))
:op2 (e4 / enzyme :name (n3 / name :op1 "phosphoglycerate" :op2 "kinase"))
:op3 (p / protein :name (n4 / name :op1 "elongation" :op2 "factor" :op3 "2")
:ARG0-of (d / detect-01
:ARG1 (p3 / protein
:ARG1-of (t / truncate-01))
:ord (o / ordinal-entity :value "-2")))
:op4 (p2 / protein :name (n5 / name :op1 "heterogeneous" :op2 "nuclear" :op3 "ribonucleoprotein" :op4 "A3")
:ARG0-of d))
:ARG1-of (r / reduce-01))
:mod (a2 / also))
# ::id bel_pmid_1023_2608.5936 ::date 2015-04-06T07:17:40 ::annotator SDL-AMR-09 ::preferred
# ::snt In support of these data, we also show that MEK1 is highly phosphorylated in vivo on Ser 217/221 in MLK3-transformed fibroblasts
# ::save-date Sun Jan 17, 2016 ::file bel_pmid_1023_2608_5936.txt
(s / show-01
:ARG0 (w / we)
:ARG1 (p / phosphorylate-01
:ARG1 (s2 / slash
:op1 (a / amino-acid :mod 217 :name (n2 / name :op1 "serine")
:part-of (e / enzyme :name (n5 / name :op1 "MEK1")))
:op2 (a3 / amino-acid :mod 221 :name (n4 / name :op1 "serine")
:part-of e))
:ARG1-of (h / high-02)
:manner (i / in-vivo)
:location (f / fibroblast
:ARG1-of (t / transform-01
:ARG0 (e2 / enzyme :name (n3 / name :op1 "MLK3")))))
:purpose (s3 / support-01
:ARG1 (d / data
:mod (t2 / this)))
:mod (a2 / also))
# ::id bel_pmid_1023_2608.16572 ::date 2015-04-06T07:26:22 ::annotator SDL-AMR-09 ::preferred
# ::snt expression of MLK3 strongly activated SAPK? to the same extent seen with the established JNK/SAPK activator arsenite (45)
# ::save-date Sun Jan 17, 2016 ::file bel_pmid_1023_2608_16572.txt
(a / activate-01
:ARG0 (e / express-03
:ARG2 (e2 / enzyme :name (n / name :op1 "MLK3")))
:ARG1 (e4 / enzyme :name (n2 / name :op1 "SAPK"))
:ARG1-of (s / strong-02)
:extent (s2 / see-01
:ARG1 (a2 / arsenite
:ARG0-of (a3 / activate-01
:ARG1 (p2 / pathway :name (n3 / name :op1 "JNK/SAPK")))
:ARG1-of (e3 / establish-01))
:ARG1-of (s3 / same-01))
:ARG1-of (d / describe-01
:ARG0 (p3 / publication
:ARG1-of (c / cite-01
:ARG2 45))))
# ::id bel_pmid_1023_2608.23890 ::date 2015-04-06T07:38:05 ::annotator SDL-AMR-09 ::preferred
# ::snt Using a coupled assay, we were able to show that MLK3-mediated phosphorylation of SEK1 resulted in activation because GST-SEK1 is able to phosphorylate recombinant SAPK? (Fig. 5D)
# ::save-date Sun Jan 17, 2016 ::file bel_pmid_1023_2608_23890.txt
(p / possible-01
:ARG1 (s / show-01
:ARG0 (w / we)
:ARG1 (r / result-01
:ARG1 (p3 / phosphorylate-01
:ARG1 (e3 / enzyme :name (n / name :op1 "SEK1"))
:ARG1-of (m / mediate-01
:ARG0 (e / enzyme :name (n2 / name :op1 "MLK3"))))
:ARG2 (a / activate-01)
:ARG1-of (c / cause-01
:ARG0 (p5 / possible-01
:ARG1 (p2 / phosphorylate-01
:ARG1 (e2 / enzyme :name (n3 / name :op1 "SAPK")
:ARG3-of (r2 / recombine-01))
:ARG2 (p7 / protein :name (n4 / name :op1 "GST-SEK1")))))))
:manner (u / use-01
:ARG0 w
:ARG1 (a2 / assay-01
:ARG1-of (c2 / couple-01)))
:ARG1-of (d / describe-01
:ARG2 (f / figure :mod "5D")))
# ::id bel_pmid_1023_2608.23894 ::date 2015-04-05T06:03:51 ::annotator SDL-AMR-09 ::preferred
# ::snt Wild type, but not KD, MLK3 was able to phosphorylate His-MEK1 (Fig. 5A) ? and GST-SEK1 (Fig. 5B) ? in vitro.
# ::save-date Wed Apr 29, 2015 ::file bel_pmid_1023_2608_23894.txt
(c / contrast-01
:ARG1 (p / possible-01
:ARG1 (p2 / phosphorylate-01
:ARG1 (a2 / and
:op1 (p3 / protein :name (n / name :op1 "His" :op2 "MEK1")
:ARG1-of (d / describe-01
:ARG2 (f / figure :mod "5A")))
:op2 (p4 / protein :name (n2 / name :op1 "GST-SEK1")
:ARG1-of (d2 / describe-01
:ARG2 (f2 / figure :mod "5B"))))
:ARG2 (e / enzyme :name (n3 / name :op1 "MLK3")
:mod (w / wild-type))
:manner (i / in-vitro)))
:ARG2 (p5 / possible-01 :polarity -
:ARG1 (p6 / phosphorylate-01
:ARG1 a2
:ARG2 (e2 / enzyme :name (n5 / name :op1 "MLK3")
:ARG0-of (f3 / function-01 :polarity -
:ARG1 (k / kinase))))))
# ::id bel_pmid_1034_3541.46 ::date 2015-04-03T11:38:00 ::annotator SDL-AMR-09 ::preferred
# ::snt Thrombin receptor mediated signal transduction could induce the expressions of IL6 and G-CSF, and increase inflammatory events in the cavum articulare via NF-kappa B activation
# ::save-date Tue Jan 19, 2016 ::file bel_pmid_1034_3541_46.txt
(p / possible-01
:ARG1 (a / and
:op1 (i / induce-01
:ARG0 (t / transduce-01
:ARG1 (s / signal-07)
:ARG1-of (m / mediate-01
:ARG0 (r / receptor :name (n / name :op1 "thrombin"))))
:ARG2 (e / express-03
:ARG2 (a2 / and
:op1 (p2 / protein :name (n2 / name :op1 "IL6"))
:op2 (p3 / protein :name (n3 / name :op1 "G-CSF")))))
:op2 (i2 / increase-01
:ARG0 t
:ARG1 (e2 / event
:mod (i3 / inflame-01))
:location (c / cavum
:mod (a3 / articulare))
:manner (a4 / activate-01
:ARG1 (p4 / protein :name (n4 / name :op1 "NF-kappa-B"))))))
# ::id bel_pmid_1034_3541.18504 ::date 2015-04-03T12:30:58 ::annotator SDL-AMR-09 ::preferred
# ::snt Thrombin receptor mediated signal transduction could induce the expressions of IL6 and G-CSF, and increase inflammatory events in the cavum articulare via NF-êB activation
# ::save-date Tue Jan 19, 2016 ::file bel_pmid_1034_3541_18504.txt
(p / possible-01
:ARG1 (a / and
:op1 (i / induce-01
:ARG0 (t / transduce-01
:ARG1 (s / signal-07)
:ARG1-of (m / mediate-01
:ARG0 (r / receptor :name (n / name :op1 "thrombin"))))
:ARG2 (e / express-03
:ARG2 (a2 / and
:op1 (p2 / protein :name (n2 / name :op1 "IL6"))
:op2 (p3 / protein :name (n3 / name :op1 "G-CSF")))))
:op2 (i2 / increase-01
:ARG0 t
:ARG1 (e2 / event
:mod (i3 / inflame-01))
:location (c / cavum
:mod (a3 / articulare))
:manner (a4 / activate-01
:ARG1 (p4 / protein :name (n4 / name :op1 "NF-κB"))))))
# ::id bel_pmid_1034_3541.23056 ::date 2015-04-05T13:16:12 ::annotator SDL-AMR-09 ::preferred
# ::snt The levels of IL6 and of G-CSF mRNAs showed a time dependent increase during two to eight hours after thrombin stimulation....Cytokines were measured by enzyme linked immunosorbent assay (ELISA) in the supernatants of cultured rheumatoid synovial fibroblasts stimulated by thrombin
# ::save-date Sun Jan 17, 2016 ::file bel_pmid_1034_3541_23056.txt
(m / multi-sentence
:snt1 (s / show-01
:ARG0 (a / and
:op1 (l / level
:quant-of (n9 / nucleic-acid :name (n / name :op1 "mRNA")
:ARG0-of (e4 / encode-01
:ARG1 (p3 / protein :name (n2 / name :op1 "IL6")))))
:op2 (l2 / level
:quant-of (n10 / nucleic-acid :name (n3 / name :op1 "mRNA")
:ARG0-of (e3 / encode-01
:ARG1 (p2 / protein :name (n4 / name :op1 "G-CSF"))))))
:ARG1 (i / increase-01
:ARG0-of (d / depend-01
:ARG1 (t / time))
:time (a2 / after
:op1 (s2 / stimulate-01
:ARG1 (e / enzyme :name (n5 / name :op1 "thrombin")))
:quant (b / between
:op1 (t2 / temporal-quantity :quant 2
:unit (h / hour))
:op2 (t3 / temporal-quantity :quant 8
:unit h)))))
:snt2 (m2 / measure-01
:ARG1 (p / protein :name (n8 / name :op1 "cytokine"))
:location (s3 / supernatant
:part-of (c2 / culture-01
:ARG1 (f / fibroblast
:location (s4 / synovia)
:mod (r3 / rheumatoid)))
:ARG1-of (s5 / stimulate-01
:ARG0 e))
:manner (a3 / assay-01
:instrument (i2 / immunosorbent
:ARG1-of (l3 / link-01
:ARG2 (e2 / enzyme))))))
# ::id bel_pmid_1034_3541.35586 ::date 2015-04-05T14:44:10 ::annotator SDL-AMR-09 ::preferred
# ::snt Thrombin receptor mediated signal transduction could induce the expressions of IL6 and G-CSF, and increase inflammatory events in the cavum articulare via NF-êB activation
# ::save-date Tue Jan 19, 2016 ::file bel_pmid_1034_3541_35586.txt
(p / possible-01
:ARG1 (a / and
:op1 (i / induce-01
:ARG0 (t / transduce-01
:ARG1 (s / signal-07)
:ARG1-of (m / mediate-01
:ARG0 (r / receptor :name (n / name :op1 "thrombin"))))
:ARG2 (e / express-03
:ARG2 (a2 / and
:op1 (p2 / protein :name (n2 / name :op1 "IL6"))
:op2 (p3 / protein :name (n3 / name :op1 "G-CSF")))))
:op2 (i2 / increase-01
:ARG0 t
:ARG1 (e2 / event
:mod (i3 / inflame-01))
:location (c / cavum
:mod (a3 / articulare))
:manner (a4 / activate-01
:ARG1 (p4 / protein :name (n4 / name :op1 "NF-κB"))))))
# ::id bel_pmid_1034_7197.8888 ::date 2015-04-05T14:56:34 ::annotator SDL-AMR-09 ::preferred
# ::snt Induction of the urokinase promoter by HGF/SF via the Met receptor was blocked by co-expression of a dominant-negative Grb2 and Sos1 expression construct.
# ::save-date Tue Feb 2, 2016 ::file bel_pmid_1034_7197_8888.txt
(b / block-01
:ARG0 (c / coexpress-01
:ARG2 (c2 / construct-01
:ARG1 (a / and
:op1 (p / protein :name (n / name :op1 "Grb2")
:ARG2-of (m / mutate-01 :mod "-/-")
:ARG0-of (d / dominate-01))
:op2 (e / express-03
:ARG2 (p2 / protein :name (n2 / name :op1 "Sos1"))))))
:ARG1 (i / induce-01
:ARG0 (p3 / protein :name (n3 / name :op1 "HGF/SF"))
:ARG2 (m2 / molecular-physical-entity
:ARG0-of (p4 / promote-01
:ARG1 (e2 / enzyme :name (n4 / name :op1 "urokinase"))))
:medium (r / receptor :name (n5 / name :op1 "Met"))))
# ::id bel_pmid_1034_7197.20912 ::date 2015-04-06T05:19:24 ::annotator SDL-AMR-09 ::preferred
# ::snt Further, the expression of the catalytically inactive mutants of Ha-Ras, RhoA, c-Raf, and Erk2 or addition of the Mek1-specific inhibitor PD 098059 abrogated the stimulation of the urokinase promoter by HGF/SF.
# ::save-date Wed Jan 13, 2016 ::file bel_pmid_1034_7197_20912.txt
(a / and
:op2 (a2 / abrogate-01
:ARG1 (s / stimulate-01
:ARG0 (p / protein :name (n / name :op1 "HGF/SF"))
:ARG1 (m / molecular-physical-entity
:ARG0-of (p2 / promote-01
:ARG1 (e / enzyme :name (n2 / name :op1 "urokinase")))))
:ARG2 (o / or
:op1 (e2 / express-03
:ARG2 (m2 / mutate-01
:ARG1 (a3 / and
:op1 (e6 / enzyme :name (n3 / name :op1 "Ha-Ras"))
:op2 (p4 / protein :name (n4 / name :op1 "RhoA"))
:op3 (e3 / enzyme :name (n5 / name :op1 "c-Raf"))
:op3 (e4 / enzyme :name (n6 / name :op1 "Erk2")))
:ARG1-of (a4 / activate-01 :polarity -
:manner (c / catalytic))))
:op2 (a5 / add-02
:ARG1 (m3 / molecular-physical-entity :name (n7 / name :op1 "PD-098059")
:ARG0-of (i / inhibit-01
:ARG1-of (s2 / specific-02
:ARG2 (e5 / enzyme :name (n8 / name :op1 "Mek1")))))))))
# ::id bel_pmid_1035_9574.24516 ::date 2015-04-06T07:13:26 ::annotator SDL-AMR-09 ::preferred
# ::snt c-Raf-1 kinase was identified as an intracellular target of a signal transduction cascade initiated by binding of TNF-alpha to TNFR-I.
# ::save-date Tue Jan 19, 2016 ::file bel_pmid_1035_9574_24516.txt
(i / identify-01
:ARG1 (e / enzyme :name (n / name :op1 "c-Raf-1" :op2 "kinase"))
:ARG2 (t / target-01
:ARG0 (c / cascade-01
:ARG2-of (t2 / transduce-01
:ARG1 (s / signal-07))
:ARG1-of (i2 / initiate-01
:ARG2 (b / bind-01
:ARG1 (p / protein :name (n2 / name :op1 "TNF-alpha"))
:ARG2 (p2 / protein :name (n3 / name :op1 "TNFR-I")))))
:ARG1 e
:location (i3 / intracellular)))
# ::id bel_pmid_1036_2260.5288 ::date 2015-04-06T08:02:50 ::annotator SDL-AMR-09 ::preferred
# ::snt Gadd45 was also able to physically interact with Cdc2, but not Cyclin B1. Addition of Gadd45 to immunoprecipitated Cdc2/Cyclin B1 in vitro led to a dissociation of this complex, and thus may represent a new checkpoint mechanism whereby Cdc2/Cyclin B1 can be inhibited.
# ::save-date Fri Feb 5, 2016 ::file bel_pmid_1036_2260_5288.txt
(m / multi-sentence
:snt1 (c / contrast-01
:ARG1 (p / possible-01
:ARG1 (i / interact-01
:ARG0 (p2 / protein :name (n / name :op1 "Gadd45"))
:ARG1 (e2 / enzyme :name (n2 / name :op1 "Cdc2"))
:manner (p3 / physical))
:mod (a / also))
:ARG2 (p4 / possible-01
:ARG1 (i2 / interact-01 :polarity -
:ARG0 p2
:ARG1 (p5 / protein :name (n3 / name :op1 "Cyclin-B1"))
:ARG2 p3)))
:snt2 (l / lead-03
:ARG0 (a2 / add-02
:ARG1 (p6 / protein :name (n4 / name :op1 "Gadd45"))
:ARG2 (m3 / macro-molecular-complex
:part (e / enzyme :name (n5 / name :op1 "Cdc2"))
:part (p7 / protein :name (n6 / name :op1 "Cyclin-B1"))
:ARG1-of (i3 / immunoprecipitate-01))
:manner (i4 / in-vitro))
:ARG2 (d / dissociate-01
:ARG0 a2
:ARG1 (c2 / complex
:mod (t / this)))
:ARG0-of (c3 / cause-01
:ARG1 (p8 / possible-01
:ARG1 (r / represent-01
:ARG0 (m5 / mechanism
:mod (c4 / checkpoint)
:ARG1-of (n7 / new-01)
:instrument-of (p9 / possible-01
:ARG1 (i5 / inhibit-01
:ARG1 m3)))
:ARG1 a2)))))
# ::id bel_pmid_1036_2713.15636 ::date 2015-04-06T09:17:54 ::annotator SDL-AMR-09 ::preferred
# ::snt Treatment with TNF-a significantly decreased the intracellular GSH content of HS-24 cells. Pretreatment of this culture with DMSO recovered the TNF-a-induced decrease in GSH (Table 1).
# ::save-date Fri Feb 12, 2016 ::file bel_pmid_1036_2713_15636.txt
(m / multi-sentence
:snt1 (d / decrease-01
:ARG0 (t / treat-04
:ARG2 (p / protein :name (n / name :op1 "TNF-α")))
:ARG1 (s3 / small-molecule :name (n2 / name :op1 "GSH")
:ARG1-of (c / contain-01
:ARG0 (c2 / cell :name (n3 / name :op1 "HS-24"))
:location (i / intracellular)))
:ARG2 (s / significant-02))
:snt2 (r / recover-02
:ARG0 (p2 / pretreat-01
:ARG1 (c3 / culture
:mod (t2 / this))
:ARG3 (s2 / small-molecule :name (n4 / name :op1 "DMSO")))
:ARG1 (d2 / decrease-01
:ARG1 (s4 / small-molecule :name (n5 / name :op1 "GSH"))
:ARG2-of (i2 / induce-01
:ARG0 (p3 / protein :name (n6 / name :op1 "TNF-α"))))
:ARG1-of (d3 / describe-01
:ARG0 (t3 / table :mod 1))))
# ::id bel_pmid_1036_2713.15640 ::date 2015-04-06T10:08:11 ::annotator SDL-AMR-09 ::preferred
# ::snt TNF-a (200 U/ml) significantly increased the levels of IL-6 mRNA in HS-24 cells and DMSO (1.0%) markedly reduced those induced with the cytokine (Fig. 5E).
# ::save-date Sun Jan 17, 2016 ::file bel_pmid_1036_2713_15640.txt
(a / and
:op1 (i / increase-01
:ARG0 (p / protein :name (n / name :op1 "TNF-α")
:quant (c / concentration-quantity :quant 200
:unit (u / unit-per-milliliter)))
:ARG1 (l / level
:quant-of (n7 / nucleic-acid :name (n2 / name :op1 "mRNA")
:ARG0-of (e / encode-01
:ARG1 (p4 / protein :name (n5 / name :op1 "IL-6")))))
:ARG2 (s / significant-02)
:location (c2 / cell :name (n3 / name :op1 "HS-24")))
:op2 (r2 / reduce-01
:ARG0 (s2 / small-molecule :name (n4 / name :op1 "DMSO")
:quant (p2 / percentage-entity :quant 1.0))
:ARG1 (l2 / level
:ARG2-of (i2 / induce-01
:ARG0 (p3 / protein :name (n6 / name :op1 "cytokine")))
:quant-of n7)
:manner (m2 / marked))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "5E")))
# ::id bel_pmid_1036_2713.18726 ::date 2015-04-06T10:58:45 ::annotator SDL-AMR-09 ::preferred
# ::snt An XO enzyme activity of 5.0 mU/ml led to a twofold increase in IL-6 secretion in NHBE cells. And incubation of HS-24 cells with XO (20 mU/ml) induced a 1.8-fold increase in IL-6 production
# ::save-date Sun Dec 20, 2015 ::file bel_pmid_1036_2713_18726.txt
(m / multi-sentence
:snt1 (l / lead-03
:ARG0 (a / activity-06
:ARG0 (e / enzyme :name (n / name :op1 "XO")
:quant (c / concentration-quantity :quant 5.0
:unit (m2 / milliunit-per-milliliter))))
:ARG2 (i / increase-01
:ARG0 a
:ARG1 (s / secrete-01
:ARG1 (p / protein :name (n2 / name :op1 "IL-6")))
:ARG2 (p2 / product-of :op1 2)
:location (c2 / cell :name (n3 / name :op1 "NHBE"))))
:snt2 (a2 / and
:op2 (i2 / induce-01
:ARG0 (i3 / incubate-01
:ARG1 (c3 / cell :name (n4 / name :op1 "HS-24"))
:ARG2 (e2 / enzyme :name (n5 / name :op1 "XO")
:quant (c4 / concentration-quantity :quant 20
:unit (m3 / milliunit-per-milliliter))))
:ARG2 (i4 / increase-01
:ARG0 i3
:ARG1 (p3 / produce-01
:ARG1 (p4 / protein :name (n6 / name :op1 "IL-6")))
:ARG2 (p5 / product-of :op1 1.8)))))
# ::id bel_pmid_1036_2713.24360 ::date 2015-04-06T11:37:34 ::annotator SDL-AMR-09 ::preferred
# ::snt SOD (250 U/ml) significantly suppressed the IL-6 production and IL-6 mRNA expression induced by XO, whereas catalase (500 U/ml) did not modulate the IL-6 response to XO (Fig. 4).
# ::save-date Sun Dec 20, 2015 ::file bel_pmid_1036_2713_24360.txt
(c / contrast-01
:ARG1 (s / suppress-01
:ARG0 (e / enzyme :name (n / name :op1 "SOD")
:quant (c2 / concentration-quantity :quant 250
:unit (u / unit-per-milliliter)))
:ARG1 (a / and
:op1 (p / produce-01
:ARG1 (p2 / protein :name (n2 / name :op1 "IL-6")))
:op2 (e2 / express-03
:ARG1 (n5 / nucleic-acid :name (n3 / name :op1 "mRNA")
:ARG0-of (e5 / encode-01
:ARG1 p2)))
:ARG2-of (i / induce-01
:ARG0 (e3 / enzyme :name (n4 / name :op1 "XO"))))
:ARG1-of (s2 / significant-02))
:ARG2 (m / modulate-01 :polarity -
:ARG0 (e4 / enzyme :name (n6 / name :op1 "catalase")
:quant (c3 / concentration-quantity :quant 500
:unit u))
:ARG1 (r2 / respond-01
:ARG0 p2
:ARG1 e3))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod 4)))
# ::id bel_pmid_1036_2713.24536 ::date 2015-04-06T12:03:56 ::annotator SDL-AMR-09 ::preferred
# ::snt TNF-a significantly increased the production of IL-6 in WI-38-40 cells. However, DMSO was not able to inhibit the TNF-a-induced IL-6 enhancement in both protein and mRNA levels (Fig. 7). These results suggest that ROIs may not be involved in the production of IL-6 in human lung fibroblasts
# ::save-date Fri Feb 12, 2016 ::file bel_pmid_1036_2713_24536.txt
(m / multi-sentence
:snt1 (i / increase-01
:ARG0 (p / protein :name (n / name :op1 "TNF-α"))
:ARG1 (p2 / produce-01
:ARG1 (p3 / protein :name (n2 / name :op1 "IL-6")))
:ARG2 (s / significant-02)
:location (c / cell :name (n3 / name :op1 "WI-38-40")))
:snt2 (h / have-concession-91
:ARG1 (p4 / possible-01 :polarity -
:ARG1 (i2 / inhibit-01
:ARG0 (s3 / small-molecule :name (n4 / name :op1 "DMSO"))
:ARG1 (e / enhance-01
:ARG1 (p5 / protein :name (n5 / name :op1 "IL-6"))
:ARG2-of (i3 / induce-01
:ARG0 (p6 / protein :name (n6 / name :op1 "TNF-α")))
:location (a / and
:op1 (l / level
:mod (p7 / protein))
:op2 (l2 / level
:mod (n10 / nucleic-acid :name (n7 / name :op1 "mRNA")))))))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod 7)))
:snt3 (s2 / suggest-01
:ARG0 (t / thing
:ARG2-of (r2 / result-01)
:mod (t2 / this))
:ARG1 (p8 / possible-01 :polarity -
:ARG1 (i4 / involve-01
:ARG1 (s4 / small-molecule :name (n8 / name :op1 "ROI"))
:ARG2 (p9 / produce-01
:ARG1 (p10 / protein :name (n9 / name :op1 "IL-6"))
:location (f2 / fibroblast
:part-of (l3 / lung
:part-of (h2 / human))))))))
# ::id bel_pmid_1036_2713.24538 ::date 2015-04-06T12:36:29 ::annotator SDL-AMR-09 ::preferred
# ::snt TNF-a was dose dependently capable of inducing IL-6 release from NHBE and HS-24 cells (Fig. 5, A and C).
# ::save-date Sun Dec 20, 2015 ::file bel_pmid_1036_2713_24538.txt
(p / possible-01
:ARG1 (i / induce-01
:ARG0 (p2 / protein :name (n / name :op1 "TNF-α"))
:ARG2 (r / release-01
:ARG1 (p3 / protein :name (n2 / name :op1 "IL-6"))
:ARG2 (a / and
:op1 (c / cell :name (n3 / name :op1 "NHBE"))
:op2 (c2 / cell :name (n4 / name :op1 "HS-24")))))
:manner (d / depend-01
:ARG0 p2
:ARG1 (d2 / dose))
:ARG1-of (d3 / describe-01
:ARG0 (a2 / and
:op1 (f / figure :mod "5A")
:op2 (f2 / figure :mod "5C"))))
# ::id bel_pmid_1036_2713.24690 ::date 2015-04-06T13:06:00 ::annotator SDL-AMR-09 ::preferred
# ::snt As shown in Fig. 3A, stimulation with XO resulted in a significant increase in the levels of IL-6 at 12 and 24 h compared with those with 0.7 mM X alone (P , 0.0001). Consistent with these protein data, stimulation of HS-24 cells with XO caused the maximum elevation in IL-6 mRNAlevels at 6 h, whereas XO did not modulate control GAPDH transcript levels (Fig. 3B).
# ::save-date Fri Jan 15, 2016 ::file bel_pmid_1036_2713_24690.txt
(m / multi-sentence
:snt1 (r / result-01
:ARG1 (s / stimulate-01
:ARG2 (e / enzyme :name (n / name :op1 "XO"))
:ARG1-of (c / compare-01
:ARG2 (s2 / stimulate-01
:ARG2 (e6 / enzyme :name (n2 / name :op1 "XO")
:quant (c2 / concentration-quantity :quant 0.7
:unit (m3 / millimolar))
:mod (a / alone))
:mod (t / that)))
:ARG1-of (s6 / statistical-test-91
:ARG2 (l / less-than :op1 0.0001)))
:ARG2 (i / increase-01
:ARG1 (l2 / level
:quant-of (p2 / protein :name (n3 / name :op1 "IL-6")))
:ARG2 (s3 / significant-02)
:time (a2 / and
:op1 (t2 / temporal-quantity :quant 12
:unit (h / hour))
:op2 (t3 / temporal-quantity :quant 24
:unit h)))
:ARG1-of (s4 / show-01
:ARG0 (f / figure :mod "3A")))
:snt2 (c3 / contrast-01
:ARG1 (c4 / cause-01
:ARG0 (s5 / stimulate-01
:ARG1 (c5 / cell :name (n4 / name :op1 "HS-24"))
:ARG2 (e2 / enzyme :name (n5 / name :op1 "XO")))
:ARG1 (e3 / elevate-01
:ARG1 (l3 / level
:mod (n9 / nucleic-acid :name (n6 / name :op1 "mRNA")
:ARG0-of (e5 / encode-01
:ARG1 (p4 / protein :name (n7 / name :op1 "IL-6")))))
:degree (m4 / maximum)
:quant (t4 / temporal-quantity :quant 6
:unit (h2 / hour))))
:ARG2 (m5 / modulate-01 :polarity -
:ARG0 e2
:ARG1 (l4 / level
:quant-of (e4 / enzyme :name (n8 / name :op1 "GAPDH")
:ARG1-of (t5 / transcribe-01)
:ARG0-of (c6 / control-01))))
:ARG1-of (c7 / consistent-01
:ARG2 (d / data
:mod (p3 / protein)
:mod (t6 / this)))
:ARG1-of (d2 / describe-01
:ARG0 (f2 / figure :mod "3B"))))
# ::id bel_pmid_1036_2713.39152 ::date 2015-04-06T15:20:44 ::annotator SDL-AMR-09 ::preferred
# ::snt TNF-a significantly increased the production of IL-6 in WI-38-40 cells. However, DMSO was not able to inhibit the TNF-a-induced IL-6 enhancement in both protein and mRNA levels (Fig. 7). These results suggest that ROIs may not be involved in the production of IL-6 in human lung fibroblasts
# ::save-date Fri Feb 12, 2016 ::file bel_pmid_1036_2713_39152.txt
(m / multi-sentence
:snt1 (i / increase-01
:ARG0 (p / protein :name (n / name :op1 "TNF-α"))
:ARG1 (p2 / produce-01
:ARG1 (p3 / protein :name (n2 / name :op1 "IL-6")))
:ARG2 (s / significant-02)
:location (c / cell :name (n3 / name :op1 "WI-38-40")))
:snt2 (h / have-concession-91
:ARG1 (p4 / possible-01 :polarity -
:ARG1 (i2 / inhibit-01
:ARG0 (s3 / small-molecule :name (n4 / name :op1 "DMSO"))
:ARG1 (e / enhance-01
:ARG1 (p5 / protein :name (n5 / name :op1 "IL-6"))
:ARG2-of (i3 / induce-01
:ARG0 (p6 / protein :name (n6 / name :op1 "TNF-α")))
:location (a / and
:op1 (l / level
:quant-of (p7 / protein))
:op2 (l2 / level
:quant-of (n10 / nucleic-acid :name (n7 / name :op1 "mRNA")))))))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod 7)))
:snt3 (s2 / suggest-01
:ARG0 (t / thing
:ARG2-of (r2 / result-01)
:mod (t2 / this))
:ARG1 (p8 / possible-01 :polarity -
:ARG1 (i4 / involve-01
:ARG1 (s4 / small-molecule :name (n8 / name :op1 "ROI"))
:ARG2 (p9 / produce-01
:ARG1 (p10 / protein :name (n9 / name :op1 "IL-6"))
:location (f2 / fibroblast
:part-of (l3 / lung
:part-of (h2 / human))))))))
# ::id bel_pmid_1036_2713.39154 ::date 2015-04-06T15:34:35 ::annotator SDL-AMR-09 ::preferred
# ::snt TNF-a was dose dependently capable of inducing IL-6 release from NHBE and HS-24 cells (Fig. 5, A and C).
# ::save-date Sun Dec 20, 2015 ::file bel_pmid_1036_2713_39154.txt
(p / possible-01
:ARG1 (i / induce-01
:ARG0 (p2 / protein :name (n / name :op1 "TNF-α"))
:ARG2 (r / release-01
:ARG1 (p3 / protein :name (n2 / name :op1 "IL-6"))
:ARG2 (a / and
:op1 (c / cell :name (n3 / name :op1 "NHBE"))
:op2 (c2 / cell :name (n4 / name :op1 "HS-24")))))
:manner (d / depend-01
:ARG0 p2
:ARG1 (d2 / dose))
:ARG1-of (d3 / describe-01
:ARG0 (a2 / and
:op1 (f / figure :mod "5A")
:op2 (f2 / figure :mod "5C"))))
# ::id bel_pmid_1037_5612.23694 ::date 2015-04-06T15:41:28 ::annotator SDL-AMR-09 ::preferred
# ::snt Northern blot analysis documented that two transcription factor genes chosen for further study, c-myc promoter-binding protein (MBP-1) and X-box binding protein 1 (XBP-1), were up-regulated in U266 cells about 3-fold relative to the cell cycle-dependent beta-actin gene 12 h after IL-6 treatment.
# ::save-date Fri Feb 12, 2016 ::file bel_pmid_1037_5612_23694.txt
(d / document-01
:ARG0 (a / analyze-01
:instrument (t / thing :name (n / name :op1 "northern" :op2 "blot")))
:ARG1 (u / upregulate-01
:ARG1 (g / gene :quant 2 :name (n2 / name :op1 "transcription" :op2 "factor")
:ARG1-of (c / choose-01
:ARG4 (s / study-01
:degree (f / further)))
:ARG1-of (m / mean-01
:ARG2 (a2 / and
:op1 (p / protein
:ARG0-of (b / bind-01
:ARG1 (m3 / molecular-physical-entity
:ARG0-of (p8 / promote-01
:ARG1 (p2 / protein :name (n3 / name :op1 "c-myc")))))
:ARG1-of (d2 / describe-01
:ARG0 (p3 / protein :name (n4 / name :op1 "MBP-1"))))
:op2 (p9 / protein :name (n11 / name :op1 "X-box" :op2 "binding" :op3 "protein" :op4 "1")
:ARG1-of (d3 / describe-01
:ARG0 (p5 / protein :name (n7 / name :op1 "XBP-1")))))))
:location (c2 / cell :name (n8 / name :op1 "U266"))
:degree (p6 / product-of :op1 3
:mod (a3 / about))
:time (a4 / after
:op1 (t2 / treat-04
:ARG2 (p7 / protein :name (n9 / name :op1 "IL-6")))
:quant (t3 / temporal-quantity :quant 12
:unit (h / hour)))
:ARG2-of (r / relative-05
:ARG3 (g2 / gene :name (n10 / name :op1 "beta-actin")
:ARG0-of (d4 / depend-01
:ARG1 (c3 / cycle-02
:ARG1 (c4 / cell)))))))
# ::id bel_pmid_1040_9724.52 ::date 2015-04-07T03:14:02 ::annotator SDL-AMR-09 ::preferred
# ::snt Signaling by the IL-6 receptor is mediated through the signal transducing subunit gp130 and involves the activation of Janus-associated kinases (JAKs), signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein (MAP) kinase.
# ::save-date Tue Jan 19, 2016 ::file bel_pmid_1040_9724_52.txt
(a / and
:op1 (m / mediate-01
:ARG1 (s / signal-07
:ARG0 (r / receptor :name (n / name :op1 "IL-6")))
:medium (p / protein :name (n2 / name :op1 "gp130")
:mod (s2 / subunit
:ARG2-of (t / transduce-01
:ARG1 (s3 / signal-07)))))
:op2 (i / involve-01
:ARG1 (a2 / activate-01
:ARG1 (a3 / and
:op1 (e / enzyme :name (n3 / name :op1 "Janus-associated" :op2 "kinase")
:ARG1-of (d / describe-01
:ARG0 (e2 / enzyme :name (n4 / name :op1 "JAK"))))
:op2 (p2 / protein :name (n5 / name :op1 "signal" :op2 "transducer" :op3 "and" :op4 "activator" :op5 "of" :op6 "transcription-3")
:ARG1-of (d2 / describe-01
:ARG0 (p3 / protein :name (n6 / name :op1 "STAT3"))))
:op3 (e3 / enzyme :name (n7 / name :op1 "mitogen-activated" :op2 "protein" :op3 "kinase")
:ARG1-of (d3 / describe-01
:ARG0 (e4 / enzyme :name (n8 / name :op1 "MAP"))))))
:ARG2 s))
# ::id bel_pmid_1040_9724.18580 ::date 2015-04-07T04:04:47 ::annotator SDL-AMR-09 ::preferred
# ::snt Signaling by the IL-6 receptor is mediated through the signal transducing subunit gp130 and involves the activation of Janus-associated kinases (JAKs), signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein (MAP) kinase.
# ::save-date Tue Jan 19, 2016 ::file bel_pmid_1040_9724_18580.txt
(a / and
:op1 (m / mediate-01
:ARG1 (s / signal-07
:ARG0 (r / receptor :name (n / name :op1 "IL-6")))
:medium (p / protein :name (n2 / name :op1 "gp130")
:mod (s2 / subunit
:ARG2-of (t / transduce-01
:ARG1 (s3 / signal-07)))))
:op2 (i / involve-01
:ARG1 (a2 / activate-01
:ARG1 (a3 / and
:op1 (e / enzyme :name (n3 / name :op1 "Janus-associated" :op2 "kinase")
:ARG1-of (d / describe-01
:ARG0 (e2 / enzyme :name (n4 / name :op1 "JAK"))))
:op2 (p2 / protein :name (n5 / name :op1 "signal" :op2 "transducer" :op3 "and" :op4 "activator" :op5 "of" :op6 "transcription-3")
:ARG1-of (d2 / describe-01
:ARG0 (p3 / protein :name (n6 / name :op1 "STAT3"))))
:op3 (e3 / enzyme :name (n7 / name :op1 "mitogen-activated" :op2 "protein" :op3 "kinase")
:ARG1-of (d3 / describe-01
:ARG0 (e4 / enzyme :name (n8 / name :op1 "MAP"))))))
:ARG2 s))
# ::id bel_pmid_1040_9724.23704 ::date 2015-04-07T04:16:59 ::annotator SDL-AMR-09 ::preferred
# ::snt This study shows that in hepatoma cells, the recruitment and tyrosine phosphorylation of SHP-2, but not SHC, is the primary signaling event associated with the activation of MAP kinases (ERK1/2) by gp130.
# ::save-date Sun Jan 17, 2016 ::file bel_pmid_1040_9724_23704.txt
(s / show-01
:ARG0 (s2 / study-01
:mod (t / this))
:ARG1 (e / event
:ARG0-of (s3 / signal-07)
:mod (p / primary)
:domain (a / and
:op1 (r / recruit-01
:ARG1 (p2 / protein :name (n / name :op1 "SHP-2")))
:op2 (p3 / phosphorylate-01
:ARG1 p2
:ARG2 (t2 / tyrosine))
:ARG1-of (c / contrast-01
:ARG2 (a2 / and
:op1 (r2 / recruit-01 :polarity -
:ARG1 (p4 / protein :name (n2 / name :op1 "SHC")))
:op2 (p5 / phosphorylate-01 :polarity -
:ARG1 p4
:ARG2 t2))))
:ARG1-of (a3 / associate-01
:ARG2 (a4 / activate-01
:ARG0 (p6 / protein :name (n3 / name :op1 "gp130"))
:ARG1 (p7 / protein-family :name (n4 / name :op1 "MAP" :op2 "kinase")))
:location (c2 / cell
:mod (m / medical-condition :name (n6 / name :op1 "hepatoma"))))))
# ::id bel_pmid_1043_6166.3510 ::date 2015-04-03T06:52:44 ::annotator SDL-AMR-09 ::preferred
# ::snt NO modulation of the signaling pathway was shown by its inhibitory effect on shear stress-induced ERK1/ERK2 phosphorylation and activity.
# ::save-date Thu Dec 17, 2015 ::file bel_pmid_1043_6166_3510.txt
(s / show-01
:ARG0 (a3 / affect-01
:ARG0 m2
:ARG1 (a / and
:op1 (p / phosphorylate-01
:ARG1 (s3 / slash
:op1 (e2 / enzyme :name (n2 / name :op1 "ERK1"))
:op2 (e3 / enzyme :name (n3 / name :op1 "ERK2"))
:ARG2-of (i2 / induce-01
:ARG0 (s4 / stress-02
:mod (s5 / shear-01)))))
:op2 (a2 / activity-06
:ARG0 s3))
:ARG2 (i / inhibit-01
:ARG1 p))
:ARG1 (m2 / modulate-01
:ARG0 (n / name :op1 "NO")
:ARG1 (p2 / pathway
:ARG0-of (s2 / signal-07))))
# ::id bel_pmid_1043_6166.18636 ::date 2015-04-03T14:02:25 ::annotator SDL-AMR-09 ::preferred
# ::snt Treatment of ECs with an NO donor, S-nitroso-N-acetylpenicillamine (SNAP) or 3-morpholinosydnonimine (SIN-1), inhibited this shear stress-induced Egr-1 expression.
# ::save-date Sun Jan 3, 2016 ::file bel_pmid_1043_6166_18636.txt
(i3 / inhibit-01
:ARG0 (t / treat-04
:ARG1 (c / cell :name (n / name :op1 "EC"))
:ARG2 (s3 / small-molecule :name (n8 / name :op1 "nitric" :op2 "oxide")
:ARG0-of (d / donate-01)
:example (o / or
:op1 (s4 / small-molecule :name (n3 / name :op1 "S-nitroso-N-acetylpenicillamine")
:ARG1-of (m / mean-01
:ARG2 (n4 / name :op1 "SNAP")))
:op2 (s5 / small-molecule :name (n5 / name :op1 "3-morpholinosydnonimine")
:ARG1-of (m2 / mean-01
:ARG2 (n6 / name :op1 "SIN-1"))))))
:ARG1 (e / express-03
:ARG2 (p2 / protein :name (n7 / name :op1 "Egr-1")
:ARG2-of (i2 / induce-01
:ARG0 (s / stress-02
:mod (s2 / shear-01))))
:mod (t2 / this)))
# ::id bel_pmid_1044_6041.18010 ::date 2015-04-05T09:32:37 ::annotator SDL-AMR-09 ::preferred
# ::snt The FAK and Fyn/Shc pathways. Integrins activate various protein tyrosine kinases, including focal adhesion kinase (FAK), Srcfamily kinases, and Abl, and a serine-threonine kinase, integrin-linked kinase (ILK) (4, 7).
# ::save-date Fri Jan 15, 2016 ::file bel_pmid_1044_6041_18010.txt
(m / multi-sentence
:snt1 (a / and
:op1 (p / pathway :name (n / name :op1 "FAK"))
:op2 (p2 / pathway :name (n2 / name :op1 "Fyn/Shc")))
:snt2 (a2 / activate-01
:ARG0 (p7 / protein :name (n3 / name :op1 "integrin"))
:ARG1 (a3 / and
:op1 (e3 / enzyme :name (n10 / name :op1 "protein" :op2 "tyrosine" :op3 "kinase")
:ARG2-of (i2 / include-91
:ARG1 (a4 / and
:op1 (e2 / enzyme :name (n4 / name :op1 "focal" :op2 "adhesion" :op3 "kinase")
:ARG1-of (m2 / mean-01
:ARG2 (n5 / name :op1 "FAK")))
:op2 (p3 / protein-family :name (n9 / name :op1 "Src"))
:op3 (p4 / protein :name (n6 / name :op1 "Abl"))))
:mod (v2 / various))
:op2 (e / enzyme :name (n7 / name :op1 "serine-threonine" :op2 "kinase")
:ARG1-of (m5 / mean-01
:ARG2 (e4 / enzyme :name (n8 / name :op1 "integrin-linked" :op2 "kinase")))))
:ARG1-of (d / describe-01
:ARG0 (p6 / publication
:ARG1-of (c / cite-01
:ARG2 (a5 / and :op1 4 :op2 7))))))
# ::id bel_pmid_1044_6041.18016 ::date 2015-04-05T10:20:04 ::annotator SDL-AMR-09 ::preferred
# ::snt (38). Integrins also stimulate the p70 S6- kinase, which may promote cyclin D1 translation (39). Finally, anchorage to the ECM is necessary for the down-regulation of the Cdk 2 inhibitors p21 and p27 and, thus, the activation of cyclin E-Cdk 2
# ::save-date Fri Feb 12, 2016 ::file bel_pmid_1044_6041_18016.txt
(m / multi-sentence
:snt1 (d2 / describe-01
:ARG0 (p / publication
:ARG1-of (c / cite-01
:ARG2 38)))
:snt2 (s / stimulate-01
:ARG0 (p8 / protein :name (n10 / name :op1 "integrin"))
:ARG2 (e / enzyme :name (n2 / name :op1 "p70" :op2 "S6" :op3 "kinase"))
:mod (a / also)
:ARG0-of (p2 / promote-01
:ARG1 (t2 / translate-01
:ARG2 (p4 / protein :name (n3 / name :op1 "cyclin" :op2 "D1")))
:ARG1-of (p3 / possible-01))
:ARG1-of (d3 / describe-01
:ARG0 (p5 / publication
:ARG1-of (c2 / cite-01
:ARG2 39))))
:snt3 (n / need-01 :li "-1"
:ARG0 (d4 / downregulate-01
:ARG1 (a3 / and
:op1 (p6 / protein :name (n6 / name :op1 "p21")
:ARG0-of (i / inhibit-01
:ARG1 (e2 / enzyme :name (n7 / name :op1 "Cdk" :op2 "2"))))
:op2 (p7 / protein :name (n8 / name :op1 "p27")
:ARG0-of (i3 / inhibit-01
:ARG1 e2))))
:ARG1 (a2 / anchor-01
:ARG1 (m2 / matrix
:mod (e4 / extracellular)))
:ARG0-of (c3 / cause-01
:ARG1 (a4 / activate-01
:ARG1 (e3 / enzyme :name (n9 / name :op1 "cyclin" :op2 "E-Cdk" :op3 "2"))))))
# ::id bel_pmid_1044_6041.18018 ::date 2015-04-05T11:10:55 ::annotator SDL-AMR-09 ::preferred
# ::snt PTP-PEST has a COOH-terminal extension that anchors it to the cytosolic aspect of the endoplasmic reticulum. Integrin-mediated adhesion activates calpain, a protease that cleaves this extension and allows the phosphatase to relocate to focal adhesions (21).
# ::save-date Wed Mar 2, 2016 ::file bel_pmid_1044_6041_18018.txt
(m / multi-sentence
:snt1 (h / have-03
:ARG0 (e4 / enzyme :name (n / name :op1 "PTP-PEST"))
:ARG1 (e / extend-01
:mod (p2 / protein-segment :name (n2 / name :op1 "COOH-terminus"))
:ARG0-of (a / anchor-01
:ARG1 e4
:location (a2 / aspect
:mod (c / cytosol)
:part-of (r / reticulum
:mod (e2 / endoplasm))))))
:snt2 (a3 / activate-01
:ARG0 (a4 / adhere-01
:ARG1-of (m2 / mediate-01
:ARG0 (p3 / protein :name (n5 / name :op1 "integrin"))))
:ARG1 (p / protease :name (n6 / name :op1 "calpain")
:ARG0-of (c2 / cleave-01
:ARG1 (e5 / extend-01
:mod (t / this)))
:ARG0-of (a5 / allow-01
:ARG1 (r2 / relocate-01
:ARG1 (e3 / enzyme :name (n4 / name :op1 "phosphatase"))
:ARG2 (a6 / adhere-01
:mod (f / focal)))))
:ARG1-of (d / describe-01
:ARG0 (p5 / publication
:ARG1-of (c3 / cite-01
:ARG2 21)))))
# ::id bel_pmid_1044_6041.18060 ::date 2015-04-05T12:28:37 ::annotator SDL-AMR-09 ::preferred
# ::snt Whereas FAK is phosphorylated on tyrosine upon assembly of focal adhesions, it becomes phosphorylated on serine and disassociates from Src and p130CAS during mitosis (14). These events may loosen cell-substrate contacts and allow cells to divide and move apart.
# ::save-date Wed Mar 2, 2016 ::file bel_pmid_1044_6041_18060.txt
(m / multi-sentence
:snt1 (c / contrast-01
:ARG1 (p / phosphorylate-01
:ARG1 (a2 / amino-acid :name (n3 / name :op1 "tyrosine")
:part-of (e2 / enzyme :name (n2 / name :op1 "FAK")))
:time (a3 / assemble-02
:ARG1 (a4 / adhere-01
:mod (f / focal))))
:ARG2 (a6 / and
:op1 (b / become-01
:ARG1 (p3 / phosphorylate-01
:ARG1 (a / amino-acid :name (n / name :op1 "serine")
:part-of e2)))
:op2 (d2 / disassociate-01
:ARG1 e2
:ARG2 (a5 / and
:op1 (p4 / protein :name (n4 / name :op1 "Src"))
:op2 (p5 / protein :name (n5 / name :op1 "p130CAS")))
:time (m2 / mitosis)))
:ARG1-of (d3 / describe-01
:ARG0 (p6 / publication
:ARG1-of (c2 / cite-01
:ARG2 14))))
:snt2 (a7 / and
:op1 (p7 / possible-01
:ARG1 (l / loosen-01
:ARG0 (e / event
:mod (t / this))
:ARG1 (c3 / contact-01
:ARG0 (c4 / cell)
:ARG1 (s / substrate))))
:op2 (a8 / allow-01
:ARG0 e
:ARG1 (a9 / and
:op1 (d4 / divide-02
:ARG0 (c5 / cell)
:ARG1 c5)
:op2 (m3 / move-01
:ARG1 c5
:mod (a10 / apart))))))
# ::id bel_pmid_1044_6041.18334 ::date 2015-04-05T14:31:28 ::annotator SDL-AMR-09 ::preferred
# ::snt Certain integrins may regulate proliferation by additional mechanisms. For example, the a6b1 integrin may in part promote exit from the cell cycle in myoblasts, because the cytoplasmic domain of a6 inhibits paxillin signaling (44).
# ::save-date Sun Jan 3, 2016 ::file bel_pmid_1044_6041_18334.txt
(m / multi-sentence
:snt2 (c2 / cause-01
:ARG0 (i3 / inhibit-01
:ARG0 (d2 / domain
:mod (c5 / cytoplasm)
:part-of p6)
:ARG1 (s / signal-07
:ARG0 (p5 / protein :name (n3 / name :op1 "paxillin"))))
:ARG1 (p / possible-01
:ARG1 (p3 / promote-01
:ARG0 (p6 / protein :name (n2 / name :op1 "a6b1" :op2 "integrin"))
:ARG1 (e2 / exit-01
:ARG1 (c3 / cycle-02
:ARG1 (c4 / cell)
:location (m3 / myoblast)))
:degree (p4 / part)))
:ARG0-of (e / exemplify-01)
:ARG1-of (d3 / describe-01
:ARG0 (p7 / publication
:ARG1-of (c6 / cite-01
:ARG2 44))))
:snt1 (p8 / possible-01
:ARG1 (r / regulate-01
:ARG0 (p9 / protein :name (n / name :op1 "integrin")
:mod (c / certain))
:ARG1 (p2 / proliferate-01)
:instrument (m2 / mechanism
:mod (a / additional)))))
# ::id bel_pmid_1044_6041.18348 ::date 2015-04-05T14:32:02 ::annotator SDL-AMR-09 ::preferred
# ::snt For example, avb3 associates with the PDGF receptor, and fibroblasts show greater proliferation in response to PDGFb when adhering to the avb3 ligand vitronectin than when they adhere to the b1 integrin ligand collagen (26).
# ::save-date Sun Jan 3, 2016 ::file bel_pmid_1044_6041_18348.txt
(a / and
:op1 (a2 / associate-01
:ARG1 (p4 / protein :name (n9 / name :op1 "avb3"))
:ARG2 (p8 / protein :name (n5 / name :op1 "PDGF" :op2 "receptor")))
:op2 (s / show-01
:ARG0 (c / cell :name (n2 / name :op1 "fibroblast"))
:ARG1 (p / proliferate-01
:mod (g2 / great
:degree (m / more)))
:ARG2-of (r2 / respond-01
:ARG1 (p2 / protein :name (n3 / name :op1 "PDGFb")))
:time (a4 / adhere-01
:ARG1 p2
:ARG2 (p7 / protein :name (n6 / name :op1 "vitronectin")
:ARG1-of (b2 / bind-01
:ARG2 p4))
:compared-to (a5 / adhere-01
:ARG1 p2
:ARG2 (p5 / protein :name (n4 / name :op1 "collagen")
:ARG1-of (b / bind-01
:ARG2 (p3 / protein :name (n8 / name :op1 "b1" :op2 "integrin")))))))
:ARG0-of (e / exemplify-01)
:ARG1-of (d / describe-01
:ARG0 (p6 / publication
:ARG1-of (c2 / cite-01
:ARG2 26))))
# ::id bel_pmid_1044_6041.18586 ::date 2015-04-05T14:32:31 ::annotator SDL-AMR-09 ::preferred
# ::snt In addition to activating FAK, some b1 and av integrins also activate the tyrosine kinase Fyn and, through it, the adapter protein Shc (4).
# ::save-date Sun Jan 17, 2016 ::file bel_pmid_1044_6041_18586.txt
(a / and
:op1 (a2 / activate-01
:ARG1 (e2 / enzyme :name (n / name :op1 "FAK")))
:op2 (a3 / and
:op1 (a4 / activate-01
:ARG0 (p4 / protein :name (n6 / name :op1 "b1" :op2 "integrin")
:quant (s / some))
:ARG1 (e / enzyme :name (n3 / name :op1 "tyrosine" :op2 "kinase" :op3 "Fyn"))
:mod (a5 / also))
:op2 (a6 / activate-01
:ARG0 (p5 / protein :name (n2 / name :op1 "b1" :op2 "integrin")
:quant s)
:ARG1 e
:mod a5)
:ARG0-of (a7 / activate-01
:ARG1 (p2 / protein :name (n5 / name :op1 "Shc")
:mod (a8 / adapter))))
:ARG1-of (d / describe-01
:ARG0 (p3 / publication
:ARG1-of (c / cite-01
:ARG2 4))))
# ::id bel_pmid_1044_6041.20870 ::date 2015-04-05T14:32:53 ::annotator SDL-AMR-09 ::preferred
# ::snt Rac promotes cell cycle progression, an effect that correlates with its ability to organize the cytoskeleton and promote spreading, rather than with its ability to activate MAP kinases (63).
# ::save-date Sun Jan 17, 2016 ::file bel_pmid_1044_6041_20870.txt
(p / promote-01
:ARG0 (e / enzyme :name (n / name :op1 "Rac"))
:ARG1 (p2 / progress-01
:ARG1 (c / cycle-02
:ARG1 (c2 / cell)))
:ARG2-of (a / affect-01
:ARG1-of (c3 / correlate-01
:ARG2 (c6 / capable-01
:ARG1 e
:ARG2 (a4 / and
:op1 (o / organize-01
:ARG0 e
:ARG1 (c4 / cytoskeleton))
:op2 (p3 / promote-01
:ARG1 (s / spread-02)))
:ARG1-of (i / instead-of-91
:ARG2 (c7 / capable-01
:ARG1 e
:ARG2 (a3 / activate-01
:ARG0 e
:ARG1 (p4 / protein-family :name (n2 / name :op1 "MAP" :op2 "kinase"))))))))
:ARG1-of (d / describe-01
:ARG0 (p5 / publication
:ARG1-of (c5 / cite-01
:ARG2 63))))
# ::id bel_pmid_1044_6041.21282 ::date 2015-04-05T14:33:17 ::annotator SDL-AMR-09 ::preferred
# ::snt Yes and Lck are known to be enriched in rafts and may mediate the activation of Shc when Fyn is not expressed.
# ::save-date Sat Apr 11, 2015 ::file bel_pmid_1044_6041_21282.txt
(a2 / and
:op1 (k / know-01
:ARG1 (e3 / enrich-01
:ARG1 (a / and
:op1 (e / enzyme :name (n / name :op1 "Yes"))
:op2 (e2 / enzyme :name (n2 / name :op1 "Lck")))
:ARG2 (r / raft)))
:op2 (p / possible-01
:ARG1 (m / mediate-01
:ARG0 a
:ARG1 (a3 / activate-01
:ARG1 (p2 / protein :name (n3 / name :op1 "Shc")))
:time (e4 / express-03 :polarity -
:ARG2 (e5 / enzyme :name (n4 / name :op1 "Fyn"))))))
# ::id bel_pmid_1044_6041.21342 ::date 2015-04-05T14:33:38 ::annotator SDL-AMR-09 ::preferred
# ::snt Integrin signaling may be needed for the transcription of cyclin D1, because the cyclin D1 promoter is coordinately regulated by JNK and ERK (37) (Fig. 4).
# ::save-date Sun Jan 3, 2016 ::file bel_pmid_1044_6041_21342.txt
(c / cause-01
:ARG0 (r / regulate-01
:ARG0 (a / and
:op1 (e2 / enzyme :name (n4 / name :op1 "JNK"))
:op2 (e3 / enzyme :name (n5 / name :op1 "ERK")))
:ARG1 (p2 / promote-01
:ARG1 p)
:manner (c2 / coordinate-01))
:ARG1 (p4 / possible-01
:ARG1 (n2 / need-01
:ARG0 (t / transcribe-01
:ARG1 (p / protein :name (n3 / name :op1 "cyclin" :op2 "D1")))
:ARG1 (s / signal-07
:ARG0 (p5 / protein :name (n / name :op1 "integrin")))))
:ARG1-of (d / describe-01
:ARG0 (p3 / publication
:ARG1-of (c3 / cite-01
:ARG2 37)))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod 4)))
# ::id bel_pmid_1044_6041.21364 ::date 2015-04-06T09:25:09 ::annotator SDL-AMR-09 ::preferred
# ::snt Activated JNK enters the nucleus and phosphorylates the transcription factor c-Jun, which combines with c-Fos to form the AP-1 transcription factor complex.
# ::save-date Wed Jun 24, 2015 ::file bel_pmid_1044_6041_21364.txt
(a / and
:op1 (e / enter-01
:ARG0 (e2 / enzyme :name (n / name :op1 "JNK")
:ARG1-of (a2 / activate-01))
:ARG1 (n2 / nucleus))
:op2 (p / phosphorylate-01
:ARG1 (p2 / protein :name (n3 / name :op1 "c-Jun")
:ARG0-of (t / transcribe-01)
:mod (f / factor)
:ARG1-of (c / combine-01
:ARG2 (p3 / protein :name (n4 / name :op1 "c-Fos"))
:ARG3 (c2 / complex
:mod (f2 / factor)
:mod (p4 / protein :name (n5 / name :op1 "AP-1")
:ARG0-of (t2 / transcribe-01)))))
:ARG2 e2))
# ::id bel_pmid_1044_6041.22694 ::date 2015-04-06T09:36:21 ::annotator SDL-AMR-09 ::preferred
# ::snt Several integrins have been found to associate laterally with the oligomeric membrane protein caveolin-1, at least in primary cells (4, 5). Although the biochemical nature of this interaction is not known, inhibiting caveolin expression suppresses the formation of focal adhesions and integrin signaling (4, 5).
# ::save-date Wed Mar 2, 2016 ::file bel_pmid_1044_6041_22694.txt
(m / multi-sentence
:snt1 (f / find-01
:ARG1 (a2 / associate-01
:ARG1 (p6 / protein :name (n3 / name :op1 "integrin")
:quant (s4 / several))
:ARG2 (p / protein :name (n / name :op1 "caveolin-1")
:mod (m2 / membrane
:mod (o / oligomer)))
:manner (l / lateral)
:location (c / cell
:mod (p2 / primary)
:mod (a / at-least)))
:ARG1-of (d / describe-01
:ARG0 (p3 / publication
:ARG1-of (c2 / cite-01
:ARG2 (a3 / and :op1 4 :op2 5)))))
:snt2 (h / have-concession-91
:ARG1 (i3 / inhibit-01
:ARG1 (e / express-03
:ARG2 (p5 / protein :name (n4 / name :op1 "caveolin")))
:ARG0-of (s2 / suppress-01
:ARG1 (f2 / form-01
:ARG1 (a4 / and
:op1 (a5 / adhere-01
:mod (f3 / focal))
:op2 (s3 / signal-07
:ARG0 (p7 / protein :name (n6 / name :op1 "integrin")))))))
:ARG2 (k / know-01 :polarity -
:ARG1 (n2 / nature
:mod (b / biochemistry)
:poss (i2 / interact-01
:mod (t / this))))
:ARG1-of (d2 / describe-01
:ARG0 (p4 / publication
:ARG1-of (c3 / cite-01
:ARG2 (a6 / and :op1 4 :op2 5))))))
# ::id bel_pmid_1044_6041.24492 ::date 2015-04-06T09:55:30 ::annotator SDL-AMR-09 ::preferred
# ::snt IAP, an immunoglobulin superfamily transmembrane protein, cooperates with b3 integrins in binding thrombospondin to cells, and it also activates an inhibitory trimeric guanine nucleotide- binding protein (29).
# ::save-date Sun Jan 3, 2016 ::file bel_pmid_1044_6041_24492.txt
(a / and
:op1 (c / cooperate-01
:ARG0 (p / protein :name (n / name :op1 "IAP")
:ARG1-of (i4 / include-91
:ARG2 (p2 / protein-family :name (n6 / name :op1 "immunoglobulin")))
:mod (t / transmembrane))
:ARG1 (p7 / protein :name (n5 / name :op1 "b3" :op2 "integrin"))
:ARG2 (b / bind-01
:ARG1 (p3 / protein :name (n2 / name :op1 "thrombospondin"))
:ARG2 (c2 / cell)))
:op2 (a2 / activate-01
:ARG0 p
:ARG1 (p4 / protein :name (n4 / name :op1 "guanine" :op2 "nucleotide-binding")
:mod (t2 / trimeric)
:ARG0-of (i3 / inhibit-01))
:mod (a3 / also))
:ARG1-of (d / describe-01
:ARG0 (p5 / publication
:ARG1-of (c3 / cite-01
:ARG2 29))))
# ::id bel_pmid_1044_6041.24730 ::date 2015-04-06T09:58:56 ::annotator SDL-AMR-09 ::preferred
# ::snt The FAK and Shc pathways are regulated both positively and negatively by tyrosine phosphatases. Integrin-mediated activation of ERK is suppressed in cells that lack the re- ceptor-type protein tyrosine phosphatase a or the cytosolic phosphatase SHP-2 (19). These enzymes dephosphorylate the negative regulatory site in Src-family kinases and thus, presumably, amplify both FAK and Shc signaling.
# ::save-date Sun Jan 17, 2016 ::file bel_pmid_1044_6041_24730.txt
(m / multi-sentence
:snt2 (s / suppress-01
:ARG1 (a3 / activate-01
:ARG1 (e / enzyme :name (n / name :op1 "ERK"))
:ARG1-of (m2 / mediate-01
:ARG0 (p8 / protein :name (n5 / name :op1 "integrin"))))
:location (c / cell
:ARG0-of (l / lack-01
:ARG1 (o / or
:op1 (e5 / enzyme :name (n8 / name :op1 "protein" :op2 "tyrosine" :op3 "phosphatase" :op4 "a")
:ARG1-of (t / type-03
:ARG2 (r2 / receptor)))
:op2 (p9 / phosphatase :name (n7 / name :op1 "SHP-2")
:mod (c2 / cytosol)))))
:ARG1-of (d / describe-01
:ARG0 (p4 / publication
:ARG1-of (c3 / cite-01
:ARG2 19))))
:snt3 (d2 / dephosphorylate-01
:ARG1 (s2 / site
:ARG1-of (d3 / downregulate-01))
:ARG2 (e3 / enzyme
:mod (t2 / this))
:ARG3 (k / kinase
:ARG1-of (i / include-91
:ARG2 (p3 / protein-family :name (n6 / name :op1 "Src"))))
:ARG0-of (c4 / cause-01
:ARG1 (a4 / amplify-01
:ARG1 (a2 / and
:op1 (s3 / signal-07
:ARG0 (p6 / pathway :name (n9 / name :op1 "FAK")))
:op2 (s4 / signal-07
:ARG0 (p7 / pathway :name (n10 / name :op1 "Shc")))))
:ARG1-of (p5 / presume-01)))
:snt1 (a6 / and
:op1 (u / upregulate-01
:ARG1 (a / and
:op1 (p / pathway :name (n2 / name :op1 "FAK"))
:op2 (p2 / pathway :name (n3 / name :op1 "Shc")))
:ARG2 (e2 / enzyme :name (n4 / name :op1 "tyrosine" :op2 "phosphatase")))
:op2 (d4 / downregulate-01
:ARG1 a
:ARG2 e2)))
# ::id bel_pmid_1044_6041.39480 ::date 2015-04-06T12:33:09 ::annotator SDL-AMR-09 ::preferred
# ::snt Two cytoplasmic protein tyrosine phosphatases, PTP-PEST and PTP-1B, target p130CAS and may specifically inhibit some of the signals downstream of FAK (20).
# ::save-date Sun Jan 3, 2016 ::file bel_pmid_1044_6041_39480.txt
(a / and
:op1 (t / target-01
:ARG0 (e / enzyme :quant 2 :name (n / name :op1 "protein" :op2 "tyrosine" :op3 "phosphatase")
:mod (c / cytoplasm)
:example (a2 / and
:op1 (e2 / enzyme :name (n2 / name :op1 "PTP-PEST"))
:op2 (e3 / enzyme :name (n3 / name :op1 "PTP-1B"))))
:ARG1 (p / protein :name (n4 / name :op1 "p130CAS")))
:op2 (p2 / possible-01
:ARG1 (i / inhibit-01
:ARG1 (s / signal-07
:ARG2-of (i2 / include-91
:ARG3 (s2 / some))
:location (r / relative-position
:op1 (p3 / pathway :name (n5 / name :op1 "FAK"))
:direction (d2 / downstream)))
:ARG1-of (s3 / specific-02)))
:ARG1-of (d3 / describe-01
:ARG0 (p4 / publication
:ARG1-of (c2 / cite-01
:ARG2 20))))
# ::id bel_pmid_1044_6219.2808 ::date 2015-04-06T12:56:39 ::annotator SDL-AMR-09 ::preferred
# ::snt Stat3 is activated by phosphorylation on Tyr-705, which leads to dimer formation, nuclear translocation, and regulation of gene expression.
# ::save-date Fri Dec 18, 2015 ::file bel_pmid_1044_6219_2808.txt
(a / activate-01
:ARG0 (p3 / phosphorylate-01
:ARG1 (a2 / amino-acid :mod 705 :name (n2 / name :op1 "tyrosine")))
:ARG1 (p2 / protein :name (n / name :op1 "Stat3"))
:ARG0-of (l / lead-03
:ARG2 (a3 / and
:op1 (f / form-01
:ARG1 (m / macro-molecular-complex :name (n3 / name :op1 "dimer")))
:op2 (t / translocate-01
:ARG2 (n4 / nucleus))
:op3 (r / regulate-01
:ARG1 (e / express-03
:ARG2 (g / gene))))))
# ::id bel_pmid_1044_6219.5996 ::date 2015-04-06T13:15:53 ::annotator SDL-AMR-09 ::preferred
# ::snt Here, we report that Stat3 was specifically associated with PKC delta in vivo in an IL-6-dependent manner in several cell types. Furthermore, Stat3 was phosphorylated by PKC delta in vivo on Ser-727,
# ::save-date Mon Dec 21, 2015 ::file bel_pmid_1044_6219_5996.txt
(m / multi-sentence
:snt1 (r / report-01
:ARG0 (w / we)
:ARG1 (a / associate-01
:ARG1 (p / protein :name (n / name :op1 "Stat3"))
:ARG2 (e / enzyme :name (n2 / name :op1 "PKC" :op2 "delta"))
:ARG1-of (s / specific-02)
:manner (i / in-vivo)
:location (t / type-03
:ARG1 (c / cell)
:quant (s2 / several))
:manner (d / depend-01
:ARG1 (p4 / protein :name (n6 / name :op1 "IL-6"))))
:location (h / here))
:snt2 (a3 / and
:op2 (p2 / phosphorylate-01
:ARG1 (a2 / amino-acid :mod 727 :name (n5 / name :op1 "serine")
:part-of (p3 / protein :name (n3 / name :op1 "Stat3")))
:ARG2 (e2 / enzyme :name (n4 / name :op1 "PKA" :op2 "delta")
:manner (i2 / in-vivo)))))
# ::id bel_pmid_1044_6219.5998 ::date 2015-04-06T13:58:27 ::annotator SDL-AMR-09 ::preferred
# ::snt Finally, we showed that the phosphorylation of Stat3 by PKC delta led to a negative regulation of Stat3 DNA binding and transcriptional activity.
# ::save-date Sat Jan 2, 2016 ::file bel_pmid_1044_6219_5998.txt
(s / show-01 :li -1
:ARG0 (w / we)
:ARG1 (l / lead-03
:ARG0 (p2 / phosphorylate-01
:ARG1 (p3 / protein
:name (n / name :op1 "Stat3"))
:ARG2 (e / enzyme
:name (n2 / name :op1 "PKC" :op2 "delta")))
:ARG2 (a / and
:op1 (d / downregulate-01
:ARG1 (p4 / protein
:name (n3 / name :op1 "Stat3")
:ARG0-of (b / bind-01
:ARG1 (n4 / nucleic-acid :wiki "DNA"
:name (n5 / name :op1 "DNA")))))
:op2 (a2 / activity-06
:ARG0 p3
:ARG1 (t / transcribe-01)))))
# ::id bel_pmid_1044_6219.7272 ::date 2015-04-06T14:12:34 ::annotator SDL-AMR-09 ::preferred
# ::snt Here, we report that Stat3 was specifically associated with PKC delta in vivo in an IL-6-dependent manner in several cell types.
# ::save-date Mon Dec 21, 2015 ::file bel_pmid_1044_6219_7272.txt
(r / report-01
:ARG0 (w / we)
:ARG1 (a / associate-01
:ARG1 (p / protein :name (n / name :op1 "Stat3"))
:ARG2 (e / enzyme :name (n2 / name :op1 "PKC" :op2 "delta"))
:manner (i / in-vivo)
:ARG1-of (s / specific-02)
:location (t / type-03
:ARG1 (c / cell
:quant (s2 / several)))
:manner (d / depend-01
:ARG1 (p2 / protein :name (n3 / name :op1 "IL-6"))))
:location (h / here))
# ::id bio.chicago_2015.55 ::date 2015-10-20T04:45:05 ::annotator SDL-AMR-09 ::preferred
# ::snt Binding of armadillo to dTCF has been shown to reduce the ability of CBP to catalyze this reaction, perhaps by steric interference [ 97].
# ::save-date Sun Jan 17, 2016 ::file bio_chicago_2015_55.txt
(s / show-01
:ARG1 (r / reduce-01
:ARG0 (b / bind-01
:ARG1 (p3 / protein :name (n3 / name :op1 "armadillo"))
:ARG2 (p5 / protein :name (n / name :op1 "dTCF")))
:ARG1 (c / capable-01
:ARG1 (p4 / protein :name (n2 / name :op1 "CBP"))
:ARG2 (c2 / catalyze-01
:ARG0 p4
:ARG1 (t / thing
:ARG2-of (r2 / react-01)
:mod (t2 / this))
:instrument (i / interfere-01
:mod (s4 / steric)
:ARG1-of (p / possible-01)))))
:ARG1-of (d / describe-01
:ARG0 (p2 / publication
:ARG1-of (c3 / cite-01
:ARG2 97))))
# ::id bio.chicago_2015.119 ::date 2015-10-20T04:50:31 ::annotator SDL-AMR-09 ::preferred
# ::snt In particular, the dCtBP corepressor may interact with Ttk69 to form a repressive complex for transcriptional repression.
# ::save-date Thu Nov 19, 2015 ::file bio_chicago_2015_119.txt
(p / possible-01
:ARG1 (i / interact-01
:ARG0 (c / corepressor :name (n / name :op1 "dCtBP"))
:ARG1 (p4 / protein :name (n2 / name :op1 "Ttk69"))
:purpose (f / form-01
:ARG0 c
:ARG1 (c2 / complex
:ARG0-of (r / repress-01
:ARG1 (t2 / transcribe-01)))))
:mod (p2 / particular))
# ::id bio.chicago_2015.125 ::date 2015-10-20T04:55:23 ::annotator SDL-AMR-09 ::preferred
# ::snt The N-termini of XTcf-3 and LEF-1 interact with the Armadillo repeat region of beta-catenin (Behrens et al., 1996 ; Huber et al., 1996 ; Molenaar et al., 1996 ).
# ::save-date Thu Nov 19, 2015 ::file bio_chicago_2015_125.txt
(i / interact-01
:ARG0 (a / and
:op1 (p / protein-segment :name (n / name :op1 "N-terminus")
:part-of (p13 / protein :name (n2 / name :op1 "XTcf-3")))
:op2 (p2 / protein-segment :name (n3 / name :op1 "N-terminus")
:part-of (p14 / protein :name (n4 / name :op1 "LEF-1"))))
:ARG1 (p9 / protein-segment :name (n5 / name :op1 "Armadillo" :op2 "repeat")
:part-of (p3 / protein :name (n6 / name :op1 "beta-catenin")))
:ARG1-of (d2 / describe-01
:ARG0 (a3 / and
:op1 (p4 / publication-91
:ARG0 (a2 / and
:op1 (p5 / person :name (n7 / name :op1 "Behrens"))
:op2 (p6 / person
:mod (o / other)))
:time (d3 / date-entity :year 1996))
:op2 (p7 / publication-91
:ARG0 (a4 / and
:op1 (p8 / person :name (n8 / name :op1 "Huber"))
:op2 p6)
:time d3)
:op3 (p10 / publication-91
:ARG0 (a5 / and
:op1 (p11 / person :name (n9 / name :op1 "Molenaar"))
:op2 p6)
:time d3))))
# ::id bio.chicago_2015.129 ::date 2015-10-20T05:07:01 ::annotator SDL-AMR-09 ::preferred
# ::snt Activation of p53 Sequence-Specific DNA Binding by Acetylation of the p53 C-Terminal Domain.
# ::save-date Thu Nov 19, 2015 ::file bio_chicago_2015_129.txt
(a / activate-01
:ARG0 (a2 / acetylate-01
:ARG1 (p3 / protein-segment :name (n / name :op1 "C-terminus" :op2 "domain")
:part-of (p2 / protein :name (n3 / name :op1 "p53"))))
:ARG1 (b / bind-01
:ARG1 (n4 / nucleic-acid :name (n5 / name :op1 "DNA")
:ARG1-of (s / specific-02
:ARG2 (s2 / sequence
:part-of p2)))))
# ::id bio.chicago_2015.132 ::date 2015-10-20T21:07:56 ::annotator SDL-AMR-09 ::preferred
# ::snt The nonmodular activation regions contain a TFIID interaction domain that binds specifically to TAFII110 and TAFII250.
# ::save-date Sun Nov 1, 2015 ::file bio_chicago_2015_132.txt
(c / contain-01
:ARG0 (r / region
:mod (n / nonmodular)
:mod (a / activate-01))
:ARG1 (d / domain
:location-of (i / interact-01
:ARG0 (p / protein :name (n2 / name :op1 "TFIID")))
:ARG1-of (b / bind-01
:ARG2 (a2 / and
:op1 (p2 / protein :name (n3 / name :op1 "TAFII110"))
:op2 (p3 / protein :name (n4 / name :op1 "TAFII250")))
:ARG1-of (s / specific-02))))
# ::id bio.chicago_2015.139 ::date 2015-10-20T21:14:38 ::annotator SDL-AMR-09 ::preferred
# ::snt (E) The TALE motif does not prevent PBX binding to CBP, but changing an arginine to lysine within HD helix 3 increases CBP binding to PBX.
# ::save-date Sun Nov 1, 2015 ::file bio_chicago_2015_139.txt
(c / contrast-01
:ARG1 (p / prevent-01 :polarity -
:ARG0 (m / motif :name (n2 / name :op1 "TALE"))
:ARG1 (b / bind-01
:ARG1 (p2 / protein :name (n3 / name :op1 "PBX"))
:ARG2 (p3 / protein :name (n4 / name :op1 "CBP"))))
:ARG2 (i / increase-01
:ARG0 (c2 / change-01
:ARG1 (a2 / amino-acid :name (n5 / name :op1 "arginine"))
:ARG2 (a3 / amino-acid :name (n6 / name :op1 "lysine"))
:location (p4 / protein-segment :name (n / name :op1 "helix" :op2 "3")
:part-of (p5 / protein :name (n7 / name :op1 "HD"))))
:ARG1 (b2 / bind-01
:ARG1 p3
:ARG2 p2))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "E")))
# ::id bio.chicago_2015.157 ::date 2015-10-20T21:28:13 ::annotator SDL-AMR-09 ::preferred
# ::snt Given that p53 interacts with p300/CBP ( 3, 26, 51), the same membrane was then probed with polyclonal anti-CBP antibodies, which detect both p300 and CBP ( 4, 56).
# ::save-date Tue Oct 20, 2015 ::file bio_chicago_2015_157.txt
(c / cause-01
:ARG0 (i / interact-01
:ARG0 (p / protein :name (n / name :op1 "p53"))
:ARG1 (s / slash
:op1 (p2 / protein :name (n2 / name :op1 "p300"))
:op2 (p3 / protein :name (n3 / name :op1 "CBP"))))
:ARG1 (p5 / probe-01
:ARG0 (a2 / antibody
:ARG0-of (o / oppose-01
:ARG1 p3)
:mod (p7 / polyclonal)
:ARG0-of (d2 / detect-01
:ARG1 (a3 / and
:op1 p2
:op2 p3)
:ARG1-of (d3 / describe-01
:ARG0 (p8 / publication
:ARG1-of (c3 / cite-01
:ARG2 (a4 / and :op1 4 :op2 56))))))
:ARG1 (m / membrane
:ARG1-of (s2 / same-01)))
:ARG1-of (d / describe-01
:ARG0 (p4 / publication
:ARG1-of (c2 / cite-01
:ARG2 (a / and :op1 3 :op2 26 :op3 51)))))
# ::id bio.chicago_2015.177 ::date 2015-10-20T22:19:22 ::annotator SDL-AMR-09 ::preferred
# ::snt Huckebein, Hairy, Goosecoid, and Engrailed are among the repressors that interact with Groucho (Paroush et al. 1994 ; Goldstein et al. 1999 ), whereas Kruppel, Knirps, and Snail interact with dCtBP (Nibu et al. 1998a ).
# ::save-date Sun Nov 1, 2015 ::file bio_chicago_2015_177.txt
(c / contrast-01
:ARG1 (i2 / include-91
:ARG1 (a / and
:op1 (p3 / protein :name (n2 / name :op1 "Huckebein"))
:op2 (p4 / protein :name (n3 / name :op1 "Hairy"))
:op3 (p18 / protein :name (n12 / name :op1 "Goosecoid"))
:op4 (p5 / protein :name (n4 / name :op1 "Engrailed")))
:ARG2 (p / protein
:ARG0-of (r / repress-01)
:ARG0-of (i / interact-01
:ARG1 (p2 / protein :name (n / name :op1 "Groucho"))))
:ARG1-of (d4 / describe-01
:ARG0 (a3 / and
:op1 (p6 / publication-91
:ARG0 (a2 / and
:op1 (p7 / person :name (n5 / name :op1 "Paroush"))
:op2 (p8 / person
:mod (o / other)))
:time (d / date-entity :year 1994))
:op2 (p9 / publication-91
:ARG0 (a4 / and
:op1 (p10 / person :name (n6 / name :op1 "Goldstein"))
:op2 p8)
:time (d2 / date-entity :year 1999)))))
:ARG2 (i3 / interact-01
:ARG0 (a5 / and
:op1 (p12 / protein :name (n7 / name :op1 "Kruppel"))
:op2 (p13 / protein :name (n8 / name :op1 "Knirps"))
:op3 (p14 / protein :name (n9 / name :op1 "Snail")))
:ARG1 (p19 / protein :name (n10 / name :op1 "dCtBP"))
:ARG1-of (d5 / describe-01
:ARG0 (p15 / publication-91
:ARG0 (a6 / and
:op1 (p16 / person :name (n11 / name :op1 "Nibu"))
:op2 p8)
:time (d3 / date-entity :year 1998)))))
# ::id bio.chicago_2015.218 ::date 2015-10-21T01:38:43 ::annotator SDL-AMR-09 ::preferred
# ::snt For example, abd-A depends on exd for the regulation of wg, but not for the regulation of dpp [14] .
# ::save-date Sun Jan 17, 2016 ::file bio_chicago_2015_218.txt
(e2 / exemplify-01
:ARG0 (c / contrast-01
:ARG1 (d / depend-01
:ARG0 (p2 / protein :name (n / name :op1 "abd-A"))
:ARG1 (p3 / protein :name (n2 / name :op1 "exd"))
:purpose (r / regulate-01
:ARG1 (p4 / protein :name (n3 / name :op1 "wg"))))
:ARG2 (d2 / depend-01 :polarity -
:ARG0 p2
:ARG1 p3
:purpose (r2 / regulate-01
:ARG1 (p5 / protein :name (n4 / name :op1 "dpp")))))
:ARG1-of (d3 / describe-01
:ARG0 (p / publication
:ARG1-of (c2 / cite-01
:ARG2 14))))
# ::id bio.chicago_2015.232 ::date 2015-10-21T01:44:49 ::annotator SDL-AMR-09 ::preferred
# ::snt This suggests that Exd is required to release the transcriptional activation function of Dfd independently of Exd enhancement of Dfd-binding affinity on the composite site.
# ::save-date Sun Nov 1, 2015 ::file bio_chicago_2015_232.txt
(s / suggest-01
:ARG0 (t / this)
:ARG1 (r / require-01
:ARG0 (r2 / release-01
:ARG0 p
:ARG1 (f / function-01
:ARG0 (p2 / protein :name (n2 / name :op1 "Dfd"))
:ARG1 (a / activate-01)
:ARG0-of (t3 / transcribe-01)))
:ARG1 (p / protein :name (n / name :op1 "Exd"))
:ARG0-of (d / depend-01 :polarity -
:ARG1 (e2 / enhance-01
:ARG0 p
:ARG1 (a2 / affinity
:mod (b / bind-01
:ARG2 p2))
:location (s2 / site
:mod (c / composite))))))
# ::id bio.chicago_2015.289 ::date 2015-10-21T02:13:12 ::annotator SDL-AMR-09 ::preferred
# ::snt Ttk activates ftz transcription in yeast cells
# ::save-date Sun Nov 1, 2015 ::file bio_chicago_2015_289.txt
(a / activate-01
:ARG0 (e / enzyme :name (n / name :op1 "Ttk"))
:ARG1 (t / transcribe-01
:ARG1 (p / protein :name (n2 / name :op1 "Ftz")))
:location (c / cell
:mod (y / yeast)))
# ::id bio.chicago_2015.325 ::date 2015-10-21T02:15:20 ::annotator SDL-AMR-09 ::preferred
# ::snt In summary, the genetic analysis of dCtBP mutants suggests that Kruppel, Knirps and Snail depend on dCtBP+ activity, while Hairy and Dorsal continue to function as repressors in the absence of the dCtBP co-repressor.
# ::save-date Mon Jan 4, 2016 ::file bio_chicago_2015_325.txt
(s2 / summarize-01
:ARG2 (c / contrast-01
:ARG1 (s3 / suggest-01
:ARG0 (a / analyze-01
:ARG1 (p7 / protein :name (n / name :op1 "dCtBP")
:ARG2-of (m / mutate-01))
:mod (g / genetic))
:ARG1 (d / depend-01
:ARG0 (a2 / and
:op1 (p2 / protein :name (n2 / name :op1 "Kruppel"))
:op2 (p3 / protein :name (n3 / name :op1 "Knirps"))
:op3 (p4 / protein :name (n4 / name :op1 "Snail")))
:ARG1 (a3 / activity-06
:ARG0 (p8 / protein :name (n5 / name :op1 "dCtBP")
:mod (w / wild-type)))))
:ARG2 (c2 / continue-01
:ARG1 (f / function-01
:ARG0 (a4 / and
:op1 (p5 / protein :name (n6 / name :op1 "Hairy"))
:op2 (p6 / protein :name (n7 / name :op1 "Dorsal")))
:ARG1 (m2 / molecular-physical-entity
:ARG0-of (r / repress-01)))
:condition (a5 / absent-01
:ARG1 (p / protein :name (n8 / name :op1 "dCtBP")
:ARG0-of (c3 / corepress-00))))))
# ::id bio.chicago_2015.328 ::date 2015-10-21T02:25:13 ::annotator SDL-AMR-09 ::preferred
# ::snt Unilateral photoactivation of UBX repressed ANTP expression on one side of the embryo, indicating that the photo-induced UBX was functional (Fig. 3C).
# ::save-date Sun Nov 1, 2015 ::file bio_chicago_2015_328.txt
(r / repress-01
:ARG0 (a / activate-01
:ARG1 (p2 / protein :name (n / name :op1 "UBX"))
:mod (p / photo)
:mod (u / unilateral))
:ARG1 (e / express-03
:ARG2 (p5 / protein :name (n2 / name :op1 "ANTP"))
:ARG3 (s / side :quant 1
:part-of (e3 / embryo)))
:ARG0-of (i / indicate-01
:ARG1 (f / function-01
:ARG0 (p3 / protein :name n
:ARG2-of (i2 / induce-01
:ARG0 (p4 / photo)))))
:ARG1-of (d / describe-01
:ARG0 (f2 / figure :mod "3C")))
# ::id bio.chicago_2015.340 ::date 2015-10-21T02:31:39 ::annotator SDL-AMR-09 ::preferred
# ::snt Binding of PC and TRX to Ubx, abd-A and Abd-B promoters during different embryonic stages.
# ::save-date Sun Nov 1, 2015 ::file bio_chicago_2015_340.txt
(b / bind-01
:ARG1 (a / and
:op1 (p / protein :name (n / name :op1 "PC"))
:op2 (p2 / protein :name (n2 / name :op1 "TRX")))
:ARG2 (a2 / and
:op1 (m / molecular-physical-entity
:ARG0-of (p3 / promote-01
:ARG1 (p4 / protein :name (n3 / name :op1 "Ubx"))))
:op2 (m2 / molecular-physical-entity
:ARG0-of (p5 / promote-01
:ARG1 (p6 / protein :name (n4 / name :op1 "abd-A"))))
:op3 (m3 / molecular-physical-entity
:ARG0-of (p7 / promote-01
:ARG1 (p8 / protein :name (n5 / name :op1 "Abd-B")))))
:time (s / stage
:mod (e / embryo)
:ARG1-of (d / differ-02)))
# ::id bio.chicago_2015.366 ::date 2015-10-21T02:36:03 ::annotator SDL-AMR-09 ::preferred
# ::snt Su(fu) regulates Ci via two distinct mechanisms
# ::save-date Wed Oct 21, 2015 ::file bio_chicago_2015_366.txt
(r / regulate-01
:ARG0 (p / protein :name (n / name :op1 "Su(fu)"))
:ARG1 (p2 / protein :name (n2 / name :op1 "Ci"))
:manner (m / mechanism :quant 2
:mod (d / distinct)))
# ::id bio.chicago_2015.376 ::date 2015-10-21T03:04:11 ::annotator SDL-AMR-09 ::preferred
# ::snt Thus, the difference between Knirps and other short-range transcriptional repressors may indicate that the mechanism of repression is not identical between these proteins, even though Giant, Knirps, and Kruppel all interact with the CtBP.
# ::save-date Thu Nov 19, 2015 ::file bio_chicago_2015_376.txt
(c / cause-01
:ARG1 (p3 / possible-01
:ARG1 (i / indicate-01
:ARG0 (d / differ-02
:ARG1 (p2 / protein :name (n / name :op1 "Knirps"))
:ARG2 (p / protein
:ARG0-of (r / repress-01
:ARG1 (t / transcribe-01))
:mod (o / other)
:mod (r2 / range
:ARG1-of (s / short-07))))
:ARG1 (i2 / identical-01 :polarity -
:ARG1 (m / mechanism
:mod r
:poss p2)
:ARG2 (m2 / mechanism
:mod r
:poss p)
:concession (i3 / interact-01
:ARG0 (a / and
:op1 (p4 / protein :name (n2 / name :op1 "Giant"))
:op2 p2
:op3 (p6 / protein :name (n4 / name :op1 "Kruppel"))
:mod (a2 / all))
:ARG1 (p7 / protein :name (n5 / name :op1 "CtBP")))))))
# ::id bio.chicago_2015.381 ::date 2015-10-21T03:34:03 ::annotator SDL-AMR-09 ::preferred
# ::snt B-C, dCtBP and Groucho can bind Hairy simultaneously in vitro.
# ::save-date Wed Oct 21, 2015 ::file bio_chicago_2015_381.txt
(p / possible-01
:ARG1 (b / bind-01
:ARG0 (a / and
:op1 (p2 / protein :name (n / name :op1 "B-C"))
:op2 (p3 / protein :name (n2 / name :op1 "dCtBP"))
:op3 (p4 / protein :name (n3 / name :op1 "Groucho")))
:ARG1 (p5 / protein :name (n4 / name :op1 "Hairy"))
:mod (s / simultaneous)
:manner (i / in-vitro)))
# ::id bio.chicago_2015.465 ::date 2015-10-21T03:35:58 ::annotator SDL-AMR-09 ::preferred
# ::snt Repression of hth by Antp is cell autonomous.
# ::save-date Fri Jan 15, 2016 ::file bio_chicago_2015_465.txt
(r / repress-01
:ARG0 (p2 / protein :name (n2 / name :op1 "Antp"))
:ARG1 (p / protein :name (n / name :op1 "Hth"))
:mod (a / autonomous
:mod (c / cell)))
# ::id bio.chicago_2015.503 ::date 2015-10-21T03:37:46 ::annotator SDL-AMR-09 ::preferred
# ::snt Whereas, 24B=> Ubx represses both Scr and Antp, leaving abd-A unaffected ( Fig. 4E-H).
# ::save-date Sun Jan 17, 2016 ::file bio_chicago_2015_503.txt
(c / contrast-01
:ARG2 (r / repress-01
:ARG0 (a3 / and
:op1 (p2 / protein :name (n6 / name :op1 "24B"))
:op2 (p / protein :name (n / name :op1 "Ubx"))
:ARG0-of (l / leave-02
:ARG1 (a2 / affect-01 :polarity -
:ARG1 (p5 / protein :name (n4 / name :op1 "abd-A")))))
:ARG1 (a / and
:op1 (p3 / protein :name (n2 / name :op1 "Scr"))
:op2 (p4 / protein :name (n3 / name :op1 "Antp"))))
:ARG1-of (d / describe-01
:ARG0 (v / value-interval
:op1 (f / figure :mod "4A")
:op2 (f2 / figure :mod "4H"))))
# ::id bio.chicago_2015.568 ::date 2015-10-21T03:41:32 ::annotator SDL-AMR-09 ::preferred
# ::snt The Ras signaling cascade leads to activation of the inductive transcription factor, Pnt, and inactivation of the Yan repressor.
# ::save-date Wed Oct 21, 2015 ::file bio_chicago_2015_568.txt
(l / lead-03
:ARG0 (c / cascade-01
:ARG1 (s / signal-07
:ARG0 (e / enzyme :name (n2 / name :op1 "Ras"))))
:ARG2 (a2 / and
:op1 (a / activate-01
:ARG1 (f / factor :name (n3 / name :op1 "Pnt")
:ARG0-of (t / transcribe-01)
:ARG0-of (i / induce-01)))
:op2 (a3 / activate-01 :polarity -
:ARG1 (p3 / protein
:ARG0-of (r / repress-01
:ARG1 (p4 / protein :name (n4 / name :op1 "Yan")))))))
# ::id bio.chicago_2015.588 ::date 2015-10-21T03:45:04 ::annotator SDL-AMR-09 ::preferred
# ::snt H3 was strongly acetylated in the active Abd-B and RpII140 promoters ( Fig. 1a, g; p10, p10b, pol2), whereas the inactive loci ( iab-4, abd-A, Ubx, en, ems and bw) showed a decrease (5 - 10 times lessR than the H3 signal in the active Abd-B and RpII140 promoters) or absence of acetylation both at the core promoters as well as downstream of the initiator ( Fig. 1b - f, h).
# ::save-date Fri Feb 26, 2016 ::file bio_chicago_2015_588.txt
(c / contrast-01
:ARG1 (a / acetylate-01
:ARG1 (p5 / protein :name (n / name :op1 "H3"))
:ARG1-of (s2 / strong-02)
:location (m2 / molecular-physical-entity
:ARG0-of (p / promote-01
:ARG1 (p6 / protein :name (n2 / name :op1 "Abd-B")
:ARG0-of (a10 / activity-06)))
:ARG1-of (l8 / label-01
:ARG2 (a11 / and
:op1 (n10 / name :op1 "p10")
:op2 (n11 / name :op1 "p10b")
:op3 (n12 / name :op1 "pol2"))))
:location (m / molecular-physical-entity
:ARG0-of (p2 / promote-01
:ARG1 (p7 / protein :name (n3 / name :op1 "RpII140"))))
:ARG1-of (d / describe-01
:ARG0 (a2 / and
:op1 (f / figure :mod "1a")
:op2 (f2 / figure :mod "1g"))))
:ARG2 (s3 / show-01
:ARG1 (o / or
:op1 (d2 / decrease-01
:ARG1 (a4 / and
:op1 (l / locus
:ARG0-of (a3 / activity-06 :polarity -)
:mod (e / enzyme :name (n4 / name :op1 "iab-4")))
:op2 (l2 / locus
:ARG0-of a3
:mod (p9 / protein :name (n5 / name :op1 "abd-A")))
:op3 (l3 / locus
:ARG0-of a3
:mod (p10 / protein :name (n6 / name :op1 "Ubx")))
:op4 (l4 / locus
:ARG0-of a3
:mod (p11 / protein :name (n7 / name :op1 "en")))
:op5 (l5 / locus
:ARG0-of a3
:mod (p12 / protein :name (n8 / name :op1 "ems")))
:op6 (l6 / locus
:ARG0-of a3
:mod (p13 / protein :name (n9 / name :op1 "bw"))))
:ARG2 (l7 / less-than
:op1 (p3 / product-of
:op1 (b / between :op1 5 :op2 10)
:op2 (s4 / signal-07
:ARG0 p5
:location (a5 / and
:op1 m2
:op2 m)))))
:op2 (a6 / absent-01
:ARG1 (a7 / acetylate-01)
:ARG2 (a8 / and
:op1 (m3 / molecular-physical-entity
:ARG0-of (p4 / promote-01)
:mod (c2 / core))
:op2 (r / relative-position
:op1 (m4 / molecular-physical-entity
:ARG0-of (i / initiate-01))
:direction (d3 / downstream)))))
:ARG1-of (d4 / describe-01
:ARG0 (a9 / and
:op1 (f5 / figure :mod "1b")
:op2 (f6 / figure :mod "1f")
:op3 (f3 / figure :mod "1g")
:op4 (f4 / figure :mod "1h")))))
# ::id bio.chicago_2015.592 ::date 2015-10-21T04:01:03 ::annotator SDL-AMR-09 ::preferred
# ::snt Since Phyl and Sina associate with the Ttk complex without reducing its apparent size, it indicates that Sina and Phyl bind to Ttk without altering its ability to multimerize.
# ::save-date Sun Jan 17, 2016 ::file bio_chicago_2015_592.txt
(c / cause-01
:ARG0 (a / associate-01
:ARG1 (a2 / and
:op1 (p / protein :name (n / name :op1 "Phyl"))
:op2 (p2 / protein :name (n2 / name :op1 "Sina")))
:ARG2 (e / enzyme :name (n3 / name :op1 "Ttk"))
:manner (r / reduce-01 :polarity -
:ARG1 (s / size
:poss e
:ARG1-of (a3 / appear-02))))
:ARG1 (i / indicate-01
:ARG0 a
:ARG1 (b / bind-01
:ARG1 a2
:ARG2 e
:manner (a4 / alter-01 :polarity -
:ARG1 (c3 / capable-01
:ARG1 e
:ARG2 (m / multimerize))))))
# ::id bio.chicago_2015.596 ::date 2015-10-21T04:19:47 ::annotator SDL-AMR-09 ::preferred
# ::snt In summary, transgenic embryos for wg-Gal4/UAS-GFP or ems-Gal4/UAS-GFP accurately reproduce the expression of wg or ems that depends on AbdA or AbdB.
# ::save-date Sun Jan 17, 2016 ::file bio_chicago_2015_596.txt
(s2 / summarize-01
:ARG2 (r / reproduce-01
:ARG0 (e / embryo
:mod (t2 / transgenic)
:poss (o / or
:op1 (o4 / organism :name (n / name :op1 "wg-Gal4/UAS-GFP"))
:op2 (o5 / organism :name (n2 / name :op1 "ems-Gal4/UAS-GFP"))))
:ARG1 (e4 / express-03
:ARG2 (o2 / or
:op1 (p3 / protein :name (n3 / name :op1 "wg"))
:op2 (p4 / protein :name (n4 / name :op1 "ems")))
:ARG0-of (d / depend-01
:ARG1 (o3 / or
:op1 (p / protein :name (n5 / name :op1 "AbdA"))
:op2 (p2 / protein :name (n6 / name :op1 "AbdB")))))
:mod (a / accurate)))
# ::id bio.chicago_2015.627 ::date 2015-10-21T04:24:52 ::annotator SDL-AMR-09 ::preferred
# ::snt Table I dCtBP specifically interacts with Hairy and E( spl)mdelta bHLH family members in directed yeast two-hybrid assays (beta-galactosidase activity in diploid yeast strains)
# ::save-date Mon Nov 2, 2015 ::file bio_chicago_2015_627.txt
(i / interact-01
:ARG0 (p3 / protein :name (n / name :op1 "dCtBP")
:ARG1-of (d / describe-01
:ARG0 (t / table :mod "I")))
:ARG1 (a / and
:op1 (p / protein :name (n2 / name :op1 "Hairy"))
:op2 (m / member
:ARG1-of (i2 / include-91
:ARG2 (p2 / protein-family :name (n3 / name :op1 "E(spl)mdelta-bHLH")))))
:ARG1-of (s / specific-02)
:location (a2 / assay-01
:mod (h / hybrid :quant 2)
:mod (y / yeast)
:ARG1-of (d3 / direct-01))
:ARG1-of (m2 / mean-01
:ARG2 (a3 / activity-06
:ARG0 (e / enzyme :name (n4 / name :op1 "beta-galactosidase"))
:location (s3 / strain
:mod (d2 / diploid)
:mod y))))
# ::id bio.chicago_2015.634 ::date 2015-10-21T04:55:19 ::annotator SDL-AMR-09 ::preferred
# ::snt dCtBP was identified in interaction studies with Knirps, Snail, and Hairy (Nibu et al., 1998b ; Poortinga et al., 1998 ) These repressor proteins interact with dCtBP through CtBP binding motifs located within the repressor domains located near their C-terminal ends.
# ::save-date Thu Nov 19, 2015 ::file bio_chicago_2015_634.txt
(m / multi-sentence
:snt1 (i / identify-01
:ARG1 (p13 / protein :name (n / name :op1 "dCtBP"))
:location (s2 / study-01
:ARG1 (i2 / interact-01
:ARG0 (a / and
:op1 (p2 / protein :name (n2 / name :op1 "Knirps"))
:op2 (p3 / protein :name (n3 / name :op1 "Snail"))
:op3 (p4 / protein :name (n4 / name :op1 "Hairy")))))
:ARG1-of (d2 / describe-01
:ARG0 (a2 / and
:op1 (p5 / publication-91
:ARG0 (a3 / and
:op1 (p6 / person :name (n5 / name :op1 "Nibu"))
:op2 (p7 / person
:mod (o / other)))
:time (d / date-entity :year 1998))
:op2 (p8 / publication-91
:ARG0 (a5 / and
:op1 (p9 / person :name (n6 / name :op1 "Poortinga"))
:op2 p7)
:time d))))
:snt2 (i3 / interact-01
:ARG0 (p / protein
:ARG0-of (r / repress-01)
:mod (t / this))
:ARG1 p13
:instrument (m2 / motif
:mod (b / bind-01
:ARG1 (p12 / protein :name (n8 / name :op1 "CtBP")))
:location (d4 / domain
:ARG1-of (n9 / near-02
:ARG2 (e / end
:poss m2
:mod (p10 / protein-segment :name (n10 / name :op1 "C-terminus"))))
:part-of p))))
# ::id bio.chicago_2015.635 ::date 2015-10-21T05:03:40 ::annotator SDL-AMR-09 ::preferred
# ::snt (E) Association of Sina with HA-tagged Ttk is specifically enhanced by Phyl.
# ::save-date Sun Jan 17, 2016 ::file bio_chicago_2015_635.txt
(e / enhance-01
:ARG0 (p / protein :name (n3 / name :op1 "Phyl"))
:ARG1 (a / associate-01
:ARG1 (p2 / protein :name (n / name :op1 "Sina"))
:ARG2 (e2 / enzyme :name (n2 / name :op1 "Ttk")
:ARG1-of (t / tag-01
:ARG2 (p4 / protein :name (n4 / name :op1 "HA")))))
:ARG1-of (s / specific-02)
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "E")))
# ::id bio.chicago_2015.679 ::date 2015-10-21T05:09:44 ::annotator SDL-AMR-09 ::preferred
# ::snt In the bug Oncopeltus fasciatus, Dfd cannot activate pb because pb is not even present in the maxillae ( 30).
# ::save-date Mon Jan 4, 2016 ::file bio_chicago_2015_679.txt
(p2 / possible-01 :polarity -
:ARG1 (a / activate-01
:ARG0 (p / protein :name (n / name :op1 "Dfd"))
:ARG1 (e / enzyme :name (n2 / name :op1 "pb")))
:ARG1-of (c / cause-01
:ARG0 (p3 / present-02 :polarity -
:ARG1 e
:ARG2 (m / maxilla)
:mod (e2 / even)))
:location (o / organism :name (n3 / name :op1 "Oncopeltus" :op2 "fasciatus")
:mod (b / bug)))
# ::id bio.chicago_2015.705 ::date 2015-10-21T05:13:57 ::annotator SDL-AMR-09 ::preferred
# ::snt We have also tested if Trl and PcG genes interact to silence the endogenous Ubx gene and MCP reporter constructs in double heterozygous animals.
# ::save-date Mon Nov 2, 2015 ::file bio_chicago_2015_705.txt
(t / test-01
:ARG0 (w / we)
:ARG1 (i / interact-01 :mode interrogative
:ARG0 (g / gene :name (n / name :op1 "Trl"))
:ARG1 (g2 / gene :name (n2 / name :op1 "PcG"))
:purpose (s / silence-01
:ARG0 (a / and
:op1 g
:op2 g2)
:ARG1 (a2 / and
:op1 (c / construct-01
:ARG1 (g3 / gene :name (n3 / name :op1 "Ubx")
:mod (e / endogenous)))
:op2 (c2 / construct-01
:ARG1 (g4 / gene :name (n4 / name :op1 "MCP")
:ARG0-of (r / report-01))))
:location (a3 / animal
:mod (h2 / heterozygous
:mod (d / double)))))
:mod (a4 / also))
# ::id bio.chicago_2015.708 ::date 2015-10-21T05:20:35 ::annotator SDL-AMR-09 ::preferred
# ::snt In these studies, Gro was found to interact specifically with Hairy and Hairy-related proteins, and maternally expressed Gro was shown to be required for the transcriptional repression of genes that direct Drosophila segmentation, neurogenesis, and sex-determination -- three processes known to be regulated by Hairy family repressors.
# ::save-date Mon Jan 4, 2016 ::file bio_chicago_2015_708.txt
(a2 / and
:op1 (f / find-01
:ARG1 (i / interact-01
:ARG0 (p2 / protein :name (n / name :op1 "Gro"))
:ARG1 (a / and
:op1 (p3 / protein-family :name (n2 / name :op1 "Hairy"))
:op2 (p4 / protein
:ARG1-of (r2 / relate-01
:ARG2 p3)))
:ARG1-of (s / specific-02))
:location (s2 / study
:mod (t / this)))
:op2 (s3 / show-01
:ARG1 (r3 / require-01
:ARG0 (r / repress-01
:ARG1 (g / gene
:ARG0-of (d / direct-01
:ARG1 (a3 / and
:op1 (s4 / segment-01
:ARG1 (o / organism :name (n3 / name :op1 "Drosophila")))
:op2 (n4 / neurogenesis)
:op3 (d2 / determine-01
:ARG1 (s5 / sex))
:ARG1-of (m / mean-01
:ARG2 (p6 / process :quant 3
:ARG1-of (k / know-02
:ARG3 (r4 / regulate-01
:ARG0 (p7 / protein-family :name (n5 / name :op1 "Hairy")
:ARG0-of (r5 / repress-01))
:ARG1 p6)))))))
:ARG0-of (t2 / transcribe-01))
:ARG1 (p / protein :name (n6 / name :op1 "Gro")
:ARG2-of (e / express-03
:ARG3 (o2 / organism
:ARG0-of (h / have-rel-role-91
:ARG2 (m2 / mother))))))))
# ::id bio.chicago_2015.710 ::date 2015-10-21T05:28:37 ::annotator SDL-AMR-09 ::preferred
# ::snt Recent studies have demonstrated that the Sina and Phyl proteins form a ternary complex with Ttk and promote ubiquitination and rapid degradation of Ttk through the proteasome pathway ( 14, 22).
# ::save-date Mon Nov 2, 2015 ::file bio_chicago_2015_710.txt
(d / demonstrate-01
:ARG0 (s / study
:time (r / recent))
:ARG1 (a2 / and
:op1 (f / form-01
:ARG1 (c / complex
:mod (t / ternary))
:ARG2 (a / and
:op1 (p / protein :name (n / name :op1 "Sina"))
:op2 (p2 / protein :name (n2 / name :op1 "Phyl"))
:op3 (e / enzyme :name (n3 / name :op1 "Ttk"))))
:op2 (p3 / promote-01
:ARG0 (a4 / and
:op1 p
:op2 p2)
:ARG1 (a3 / and
:op1 (u / ubiquitinate-01
:ARG1 e)
:op2 (d2 / degrade-01
:ARG1 e
:mod (r2 / rapid))))
:instrument (p4 / pathway :name (n4 / name :op1 "proteasome")))
:ARG1-of (d3 / describe-01
:ARG0 (p6 / publication
:ARG1-of (c2 / cite-01
:ARG2 (a5 / and :op1 14 :op2 22)))))
# ::id bio.chicago_2015.717 ::date 2015-10-21T05:33:10 ::annotator SDL-AMR-09 ::preferred
# ::snt If this model is correct, iab-4 mutations must therefore affect abd-A expression in a specific subset of mesodermal cells which they were not able to identify.
# ::save-date Sun Jan 17, 2016 ::file bio_chicago_2015_717.txt
(o2 / obligate-01
:ARG2 (a / affect-01
:ARG0 (e3 / enzyme :name (n2 / name :op1 "iab-4")
:ARG2-of (m2 / mutate-01))
:ARG1 (e / express-03
:ARG2 (p2 / protein :name (n / name :op1 "abd-A"))
:ARG3 (s / subset
:ARG1-of (s2 / specific-02)
:consist-of (c / cell
:mod (m / mesodermal)
:ARG1-of (i / identify-01
:ARG0 (t / they)
:ARG1-of (p / possible-01 :polarity -)))))
:ARG1-of (c3 / cause-01))
:condition (c2 / correct-02
:ARG1 (m3 / model
:mod (t2 / this))))
# ::id bio.chicago_2015.725 ::date 2015-10-21T05:45:14 ::annotator SDL-AMR-09 ::preferred
# ::snt Dm-Ftz generated strong segmentation phenotypes and interacted strongly with Ftz-F1, Tc-Ftz caused moderate phenotypes and interacted with Ftz-F1 to a lesser extent than Dm-Ftz, while Sg-Ftz generated extremly weak phenotypes and only interacted marginally with Ftz-F1.
# ::save-date Thu Nov 19, 2015 ::file bio_chicago_2015_725.txt
(c2 / contrast-01
:ARG1 (a2 / and
:op1 (a / and
:op1 (g / generate-01
:ARG0 (g2 / gene :name (n / name :op1 "Dm-Ftz"))
:ARG1 (p / phenotype
:mod (s / segment-01
:ARG1-of (s2 / strong-02))))
:op2 (i / interact-01
:ARG0 g2
:ARG1 (g3 / gene :name (n2 / name :op1 "Ftz-F1"))
:ARG1-of s2))
:op2 (a3 / and
:op1 (c / cause-01
:ARG0 (g4 / gene :name (n3 / name :op1 "Tc-Ftz"))
:ARG1 (p2 / phenotype
:ARG1-of (m / moderate-03)))
:op2 (i2 / interact-01
:ARG0 g4
:ARG1 g3
:extent (l / less)
:compared-to g2)))
:ARG2 (a4 / and
:op1 (g5 / generate-01
:ARG0 (g6 / gene :name (n4 / name :op1 "Sg-Ftz"))
:ARG1 (p3 / phenotype
:ARG1-of (w / weak-02
:degree (e / extreme))))
:op2 (i3 / interact-01
:ARG0 g6
:ARG1 g3
:ARG1-of (m2 / marginal-02
:mod (o / only)))))
# ::id bio.chicago_2015.734 ::date 2015-10-21T05:55:13 ::annotator SDL-AMR-09 ::preferred
# ::snt Regulation of pb expression by Dfd and Scr
# ::save-date Mon Nov 2, 2015 ::file bio_chicago_2015_734.txt
(r / regulate-01
:ARG0 (a / and
:op1 (p / protein :name (n2 / name :op1 "Dfd"))
:op2 (p2 / protein :name (n3 / name :op1 "Scr")))
:ARG1 (e / express-03
:ARG2 (e2 / enzyme :name (n / name :op1 "pb"))))
# ::id bio.chicago_2015.746 ::date 2015-10-21T05:56:36 ::annotator SDL-AMR-09 ::preferred
# ::snt While iab-2, iab-3 and iab-4 regulate abd-A in PS7, PS8 and PS9 respectively, iab-5, iab-6, iab-7 and iab-8 regulate Abd-B expression in PS10, PS11, PS12 and PS13.
# ::save-date Mon Nov 2, 2015 ::file bio_chicago_2015_746.txt
(c / contrast-01
:ARG1 (r / regulate-01
:ARG0 (a / and
:op1 (e / enzyme :name (n / name :op1 "iab-2"))
:op2 (e2 / enzyme :name (n2 / name :op1 "iab-3"))
:op3 (e3 / enzyme :name (n3 / name :op1 "iab-4")))
:ARG1 (p / protein :name (n11 / name :op1 "abd-A"))
:location (a2 / and
:op1 (t / thing :name (n4 / name :op1 "PS7"))
:op2 (t2 / thing :name (n5 / name :op1 "PS8"))
:op3 (t3 / thing :name (n6 / name :op1 "PS9"))))
:ARG2 (r2 / regulate-01
:ARG0 (a3 / and
:op1 (e4 / enzyme :name (n7 / name :op1 "iab-5"))
:op2 (e5 / enzyme :name (n8 / name :op1 "iab-6"))
:op3 (e6 / enzyme :name (n9 / name :op1 "iab-7"))
:op4 (e7 / enzyme :name (n10 / name :op1 "iab-8")))
:ARG1 (e9 / express-03
:ARG2 (p2 / protein :name (n12 / name :op1 "Abd-B")))
:location (a4 / and
:op1 (t4 / thing :name (n13 / name :op1 "PS10"))
:op2 (t5 / thing :name (n14 / name :op1 "PS11"))
:op3 (t6 / thing :name (n15 / name :op1 "PS12"))
:op4 (t7 / thing :name (n16 / name :op1 "PS13")))))
# ::id bio.chicago_2015.756 ::date 2015-10-21T06:06:53 ::annotator SDL-AMR-09 ::preferred
# ::snt In fact, all PRD=>Hox combinations, except Lab (data not shown) and Dfd ( Fig. 3D), negatively regulate mesodermal pb expression (data not shown).
# ::save-date Mon Nov 2, 2015 ::file bio_chicago_2015_756.txt
(d4 / downregulate-01
:ARG0 (c / combine-01
:ARG1 (p / protein :name (n / name :op1 "PRD"))
:ARG2 (p2 / protein :name (n2 / name :op1 "Hox"))
:mod (a / all
:ARG2-of (e / except-01
:ARG1 (a2 / and
:op1 (p4 / protein :name (n3 / name :op1 "Lab")
:ARG1-of (d / describe-01
:ARG0 (d2 / data
:ARG1-of (s / show-01 :polarity -))))
:op2 (p3 / protein :name (n4 / name :op1 "Dfd")
:ARG1-of (d3 / describe-01
:ARG0 (f / figure :mod "3D")))))))
:ARG1 (e2 / express-03
:ARG2 (e3 / enzyme :name (n5 / name :op1 "pb"))
:mod (m / mesodermal)
:ARG1-of d)
:mod (i / in-fact))
# ::id bio.chicago_2015.761 ::date 2015-10-21T06:12:01 ::annotator SDL-AMR-09 ::preferred
# ::snt Mutations in dTCF and expression of a dominant-negative dTCF transgene cause a segment polarity phenotype and affect expression of the Wingless target genes engrailed and Ultrabithorax.
# ::save-date Fri Feb 5, 2016 ::file bio_chicago_2015_761.txt
(a2 / and
:op1 (c / cause-01
:ARG0 (a / and
:op1 (m / mutate-01
:ARG1 (p / protein :name (n / name :op1 "dTCF")))
:op2 (e / express-03
:ARG1 (t / transgene :name (n4 / name :op1 "dTCF")
:ARG0-of (d / dominate-01)
:ARG2-of (m2 / mutate-01 :mod "-/-"))))
:ARG1 (p2 / phenotype
:mod (s / segment)
:mod (p3 / polarity)))
:op2 (a3 / affect-01
:ARG0 a
:ARG1 (e2 / express-03
:ARG1 (a4 / and
:op1 (g2 / gene :name (n3 / name :op1 "Wingless")
:ARG1-of (t2 / target-01))
:op2 (g3 / gene :name (n6 / name :op1 "Engrailed"))
:op3 (g / gene :name (n5 / name :op1 "Ultrabithorax"))))))
# ::id bio.chicago_2015.772 ::date 2015-10-21T06:16:31 ::annotator SDL-AMR-09 ::preferred
# ::snt Treatment with either of the PI 3-kinase inhibitors, wortmannin or LY294002, or the MEK inhibitor PD 098059, which prevents MAPK signaling, attenuated the dexamethasone stimulation of TER without affecting apical junction remodeling.
# ::save-date Sun Jan 17, 2016 ::file bio_chicago_2015_772.txt
(a / attenuate-01
:ARG0 (t2 / treat-04
:ARG2 (o2 / or
:op1 (m / molecular-physical-entity
:ARG0-of (i2 / inhibit-01
:ARG1 (k / kinase :name (n3 / name :op1 "PI3")))
:ARG1-of (m2 / mean-01
:ARG2 (o / or
:op1 (s3 / small-molecule :name (n4 / name :op1 "wortmannin"))
:op2 (s4 / small-molecule :name (n5 / name :op1 "LY294002"))))
:mod (e5 / either))
:op2 (s6 / small-molecule :name (n / name :op1 "PD098059")
:ARG0-of (i3 / inhibit-01
:ARG1 (p / protein-family :name (n6 / name :op1 "MEK")))))
:ARG0-of (p4 / prevent-01
:ARG1 (s / signal-07
:ARG0 (p2 / pathway :name (n2 / name :op1 "MAPK")))))
:ARG1 (s2 / stimulate-01
:ARG0 (s5 / small-molecule :name (n8 / name :op1 "dexamethasone"))
:ARG1 (e4 / enzyme :name (n7 / name :op1 "TER"))
:manner (a2 / affect-01 :polarity -
:ARG1 (r / remodel-01
:ARG1 (j / junction
:mod (a3 / apical))))))
# ::id bio.chicago_2015.777 ::date 2015-10-21T04:41:36 ::annotator SDL-AMR-09 ::preferred
# ::snt The recent finding that the dCtBP protein interacts with the repressors Knirps and Snail ( 14) and Hairy ( 17) supports this notion.
# ::save-date Thu Nov 5, 2015 ::file bio_chicago_2015_777.txt
(s / support-01
:ARG0 (i / interact-01
:ARG0 (p / protein :name (n / name :op1 "dCtBP"))
:ARG1 (a / and
:op1 (a2 / and
:op1 (p2 / protein :name (n2 / name :op1 "Knirps"))
:op2 (p3 / protein :name (n3 / name :op1 "Snail"))
:ARG1-of (d / describe-01
:ARG0 (p4 / publication
:ARG1-of (c / cite-01
:ARG2 14))))
:op2 (p5 / protein :name (n4 / name :op1 "Hairy")
:ARG1-of (d2 / describe-01
:ARG0 (p6 / publication
:ARG1-of (c2 / cite-01
:ARG2 17))))
:ARG0-of (r / repress-01))
:ARG1-of (f / find-01
:time (r2 / recent)))
:ARG1 (n5 / notion
:mod (t / this)))
# ::id bio.chicago_2015.798 ::date 2015-10-21T05:00:17 ::annotator SDL-AMR-09 ::preferred
# ::snt Later in development, the transcription patterns in Mcp mutant and yw67 embryos are indistinguishable, suggesting that the Mcp deletion disrupts iab4 transcription only early in development.
# ::save-date Thu Nov 5, 2015 ::file bio_chicago_2015_798.txt
(d / distinguish-01 :polarity -
:ARG1 (p / pattern-01
:ARG1 (a / and
:op1 (p2 / protein :name (n / name :op1 "Mcp")
:ARG2-of (m / mutate-01))
:op2 (e / embryo :name (n2 / name :op1 "yw67")))
:mod (t / transcribe-01))
:ARG0-of (s / suggest-01
:ARG1 (d2 / disrupt-01
:ARG0 (d3 / delete-01
:ARG1 p2)
:ARG1 (t2 / transcribe-01
:ARG1 (g / gene :name (n3 / name :op1 "iab4")))
:time (e2 / early
:op1 (d4 / develop-01)
:mod (o / only))))
:time (l / late
:op1 (d5 / develop-01)
:degree (m2 / more)))
# ::id bio.chicago_2015.807 ::date 2015-10-21T05:12:25 ::annotator SDL-AMR-09 ::preferred
# ::snt We present evidence that Apterous activity depends on the formation of a LIM homeodomain dimer bridged by a dimer of cofactor.
# ::save-date Thu Nov 5, 2015 ::file bio_chicago_2015_807.txt
(p / present-01
:ARG0 (w / we)
:ARG1 (t / thing
:ARG0-of (e / evidence-01
:ARG1 (d / depend-01
:ARG0 (a / activity-06
:ARG0 (g / gene :name (n / name :op1 "Apterous")))
:ARG1 (f / form-01
:ARG1 (d2 / dimer
:mod (p2 / protein-segment :name (n2 / name :op1 "LIM" :op2 "homeodomain"))
:ARG1-of (b / bridge-01
:ARG2 (d3 / dimer
:mod (c / cofactor)))))))))
# ::id bio.chicago_2015.830 ::date 2015-10-21T06:54:05 ::annotator SDL-AMR-09 ::preferred
# ::snt Brinker is an antagonist of the Dpp-signaling because it prevents the transcription of a subset of Mad activated genes (Kirkpatrick et al., 2001 ; Rushlow et al., 2001 ; Saller and Bienz, 2001 ), but Brinker is itself a Dpp target (Minami et al., 1999 ) because Mad and Schnurri heterodimers can block brk transcription in dpp-responsive cells (Marty et al., 2000 ).
# ::save-date Sun Jan 17, 2016 ::file bio_chicago_2015_830.txt
(c / contrast-01
:ARG1 (c2 / cause-01
:ARG0 (p / prevent-01
:ARG0 (p2 / protein :name (n / name :op1 "brinker"))
:ARG1 (t / transcribe-01
:ARG1 (s / subset
:ARG2-of (i / include-91
:ARG1 (g / gene
:ARG1-of (a / activate-01
:ARG0 (p3 / protein :name (n2 / name :op1 "Mad"))))))))
:ARG1 (a2 / antagonist
:domain p2
:topic (s2 / signal-07
:ARG0 (p4 / pathway :name (n3 / name :op1 "Dpp"))))
:ARG1-of (d / describe-01
:ARG0 (a3 / and
:op1 (p5 / publication-91
:ARG0 (a4 / and
:op1 (p6 / person :name (n4 / name :op1 "Kirkpatrick"))
:op2 (p7 / person
:mod (o / other)))
:time (d2 / date-entity :year 2001))
:op2 (p8 / publication-91
:ARG0 (a5 / and
:op1 (p9 / person :name (n5 / name :op1 "Rushlow"))
:op2 p7)
:time d2)
:op3 (p10 / publication-91
:ARG0 (a6 / and
:op1 (p11 / person :name (n6 / name :op1 "Saller"))
:op2 (p12 / person :name (n7 / name :op1 "Bienz")))
:time d2))))
:ARG2 (c3 / cause-01
:ARG0 (p13 / possible-01
:ARG1 (b / block-01
:ARG0 (a7 / and
:op1 p3
:op2 (p14 / protein :name (n8 / name :op1 "Schnurri"))
:mod (h / heterodimer))
:ARG1 (t2 / transcribe-01
:ARG1 p2))
:location (c4 / cell
:ARG0-of (r / responsive-02
:ARG1 p4))
:ARG1-of (d3 / describe-01
:ARG0 (p15 / publication-91
:ARG0 (a8 / and
:op1 (p16 / person :name (n9 / name :op1 "Marty"))
:op2 p7)
:time (d4 / date-entity :year 2000))))
:ARG1 (t3 / target-01
:ARG0 p4
:ARG1 p2
:ARG1-of (d5 / describe-01
:ARG0 (p17 / publication-91
:ARG0 (a9 / and
:op1 (p18 / person :name (n10 / name :op1 "Minami"))
:op2 p7)
:time (d6 / date-entity :year 1999))))))
# ::id bio.chicago_2015.858 ::date 2015-10-21T17:35:21 ::annotator SDL-AMR-09 ::preferred
# ::snt CtBP and Giant exhibited repression activity similar to the Knirps repression domains.
# ::save-date Thu Oct 22, 2015 ::file bio_chicago_2015_858.txt
(e / exhibit-01
:ARG0 (a / and
:op1 (p / protein :name (n / name :op1 "CtBP"))
:op2 (p2 / protein :name (n2 / name :op1 "Giant")))
:ARG1 (a2 / activity-06
:ARG0 a
:ARG1 (r / repress-01
:ARG0 a)
:ARG1-of (r2 / resemble-01
:ARG2 (d / domain
:ARG0-of (r3 / repress-01
:ARG1 (p3 / protein :name (n3 / name :op1 "Knirps")))))))
# ::id bio.chicago_2015.867 ::date 2015-10-22T02:02:54 ::annotator SDL-AMR-09 ::preferred
# ::snt Pan is bound and its transcriptional activity inhibited by dCBP ( 33).
# ::save-date Thu Nov 5, 2015 ::file bio_chicago_2015_867.txt
(a / and
:op1 (b / bind-01
:ARG1 (p / protein :name (n / name :op1 "Pan"))
:ARG2 (p2 / protein :name (n2 / name :op1 "dCBP")))
:op2 (i / inhibit-01
:ARG0 p2
:ARG1 (a2 / activity-06
:ARG0 p
:ARG1 (t / transcribe-01
:ARG0 p)))
:ARG1-of (d / describe-01
:ARG0 (p3 / publication-91
:ARG1-of (c / cite-01
:ARG2 33))))
# ::id bio.chicago_2015.875 ::date 2015-10-22T02:27:19 ::annotator SDL-AMR-09 ::preferred
# ::snt Similarly, ectopic Scr and Dfd proteins have no effect on lab gene expression while we find positive regulation of pb by Dfd and Scr as discussed above.
# ::save-date Sun Jan 17, 2016 ::file bio_chicago_2015_875.txt
(c / contrast-01
:ARG1 (a / affect-01 :polarity -
:ARG0 (a2 / and
:op1 (p / protein :name (n / name :op1 "Scr"))
:op2 (p2 / protein :name (n2 / name :op1 "Dfd"))
:mod (e / ectopic))
:ARG1 (e2 / express-03
:ARG1 (g / gene
:mod (l / lab))))
:ARG2 (f / find-01
:ARG0 (w / we)
:ARG1 (u / upregulate-01
:ARG0 a2
:ARG1 (e3 / enzyme :name (n3 / name :op1 "pb")))
:ARG1-of (d / discuss-01
:location (a3 / above)))
:ARG1-of (r / resemble-01))
# ::id bio.chicago_2015.887 ::date 2015-10-22T02:44:41 ::annotator SDL-AMR-09 ::preferred
# ::snt Impact of CSN-specific phosphorylation on degradation of p53wt and p53 mutants by the Ub - 26S proteasome system Ub - 26S proteasome-dependent degradation of p53 was studied in reticulocyte lysate containing an intact Ub - 26S proteasome system and the CSN complex.
# ::save-date Thu Nov 5, 2015 ::file bio_chicago_2015_887.txt
(m / multi-sentence
:snt1 (i / impact-01
:ARG0 (p / phosphorylate-01
:ARG1-of (s / specific-02
:ARG2 (m2 / macro-molecular-complex :name (n / name :op1 "CSN"))))
:ARG1 (d / degrade-01
:ARG0 (s2 / system
:mod (p2 / proteasome :name (n2 / name :op1 "Ub-26S")))
:ARG1 (a / and
:op1 (p3 / protein :name (n3 / name :op1 "p53")
:mod (w / wild-type))
:op2 (p4 / protein :name (n4 / name :op1 "p53"))
:ARG2-of (m3 / mutate-01))))
:snt2 (s3 / study-01
:ARG1 (d2 / degrade-01
:ARG1 (p5 / protein :name (n5 / name :op1 "p53"))
:ARG0-of (d3 / depend-01
:ARG1 (p6 / proteasome :name (n6 / name :op1 "Ub-26S"))))
:location (l / lysate
:mod (r / reticulocyte)
:ARG0-of (c4 / contain-01
:ARG1 (a2 / and
:op1 (s4 / system
:mod p6
:mod (i2 / intact))
:op2 (m4 / macro-molecular-complex :name (n7 / name :op1 "CSN")))))))
# ::id bio.chicago_2015.894 ::date 2015-10-22T03:21:11 ::annotator SDL-AMR-09 ::preferred
# ::snt E6 promotes the ubiquitin-mediated degradation of p53 by the proteasome.
# ::save-date Wed Jan 13, 2016 ::file bio_chicago_2015_894.txt
(p / promote-01
:ARG0 (p2 / protein :name (n / name :op1 "E6"))
:ARG1 (d / degrade-01
:ARG0 p2
:ARG1 (p3 / protein :name (n2 / name :op1 "p53"))
:ARG2 (m2 / macro-molecular-complex :name (n4 / name :op1 "proteasome"))
:ARG1-of (m / mediate-01
:ARG0 (p5 / protein :name (n3 / name :op1 "ubiquitin")))))
# ::id bio.chicago_2015.900 ::date 2015-10-22T03:32:21 ::annotator SDL-AMR-09 ::preferred
# ::snt The exception to this hierarchy is seen for pb where we find that ectopic epidermal expression of Scr and Dfd actually activate epidermal pb expression ( Fig. 3).
# ::save-date Sun Jan 17, 2016 ::file bio_chicago_2015_900.txt
(s / see-01
:ARG1 (e / except-01
:ARG1 (e7 / enzyme :name (n / name :op1 "pb"))
:ARG2 (h / hierarchy
:mod (t / this))
:location-of (f / find-01
:ARG0 (w / we)
:ARG1 (a / activate-01
:ARG0 (e2 / express-03
:ARG2 (a2 / and
:op1 (p2 / protein :name (n2 / name :op1 "Scr"))
:op2 (p3 / protein :name (n3 / name :op1 "Dfd")))
:ARG3 (e3 / epidermis
:mod (e4 / ectopic)))
:ARG1 (e5 / express-03
:ARG2 e7
:ARG3 (e6 / epidermis))
:ARG1-of (a3 / actual-02))))
:ARG1-of (d / describe-01
:ARG0 (f2 / figure :mod 3)))
# ::id bio.chicago_2015.901 ::date 2015-10-22T05:48:28 ::annotator SDL-AMR-09 ::preferred
# ::snt beta-catenin contains amino- and carboxy-terminal transcriptional activation domains and a covalent fusion of either domain with the amino terminus of LEF-1 generates a fusion protein that functions constitutively and activates transcription independently of a Wnt signal ( 19). .
# ::save-date Sun Nov 15, 2015 ::file bio_chicago_2015_901.txt
(a / and
:op1 (c / contain-01
:ARG0 (p / protein :name (n / name :op1 "beta-catenin"))
:ARG1 (a2 / and
:op1 (p2 / protein-segment :name (n2 / name :op1 "amino-terminus"))
:op2 (p3 / protein-segment :name (n3 / name :op1 "carboxy-terminus"))
:ARG0-of (a3 / activate-01
:ARG1 (t / transcribe-01))))
:op2 (g / generate-01
:ARG0 (f / fuse-01
:ARG1 (o / or
:op1 p2
:op2 p3)
:ARG2 (p4 / protein-segment :name (n4 / name :op1 "amino-terminus")
:part-of (p5 / protein :name (n5 / name :op1 "LEF-1")))
:mod (c2 / covalent))
:ARG1 (p6 / protein
:ARG3-of (f2 / fuse-01)
:ARG0-of (f3 / function-01
:manner (c3 / constitutive))
:ARG0-of (a4 / activate-01
:ARG1 t
:ARG0-of (d2 / depend-01 :polarity -
:ARG1 (s / signal-07
:ARG0 (p7 / protein :name (n6 / name :op1 "Wnt")))))))
:ARG1-of (d3 / describe-01
:ARG0 (p8 / publication-91
:ARG1-of (c4 / cite-01
:ARG2 19))))
# ::id bio.chicago_2015.936 ::date 2015-10-22T18:25:38 ::annotator SDL-AMR-09 ::preferred
# ::snt Binding to Mdm2 inhibits the transcriptional activity of p53 (Momand et al., 1992 ; Oliner et al., 1993 ) and promotes the degradation of p53 by the 26S proteasome (Haupt et al., 1997 ; Kubbutat et al., 1997 ; Honda et al., 1997 ).
# ::save-date Fri Nov 6, 2015 ::file bio_chicago_2015_936.txt
(a / and
:op1 (i / inhibit-01
:ARG0 (b / bind-01
:ARG2 (p / protein :name (n / name :op1 "Mdm2")))
:ARG1 (a2 / activity-06
:ARG0 (p2 / protein :name (n2 / name :op1 "p53"))
:ARG1 (t / transcribe-01))
:ARG1-of (d / describe-01
:ARG0 (a3 / and
:op1 (p3 / publication-91
:ARG0 (a4 / and
:op1 (p4 / person :name (n3 / name :op1 "Momand"))
:op2 (p5 / person
:mod (o / other)))
:time (d2 / date-entity :year 1992))
:op2 (p6 / publication-91
:ARG0 (a5 / and
:op1 (p7 / person :name (n4 / name :op1 "Oliner"))
:op2 p5)
:time (d3 / date-entity :year 1993)))))
:op2 (p8 / promote-01
:ARG0 b
:ARG1 (d4 / degrade-01
:ARG0 (p9 / proteasome :name (n5 / name :op1 "26S"))
:ARG1 p2)
:ARG1-of (d5 / describe-01
:ARG0 (a6 / and
:op1 (p10 / publication-91
:ARG0 (a7 / and
:op1 (p11 / person :name (n6 / name :op1 "Haupt"))
:op2 p5)
:time (d6 / date-entity :year 1997))
:op2 (p12 / publication-91
:ARG0 (a8 / and
:op1 (p13 / person :name (n7 / name :op1 "Kubbutat"))
:op2 p5)
:time d6)
:op3 (p14 / publication-91
:ARG0 (a9 / and
:op1 (p15 / person :name (n8 / name :op1 "Honda"))
:op2 p5)
:time d6)))))
# ::id bio.chicago_2015.970 ::date 2015-10-22T18:45:03 ::annotator SDL-AMR-09 ::preferred
# ::snt Functionally, CBP and p300 enhance CREB-mediated transcription upon PKA activation [1,2,4] .
# ::save-date Sun Nov 15, 2015 ::file bio_chicago_2015_970.txt
(e / enhance-01
:ARG0 (a / and
:op1 (p / protein :name (n / name :op1 "CBP"))
:op2 (p2 / protein :name (n2 / name :op1 "p300")))
:ARG1 (t / transcribe-01
:ARG1-of (m / mediate-01
:ARG0 (p3 / protein :name (n3 / name :op1 "CREB"))))
:time (a2 / activate-01
:ARG0 (e2 / enzyme :name (n4 / name :op1 "PKA")))
:ARG1-of (d / describe-01
:ARG0 (a3 / and
:op1 (p4 / publication
:ARG1-of (c / cite-01
:ARG2 (a4 / and :op1 1 :op2 2 :op3 4)))))
:ARG1-of (f / function-01))
# ::id bio.chicago_2015.1058 ::date 2015-10-22T18:56:38 ::annotator SDL-AMR-09 ::preferred
# ::snt Purified CREB and CREMalpha proteins were then phosphorylated with PKA.
# ::save-date Thu Oct 22, 2015 ::file bio_chicago_2015_1058.txt
(p / phosphorylate-01
:ARG1 (a / and
:op1 (p2 / protein :name (n / name :op1 "CREB"))
:op2 (p3 / protein :name (n2 / name :op1 "CREMalpha"))
:ARG1-of (p4 / purify-01))
:ARG2 (e / enzyme :name (n3 / name :op1 "PKA"))
:time (t / then))
# ::id bio.chicago_2015.1064 ::date 2015-10-22T18:59:54 ::annotator SDL-AMR-09 ::preferred
# ::snt Although a mammalian homologue of STE5 has not yet been identified, two proteins, MP1 and JIP-1, have been suggested to function as a scaffold for MAPK modules that leads to specific activation of ERK and JNK ( 41, 52).
# ::save-date Sat Jan 16, 2016 ::file bio_chicago_2015_1064.txt
(s / suggest-01
:ARG1 (f / function-01
:ARG0 (p / protein :quant 2
:ARG1-of (m / mean-01
:ARG2 (a / and
:op1 (p2 / protein :name (n / name :op1 "MP1"))
:op2 (p3 / protein :name (n2 / name :op1 "JIP-1")))))
:ARG1 (s2 / scaffold
:ARG0-of (l / lead-03
:ARG2 (a2 / activate-01
:ARG0 f
:ARG1 (a3 / and
:op1 (e / enzyme :name (n4 / name :op1 "ERK"))
:op2 (e2 / enzyme :name (n5 / name :op1 "JNK")))
:ARG1-of (s3 / specific-02))))
:beneficiary (m2 / module
:mod (p4 / pathway :name (n3 / name :op1 "MAPK"))))
:concession (i / identify-01 :polarity -
:ARG1 (h / homologue
:mod (m3 / mammal)
:mod (p5 / protein :name (n6 / name :op1 "STE5")))
:time (y / yet))
:ARG1-of (d / describe-01
:ARG0 (p6 / publication
:ARG1-of (c / cite-01
:ARG2 (a4 / and :op1 41 :op2 52)))))
# ::id bio.chicago_2015.1117 ::date 2015-10-25T19:10:17 ::annotator SDL-AMR-09 ::preferred
# ::snt Since the Asp replacement at Ser greatly decreases, but does not completely block, the activation of CREB by PKA, it is possible that the effect of this mutation is a quantitative rather than a complete block of CREB binding to CBP.
# ::save-date Sun Nov 15, 2015 ::file bio_chicago_2015_1117.txt
(c / cause-01
:ARG0 (c2 / contrast-01
:ARG1 (d / decrease-01
:ARG0 (r / replace-01
:ARG1 (a / amino-acid :name (n / name :op1 "aspartic" :op2 "acid"))
:location (a2 / amino-acid :name (n2 / name :op1 "serine")))
:ARG1 a3
:ARG2 (g / great))
:ARG2 (b / block-01 :polarity -
:ARG0 r
:ARG1 (a3 / activate-01
:ARG0 (e / enzyme :name (n3 / name :op1 "PKA"))
:ARG1 (p / protein :name (n4 / name :op1 "CREB")))
:ARG1-of (c3 / complete-01)))
:ARG1 (p2 / possible-01
:ARG1 (i / instead-of-91
:ARG1 (b2 / block-01
:mod (q / quantitative)
:ARG2-of (a4 / affect-01
:ARG0 r))
:ARG2 (b3 / block-01
:ARG1 (b4 / bind-01
:ARG1 p
:ARG2 (p3 / protein :name (n5 / name :op1 "CBP")))
:ARG1-of c3))))
# ::id bio.chicago_2015.1141 ::date 2015-10-26T17:37:11 ::annotator SDL-AMR-09 ::preferred
# ::snt p300/CBP interacts with CREB, E1A, PCAF, c-jun, c-fos, c-Myb, MyoD, and TFIIB
# ::save-date Mon Oct 26, 2015 ::file bio_chicago_2015_1141.txt
(i / interact-01
:ARG0 (p / protein-family :name (n / name :op1 "p300/CBP"))
:ARG1 (a / and
:op1 (p2 / protein :name (n2 / name :op1 "CREB"))
:op2 (p3 / protein :name (n3 / name :op1 "E1A"))
:op3 (p4 / protein :name (n4 / name :op1 "PCAF"))
:op4 (p5 / protein :name (n5 / name :op1 "c-jun"))
:op5 (p6 / protein :name (n6 / name :op1 "c-fos"))
:op6 (p7 / protein :name (n7 / name :op1 "c-Myb"))
:op7 (p8 / protein :name (n8 / name :op1 "MyoD"))
:op8 (p9 / protein :name (n9 / name :op1 "TFIIB"))))
# ::id bio.chicago_2015.1157 ::date 2015-10-26T17:55:24 ::annotator SDL-AMR-09 ::preferred
# ::snt Somatostatin exerts its antiproliferative effect inhibiting more upstream the TSH stimulation of PKA and PI 3-kinase, interfering with the TSH-mediated increases of intracellular cAMP levels by inactivation of adenylyl cyclase activity.
# ::save-date Sun Nov 15, 2015 ::file bio_chicago_2015_1157.txt
(e / exert-01
:ARG0 (s / small-molecule :name (n / name :op1 "Somatostatin"))
:ARG1 (a / affect-01
:ARG0 s
:ARG0-of (c / counter-01
:ARG1 (p / proliferate-01)))
:manner (i / inhibit-01
:ARG0 s
:ARG1 (s2 / stimulate-01
:ARG0 (s3 / small-molecule :name (n2 / name :op1 "TSH"))
:ARG1 (a2 / and
:op1 (e2 / enzyme :name (n3 / name :op1 "PKA"))
:op2 (e3 / enzyme :name (n4 / name :op1 "PI3-kinase"))))
:location (u / upstream
:degree (m / more))
:manner (i2 / interfere-01
:ARG0 s
:ARG1 (i3 / increase-01
:ARG1 (l / level
:quant-of (s4 / small-molecule :name (n5 / name :op1 "cAMP"))
:mod (i4 / intracellular))
:ARG1-of (m2 / mediate-01
:ARG0 s3))
:manner (a3 / activate-01 :polarity -
:ARG0 s
:ARG1 (a4 / activity-06
:ARG0 (e4 / enzyme :name (n6 / name :op1 "adenylyl" :op2 "cyclase")))))))
# ::id bio.chicago_2015.1195 ::date 2015-10-27T18:57:02 ::annotator SDL-AMR-09 ::preferred
# ::snt We have previously shown that when the four consensus PKA sites are mutated, CI is no longer proteolyzed, regulated by PKA, or regulated by hedgehog signaling to activate wg ( 7, 8).
# ::save-date Sun Nov 15, 2015 ::file bio_chicago_2015_1195.txt
(s / show-01
:ARG0 (w / we)
:ARG1 (o / or
:op1 (p / proteolyze-00 :polarity -
:ARG1 (p2 / protein :name (n / name :op1 "CI")))
:op2 (r / regulate-01 :polarity -
:ARG0 (e / enzyme :name (n2 / name :op1 "PKA"))
:ARG1 p2)
:op3 (r2 / regulate-01
:ARG0 (s2 / signal-07
:ARG0 (p3 / protein :name (n3 / name :op1 "hedgehog")))
:ARG1 p2)
:purpose (a / activate-01
:ARG0 p2
:ARG1 (p4 / protein :name (n4 / name :op1 "wg")))
:time (m2 / mutate-01
:ARG1 (s3 / site-01 :quant 4
:ARG1 e
:mod (c / consensus)))
:ARG1-of (l / long-03
:degree (m / more)))
:time (p5 / previous)
:ARG1-of (d / describe-01
:ARG0 (p6 / publication
:ARG1-of (c2 / cite-01
:ARG2 (a2 / and :op1 7 :op2 8)))))
# ::id bio.chicago_2015.1205 ::date 2015-10-28T04:26:45 ::annotator SDL-AMR-09 ::preferred
# ::snt PKA and MAPK lead to the activation of CREB and to the induction of immediate-early genes, one of which--the ubiquitin hydrolase--is neuron specific.
# ::save-date Sun Jan 17, 2016 ::file bio_chicago_2015_1205.txt
(l / lead-03
:ARG0 (a / and
:op1 (e / enzyme :name (n / name :op1 "PKA"))
:op2 (e2 / enzyme :name (n2 / name :op1 "MAPK")))
:ARG2 (a2 / and
:op1 (a3 / activate-01
:ARG0 a
:ARG1 (p / protein :name (n3 / name :op1 "CREB")))
:op2 (i / induce-01
:ARG0 a
:ARG2 (g / gene
:mod (e3 / early
:mod (i2 / immediate))
:ARG2-of (i3 / include-91
:ARG1 (g2 / gene :quant 1 :name (n4 / name :op1 "ubiquitin" :op2 "hydrolase")
:ARG1-of (s / specific-02
:ARG2 (n5 / neuron))))))))
# ::id bio.chicago_2015.1221 ::date 2015-10-28T04:43:16 ::annotator SDL-AMR-09 ::preferred
# ::snt Coexpressing axin inhibited the Lef-1 reporter activation induced by CKI (Fig. 3 b).
# ::save-date Tue Feb 2, 2016 ::file bio_chicago_2015_1221.txt
(i / inhibit-01
:ARG0 (p / protein :name (n / name :op1 "axin")
:ARG2-of (c / coexpress-01))
:ARG1 (a / activate-01
:ARG0 (e / enzyme :name (n2 / name :op1 "CKI"))
:ARG1 (p3 / protein :name (n3 / name :op1 "Lef-1")
:ARG0-of (r / report-01))
:ARG2-of (i2 / induce-01
:ARG0 e))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "3b")))
# ::id bio.chicago_2015.1253 ::date 2015-10-28T05:08:47 ::annotator SDL-AMR-09 ::preferred
# ::snt Activation of alpha 1A Adrenergic Receptors in Rat1 Cells Does Not Activate MAPK and RSK2-- Other investigators have reported that activation of MAPK (ERK1 and ERK2) by growth factors such as epidermal growth factor can lead to CREB phosphorylation and stimulation of gene expression via CRE elements ( 17).
# ::save-date Mon Jan 4, 2016 ::file bio_chicago_2015_1253.txt
(m / multi-sentence
:snt1 (a / activate-01 :polarity -
:ARG0 (a2 / activate-01
:ARG1 (p / protein-family :name (n / name :op1 "alpha" :op2 "1A" :op3 "adrenergic" :op4 "receptor"))
:location (c / cell :name (n2 / name :op1 "Rat1")))
:ARG1 (a3 / and
:op1 (p8 / protein-family :name (n3 / name :op1 "MAPK"))
:op2 (e2 / enzyme :name (n4 / name :op1 "RSK2"))))
:snt2 (r / report-01
:ARG0 (p2 / person
:ARG0-of (i / investigate-01)
:mod (o / other))
:ARG1 (p3 / possible-01
:ARG1 (l / lead-03
:ARG0 (a4 / activate-01
:ARG0 (f / factor
:ARG0-of (g / grow-01)
:example (p4 / protein :name (n5 / name :op1 "epidermal" :op2 "growth" :op3 "factor")))
:ARG1 (p9 / protein-family :name (n6 / name :op1 "MAPK")
:ARG1-of (m2 / mean-01
:ARG2 (a5 / and
:op1 (e4 / enzyme :name (n7 / name :op1 "ERK1"))
:op2 (e5 / enzyme :name (n8 / name :op1 "ERK2"))))))
:ARG2 (a6 / and
:op1 (p5 / phosphorylate-01
:ARG1 (p6 / protein :name (n9 / name :op1 "CREB"))
:ARG2 p9)
:op2 (s / stimulate-01
:ARG0 a4
:ARG1 (e6 / express-03
:ARG1 (g2 / gene))))
:instrument (e7 / element
:mod (e8 / enzyme :name (n10 / name :op1 "CRE")))))
:ARG1-of (d / describe-01
:ARG0 (p7 / publication
:ARG1-of (c2 / cite-01
:ARG2 17)))))
# ::id bio.chicago_2015.1255 ::date 2015-10-28T07:39:52 ::annotator SDL-AMR-09 ::preferred
# ::snt These findings indicate that a PKA-dependent event other than CREB Ser133 phosphorylation is required for Ca2+ induction of CaRE-dependent transcription.
# ::save-date Sat Feb 13, 2016 ::file bio_chicago_2015_1255.txt
(i / indicate-01
:ARG0 (t / thing
:ARG1-of (f / find-01)
:mod (t2 / this))
:ARG1 (r / require-01
:ARG0 (i2 / induce-01
:ARG0 (s / small-molecule :name (n6 / name :op1 "calcium")
:ARG1-of (i3 / ionize-01 :value "2+"))
:ARG2 (t3 / transcribe-01
:ARG0-of (d2 / depend-01
:ARG1 (s2 / small-molecule :name (n5 / name :op1 "CaRE")))))
:ARG1 (e / event
:ARG0-of (d / depend-01
:ARG1 (e2 / enzyme :name (n / name :op1 "PKA")))
:ARG2-of (e3 / except-01
:ARG1 (p / phosphorylate-01
:ARG1 (a / amino-acid :mod 133 :name (n2 / name :op1 "serine")
:part-of (p2 / protein :name (n3 / name :op1 "CREB")))))
:mod (o / other))))
# ::id pmid_1592_8660.1 ::date 2015-06-30T06:29:45 ::annotator SDL-AMR-09 ::preferred
# ::snt Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS (PMID:15928660)
# ::save-date Sat Jan 16, 2016 ::file pmid_1592_8660_1.txt
(h / have-concession-91
:ARG1 (e / event
:mod (c / common)
:location (m / medical-condition :name (n / name :op1 "melanoma")
:mod (u / uveal))
:domain (a / activate-01
:ARG1 (p / pathway :name (n2 / name :op1 "MAPK"))))
:ARG2 (m2 / mutate-01
:ARG1 (o2 / or
:op1 (g / gene :name (n3 / name :op1 "BRAF"))
:op2 (g2 / gene :name (n4 / name :op1 "RAS")))
:manner-of e
:ARG1-of (r / rare-02))
:ARG1-of (d2 / describe-01
:ARG0 (p2 / publication-91
:ARG8 "PMID15928660")))
# ::id pmid_1592_8660.81 ::date 2015-06-30T08:42:48 ::annotator SDL-AMR-09 ::preferred
# ::snt RESULTS
# ::save-date Tue Jul 21, 2015 ::file pmid_1592_8660_81.txt
(t / thing
:ARG2-of (r / result-01))
# ::id pmid_1592_8660.82 ::date 2015-06-30T09:29:29 ::annotator SDL-AMR-09 ::preferred
# ::snt Mutation analysis
# ::save-date Tue Jun 30, 2015 ::file pmid_1592_8660_82.txt
(a / analyze-01
:ARG1 (m / mutate-01))
# ::id pmid_1592_8660.83 ::date 2015-06-30T09:31:21 ::annotator SDL-AMR-09 ::preferred
# ::snt Of the 11 uveal melanoma cell lines under study, only one cell line (Ocm 1) carried a BRAF mutation, the common V599E (also described by Calipel et al and Kilic et al).
# ::save-date Sat Jan 16, 2016 ::file pmid_1592_8660_83.txt
(i / include-91
:ARG1 (c2 / cell-line :quant 1 :name (n3 / name :op1 "Ocm" :op2 "1")
:mod (o / only)
:ARG0-of (c3 / carry-01
:ARG1 (m / mutate-01 :value "V599E"
:ARG1 (g / gene :name (n2 / name :op1 "BRAF"))
:ARG1-of (d2 / describe-01
:ARG0 (a5 / and
:op1 (p / publication-91
:ARG0 (a3 / and
:op1 (p2 / person :name (n4 / name :op1 "Calipel"))
:op2 (p3 / person
:mod (o2 / other))))
:op2 (p6 / publication-91
:ARG0 (a4 / and
:op1 (p4 / person :name (n5 / name :op1 "Kilic"))
:op2 p3)))
:mod (a / also))
:mod (c4 / common))))
:ARG2 (c / cell-line :quant 11
:mod (m2 / medical-condition :name (n / name :op1 "melanoma")
:mod (u / uveal))
:ARG1-of (s / study-01)))
# ::id pmid_1592_8660.84 ::date 2015-06-30T10:14:11 ::annotator SDL-AMR-09 ::preferred
# ::snt All primary tumour specimens were wild type for BRAF.
# ::save-date Sat Jan 16, 2016 ::file pmid_1592_8660_84.txt
(w / wild-type
:domain (s / specimen
:mod (t / tumor)
:mod (a / all)
:mod (p / primary))
:prep-for (g / gene :name (n / name :op1 "BRAF")))
# ::id pmid_1592_8660.85 ::date 2015-06-30T10:36:01 ::annotator SDL-AMR-09 ::preferred
# ::snt No mutations were found in the NRAS, HRAS or KRAS genes, in both the cell lines and primary tissue.
# ::save-date Thu Jul 23, 2015 ::file pmid_1592_8660_85.txt
(f / find-01 :polarity -
:ARG1 (m / mutate-01
:ARG1 (a / and
:op1 (g / gene :name (n / name :op1 "NRAS"))
:op2 (g2 / gene :name (n2 / name :op1 "HRAS")
:location a2)
:op3 (g3 / gene :name (n3 / name :op1 "KRAS")
:location a2)))
:location (a2 / and
:op1 (c / cell-line)
:op2 (t / tissue
:mod (p / primary))))
# ::id pmid_1592_8660.86 ::date 2015-06-30T10:50:20 ::annotator SDL-AMR-09 ::preferred
# ::snt Western blotting
# ::save-date Wed Dec 30, 2015 ::file pmid_1592_8660_86.txt
(i / immunoblot-01)
# ::id pmid_1592_8660.87 ::date 2015-06-30T10:56:22 ::annotator SDL-AMR-09 ::preferred
# ::snt In order to assess the level of expression and the activation (by phosphorylation) of members of the MAPK pathway downstream of RAS and BRAF, Western blot analysis was performed on uveal melanoma cell lines (Table 2A).
# ::save-date Sat Jan 16, 2016 ::file pmid_1592_8660_87.txt
(p3 / perform-01
:ARG1 (i2 / immunoblot-01
:ARG2 (c / cell-line
:mod (m2 / medical-condition :name (n2 / name :op1 "melanoma")
:mod (u / uveal)))
:purpose (a2 / assess-01
:ARG1 (a3 / and
:op1 (l / level
:degree-of (e / express-03
:ARG2 (m / member
:ARG1-of (i / include-91
:ARG2 (p2 / pathway :name (n3 / name :op1 "MAPK"))))
:location (r / relative-position
:op1 (g / gene :name (n4 / name :op1 "RAS"))
:op2 (g2 / gene :name (n5 / name :op1 "BRAF"))
:direction (d2 / downstream))))
:op2 (a4 / activate-01
:ARG0 (p / phosphorylate-01)
:ARG1 m
:location r)))
:ARG1-of (d3 / describe-01
:ARG0 (t2 / table :mod "2A"))))
# ::id pmid_1592_8660.88 ::date 2015-06-30T12:14:56 ::annotator SDL-AMR-09 ::preferred
# ::snt The expression levels of the downstream members of RAS and BRAF are presented in Figure 1.
# ::save-date Sat Jan 16, 2016 ::file pmid_1592_8660_88.txt
(p / present-01
:ARG1 (l / level
:degree-of (e / express-03
:ARG2 (m / member
:ARG1-of (i / include-91
:ARG2 (a / and
:op1 (p2 / protein-family :name (n / name :op1 "RAS"))
:op2 (e3 / enzyme :name (n2 / name :op1 "BRAF"))))
:mod (d / downstream))))
:location (f / figure :mod 3))
# ::id pmid_1592_8660.89 ::date 2015-06-30T12:39:19 ::annotator SDL-AMR-09 ::preferred
# ::snt In response to the constitutively activating BRAF mutation in Ocm 1, downstream members of the MAPK pathway show activation (phosphorylated MEK, ERK and ELK).
# ::save-date Sat Jan 16, 2016 ::file pmid_1592_8660_89.txt
(s / show-01
:ARG0 (m / member
:ARG1-of (i / include-91
:ARG2 (p / pathway :name (n / name :op1 "MAPK")))
:mod (d / downstream))
:ARG1 (a / activate-01
:ARG1 (a2 / and
:op1 (e / enzyme :name (n2 / name :op1 "MEK")
:ARG3-of (p2 / phosphorylate-01))
:op2 (e2 / enzyme :name (n3 / name :op1 "ERK")
:ARG3-of p2)
:op3 (e3 / enzyme :name (n4 / name :op1 "ELK")
:ARG3-of p2)))
:ARG2-of (r / respond-01
:ARG1 (m2 / mutate-01
:ARG1 (g / gene :name (n5 / name :op1 "BRAF"))
:ARG0-of (a3 / activate-01
:manner (c / constitutive))
:location (c2 / cell-line :name (n6 / name :op1 "Ocm" :op2 "1")))))
# ::id pmid_1592_8660.90 ::date 2015-06-30T13:10:18 ::annotator SDL-AMR-09 ::preferred
# ::snt Levels of expression of the downstream members were not different in the two cell lines derived from the same primary tumour (92.1 and 92.2), except for phosphorylated MEK, indicating that there had been little clonal divergence between the cell populations during in vitro culturing.
# ::save-date Fri Nov 6, 2015 ::file pmid_1592_8660_90.txt
(d / differ-02 :polarity -
:ARG1 (l / level
:degree-of (e / express-03
:ARG2 (m / member
:mod (d2 / downstream)
:ARG2-of (e2 / except-01
:ARG1 (e3 / enzyme :name (n / name :op1 "MEK")
:ARG3-of (p2 / phosphorylate-01))))))
:location (a / and
:op1 (c6 / cell-line :name (n4 / name :op1 "92.1")
:ARG1-of (d3 / derive-01
:ARG2 (t / tumor
:ARG1-of (s / same-01)
:mod (p / primary))))
:op2 (c / cell-line :name (n2 / name :op1 "92.2")
:ARG1-of d3))
:ARG0-of (i / indicate-01
:ARG1 (d4 / diverge-01
:ARG0 (p3 / population
:mod (c3 / cell))
:degree (l2 / little)
:location (t2 / there)
:mod (c2 / clone-01)
:time (c4 / culture-01
:manner (i2 / in-vitro)))))
# ::id pmid_1592_8660.91 ::date 2015-06-30T14:23:57 ::annotator SDL-AMR-09 ::preferred
# ::snt Interestingly, compared to the phosphorylation status of these members in Ocm 1, most cell lines show activation of MEK, ERK and ELK; however, these cell lines show this activation in the absence of mutations in the upstream RAS and BRAF genes.
# ::save-date Sat Jan 16, 2016 ::file pmid_1592_8660_91.txt
(s / show-01
:ARG0 (c / cell-line
:quant (m / most))
:ARG1 (a / activate-01
:ARG1 (a2 / and
:op1 (e / enzyme :name (n / name :op1 "MEK"))
:op2 (e2 / enzyme :name (n2 / name :op1 "ERK"))
:op3 (e3 / enzyme :name (n3 / name :op1 "ELK")))
:compared-to (s2 / status
:mod (p / phosphorylate-01)
:poss (m2 / member
:mod (t / this))
:location (c2 / cell-line :name (n4 / name :op1 "Ocm" :op2 "1"))))
:mod (i / interesting)
:concession-of (s3 / show-01
:ARG0 c
:ARG1 a
:condition (a3 / absent-01
:ARG1 (m3 / mutate-01
:ARG1 (a4 / and
:op1 (g / gene :name (n5 / name :op1 "RAS")
:location (u / upstream))
:op2 (g2 / gene :name (n6 / name :op1 "BRAF")
:location u))))))
# ::id pmid_1592_8660.92 ::date 2015-06-30T21:20:26 ::annotator SDL-AMR-09 ::preferred
# ::snt The levels of total ERK were remarkably similar across all cell lines, with the exception of two cell lines Mel 285 and Mel 290, which had significantly higher levels of total ERK than the others.
# ::save-date Sat Jan 16, 2016 ::file pmid_1592_8660_92.txt
(r2 / resemble-01
:ARG1 (l / level
:quant-of (e / enzyme :name (n / name :op1 "ERK")
:mod (t / total)))
:ARG1-of (r / remarkable-02)
:location (a / across
:op1 (c / cell-line
:mod (a2 / all)
:ARG2-of (e2 / except-01
:ARG1 (a3 / and
:op1 (c3 / cell-line :name (n3 / name :op1 "Mel" :op2 "285")
:ARG0-of (h / have-03
:ARG1 (l2 / level
:ARG1-of (h2 / high-02
:degree (m / more)
:ARG1-of (s / significant-02)
:compared-to (c2 / cell-line
:mod (o / other)))
:quant-of e)))
:op2 (c4 / cell-line :name (n5 / name :op1 "Mel" :op2 "290")
:ARG0-of h))))))
# ::id pmid_1592_8660.93 ::date 2015-07-01T03:03:20 ::annotator SDL-AMR-09 ::preferred
# ::snt In keeping with this observation, these two cell lines also have the highest levels of phosphorylated-ERK.
# ::save-date Sat Jan 16, 2016 ::file pmid_1592_8660_93.txt
(h / have-03
:ARG0 (c / cell-line :quant 2
:mod (t / this))
:ARG1 (l / level
:ARG1-of (h2 / high-02
:degree (m / most))
:quant-of (e / enzyme :name (n / name :op1 "ERK")
:ARG3-of (p / phosphorylate-01)))
:mod (a / also)
:ARG1-of (k / keep-06
:ARG2 (o / observe-01
:ARG1 (t2 / this))))
# ::id pmid_1592_8660.94 ::date 2015-07-01T09:03:14 ::annotator SDL-AMR-09 ::preferred
# ::snt Figure 2 shows that there is no significant influence of serum on the activity of ERK1/2 in these cell lines, as reported recently by Calipel et al (2003).
# ::save-date Tue Jul 21, 2015 ::file pmid_1592_8660_94.txt
(s / show-01
:ARG0 (f / figure :mod 2)
:ARG1 (i / influence-01
:ARG0 (s3 / serum)
:ARG1 (a / activity-06
:ARG0 (e / enzyme :name (n / name :op1 "ERK1/2")))
:ARG1-of (s2 / significant-02 :polarity -)
:location (c / cell-line
:mod (t / this)))
:ARG1-of (r / report-01
:ARG0 (p4 / publication-91
:ARG0 (a2 / and
:op1 (p / person :name (n2 / name :op1 "Calipel"))
:op2 (p2 / person
:mod (o / other)))))
:ARG1-of (d / describe-01
:ARG0 (p3 / publication-91
:time (d2 / date-entity :year 2003))))
# ::id pmid_1592_8660.95 ::date 2015-07-01T09:36:22 ::annotator SDL-AMR-09 ::preferred
# ::snt Immunohistochemistry
# ::save-date Wed Jul 1, 2015 ::file pmid_1592_8660_95.txt
(i / immunohistochemistry)
# ::id pmid_1592_8660.96 ::date 2015-07-01T09:41:34 ::annotator SDL-AMR-09 ::preferred
# ::snt Immunofluorescence results of total and phospho-ERK1/2 on a panel of 19 fresh frozen uveal melanoma sections are listed in Table 2 (B).
# ::save-date Tue Feb 2, 2016 ::file pmid_1592_8660_96.txt
(l / list-01
:ARG1 (r / result-01
:ARG2 (a / and
:op1 (e / enzyme :name (n / name :op1 "ERK1/2")
:mod (t / total))
:op2 (e2 / enzyme :name (n3 / name :op1 "ERK1/2")
:ARG3-of (p / phosphorylate-01)))
:location (p2 / panel
:consist-of (s / section-01
:mod (m / medical-condition :name (n2 / name :op1 "melanoma"))
:mod (u / uveal :quant 19
:ARG1-of (f / fresh-04)
:ARG1-of (f2 / freeze-01))))
:instrument (i / immunofluoresce-01))
:ARG2 (t2 / table :mod 2
:ARG1-of (d2 / describe-01
:ARG0 (f3 / figure :mod "B"))))
# ::id pmid_1592_8660.97 ::date 2015-07-01T10:35:38 ::annotator SDL-AMR-09 ::preferred
# ::snt In seven of the 19 primary tumours, less than 5% of the tumour cells stained positively for ERK1/2 and nine tumours for phosphorylated ERK1/2.
# ::save-date Mon Dec 21, 2015 ::file pmid_1592_8660_97.txt
(a / and
:op1 (s / stain-01
:ARG1 (c / cell
:ARG1-of (i / include-91
:ARG2 (c2 / cell
:mod (t / tumor))
:ARG3 (l / less-than
:op1 (p / percentage-entity :value 5)))
:mod t)
:manner (p2 / positive)
:location (t3 / tumor :quant 7
:ARG1-of (i3 / include-91
:ARG2 (t4 / tumor :quant 19
:mod (p4 / primary))))
:beneficiary (e / enzyme :name (n2 / name :op1 "ERK1/2")))
:op2 (s2 / stain-01
:ARG1 (t2 / tumor :quant 9
:ARG1-of (i2 / include-91
:ARG2 t4))
:beneficiary (e2 / enzyme :name (n3 / name :op1 "ERK1/2")
:ARG3-of (p3 / phosphorylate-01))))
# ::id pmid_1592_8660.98 ::date 2015-07-01T11:14:08 ::annotator SDL-AMR-09 ::preferred
# ::snt Despite the lack of mutations in the RAS and BRAF genes in this set of uveal melanomas, it is noteworthy that we observed phosphorylated (active) ERK1/2 expression in 10 of 19 tumours.
# ::save-date Thu Dec 10, 2015 ::file pmid_1592_8660_98.txt
(n / note-01
:ARG1 (o / observe-01
:ARG0 (w / we)
:ARG1 (e / express-01
:ARG2 (e2 / enzyme :name (n2 / name :op1 "ERK1/2")
:ARG3-of (p / phosphorylate-01
:ARG1-of (m / mean-01
:ARG2 (a / activity-06)))))
:location (t / tumor :quant 10
:ARG1-of (i / include-91
:ARG2 (t2 / tumor :quant 19)))
:concession (l / lack-01
:ARG1 (m2 / mutate-01
:ARG1 (a2 / and
:op1 (g / gene :name (n3 / name :op1 "RAS")
:location (s / set
:mod (t3 / this)
:consist-of (m3 / medical-condition :name (n5 / name :op1 "melanoma")
:mod (u / uveal))))
:op2 (g2 / gene :name (n4 / name :op1 "BRAF")
:location s)))))
:ARG1-of (r / recommend-01))
# ::id pmid_1592_8660.99 ::date 2015-07-01T12:06:57 ::annotator SDL-AMR-09 ::preferred
# ::snt There was no significant association between ERK1/2 activation and tumour location or cell type.
# ::save-date Mon Dec 21, 2015 ::file pmid_1592_8660_99.txt
(a / associate-01
:ARG1 (a2 / activate-01
:ARG1 (e / enzyme :name (n / name :op1 "ERK1/2")))
:ARG2 (o / or
:op1 (l / location
:location-of (t / tumor))
:op2 (t2 / type-03
:ARG1 (c / cell)))
:ARG1-of (s / significant-02 :polarity -))
# ::id pmid_1592_8660.100 ::date 2015-07-01T12:18:55 ::annotator SDL-AMR-09 ::preferred
# ::snt The scoring system for each antibody cannot be compared between antibodies since the antibodies recognise different epitopes and with different affinities; therefore, the staining intensity on Western or by immunohistochemistry is relative only to the other samples for the particular antibody used.
# ::save-date Sun Dec 20, 2015 ::file pmid_1592_8660_100.txt
(p2 / possible-01 :polarity -
:ARG1 (c / compare-01
:ARG1 (s / system
:instrument-of (s2 / score-01
:ARG1 (a / antibody
:mod (e / each))))
:ARG2 (s3 / system
:instrument-of (s4 / score-01
:ARG1 (a2 / antibody)))
:ARG1-of (c2 / cause-01
:ARG0 (r / recognize-02
:ARG0 a
:ARG1 (e2 / epitope
:ARG1-of (d / differ-02)
:ARG0-of (h / have-03
:ARG1 (a3 / affinity
:ARG1-of d)))))
:ARG0-of (c3 / cause-01
:ARG1 (r2 / relative-05
:ARG1 (i / intensity
:mod (s5 / stain-01)
:instrument (o / or
:op1 (i3 / immunoblot-01)
:op2 (i2 / immunohistochemistry)))
:ARG3 (t / thing
:mod (o3 / other)
:beneficiary (a4 / antibody
:mod (p / particular)
:ARG1-of (u / use-01))
:ARG1-of (s6 / sample-01))
:mod (o2 / only)))))
# ::id pmid_1684_6534.1 ::date 2015-08-13T06:22:08 ::annotator SDL-AMR-09 ::preferred
# ::snt MUC1 alters oncogenic events and transcription in human breast cancer cells (PMID:16846534)
# ::save-date Thu Dec 10, 2015 ::file pmid_1684_6534_1.txt
(a / alter-01
:ARG0 (p / protein :name (n / name :op1 "MUC1"))
:ARG1 (a2 / and
:op1 (e / event
:ARG0-of (c / cause-01
:ARG1 (d3 / disease :wiki "Cancer" :name (n3 / name :op1 "cancer"))))
:op2 (t / transcribe-01))
:location (c3 / cell
:source (d2 / disease :wiki "Breast_cancer" :name (n2 / name :op1 "breast" :op2 "cancer"))
:mod (h / human))
:ARG1-of (d / describe-01
:ARG0 (p2 / publication-91
:ARG8 "PMID16846534")))
# ::id pmid_1684_6534.8 ::date 2015-08-13T06:25:56 ::annotator SDL-AMR-09 ::preferred
# ::snt Results
# ::save-date Thu Aug 13, 2015 ::file pmid_1684_6534_8.txt
(t / thing
:ARG2-of (r / result-01))
# ::id pmid_1684_6534.9 ::date 2015-08-13T06:27:54 ::annotator SDL-AMR-09 ::preferred
# ::snt Transcription of several genes was altered after transfection of MUC1 siRNA, including decreased MAP2K1 (MEK1), JUN, PDGFA, CDC25A, VEGF and ITGAV (integrin αv), and increased TNF, RAF1, and MMP2.
# ::save-date Mon Aug 24, 2015 ::file pmid_1684_6534_9.txt
(a / alter-01
:ARG1 (t / transcribe-01
:ARG1 (g / gene
:quant (s / several))
:ARG2-of (i / include-01
:ARG1 (a3 / and
:op1 (a4 / and
:op1 (t3 / transcribe-01
:ARG1 (g2 / gene :name (n3 / name :op1 "MAP2K1")
:ARG1-of (m / mean-01
:ARG2 (g8 / gene
:ARG0-of (e / encode-01
:ARG1 (e2 / enzyme :name (n13 / name :op1 "MEK1")))))))
:op2 (t4 / transcribe-01
:ARG1 (g3 / gene :name (n4 / name :op1 "JUN")))
:op3 (t5 / transcribe-01
:ARG1 (g4 / gene :name (n5 / name :op1 "PDGFA")))
:op4 (t6 / transcribe-01
:ARG1 (g5 / gene :name (n6 / name :op1 "CDC25A")))
:op5 (t7 / transcribe-01
:ARG1 (g6 / gene :name (n7 / name :op1 "VEGF")))
:op6 (t8 / transcribe-01
:ARG1 (g7 / gene :name (n8 / name :op1 "ITGAV")
:ARG0-of (e3 / encode-01
:ARG1 (p2 / protein :name (n9 / name :op1 "integrin" :op2 "αv")))))
:ARG1-of (d / decrease-01))
:op2 (a5 / and
:op1 (t9 / transcribe-01
:ARG1 (g9 / gene :name (n10 / name :op1 "TNF")))
:op2 (t10 / transcribe-01
:ARG1 (g10 / gene :name (n11 / name :op1 "RAF1")))
:op3 (t11 / transcribe-01
:ARG1 (g11 / gene :name (n12 / name :op1 "MMP2")))
:ARG1-of (i2 / increase-01)))))
:time (a2 / after
:op1 (t2 / transfect-01
:ARG2 (n14 / nucleic-acid :name (n / name :op1 "siRNA")
:ARG0-of (e4 / encode-01
:ARG1 (p / protein :name (n2 / name :op1 "MUC1")))))))
# ::id pmid_1684_6534.10 ::date 2015-08-13T06:36:42 ::annotator SDL-AMR-09 ::preferred
# ::snt Additional changes were seen at the protein level, such as increased expression of c-Myc, heightened phosphorylation of AKT, and decreased activation of MEK1/2 and ERK1/2.
# ::save-date Mon Aug 24, 2015 ::file pmid_1684_6534_10.txt
(s / see-01
:ARG1 (c / change-01
:ARG1 (l / level
:quant-of (p / protein))
:mod (a / additional)
:example (a2 / and
:op1 (e / express-03
:ARG2 (p3 / protein :name (n / name :op1 "c-Myc"))
:ARG1-of (i / increase-01))
:op2 (p2 / phosphorylate-01
:ARG1 (e2 / enzyme :name (n2 / name :op1 "AKT"))
:ARG1-of (h / heighten-01))
:op3 (a3 / activate-01
:ARG1 (a4 / and
:op1 (e3 / enzyme :name (n3 / name :op1 "MEK1"))
:op2 (e4 / enzyme :name (n4 / name :op1 "MEK2"))
:op3 (e5 / enzyme :name (n5 / name :op1 "ERK1"))
:op4 (e6 / enzyme :name (n6 / name :op1 "ERK2")))
:ARG1-of (d / decrease-01)))))
# ::id pmid_1684_6534.11 ::date 2015-08-13T06:42:53 ::annotator SDL-AMR-09 ::preferred
# ::snt These were correlated with cellular events, as MUC1 siRNA in the MDA-MB-468 line decreased proliferation and invasion, and increased stress-induced apoptosis.
# ::save-date Mon Dec 14, 2015 ::file pmid_1684_6534_11.txt
(c / correlate-01
:ARG1 (t / this)
:ARG2 (e / event
:mod (c2 / cell))
:ARG1-of (c4 / cause-01
:ARG0 (a / and
:op1 (d / decrease-01
:ARG0 (n4 / nucleic-acid :name (n / name :op1 "siRNA")
:ARG0-of (e2 / encode-01
:ARG1 (p / protein :name (n2 / name :op1 "MUC1"))))
:ARG1 (a3 / and
:op1 (p2 / proliferate-01)
:op2 (i / invade-01)))
:op2 (i2 / increase-01
:ARG0 n4
:ARG1 (a2 / apoptosis
:ARG2-of (i3 / induce-01
:ARG0 (s / stress))))
:location (c3 / cell-line :name (n3 / name :op1 "MDA-MB-468")))))
# ::id pmid_1684_6534.12 ::date 2015-08-13T06:48:18 ::annotator SDL-AMR-09 ::preferred
# ::snt Intriguingly, BT-20 cells displayed similar levels of apoptosis regardless of siRNA, and actually increased proliferation after MUC1 siRNA.
# ::save-date Thu Jan 7, 2016 ::file pmid_1684_6534_12.txt
(a5 / and
:op1 (d / display-01
:ARG0 (c / cell-line :name (n / name :op1 "BT-20"))
:ARG1 (l / level
:degree-of (a2 / apoptosis)
:ARG1-of (r / resemble-01))
:ARG1-of (r2 / regardless-91
:ARG2 (n5 / nucleic-acid :name (n2 / name :op1 "siRNA"))))
:op2 (i / increase-01
:ARG0 c
:ARG1 (p / proliferate-01
:ARG0 c)
:ARG1-of (a / actual-02)
:time (a4 / after
:op1 (n6 / nucleic-acid :name (n3 / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (p2 / protein :name (n4 / name :op1 "MUC1"))))))
:ARG0-of (i2 / intrigue-01))
# ::id pmid_1684_6534.100 ::date 2015-08-13T06:55:36 ::annotator SDL-AMR-09 ::preferred
# ::snt Results
# ::save-date Thu Aug 13, 2015 ::file pmid_1684_6534_100.txt
(t / thing
:ARG2-of (r / result-01))
# ::id pmid_1684_6534.101 ::date 2015-08-13T07:00:22 ::annotator SDL-AMR-09 ::preferred
# ::snt siRNA transfection decreases MUC1 expression in breast cancer cell lines
# ::save-date Wed Dec 9, 2015 ::file pmid_1684_6534_101.txt
(d / decrease-01
:ARG0 (t / transfect-01
:ARG2 (n3 / nucleic-acid :name (n / name :op1 "siRNA")))
:ARG1 (e / express-03
:ARG2 (p / protein :name (n2 / name :op1 "MUC1"))
:ARG3 (c / cell-line
:source (d2 / disease :wiki "Breast_cancer" :name (n4 / name :op1 "breast" :op2 "cancer")))))
# ::id pmid_1684_6534.102 ::date 2015-08-13T07:03:23 ::annotator SDL-AMR-09 ::preferred
# ::snt Two human breast cancer cell lines, MDA-MB-468 and BT-20, were transiently transfected with a pool of four siRNA oligonucleotides directed against the MUC1 mRNA (468.siMUC1 and BT.siMUC1), or a control oligonucleotide directed against luciferase (468.siLuc and BT.siLuc).
# ::save-date Wed Dec 9, 2015 ::file pmid_1684_6534_102.txt
(t / transfect-01
:ARG1 (c / cell-line :quant 2
:ARG1-of (m / mean-01
:ARG2 (a / and
:op1 (c3 / cell-line :name (n / name :op1 "MDA-MB-468"))
:op2 (c4 / cell-line :name (n2 / name :op1 "BT-20"))))
:source (d3 / disease :wiki "Breast_cancer" :name (n8 / name :op1 "breast" :op2 "cancer")
:mod (h / human)))
:ARG2 (o / or
:op1 (p / pool
:consist-of (o2 / oligonucleotide :quant 4
:mod (n11 / nucleic-acid :name (n3 / name :op1 "siRNA")))
:ARG1-of (d / direct-01
:ARG2 (n12 / nucleic-acid :name (n4 / name :op1 "mRNA")
:ARG0-of (e2 / encode-01
:ARG1 (p2 / protein :name (n5 / name :op1 "MUC1")))))
:ARG1-of (m2 / mean-01
:ARG2 (a2 / and
:op1 (c6 / cell-line :name (n6 / name :op1 "468.siMUC1"))
:op2 (c7 / cell-line :name (n7 / name :op1 "BT.siMUC1")))))
:op2 (o5 / oligonucleotide
:mod (c5 / control)
:ARG1-of (d2 / direct-01
:ARG2 (l / luciferase))
:ARG1-of (m3 / mean-01
:ARG2 (a3 / and
:op1 (c8 / cell-line :name (n9 / name :op1 "468.siLuc"))
:op2 (c9 / cell-line :name (n10 / name :op1 "BT.siLuc"))))))
:manner (t2 / transient-02))
# ::id pmid_1684_6534.103 ::date 2015-08-13T07:14:15 ::annotator SDL-AMR-09 ::preferred
# ::snt Both cell lines express high levels of MUC1, making them promising targets for this analysis.
# ::save-date Thu Aug 13, 2015 ::file pmid_1684_6534_103.txt
(e / express-03
:ARG2 (l / level
:ARG1-of (h / high-02)
:quant-of (p / protein :name (n / name :op1 "MUC1")))
:ARG3 c2
:ARG0-of (m / make-02
:ARG1 (c2 / cell-line
:mod (b / both)
:ARG1-of (t / target-01
:ARG0 (a / analyze-01
:mod (t2 / this)))
:ARG0-of (p2 / promise-01))))
# ::id pmid_1684_6534.104 ::date 2015-08-13T07:21:19 ::annotator SDL-AMR-09 ::preferred
# ::snt Western blots (Figure 1a) show successful knockdown of both the extracellular domain and cytoplasmic tail fragments of MUC1; luciferase siRNA does not substantially change the level of MUC1 compared to parental cells.
# ::save-date Sun Dec 13, 2015 ::file pmid_1684_6534_104.txt
(m / multi-sentence
:snt1 (s / show-01
:ARG0 (i / immunoblot-01
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "1a")))
:ARG1 (k / knock-down-02
:ARG1 (a / and
:op1 (p / protein-segment
:mod (e / extracellular)
:part-of (p2 / protein :name (n2 / name :op1 "MUC1")))
:op2 (f2 / fragment
:part-of (t2 / tail
:mod (c / cytoplasm)
:part-of p2)))
:ARG0-of (s3 / succeed-01)))
:snt2 (c2 / change-01 :polarity -
:ARG0 (n4 / nucleic-acid :name (n3 / name :op1 "siRNA")
:ARG0-of (e2 / encode-01
:ARG1 (l2 / luciferase)))
:ARG1 (l / level
:quant-of (p3 / protein :name (n5 / name :op1 "MUC1")))
:degree (s2 / substantial)
:compared-to (c3 / cell
:mod (p4 / parental))))
# ::id pmid_1684_6534.105 ::date 2015-08-13T07:29:42 ::annotator SDL-AMR-09 ::preferred
# ::snt 468.siMUC1 show a substantial decrease in the amount of MUC1-CT, while BT.siMUC1 show slightly less knockdown of MUC1-CT.
# ::save-date Fri Aug 14, 2015 ::file pmid_1684_6534_105.txt
(c / contrast-01
:ARG1 (s / show-01
:ARG0 (c2 / cell-line :name (n2 / name :op1 "468.siMUC1"))
:ARG1 (d / decrease-01
:ARG1 (a / amount
:quant-of (p / protein-segment :name (n / name :op1 "MUC1-CT")))
:ARG2 (s2 / substantial)))
:ARG2 (s3 / show-01
:ARG0 (c3 / cell-line :name (n3 / name :op1 "BT.siMUC1"))
:ARG1 (k / knock-down-02
:ARG1 p
:ARG2 (l / less
:degree (s4 / slight)))))
# ::id pmid_1684_6534.106 ::date 2015-08-13T07:34:33 ::annotator SDL-AMR-09 ::preferred
# ::snt Both MDA-MB-468 and BT-20 display a less dramatic decrease of MUC1 extracellular domain compared to MUC1-CT (Figure 1a); this likely represents protein synthesized prior to transfection, and may reflect differences in the turnover rates of the two subunits.
# ::save-date Fri Aug 14, 2015 ::file pmid_1684_6534_106.txt
(d / display-01
:ARG0 (a / and
:op1 (c / cell-line :name (n / name :op1 "MDA-MB-468"))
:op2 (c2 / cell-line :name (n2 / name :op1 "BT-20")))
:ARG1 (d2 / decrease-01
:ARG1 (p2 / protein-segment
:mod (e / extracellular)
:part-of (p / protein :name (n3 / name :op1 "MUC1")))
:ARG2 (d3 / dramatic
:degree (l / less))
:compared-to (p3 / protein-segment :name (n4 / name :op1 "MUC1-CT")))
:ARG1-of (d4 / describe-01
:ARG0 (f / figure :mod "1a"))
:ARG0-of (r / represent-01
:ARG1 (p4 / protein
:ARG1-of (s / synthesize-01
:time (p6 / prior
:op1 (t / transfect-01))))
:ARG1-of (l2 / likely-01))
:ARG1-of (r2 / reflect-01
:ARG2 (d5 / differ-02
:ARG1 (r3 / rate
:degree-of (t2 / turnover)
:poss (a2 / and
:op1 p2
:op2 p3)))
:ARG1-of (p5 / possible-01)))
# ::id pmid_1684_6534.107 ::date 2015-08-13T07:42:39 ::annotator SDL-AMR-09 ::preferred
# ::snt Analysis of the MUC1 extracellular domain by flow cytometry confirms that both cell lines substantially decrease MUC1 expression after siRNA (Figure 1b).
# ::save-date Thu Aug 13, 2015 ::file pmid_1684_6534_107.txt
(c / confirm-01
:ARG0 (a / analyze-01
:ARG1 (p / protein-segment
:mod (e / extracellular)
:part-of (p2 / protein :name (n / name :op1 "MUC1")))
:instrument (c2 / cytometry
:mod (f / flow)))
:ARG1 (d / decrease-01
:ARG0 (c3 / cell-line
:mod (b / both))
:ARG1 (e2 / express-03
:ARG2 p2)
:ARG2 (s / substantial)
:time (a2 / after
:op1 (n3 / nucleic-acid :name (n2 / name :op1 "siRNA"))))
:ARG1-of (d2 / describe-01
:ARG0 (f2 / figure :mod "1b")))
# ::id pmid_1684_6534.108 ::date 2015-08-13T07:48:54 ::annotator SDL-AMR-09 ::preferred
# ::snt By flow cytometry, 468.siMUC1 averaged 75% knockdown of MUC1 compared to 468.siLuc; and BT.siMUC1 averaged 50% knockdown relative to BT.siLuc.
# ::save-date Fri Aug 14, 2015 ::file pmid_1684_6534_108.txt
(a / and
:op1 (a2 / average-01
:ARG0 (c2 / cell-line :name (n2 / name :op1 "468.siMUC1")
:compared-to (c3 / cell-line :name (n3 / name :op1 "468.siLuc")))
:ARG1 (k / knock-down-02
:ARG1 (p2 / protein :name (n / name :op1 "MUC1")))
:ARG2 (p / percentage-entity :value 75))
:op2 (a3 / average-01
:ARG0 (c5 / cell-line :name (n5 / name :op1 "BT.siMUC1")
:ARG1-of (r / relative-05
:ARG3 (c4 / cell-line :name (n4 / name :op1 "BT.siLuc"))))
:ARG1 (k2 / knock-down-02)
:ARG2 (p3 / percentage-entity :value 50))
:time (c / cytometry
:mod (f / flow)))
# ::id pmid_1684_6534.109 ::date 2015-08-13T07:52:32 ::annotator SDL-AMR-09 ::preferred
# ::snt These effects could be titrated with the concentration of siRNA, were seen as early as 24 hours post-transfection (data not shown) and lasted to at least 96 h post-transfection (Figure 1b).
# ::save-date Tue Aug 25, 2015 ::file pmid_1684_6534_109.txt
(a / and
:op1 (p / possible-01
:ARG1 (t / titrate-01
:ARG0 (c / concentrate-02
:ARG1 (n2 / nucleic-acid :name (n / name :op1 "siRNA")))
:ARG1 (a2 / affect-01
:mod (t2 / this))))
:op2 (s / see-01
:ARG1 a2
:ARG1-of (d / describe-01
:ARG0 (d2 / data
:ARG1-of (s2 / show-01 :polarity -)))
:time (a3 / after
:op1 (t3 / transfect-01)
:quant (t4 / temporal-quantity :quant 24
:unit (h / hour)
:mod (e2 / early))))
:op3 (l / last-01
:ARG1 a2
:ARG2 (u / until
:op1 (a4 / after
:op1 t3
:quant (t5 / temporal-quantity :quant 96
:unit h)))
:mod (a5 / at-least)
:ARG1-of (d3 / describe-01
:ARG0 (f / figure :mod "1b"))))
# ::id pmid_1684_6534.110 ::date 2015-08-13T08:03:02 ::annotator SDL-AMR-09 ::preferred
# ::snt All experiments were conducted within 48 to 96 hours after siRNA transfection.
# ::save-date Wed Dec 30, 2015 ::file pmid_1684_6534_110.txt
(c / conduct-01
:ARG1 (e / experiment-01
:mod (a / all))
:time (a2 / after
:op1 (t / transfect-01
:ARG2 (n2 / nucleic-acid :name (n / name :op1 "siRNA")))
:quant (u / up-to
:op1 (v / value-interval
:op1 (t2 / temporal-quantity :quant 48
:unit (h / hour))
:op2 (t3 / temporal-quantity :quant 96
:unit h)))))
# ::id pmid_1684_6534.111 ::date 2015-08-13T08:07:04 ::annotator SDL-AMR-09 ::preferred
# ::snt Similar results were obtained using two independent oligonucleotides designed in our lab (data not shown), designated '882' and '956' for the initial codon recognized by each.
# ::save-date Wed Dec 30, 2015 ::file pmid_1684_6534_111.txt
(o / obtain-01
:ARG1 (t / thing
:ARG2-of (r / result-01)
:ARG1-of (r2 / resemble-01))
:manner (u / use-01
:ARG1 (o2 / oligonucleotide :quant 2
:ARG0-of (d / depend-01 :polarity -)
:ARG1-of (d3 / describe-01
:ARG0 (d4 / data
:ARG1-of (s / show-01 :polarity -)))
:ARG1-of (d5 / designate-01
:ARG2 (a / and
:op1 (o3 / oligonucleotide :mod 882)
:op2 (o4 / oligonucleotide :mod 956))
:ARG1-of (c / cause-01
:ARG0 (c2 / codon
:mod (i / initial)
:ARG1-of (r3 / recognize-02
:location o2))))
:ARG1-of (d2 / design-01
:location (l / laboratory
:poss (w / we))))))
# ::id pmid_1684_6534.112 ::date 2015-08-13T08:16:26 ::annotator SDL-AMR-09 ::preferred
# ::snt Transcriptional changes are seen after MUC1 siRNA
# ::save-date Mon Aug 24, 2015 ::file pmid_1684_6534_112.txt
(s / see-01
:ARG1 (c / change-01
:ARG1 (t / transcribe-01))
:time (a / after
:op1 (n3 / nucleic-acid :name (n / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (p / protein :name (n2 / name :op1 "MUC1"))))))
# ::id pmid_1684_6534.113 ::date 2015-08-13T08:19:27 ::annotator SDL-AMR-09 ::preferred
# ::snt Recent work indicates that MUC1 may affect transcription both directly via interaction with transcription factors and indirectly (for example, through modulating signaling).
# ::save-date Tue Aug 25, 2015 ::file pmid_1684_6534_113.txt
(i / indicate-01
:ARG0 (w / work-01
:time (r / recent))
:ARG1 (p / possible-01
:ARG1 (a / affect-01
:ARG0 (p2 / protein :name (n / name :op1 "MUC1"))
:ARG1 (t / transcribe-01)
:manner (a2 / and
:op1 (d / direct-02
:manner (i2 / interact-01
:ARG0 p2
:ARG1 (f / factor
:ARG0-of t)))
:op2 (d2 / direct-02 :polarity -
:example (m / modulate-01
:ARG0 p2
:ARG1 (s / signal-07)))))))
# ::id pmid_1684_6534.114 ::date 2015-08-13T08:24:05 ::annotator SDL-AMR-09 ::preferred
# ::snt To study the effects of MUC1 knockdown in breast cancer cell lines, real-time PCR arrays were used to analyze transcription of 84 genes implicated in cancer.
# ::save-date Wed Dec 9, 2015 ::file pmid_1684_6534_114.txt
(u / use-01
:ARG1 (a / array-01
:mod (r2 / react-01
:ARG0 (p / polymerase)
:mod (r / real-time)
:mod (c4 / chain)))
:ARG2 (a2 / analyze-01
:ARG1 (t / transcribe-01
:ARG1 (g / gene :quant 84
:ARG1-of (i / implicate-01
:ARG2 (d / disease :wiki "Cancer" :name (n2 / name :op1 "cancer"))))))
:purpose (s / study-01
:ARG1 (a3 / affect-01
:ARG0 (k / knock-down-02
:ARG1 (p2 / protein :name (n / name :op1 "MUC1")))
:ARG1 (c2 / cell-line
:source (d2 / disease :wiki "Breast_cancer" :name (n3 / name :op1 "breast" :op2 "cancer"))))))
# ::id pmid_1684_6534.115 ::date 2015-08-13T08:32:00 ::annotator SDL-AMR-09 ::preferred
# ::snt Only genes with greater than two-fold change were considered.
# ::save-date Thu Aug 13, 2015 ::file pmid_1684_6534_115.txt
(c / consider-02
:ARG1 (g / gene
:ARG1-of (c2 / change-01
:ARG2 (g2 / great
:degree (m / more)
:compared-to (c3 / change-01
:ARG2 (p / product-of :op1 2)))))
:mod (o / only))
# ::id pmid_1684_6534.116 ::date 2015-08-13T08:34:41 ::annotator SDL-AMR-09 ::preferred
# ::snt Three genes (MAP2K1, VEGF, PDGFA) were altered two-fold or more after MUC1 siRNA in both MDA-MB-468 and BT-20 cells (Figure 2); two genes (ITGAV, MMP2) changed only in 468.siMUC1; and five genes (TIMP3, RAF1, JUN, TNF, CDC25A) only in BT.siMUC1.
# ::save-date Mon Aug 24, 2015 ::file pmid_1684_6534_116.txt
(a6 / and
:op1 (a / alter-01
:ARG1 (g / gene :quant 3
:ARG1-of (m2 / mean-01
:ARG2 (a2 / and
:op1 (g2 / gene :name (n / name :op1 "MAP2K1"))
:op2 (g3 / gene :name (n2 / name :op1 "VEGF"))
:op3 (g4 / gene :name (n3 / name :op1 "PDGFA")))))
:degree (o / or
:op1 (p / product-of :op1 2)
:op2 (m3 / more-than
:op1 p))
:time (a3 / after
:op1 (n17 / nucleic-acid :name (n4 / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (p2 / protein :name (n5 / name :op1 "MUC1")))))
:location (a4 / and
:op1 (c / cell-line :name (n6 / name :op1 "MDA-MB-468"))
:op2 (c2 / cell-line :name (n7 / name :op1 "BT-20")))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod 2)))
:op2 (c3 / change-01
:ARG1 (g5 / gene :quant 2
:ARG1-of (m4 / mean-01
:ARG2 (a5 / and
:op1 (g6 / gene :name (n8 / name :op1 "ITGAV"))
:op2 (g7 / gene :name (n9 / name :op1 "MMP2")))))
:mod o2
:location (c5 / cell-line :name (n15 / name :op1 "468.siMUC1")))
:op3 (c4 / change-01
:ARG1 (g8 / gene :quant 5
:ARG1-of (m / mean-01
:ARG2 (a7 / and
:op1 (g9 / gene :name (n10 / name :op1 "TIMP3"))
:op2 (g10 / gene :name (n11 / name :op1 "RAF1"))
:op3 (g11 / gene :name (n12 / name :op1 "JUN"))
:op4 (g12 / gene :name (n13 / name :op1 "TNF"))
:op5 (g13 / gene :name (n14 / name :op1 "CDC25A")))))
:mod (o2 / only)
:location (c6 / cell-line :name (n16 / name :op1 "BT.siMUC1"))))
# ::id pmid_1684_6534.117 ::date 2015-08-13T08:45:07 ::annotator SDL-AMR-09 ::preferred
# ::snt This list represents all genes affected greater than two-fold after MUC1 siRNA, rather than a select group.
# ::save-date Mon Aug 24, 2015 ::file pmid_1684_6534_117.txt
(r / represent-01
:ARG0 (l / list
:mod (t / this))
:ARG1 (g / gene
:mod (a / all)
:ARG1-of (a2 / affect-01
:degree (g2 / great
:degree (m / more)
:compared-to (p / product-of :op1 2))
:time (a3 / after
:op1 (n3 / nucleic-acid :name (n / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (p2 / protein :name (n2 / name :op1 "MUC1")))))))
:ARG1-of (i / instead-of-91
:ARG2 (g3 / group
:ARG1-of (s / select-01))))
# ::id pmid_1684_6534.118 ::date 2015-08-13T08:48:48 ::annotator SDL-AMR-09 ::preferred
# ::snt Three genes whose transcription was changed by less than two-fold are shown, two of which (PDGFB and ITGB1) are listed because they relate closely to genes altered by two-fold (PDGFA and ITGAV).
# ::save-date Thu Aug 13, 2015 ::file pmid_1684_6534_118.txt
(s / show-01
:ARG1 (g / gene :quant 3
:ARG1-of (t / transcribe-01
:ARG1-of (c / change-01
:ARG2 (l / less-than
:op1 (p / product-of :op1 2))))
:ARG2-of (i / include-91
:ARG1 (g2 / gene :quant 2
:ARG1-of (m / mean-01
:ARG2 (a / and
:op1 (g3 / gene :name (n / name :op1 "PDGFB"))
:op2 (g4 / gene :name (n2 / name :op1 "ITGB1"))))
:ARG1-of (l2 / list-01
:ARG1-of (c2 / cause-01
:ARG0 (r / relate-01
:ARG1 g2
:ARG2 (g5 / gene
:ARG1-of (a2 / alter-01
:degree p)
:ARG1-of (m2 / mean-01
:ARG2 (a3 / and
:op1 (g6 / gene :name (n3 / name :op1 "PDGFA"))
:op2 (g7 / gene :name (n4 / name :op1 "ITGAV")))))
:manner (c3 / close-10))))))))
# ::id pmid_1684_6534.119 ::date 2015-08-13T08:55:46 ::annotator SDL-AMR-09 ::preferred
# ::snt The third, MYC, is included because western blots confirmed a substantial change at the protein level (Figure 3a) that may reflect both transcriptional and post-transcriptional regulation.
# ::save-date Sun Dec 13, 2015 ::file pmid_1684_6534_119.txt
(i / include-01
:ARG1 (g / gene
:ord (o / ordinal-entity :value 3)
:ARG1-of (m / mean-01
:ARG2 (g2 / gene :name (n / name :op1 "MYC"))))
:ARG1-of (c / cause-01
:ARG0 (c2 / confirm-01
:ARG0 (i2 / immunoblot-01)
:ARG1 (c3 / change-01
:ARG1 (l / level
:quant-of (p / protein))
:degree (s / substantial)
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "3a"))
:ARG1-of (r / reflect-01
:ARG2 (a / and
:op1 (r2 / regulate-01
:time (t2 / transcribe-01))
:op1 (r3 / regulate-01
:time (a2 / after
:op1 t2)))
:ARG1-of (p2 / possible-01))))))
# ::id pmid_1684_6534.120 ::date 2015-08-13T09:02:18 ::annotator SDL-AMR-09 ::preferred
# ::snt Interestingly, transcription of MAP2K1 was decreased in both cell lines after MUC1 siRNA.
# ::save-date Mon Aug 24, 2015 ::file pmid_1684_6534_120.txt
(d / decrease-01
:ARG1 (t / transcribe-01
:ARG1 (g / gene :name (n / name :op1 "MAP2K1")))
:location (c / cell-line
:mod (b / both))
:time (a / after
:op1 (n4 / nucleic-acid :name (n2 / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (p / protein :name (n3 / name :op1 "MUC1")))))
:ARG2-of (i / interest-01))
# ::id pmid_1684_6534.121 ::date 2015-08-13T09:10:40 ::annotator SDL-AMR-09 ::preferred
# ::snt This gene encodes MEK1, one of the primary regulators of the ERK1/2 MAPK pathway [33], a network that has been linked several times to MUC1 [12,34-36].
# ::save-date Thu Aug 13, 2015 ::file pmid_1684_6534_121.txt
(e / encode-01
:ARG0 (g / gene
:mod (t / this))
:ARG1 (e2 / enzyme :name (n / name :op1 "MEK1")
:ARG1-of (i / include-91
:ARG2 (m / molecular-physical-entity
:ARG0-of (r / regulate-01
:ARG1 (p2 / pathway :name (n2 / name :op1 "ERK1/2" :op2 "MAPK")
:mod (n3 / network
:ARG1-of (l / link-01
:ARG2 (p4 / protein :name (n4 / name :op1 "MUC1"))
:frequency (s / several)
:ARG1-of (d2 / describe-01
:ARG0 (a / and
:op1 (p5 / publication
:ARG1-of (c2 / cite-01
:ARG2 12))
:op2 (p6 / publication
:ARG1-of (c3 / cite-01
:ARG2 (v / value-interval :op1 34 :op2 36)))))))))
:mod (p / primary))
:ARG1-of (d / describe-01
:ARG0 (p3 / publication
:ARG1-of (c / cite-01
:ARG2 33))))))
# ::id pmid_1684_6534.122 ::date 2015-08-13T09:18:52 ::annotator SDL-AMR-09 ::preferred
# ::snt We examined MEK1 and MEK2 levels by western blot to confirm decreased protein in MUC1 siRNA-treated cells (Figure 3a), and found that not only were total MEK1/2 levels lower in 468.siMUC1 and BT.siMUC1 compared to controls (0.48 and 0.68 relative to siLuc, respectively), but so were the basal amounts of active (phosphorylated) MEK1/2 (pMEK1/2; 0.12 and 0.42 relative to siLuc, respectively).
# ::save-date Mon Jan 4, 2016 ::file pmid_1684_6534_122.txt
(a / and
:op1 (e / examine-01
:ARG0 (w / we)
:ARG1 (a2 / and
:op1 (l / level
:quant-of (e2 / enzyme :name (n / name :op1 "MEK1")))
:op2 (l2 / level
:quant-of (e3 / enzyme :name (n2 / name :op1 "MEK2"))))
:manner (i / immunoblot-01)
:purpose (c / confirm-01
:ARG0 w
:ARG1 (p / protein
:ARG1-of (d / decrease-01
:location (c2 / cell
:ARG1-of (t2 / treat-04
:ARG2 (n11 / nucleic-acid :name (n4 / name :op1 "siRNA")
:ARG0-of (e4 / encode-01
:ARG1 (p2 / protein :name (n5 / name :op1 "MUC1")))))))))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod "3a")))
:op2 (f2 / find-01
:ARG0 w
:ARG1 (a3 / and
:op1 (a4 / and
:op1 (l3 / level
:quant-of e2)
:op2 (l4 / level
:quant-of e3)
:mod (t3 / total)
:ARG1-of (l5 / low-04
:degree (m / more)
:compared-to (c3 / control))
:ARG1-of (m2 / mean-01
:ARG2 (a14 / and
:op1 (l6 / level :quant 0.48)
:op2 (l7 / level :quant 0.68)
:manner r2
:ARG1-of (r3 / relative-05
:ARG3 (c6 / cell-line :name (n8 / name :op1 "siLuc")))
:mod t3)))
:op2 (a7 / and
:op1 (a8 / amount
:quant-of (e5 / enzyme :name (n9 / name :op1 "MEK1")
:ARG1-of (a10 / activate-01
:ARG1-of (m3 / mean-01
:ARG2 (p3 / phosphorylate-01
:ARG3 e5)))))
:op2 (a9 / amount
:quant-of (e6 / enzyme :name (n10 / name :op1 "MEK2")
:ARG1-of (a11 / activate-01
:ARG1-of (m5 / mean-01
:ARG2 (p4 / phosphorylate-01
:ARG3 e6)))))
:mod (b / basal)
:ARG1-of l5
:ARG1-of (m4 / mean-01
:ARG2 (a12 / and
:op1 (a6 / amount :quant 0.12)
:op2 (a13 / amount :quant 0.42)
:manner (r2 / respective)
:ARG1-of r3
:mod b))))
:location (a5 / and
:op1 (c4 / cell-line :name (n6 / name :op1 "468.siMUC1"))
:op2 (c5 / cell-line :name (n7 / name :op1 "BT.siMUC1")))))
# ::id pmid_1684_6534.123 ::date 2015-08-13T09:34:57 ::annotator SDL-AMR-09 ::preferred
# ::snt Both 468.siMUC1 and BT.siMUC1 also showed reduced activation of ERK1/2 (dpERK1/2; 0.21 and 0.27 relative to siLuc, respectively), as would be expected with diminished signaling through MEK1/2; total ERK1/2 levels remain unchanged.
# ::save-date Thu Nov 19, 2015 ::file pmid_1684_6534_123.txt
(m2 / multi-sentence
:snt1 (s / show-01
:ARG0 (a / and
:op1 (c3 / cell-line :name (n7 / name :op1 "468.siMUC1"))
:op2 (c4 / cell-line :name (n8 / name :op1 "BT.siMUC1")))
:ARG1 (a3 / activate-01
:ARG1 (s2 / slash
:op1 (e / enzyme :name (n / name :op1 "ERK1"))
:op2 (e2 / enzyme :name (n2 / name :op1 "ERK2"))
:ARG3-of (p / phosphorylate-01
:mod (d3 / dual)))
:ARG1-of (r / reduce-01)
:ARG1-of (m / mean-01
:ARG2 (a4 / and
:op1 (a5 / activate-01 :degree 0.21)
:op2 (a6 / activate-01 :degree 0.27)
:manner (r2 / respective)
:ARG1-of (r4 / relative-05
:ARG3 (c5 / cell-line :name (n9 / name :op1 "siLuc"))))))
:mod (a2 / also)
:ARG1-of (e3 / expect-01
:ARG1-of (c / cause-01
:ARG0 (s3 / signal-07
:ARG0 (s4 / slash
:op1 (e4 / enzyme :name (n3 / name :op1 "MEK1"))
:op2 (e5 / enzyme :name (n4 / name :op1 "MEK2")))
:ARG1-of (d / diminish-01)))))
:snt2 (r3 / remain-01
:ARG1 (l2 / level
:mod (t / total)
:quant-of s2)
:ARG3 (c2 / change-01 :polarity -)))
# ::id pmid_1684_6534.124 ::date 2015-08-13T09:48:48 ::annotator SDL-AMR-09 ::preferred
# ::snt As both lines have high levels of EGFR and thus activate the MEK-ERK cascade intensely when stimulated with EGF [37], siRNA-transfected cells were treated with EGF.
# ::save-date Sun Jan 17, 2016 ::file pmid_1684_6534_124.txt
(t / treat-04
:ARG1 (c / cell
:ARG1-of (t2 / transfect-01
:ARG2 (n5 / nucleic-acid :name (n2 / name :op1 "siRNA"))))
:ARG2 (p3 / protein :name (n3 / name :op1 "EGF"))
:ARG1-of (c2 / cause-01
:ARG0 (h / have-03
:ARG0 (c3 / cell-line
:mod (b / both))
:ARG1 (l / level
:ARG1-of (h2 / high-02)
:quant-of (e / enzyme :name (n / name :op1 "EGFR")))
:ARG2-of (i / infer-01
:ARG1 (a / activate-01
:ARG0 c3
:ARG1 (p / pathway :name (n4 / name :op1 "MEK-ERK"))
:manner (i2 / intense-02)
:time (s2 / stimulate-01
:ARG1 c3
:ARG2 p3))))
:ARG1-of (d / describe-01
:ARG0 (p2 / publication
:ARG1-of (c5 / cite-01
:ARG2 37)))))
# ::id pmid_1684_6534.125 ::date 2015-08-13T09:55:17 ::annotator SDL-AMR-09 ::preferred
# ::snt Notably, MUC1 siRNA impairs this important oncogenic pathway in MDA-MB-468 cells, as 468.siMUC1 display less pMEK1/2 in response to EGF than do 468.siLuc (Figure 3b).
# ::save-date Sun Jan 17, 2016 ::file pmid_1684_6534_125.txt
(i / impair-01
:ARG0 (n11 / nucleic-acid :name (n / name :op1 "siRNA")
:ARG0-of (e3 / encode-01
:ARG1 (p / protein :name (n2 / name :op1 "MUC1"))))
:ARG1 (p2 / pathway
:mod (t / this)
:mod (i2 / important)
:ARG0-of (c / cause-01
:ARG1 (d4 / disease :wiki "Cancer" :name (n10 / name :op1 "cancer"))))
:location (c3 / cell-line :name (n3 / name :op1 "MDA-MB-468"))
:ARG1-of (n4 / notable-04)
:ARG1-of (c4 / cause-01
:ARG0 (d / display-01
:ARG0 (c5 / cell-line :name (n8 / name :op1 "468.siMUC1"))
:ARG1 (s / slash
:op1 (e / enzyme :name (n5 / name :op1 "MEK1"))
:op2 (e2 / enzyme :name (n6 / name :op1 "MEK2"))
:ARG3-of (p3 / phosphorylate-01)
:quant (l / less))
:ARG2-of (r2 / respond-01
:ARG1 (p4 / protein :name (n7 / name :op1 "EGF")))
:compared-to (d2 / display-01
:ARG0 (c6 / cell-line :name (n9 / name :op1 "468.siLuc"))
:ARG1 (s3 / slash
:op1 e
:op2 e2))))
:ARG1-of (d3 / describe-01
:ARG0 (f / figure :mod "3b")))
# ::id pmid_1684_6534.126 ::date 2015-08-13T10:03:21 ::annotator SDL-AMR-09 ::preferred
# ::snt Interestingly, EGF treatment of BT-20 cells results in slightly higher pMEK1/2 levels in BT.siMUC1 compared to BT.siLuc.
# ::save-date Fri Aug 14, 2015 ::file pmid_1684_6534_126.txt
(r / result-01
:ARG1 (t / treat-04
:ARG1 (c / cell-line :name (n2 / name :op1 "BT-20"))
:ARG2 (s / small-molecule :name (n / name :op1 "EGF")))
:ARG2 (l / level
:ARG1-of (h / high-02
:degree (m / more
:degree (s2 / slight))
:compared-to (c2 / cell-line :name (n5 / name :op1 "BT.siLuc")))
:quant-of (s3 / slash
:op1 (e / enzyme :name (n3 / name :op1 "MEK1"))
:op2 (e2 / enzyme :name (n4 / name :op1 "MEK2"))
:ARG3-of (p / phosphorylate-01))
:location (c3 / cell-line :name (n6 / name :op1 "BT.siMUC1")))
:ARG2-of (i / interest-01))
# ::id pmid_1684_6534.127 ::date 2015-08-14T01:03:53 ::annotator SDL-AMR-09 ::preferred
# ::snt Though this result seems paradoxical in light of decreased MAP2K1 transcription in BT.siMUC1, it likely results from differential functions of Raf isoforms in combination with the increased RAF1 transcription (Figure 2) and protein level (Figure 3a) in these cells.
# ::save-date Fri Aug 14, 2015 ::file pmid_1684_6534_127.txt
(h / have-concession-91
:ARG1 (l / likely-01
:ARG1 (r3 / result-01
:ARG1 (c / combine-01
:ARG1 (f / function-01
:ARG0 (e / enzyme :name (n / name :op1 "Raf")
:mod (i / isoform))
:mod (d2 / differential))
:ARG2 (a / and
:op1 (t4 / transcribe-01
:ARG1 (g2 / gene :name (n4 / name :op1 "RAF1"))
:ARG1-of (d4 / describe-01
:ARG0 (f3 / figure :mod 2)))
:op2 (l2 / level
:quant-of (p / protein)
:ARG1-of (d3 / describe-01
:ARG0 (f2 / figure :mod "3a")))
:location c3
:ARG1-of (i2 / increase-01)))
:ARG2 t))
:ARG2 (s / seem-01
:ARG1 (p2 / paradox
:domain (t / thing
:ARG2-of (r / result-01)
:mod (t2 / this)))
:ARG1-of (c4 / cause-01
:ARG0 (d / decrease-01
:ARG1 (t3 / transcribe-01
:ARG1 (g / gene :name (n2 / name :op1 "MAP2K1"))
:location (c3 / cell-line :name (n3 / name :op1 "BT.siMUC1")))))))
# ::id pmid_1684_6534.128 ::date 2015-08-14T01:13:56 ::annotator SDL-AMR-09 ::preferred
# ::snt Specifically, B-Raf is thought to be the main activator of MEK under normal conditions; Raf-1 activates MEK in response to stimulus [38].
# ::save-date Fri Aug 14, 2015 ::file pmid_1684_6534_128.txt
(a2 / and
:op1 (t2 / think-01
:ARG1 (a3 / activate-01
:ARG0 (e / enzyme :name (n / name :op1 "B-Raf"))
:ARG1 (e3 / enzyme :name (n3 / name :op1 "MEK"))
:mod (m / main)
:condition (n4 / normal)))
:op2 (a4 / activate-01
:ARG0 (e4 / enzyme :name (n5 / name :op1 "Raf-1"))
:ARG1 e3
:ARG2-of (r / respond-01
:ARG1 (s / stimulus)))
:ARG1-of (s2 / specific-02)
:ARG1-of (d / describe-01
:ARG0 (p / publication
:ARG1-of (c / cite-01
:ARG2 38))))
# ::id pmid_1684_6534.129 ::date 2015-08-14T01:24:38 ::annotator SDL-AMR-09 ::preferred
# ::snt Thus, it appears that basal pMEK1/2 levels are not greatly affected by Raf-1 overexpression in BT.siMUC1 cells, likely because MEK is regulated primarily by B-Raf under normal growth conditions.
# ::save-date Tue Aug 25, 2015 ::file pmid_1684_6534_129.txt
(c2 / cause-01
:ARG0 (r / regulate-01
:ARG0 (e2 / enzyme :name (n3 / name :op1 "B-Raf"))
:ARG1 (e5 / enzyme :name (n / name :op1 "MEK"))
:ARG1-of (l2 / likely-01)
:manner (p / primary)
:condition (g2 / grow-01
:ARG1-of (n7 / normal-02)))
:ARG1 (a / appear-02
:ARG1 (a2 / affect-01 :polarity -
:ARG0 (o / overexpress-01
:ARG1 (e / enzyme :name (n2 / name :op1 "Raf-1"))
:location (c / cell-line :name (n6 / name :op1 "BT.siMUC1")))
:ARG1 (l / level
:quant-of (s / slash
:op1 (e3 / enzyme :name (n4 / name :op1 "MEK1"))
:op2 (e4 / enzyme :name (n5 / name :op1 "MEK2"))
:ARG3-of (p2 / phosphorylate-01))
:mod (b / basal))
:extent (g / great))))
# ::id pmid_1684_6534.130 ::date 2015-08-14T01:31:02 ::annotator SDL-AMR-09 ::preferred
# ::snt In contrast, when the cells are stimulated (EGF), increased Raf-1 levels in BT.siMUC1 leads to heightened pMEK1/2 (Figure 3b).
# ::save-date Sun Jan 17, 2016 ::file pmid_1684_6534_130.txt
(c / contrast-01
:ARG2 (l / lead-03
:ARG0 (l2 / level
:quant-of (e / enzyme :name (n / name :op1 "Raf-1"))
:location (c2 / cell-line :name (n2 / name :op1 "BT.siMUC1"))
:ARG1-of (i / increase-01))
:ARG2 (s / slash
:op1 (e2 / enzyme :name (n3 / name :op1 "MEK1"))
:op2 (e3 / enzyme :name (n4 / name :op1 "MEK2"))
:ARG3-of (p / phosphorylate-01)
:ARG1-of (h / heighten-01))
:time (s2 / stimulate-01
:ARG1 (c3 / cell)
:ARG2 (p2 / protein :name (n5 / name :op1 "EGF"))))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "3b")))
# ::id pmid_1684_6534.131 ::date 2015-08-14T01:34:58 ::annotator SDL-AMR-09 ::preferred
# ::snt MUC1 siRNA increases apoptosis in MDA-MB-468 but not BT-20
# ::save-date Mon Dec 14, 2015 ::file pmid_1684_6534_131.txt
(c / contrast-01
:ARG1 (i / increase-01
:ARG0 (n5 / nucleic-acid :name (n / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (p / protein :name (n2 / name :op1 "MUC1"))))
:ARG1 (a / apoptosis)
:location (c2 / cell-line :name (n3 / name :op1 "MDA-MB-468")))
:ARG2 (i2 / increase-01 :polarity -
:ARG0 n5
:ARG1 a
:location (c3 / cell-line :name (n4 / name :op1 "BT-20"))))
# ::id pmid_1684_6534.132 ::date 2015-08-14T02:18:32 ::annotator SDL-AMR-09 ::preferred
# ::snt We next examined whether MUC1 knockdown and its associated transcriptional alterations would affect overall cellular events.
# ::save-date Fri Aug 14, 2015 ::file pmid_1684_6534_132.txt
(e / examine-01
:ARG0 (w / we)
:ARG1 (a / affect-01 :mode interrogative
:ARG0 (a2 / and
:op1 (k / knock-down-02
:ARG1 (p / protein :name (n2 / name :op1 "MUC1")))
:op2 (a3 / alter-01
:ARG1 (t / transcribe-01
:ARG1 p)
:ARG1-of (a4 / associate-01
:ARG2 k)))
:ARG1 (e2 / event
:mod (c / cell)
:mod (o / overall)))
:time (n / next))
# ::id pmid_1684_6534.133 ::date 2015-08-14T02:22:33 ::annotator SDL-AMR-09 ::preferred
# ::snt As several of the genes shown in Figure 2 are important in regulating proliferation and survival, and because of the recently described role of MUC1 in modulating apoptosis in response to cellular stresses [20,21,24], we first analyzed whether MUC1 siRNA would alter apoptosis in these lines.
# ::save-date Mon Aug 24, 2015 ::file pmid_1684_6534_133.txt
(a / analyze-01
:ARG0 (w / we)
:ARG1 (a2 / alter-01 :mode interrogative
:ARG0 (n3 / nucleic-acid :name (n / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (p / protein :name (n2 / name :op1 "MUC1"))))
:ARG1 (a3 / apoptosis)
:location (c / cell-line
:mod (t / this)))
:time (f / first)
:ARG1-of (c2 / cause-01
:ARG0 (a4 / and
:op1 (i / important
:domain (g / gene
:quant (s / several)
:ARG1-of (i2 / include-91
:ARG2 (g2 / gene
:ARG1-of (s2 / show-01
:medium (f2 / figure :mod 2)))))
:purpose (r2 / regulate-01
:ARG1 (a5 / and
:op1 (p2 / proliferate-01)
:op2 (s3 / survive-01))))
:op2 (p3 / play-02
:ARG0 p
:ARG1 (m / modulate-01
:ARG0 p
:ARG1 a3
:ARG2-of (r3 / respond-01
:ARG1 (s4 / stress
:mod (c3 / cell))))
:ARG1-of (d / describe-01
:time (r4 / recent)))
:ARG1-of (d2 / describe-01
:ARG0 (a6 / and
:op1 (p4 / publication
:ARG1-of (c4 / cite-01
:ARG2 20))
:op2 (p5 / publication
:ARG1-of (c5 / cite-01
:ARG2 21))
:op3 (p6 / publication
:ARG1-of (c6 / cite-01
:ARG2 24)))))))
# ::id pmid_1684_6534.134 ::date 2015-08-14T02:29:39 ::annotator SDL-AMR-09 ::preferred
# ::snt Although there was no change in basal apoptosis in either line (Figure 4a), we observed that the cell lines responded differently when trypsinized for re-plating 24 hours after transfection (Figure 4b).
# ::save-date Tue Aug 25, 2015 ::file pmid_1684_6534_134.txt
(h2 / have-concession-91
:ARG1 (o / observe-01
:ARG0 (w / we)
:ARG1 (r / respond-01
:ARG0 c2
:ARG1-of (d2 / differ-01)
:time (t2 / trypsinize-00
:ARG1 c2
:purpose (r2 / replate-00)
:time (a2 / after
:op1 (t3 / transfect-01
:ARG1 c2)
:quant (t / temporal-quantity :quant 24
:unit (h / hour)))))
:ARG1-of (d3 / describe-01
:ARG0 (f2 / figure :mod "4b")))
:ARG2 (c / change-01 :polarity -
:ARG1 (a / apoptosis
:mod (b / basal))
:location (c2 / cell-line
:mod (e / either))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "4a"))))
# ::id pmid_1684_6534.135 ::date 2015-08-14T02:35:58 ::annotator SDL-AMR-09 ::preferred
# ::snt Interestingly, 468.siMUC1 cells show greater apoptosis after trypsinization than do 468.siLuc (49.8% versus 34.0%, respectively), while BT-20 cells from both siRNA treatments display similar levels of apoptosis (around 22%).
# ::save-date Fri Aug 14, 2015 ::file pmid_1684_6534_135.txt
(c / contrast-01
:ARG1 (s / show-01
:ARG0 (c2 / cell-line :name (n / name :op1 "468.siMUC1"))
:ARG1 (a / apoptosis
:mod (g / great
:degree (m / more)
:compared-to (c3 / cell-line :name (n2 / name :op1 "468.siLuc")
:ARG1-of (m3 / mean-01
:ARG2 (p2 / percentage-entity :value 34.0)))
:ARG1-of (m2 / mean-01
:ARG2 (p / percentage-entity :value 49.8))))
:time (a2 / after
:op1 (t / trypsinize-00)))
:ARG2 (d / display-01
:ARG0 (c4 / cell-line :name (n3 / name :op1 "BT-20")
:source (t2 / treat-04
:ARG2 (n5 / nucleic-acid :name (n4 / name :op1 "siRNA"))
:mod (b / both)))
:ARG1 (l / level
:degree-of a
:ARG1-of (r / resemble-01)
:ARG1-of (m4 / mean-01
:ARG2 (p3 / percentage-entity :value 22))))
:ARG2-of (i / interest-01))
# ::id pmid_1684_6534.136 ::date 2015-08-14T02:40:34 ::annotator SDL-AMR-09 ::preferred
# ::snt To examine whether this phenomenon is specific to trypsin treatment or part of a general stress response involving MUC1, we subjected cells to a panel of stresses and measured cell death.
# ::save-date Mon Aug 24, 2015 ::file pmid_1684_6534_136.txt
(a / and
:op1 (s / subject-01
:ARG0 (w / we)
:ARG1 (c / cell)
:ARG2 (p / panel
:consist-of (s2 / stress)))
:op2 (m / measure-01
:ARG0 w
:ARG1 (d / die-01
:ARG1 c))
:purpose (e2 / examine-01
:ARG0 w
:ARG1 (o / or :mode interrogative
:op1 (s3 / specific-02
:ARG1 p2
:ARG2 (t2 / treat-04
:ARG2 (e / enzyme :name (n / name :op1 "trypsin"))))
:op2 (p2 / phenomenon
:mod (t / this)
:subevent-of (r / respond-01
:ARG1 (s4 / stress)
:ARG1-of (g / general-02)
:ARG2-of (i / involve-01
:ARG1 (p3 / protein :name (n2 / name :op1 "MUC1"))))))))
# ::id pmid_1684_6534.137 ::date 2015-08-14T02:49:17 ::annotator SDL-AMR-09 ::preferred
# ::snt In agreement with the patterns seen with trypsinization, BT.siLuc and BT.siMUC1 respond similarly to all treatments (data not shown), while 468.siMUC1 die more readily than 468.siLuc in response to trypsin, G418, hydrogen peroxide, or celecoxib, a chemotherapeutic that targets the cyclooxygenase-2 (COX-2) pathway (Figure 4c); these data were confirmed with two independent siRNA constructs (data not shown).
# ::save-date Thu Nov 19, 2015 ::file pmid_1684_6534_137.txt
(m / multi-sentence
:snt1 (c / contrast-01
:ARG1 (r / respond-01
:ARG0 (a / and
:op1 (c2 / cell-line :name (n2 / name :op1 "BT.siLuc"))
:op2 (c3 / cell-line :name (n3 / name :op1 "BT.siMUC1")))
:ARG1 (t / treat-04
:mod (a2 / all))
:ARG1-of (r2 / resemble-01)
:ARG1-of (d / describe-01
:ARG0 (d2 / data
:ARG1-of (s / show-01 :polarity -))))
:ARG2 (d3 / die-01
:ARG1 (c4 / cell-line :name (n4 / name :op1 "468.siMUC1"))
:manner (r3 / ready-02
:degree (m2 / more)
:compared-to (c5 / cell-line :name (n5 / name :op1 "468.siLuc")))
:ARG2-of (r4 / respond-01
:ARG1 (o / or
:op1 (e / enzyme :name (n / name :op1 "trypsin"))
:op2 (s2 / small-molecule :name (n6 / name :op1 "G418"))
:op3 (s3 / small-molecule :name (n7 / name :op1 "hydrogen" :op2 "peroxide"))
:op4 (s4 / small-molecule :name (n8 / name :op1 "celecoxib")
:mod (s5 / small-molecule
:mod (c6 / chemotherapy)
:ARG0-of (t2 / target-01
:ARG1 (p / pathway :name (n9 / name :op1 "cyclooxygenase-2"))))))))
:ARG1-of (d4 / describe-01
:ARG0 (f / figure :mod "4c"))
:ARG0-of (a3 / agree-01
:ARG2 (p2 / pattern
:ARG1-of (s7 / see-01
:time (t4 / trypsinize-00)))))
:snt2 (c7 / confirm-01
:ARG0 (c8 / construct :quant 2
:mod (n11 / nucleic-acid :name (n10 / name :op1 "siRNA"))
:ARG0-of (d6 / depend-01 :polarity -))
:ARG1 (d5 / data
:mod (t3 / this))
:ARG1-of (d7 / describe-01
:ARG0 (d8 / data
:ARG1-of (s6 / show-01 :polarity -)))))
# ::id pmid_1684_6534.138 ::date 2015-08-14T03:04:36 ::annotator SDL-AMR-09 ::preferred
# ::snt Like the MAPK pathway, AKT signaling has been linked to MUC1 in cancer.
# ::save-date Wed Dec 9, 2015 ::file pmid_1684_6534_138.txt
(l / link-01
:ARG1 (s / signal-07
:ARG0 (e / enzyme :name (n3 / name :op1 "AKT")))
:ARG2 (p2 / protein :name (n4 / name :op1 "MUC1"))
:ARG1-of (r / resemble-01
:ARG2 (p / pathway :name (n / name :op1 "MAPK")))
:location (d / disease :wiki "Cancer" :name (n2 / name :op1 "cancer")))
# ::id pmid_1684_6534.139 ::date 2015-08-14T03:07:43 ::annotator SDL-AMR-09 ::preferred
# ::snt Although transcription of AKT was not altered in MUC1 siRNA-treated cells, the results of our apoptosis studies prompted us to investigate levels of AKT further.
# ::save-date Mon Aug 24, 2015 ::file pmid_1684_6534_139.txt
(h / have-concession-91
:ARG1 (p / prompt-02
:ARG0 (t / thing
:ARG2-of (r / result-01
:ARG1 (s / study-01
:ARG0 (w / we)
:ARG1 (a / apoptosis))))
:ARG1 w
:ARG2 (i / investigate-01
:ARG0 w
:ARG1 (l / level
:quant-of (e / enzyme :name (n2 / name :op1 "AKT")))
:degree (f / further)))
:ARG2 (a2 / alter-01 :polarity -
:ARG1 (t2 / transcribe-01
:ARG1 (g / gene :name (n / name :op1 "AKT")))
:location (c / cell
:ARG1-of (t3 / treat-04
:ARG2 (n5 / nucleic-acid :name (n3 / name :op1 "siRNA")
:ARG0-of (e2 / encode-01
:ARG1 (p2 / protein :name (n4 / name :op1 "MUC1"))))))))
# ::id pmid_1684_6534.140 ::date 2015-08-14T03:12:21 ::annotator SDL-AMR-09 ::preferred
# ::snt As expected, the total AKT protein level is not greatly changed after MUC1 siRNA in either cell line, though the active form (pAKT) is increased in both 468.siMUC1 and BT.siMUC1 compared to controls (Figure 3a).
# ::save-date Thu Nov 19, 2015 ::file pmid_1684_6534_140.txt
(c / change-01 :polarity -
:ARG1 (l / level
:mod (t / total)
:quant-of (e4 / enzyme :name (n / name :op1 "AKT")))
:degree (g / great)
:time (a / after
:op1 (n7 / nucleic-acid :name (n2 / name :op1 "siRNA")
:ARG0-of (e3 / encode-01
:ARG1 (p2 / protein :name (n3 / name :op1 "MUC1")))))
:location (c2 / cell-line
:mod (e / either))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "3a"))
:ARG1-of (e2 / expect-01)
:concession (i / increase-01
:ARG1 (f2 / form
:mod e4
:ARG1-of (a2 / activate-01)
:ARG1-of (m / mean-01
:ARG2 (e5 / enzyme :name (n6 / name :op1 "AKT")
:ARG3-of (p5 / phosphorylate-01))))
:location (a3 / and
:op1 (c3 / cell-line :name (n4 / name :op1 "468.siMUC1"))
:op2 (c4 / cell-line :name (n5 / name :op1 "BT.siMUC1")))
:compared-to (c5 / control)))
# ::id pmid_1684_6534.141 ::date 2015-08-14T03:16:22 ::annotator SDL-AMR-09 ::preferred
# ::snt This result disagrees with MUC1 activation of the AKT pathway in rat 3Y1 cells [18], and may reflect regulation more appropriate to breast cancer cells; this is supported by activation of AKT in response to MUC1 siRNA in other lines [21].
# ::save-date Wed Dec 9, 2015 ::file pmid_1684_6534_141.txt
(a / and
:op1 (d3 / disagree-01
:ARG0 (t / thing
:mod (t2 / this)
:ARG2-of (r / result-01))
:ARG1 (a2 / activate-01
:ARG0 (p / protein :name (n2 / name :op1 "MUC1"))
:ARG1 (p2 / pathway :name (n3 / name :op1 "AKT"))
:location (c / cell :name (n4 / name :op1 "3Y1")
:source (r2 / rat)))
:ARG1-of (d4 / describe-01
:ARG0 (p3 / publication
:ARG1-of (c2 / cite-01
:ARG2 18))))
:op2 (p4 / possible-01
:ARG1 (r3 / reflect-01
:ARG1 t
:ARG2 (r4 / regulate-01
:ARG1-of (a3 / appropriate-02
:ARG2 (c3 / cell
:source (d2 / disease :wiki "Breast_cancer" :name (n / name :op1 "breast" :op2 "cancer")))
:degree (m / more)))))
:ARG1-of (s / support-01
:ARG0 (a4 / activate-01
:ARG1 p2
:ARG2-of (r5 / respond-01
:ARG1 (n6 / nucleic-acid :name (n5 / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 p)))
:location (c5 / cell-line
:mod (o / other)))
:ARG1-of (d / describe-01
:ARG0 (p5 / publication
:ARG1-of (c6 / cite-01
:ARG2 21)))))
# ::id pmid_1684_6534.142 ::date 2015-08-14T03:34:15 ::annotator SDL-AMR-09 ::preferred
# ::snt In addition, there is a striking difference in the relative amounts of AKT and pAKT in the two cell lines (Figure 4d).
# ::save-date Fri Aug 14, 2015 ::file pmid_1684_6534_142.txt
(a4 / and
:op2 (d / differ-02
:ARG1 (a2 / and
:op1 (a / amount
:ARG1-of (r / relative-05)
:quant-of (e / enzyme :name (n / name :op1 "AKT")))
:op2 (a3 / amount
:ARG1-of r
:quant-of (e2 / enzyme :name (n2 / name :op1 "AKT")
:ARG3-of (p / phosphorylate-01))))
:ARG0-of (s / strike-01)
:location (c / cell-line :quant 2)
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod "4d"))))
# ::id pmid_1684_6534.143 ::date 2015-08-14T03:41:50 ::annotator SDL-AMR-09 ::preferred
# ::snt When lysates from both lines are exposed to film for the same length of time (overexposure masks the differences between BT.siLuc and BT.siMUC1 that are apparent in Figure 3a), it is clear that pAKT levels are much higher in BT-20 than in MDA-MB-468, despite lower total AKT expression.
# ::save-date Mon Aug 24, 2015 ::file pmid_1684_6534_143.txt
(c / clear-06
:ARG1 (h2 / high-02
:ARG1 (l2 / level
:quant-of (e / enzyme :name (n / name :op1 "AKT")
:ARG3-of (p / phosphorylate-01)))
:degree (m / more
:quant (m3 / much))
:location (c2 / cell-line :name (n2 / name :op1 "BT-20"))
:compared-to (c3 / cell-line :name (n3 / name :op1 "MDA-MB-468")))
:time (e3 / expose-01
:ARG1 (l3 / lysate
:source (a / and
:op1 c2
:op2 c3))
:ARG2 (f / film)
:duration (s / same-01)
:ARG1-of (m4 / mean-01
:ARG2 (m5 / mask-01
:ARG0 (o / overexpose-00
:ARG1 l3)
:ARG1 (d / differ-02
:ARG1 (c4 / cell-line :name (n4 / name :op1 "BT.siLuc"))
:ARG2 (c5 / cell-line :name (n5 / name :op1 "BT.siMUC1"))
:ARG1-of (a2 / appear-02
:medium (f2 / figure :mod "3a"))))))
:concession (e2 / express-03
:ARG2 e
:degree (t / total)
:ARG1-of (l / low-04
:degree (m2 / more))))
# ::id pmid_1684_6534.144 ::date 2015-08-14T00:41:43 ::annotator SDL-AMR-09 ::preferred
# ::snt This difference in AKT activation between MDA-MB-468 and BT-20 likely contributes to the disparity in their sensitivity to the increased apoptosis expected with loss of MUC1.
# ::save-date Mon Aug 24, 2015 ::file pmid_1684_6534_144.txt
(l / likely-01
:ARG1 (c / contribute-01
:ARG0 (d / differ-02
:ARG1 (c3 / cell-line :name (n2 / name :op1 "MDA-MB-468"))
:ARG2 (c2 / cell-line :name (n3 / name :op1 "BT-20"))
:ARG3 (a / activate-01
:ARG1 (e / enzyme :name (n / name :op1 "AKT")))
:mod (t / this))
:ARG2 (d2 / disparity
:domain (s / sensitive-03
:ARG0 (a3 / and
:op1 c3
:op2 c2)
:ARG1 (a2 / apoptosis
:ARG1-of (i / increase-01)
:ARG1-of (e2 / expect-01
:time (l2 / lose-02
:ARG1 (p / protein :name (n4 / name :op1 "MUC1")))))))))
# ::id pmid_1684_6534.145 ::date 2015-08-14T01:34:31 ::annotator SDL-AMR-09 ::preferred
# ::snt MUC1 siRNA alters proliferation and invasion
# ::save-date Wed Aug 19, 2015 ::file pmid_1684_6534_145.txt
(a / alter-01
:ARG0 (n3 / nucleic-acid :name (n / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (p2 / protein :name (n2 / name :op1 "MUC1"))))
:ARG1 (a2 / and
:op1 (p / proliferate-01)
:op2 (i / invade-01)))
# ::id pmid_1684_6534.146 ::date 2015-08-14T01:40:06 ::annotator SDL-AMR-09 ::preferred
# ::snt As MUC1 is involved in apoptosis, we next analyzed its effects on proliferation.
# ::save-date Wed Aug 19, 2015 ::file pmid_1684_6534_146.txt
(c / cause-01
:ARG0 (i / involve-01
:ARG1 (p2 / protein :name (n2 / name :op1 "MUC1"))
:ARG2 (a3 / apoptosis))
:ARG1 (a / analyze-01
:ARG0 (w / we)
:ARG1 (a2 / affect-01
:ARG0 p2
:ARG1 (p / proliferate-01))
:time (n / next)))
# ::id pmid_1684_6534.147 ::date 2015-08-14T01:43:41 ::annotator SDL-AMR-09 ::preferred
# ::snt BrdU and [3H]thymidine incorporation were used to analyze proliferation after MUC1 siRNA.
# ::save-date Wed Aug 19, 2015 ::file pmid_1684_6534_147.txt
(u / use-01
:ARG1 (a / and
:op1 (i / incorporate-02
:ARG1 (s2 / small-molecule :name (n / name :op1 "BrdU")))
:op2 (i2 / incorporate-02
:ARG1 (s / small-molecule :name (n2 / name :op1 "3H-thymidine"))))
:ARG2 (a2 / analyze-01
:ARG1 (p / proliferate-01))
:time (a3 / after
:op1 (n5 / nucleic-acid :name (n3 / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (p3 / protein :name (n4 / name :op1 "MUC1"))))))
# ::id pmid_1684_6534.148 ::date 2015-08-15T12:22:08 ::annotator SDL-AMR-09 ::preferred
# ::snt 468.siMUC1 cells show a significant decrease in [3H]thymidine incorporation compared to 468.siLuc, while intriguingly, BT.siMUC1 cells show a significant increase in proliferation (Figure 5a).
# ::save-date Wed Aug 19, 2015 ::file pmid_1684_6534_148.txt
(c / contrast-01
:ARG1 (s / show-01
:ARG0 (c3 / cell-line :name (n / name :op1 "468.siMUC1"))
:ARG1 (d2 / decrease-01
:ARG1 (i / incorporate-02
:ARG1 (s5 / small-molecule :name (n3 / name :op1 "3H-thymidine")))
:ARG1-of (s3 / significant-02))
:compared-to (s2 / show-01
:ARG0 (c2 / cell-line :name (n2 / name :op1 "468.siLuc"))))
:ARG2 (s4 / show-01
:ARG0 (c4 / cell-line :name (n4 / name :op1 "BT.siMUC1"))
:ARG1 (i2 / increase-01
:ARG1 (p / proliferate-01)
:ARG1-of s3)
:ARG0-of (i3 / intrigue-01))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "5a")))
# ::id pmid_1684_6534.149 ::date 2015-08-15T11:58:09 ::annotator SDL-AMR-09 ::preferred
# ::snt Growth curves mirror these results, as do experiments with the two independent MUC1 siRNA oligonucleotides (data not shown).
# ::save-date Mon Aug 24, 2015 ::file pmid_1684_6534_149.txt
(m / mirror-01
:ARG1 (t / thing
:ARG2-of (r / result-01)
:mod (t2 / this))
:ARG2 (c / curve-01
:ARG1 (g / grow-01))
:ARG1-of (r3 / resemble-01
:ARG2 (m2 / mirror-01
:ARG2 (e2 / experiment-01
:ARG1 (o / oligonucleotide :quant 2
:mod (n3 / nucleic-acid :name (n2 / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (p / protein :name (n / name :op1 "MUC1"))))
:ARG0-of (d / depend-01 :polarity -)))))
:ARG1-of (d2 / describe-01
:ARG0 (d3 / data
:ARG1-of (s / show-01 :polarity -))))
# ::id pmid_1684_6534.150 ::date 2015-08-15T12:03:35 ::annotator SDL-AMR-09 ::preferred
# ::snt Note that these assays require trypsinizing cells 24 hours post-transfection; therefore, the results in the MDA-MB-468 line could stem from the changes in apoptosis described in the previous section, rather than a true effect on proliferation.
# ::save-date Mon Aug 24, 2015 ::file pmid_1684_6534_150.txt
(m / multi-sentence
:snt1 (n / note-01
:ARG1 (r2 / require-01
:ARG0 (a3 / assay-01
:mod (t4 / this))
:ARG1 (t5 / trypsinize-00
:ARG1 (c4 / cell)
:time (a4 / after
:op1 (t6 / transfect-01)
:quant (t / temporal-quantity :quant 24
:unit (h / hour))))))
:snt2 (c / cause-01
:ARG1 (p2 / possible-01
:ARG1 (i / instead-of-91
:ARG1 (s / stem-01
:ARG1 (t2 / thing
:ARG2-of (r / result-01)
:location (c3 / cell-line :name (n2 / name :op1 "MDA-MB-468")))
:ARG2 (c2 / change-01
:ARG1 (a2 / apoptosis)
:ARG1-of (d / describe-01
:ARG0 (s2 / section
:mod (p4 / previous)))))
:ARG2 (a / affect-01
:ARG0 t2
:ARG1 (p3 / proliferate-01)
:ARG1-of (t3 / true-01))))))
# ::id pmid_1684_6534.151 ::date 2015-08-15T11:48:01 ::annotator SDL-AMR-09 ::preferred
# ::snt To control for this, we incubated non-trypsinized, siRNA-transfected cells at similar confluence with BrdU to measure incorporation.
# ::save-date Wed Aug 19, 2015 ::file pmid_1684_6534_151.txt
(i / incubate-01
:ARG0 (w / we)
:ARG1 (c / cell
:ARG1-of (t / transfect-01
:ARG2 (n3 / nucleic-acid :name (n / name :op1 "siRNA")))
:ARG1-of (t2 / trypsinize-00 :polarity -))
:ARG3 (c2 / confluence
:ARG1-of (r / resemble-01
:ARG2 (c3 / confluence
:mod (s / small-molecule :name (n2 / name :op1 "BrdU")))))
:ARG4 (m / measure-01
:ARG0 w
:ARG1 (i2 / incorporate-02))
:purpose (c4 / control-01
:ARG0 w
:ARG1 (t3 / this)))
# ::id pmid_1684_6534.152 ::date 2015-08-15T11:57:15 ::annotator SDL-AMR-09 ::preferred
# ::snt The 'clumped' profile of cells (contrast to Figure 4b) is likely a result of the acid denaturation (recommended by the antibody manufacturer), as it occurs uniformly in these experiments.
# ::save-date Sun Aug 16, 2015 ::file pmid_1684_6534_152.txt
(c2 / cause-01
:ARG0 (u / uniform-02
:ARG1 p
:location (t / thing
:ARG1-of (e / experiment-01)
:mod (t2 / this)))
:ARG1 (l / likely-01
:ARG1 (r / result-01
:ARG1 (n / natural-02 :polarity -
:ARG1 (a / acid)
:ARG1-of (r2 / recommend-01
:ARG0 (t3 / thing
:ARG0-of (m / manufacture-01
:ARG1 (a2 / antibody)))))
:ARG2 (p / profile-01
:ARG1 (c3 / cell)
:ARG1-of (c4 / clump-02)))
:ARG1-of (c / contrast-01
:ARG2 (f / figure :mod "4b"))))
# ::id pmid_1684_6534.153 ::date 2015-08-16T10:55:53 ::annotator SDL-AMR-09 ::preferred
# ::snt BrdU incorporation (Figure 5b) confirms that the [3H]thymidine results are not solely due to alterations in apoptosis, as 468.siMUC1 cells incorporate less BrdU than 468.siLuc; once again, BT.siMUC1 cells show increased proliferation over BT.siLuc.
# ::save-date Thu Nov 19, 2015 ::file pmid_1684_6534_153.txt
(m / multi-sentence
:snt2 (s / show-01
:ARG0 (c / cell-line :name (n / name :op1 "BT.siMUC1"))
:ARG1 (i / increase-01
:ARG1 (p / proliferate-01
:compared-to (c2 / cell-line :name (n2 / name :op1 "BT.siLuc"))))
:mod (a / again
:mod (o / once)))
:snt1 (c3 / confirm-01
:ARG0 (i2 / incorporate-02
:ARG1 (s4 / small-molecule :name (n3 / name :op1 "BrdU"))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "5b")))
:ARG1 (c4 / cause-01 :polarity -
:ARG0 (a2 / alter-01
:ARG1 (a3 / apoptosis)
:mod (s2 / sole))
:ARG1 (r / result-01
:ARG1 (s3 / small-molecule :name (n4 / name :op1 "3H-thymidine")))
:ARG1-of (c5 / cause-01
:ARG0 (i3 / incorporate-02
:ARG0 (c6 / cell-line :name (n5 / name :op1 "468.siMUC1"))
:ARG1 s4
:degree (l / less)
:compared-to (i4 / incorporate-02
:ARG0 (c7 / cell-line :name (n6 / name :op1 "468.siLuc"))
:ARG1 s4))))))
# ::id pmid_1684_6534.154 ::date 2015-08-14T01:44:10 ::annotator SDL-AMR-09 ::preferred
# ::snt Given the role of MUC1 in adhesion, we examined whether MUC1 siRNA affects cellular invasion.
# ::save-date Wed Aug 19, 2015 ::file pmid_1684_6534_154.txt
(c / cause-01
:ARG0 (r / role
:poss (p / protein :name (n / name :op1 "MUC1"))
:purpose (a / adhere-01))
:ARG1 (e / examine-01
:ARG0 (w / we)
:ARG1 (a2 / affect-01 :mode interrogative
:ARG0 (n3 / nucleic-acid :name (n2 / name :op1 "siRNA")
:ARG0-of (e2 / encode-01
:ARG1 p))
:ARG1 (i / invade-01
:ARG1 (c2 / cell)))))
# ::id pmid_1684_6534.155 ::date 2015-08-14T01:47:01 ::annotator SDL-AMR-09 ::preferred
# ::snt In transwell assays, BT-20 cells invaded poorly, regardless of the siRNA used (data not shown).
# ::save-date Thu Jan 7, 2016 ::file pmid_1684_6534_155.txt
(i / invade-01
:ARG0 (c2 / cell-line :name (n2 / name :op1 "BT-20"))
:ARG1 (a / assay-01
:mod (t / transwell))
:manner (p / poor)
:ARG1-of (d / describe-01
:ARG0 (d2 / data
:ARG1-of (s / show-01 :polarity -)))
:ARG1-of (d3 / describe-01
:ARG0 (d4 / data
:ARG1-of (s2 / show-01 :polarity -)))
:ARG1-of (r / regardless-91
:ARG2 (n3 / nucleic-acid :name (n / name :op1 "siRNA")
:ARG1-of (u / use-01))))
# ::id pmid_1684_6534.156 ::date 2015-08-14T01:54:05 ::annotator SDL-AMR-09 ::preferred
# ::snt However, MDA-MB-468 cells invade more readily, and were analyzed on a panel of three different extracellular matrix proteins.
# ::save-date Wed Aug 19, 2015 ::file pmid_1684_6534_156.txt
(h / have-concession-91
:ARG1 (a / and
:op1 (i / invade-01
:ARG0 (c2 / cell-line :name (n / name :op1 "MDA-MB-468"))
:manner (r / ready-02
:degree (m / more)))
:op2 (a2 / analyze-01
:ARG1 c2
:location (p / panel
:consist-of (p2 / protein :quant 3
:ARG1-of (d / differ-02)
:mod (m2 / matrix
:mod (e / extracellular)))))))
# ::id pmid_1684_6534.157 ::date 2015-08-14T02:04:35 ::annotator SDL-AMR-09 ::preferred
# ::snt Interestingly, 468.siMUC1 cells display somewhat decreased invasion on collagen IV, laminin, and fibronectin matrices, and on a no-matrix control (Figure 5c), which is in agreement with the trend towards decreased metastasis observed in Muc1-/- × MMTV-PyV MT mice [8].
# ::save-date Fri Jan 15, 2016 ::file pmid_1684_6534_157.txt
(d / display-01
:ARG0 (c / cell-line :name (n / name :op1 "468.siMUC1"))
:ARG1 (i2 / invade-01
:ARG0 c
:ARG1 (a / and
:op1 (p4 / protein :name (n5 / name :op1 "collagen" :op2 "IV"))
:op2 (l / laminin)
:op3 (m / matrix
:mod (f / fibronectin))
:op4 (c3 / control-01
:ARG1 (m2 / matrix :polarity -)))
:ARG1-of (d2 / describe-01
:ARG0 (f2 / figure :mod "5c"))
:ARG1-of (d5 / decrease-01
:degree (s / somewhat)))
:ARG2-of (i / interest-01)
:ARG0-of (a2 / agree-01
:ARG2 (t / trend-01
:ARG1 (m3 / metastasis
:ARG1-of (d3 / decrease-01)
:ARG1-of (o / observe-01
:location (p2 / protein :name (n2 / name :op1 "Muc1")
:ARG2-of (m4 / mutate-01 :mod "-/-"))
:location (m5 / mouse
:mod (p3 / protein :name (n3 / name :op1 "PyV" :op2 "MT")
:mod (o2 / organism :name (n4 / name :op1 "MMTV"))))
:ARG1-of (d4 / describe-01
:ARG0 (p / publication
:ARG0-of (c4 / cite-01
:ARG1 8))))))))
# ::id pmid_1684_6534.158 ::date 2015-08-14T15:04:44 ::annotator SDL-AMR-09 ::preferred
# ::snt Transfection of MUC1 rescues the 468.siMUC1 phenotype
# ::save-date Wed Aug 19, 2015 ::file pmid_1684_6534_158.txt
(r / rescue-01
:ARG0 (t / transfect-01
:ARG1 (p2 / protein :name (n / name :op1 "MUC1")))
:ARG1 (p / phenotype
:mod (c / cell-line :name (n2 / name :op1 "468.siMUC1"))))
# ::id pmid_1684_6534.159 ::date 2015-08-14T15:07:41 ::annotator SDL-AMR-09 ::preferred
# ::snt To determine if the above effects are specific to MUC1, we created stable transfectants of the MDA-MB-468 line using empty vector (468.Neo) or a full-length MUC1 construct (468.MUC1Δ8) that is resistant to one of the independent MUC1-directed oligonucleotides ('882').
# ::save-date Wed Mar 2, 2016 ::file pmid_1684_6534_159.txt
(c / create-01
:ARG0 (w / we)
:ARG1 (t / transfect-01
:ARG1 (c2 / cell-line :name (n / name :op1 "MDA-MB-468"))
:ARG1-of (s2 / stable-02))
:ARG2 (o / or
:op1 (v / vector :name (n3 / name :op1 "468.Neo")
:ARG1-of (e / empty-02))
:op2 (c3 / construct-01
:ARG2 p2
:ARG1-of (m / mean-01
:ARG2 (c4 / cell-line :name (n4 / name :op1 "468.MUC1Δ8")))
:ARG0-of (r / resist-01
:ARG1 (o2 / oligonucleotide :mod 882
:ARG1-of (i / include-91
:ARG2 (o3 / oligonucleotide
:ARG1-of (d2 / direct-01
:ARG0 p2)
:ARG0-of (d3 / depend-01 :polarity -)))))
:ARG1-of (l / long-03
:mod (f / full))))
:purpose (d / determine-01
:ARG0 w
:ARG1 (s / specific-02 :mode interrogative
:ARG1 (a / affect-02
:mod (a2 / above))
:ARG2 (p2 / protein :name (n2 / name :op1 "MUC1")))))
# ::id pmid_1684_6534.160 ::date 2015-08-14T02:05:50 ::annotator SDL-AMR-09 ::preferred
# ::snt These cells were maintained in G418-containing medium to retain transgene selection.
# ::save-date Fri Feb 5, 2016 ::file pmid_1684_6534_160.txt
(m / maintain-01
:ARG1 (c / cell
:mod (t2 / this))
:purpose (r / retain-01
:ARG0 c
:ARG1 (s / select-01
:ARG1 (t / transgene)))
:location (m2 / medium
:ARG0-of (c2 / contain-01
:ARG1 (s2 / small-molecule :name (n / name :op1 "G418")))))
# ::id pmid_1684_6534.161 ::date 2015-08-14T02:09:30 ::annotator SDL-AMR-09 ::preferred
# ::snt As expected, 468.MUC1Δ8 cells show higher levels of both the MUC1 extracellular domain and the MUC1-CT than do 468.Neo (Figure 6a).
# ::save-date Sun Jan 17, 2016 ::file pmid_1684_6534_161.txt
(s3 / show-01
:ARG0 (c / cell-line :name (n2 / name :op1 "468.MUC1Δ8"))
:ARG1 (a2 / and
:op1 (l / level
:quant-of (p / protein-segment :name (n4 / name :op1 "MUC1")))
:op2 (l2 / level
:quant-of (p2 / protein-segment :name (n3 / name :op1 "MUC1-CT")))
:ARG1-of (h / high-02
:degree (m / more)
:compared-to c2)
:mod (d / domain
:mod (e2 / extracellular)))
:compared-to (c2 / cell-line :name (n / name :op1 "468.Neo"))
:ARG1-of (e / expect-01)
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod "6a")))
# ::id pmid_1684_6534.162 ::date 2015-08-14T12:30:40 ::annotator SDL-AMR-09 ::preferred
# ::snt Note that 468.Neo have MUC1 expression comparable to parental MDA-MB-468; the exposures in Figure 6a are lighter than those in Figure 1a, in order to clearly show the relative levels of MUC1 in the stable transfectants.
# ::save-date Mon Jan 4, 2016 ::file pmid_1684_6534_162.txt
(m / multi-sentence
:snt1 (n / note-01
:ARG1 (e3 / express-03
:ARG2 p2
:ARG3 (c2 / cell-line :name (n4 / name :op1 "468.Neo"))
:ARG1-of (c5 / comparable-03
:ARG2 (c3 / cell-line :name (n5 / name :op1 "MDA-MB-468")
:mod (p / parent)))))
:snt2 (l / light-06
:ARG1 (e / exposure
:medium (f / figure :mod "6a"))
:degree (m2 / more)
:compared-to (e2 / expose-01
:source (f2 / figure :mod "1a"))
:purpose (s / show-01
:ARG0 e
:ARG1 (l2 / level
:quant-of (p2 / protein :name (n2 / name :op1 "MUC1"))
:ARG1-of (r / relative-05))
:ARG1-of (c / clear-06)
:location (c4 / cell
:ARG1-of (s2 / stable-02)
:ARG1-of (t / transfect-01)))))
# ::id pmid_1684_6534.163 ::date 2015-08-16T04:01:17 ::annotator SDL-AMR-09 ::preferred
# ::snt After MUC1 siRNA, 468.MUC1Δ8 lose some MUC1 (likely endogenous protein, which is not siRNA-resistant) but retain high-level expression, while 468.Neo show a decrease in MUC1 levels similar to parental 468.siMUC1 cells (Figures 6a,b).
# ::save-date Sun Jan 17, 2016 ::file pmid_1684_6534_163.txt
(c / contrast-01
:ARG1 (c5 / contrast-01
:ARG1 (l / lose-02
:ARG0 (c2 / cell-line :name (n2 / name :op1 "468.MUC1Δ8"))
:ARG1 (p3 / protein :name (n3 / name :op1 "MUC1")
:mod (s2 / some)
:ARG1-of (m / mean-01
:ARG2 (l3 / likely-01
:ARG1 (p2 / protein
:mod (m2 / monocot)
:ARG0-of (r / resist-01 :polarity -
:ARG1 n6)))))
:ARG2 (r3 / retain-01
:ARG0 c2
:ARG1 (e / express-03)
:ARG1-of (h / high-02))
:time (a / after
:op1 (n6 / nucleic-acid :name (n / name :op1 "siRNA")
:ARG0-of (e2 / encode-01
:ARG1 p3)))))
:ARG2 (s / show-01
:ARG0 (c3 / cell-line :name (n4 / name :op1 "468.Neo"))
:ARG1 (d / decrease-01
:ARG1 (l2 / level
:quant-of p3)
:ARG1-of (r4 / resemble-01
:ARG2 (c4 / cell-line :name (n5 / name :op1 "468.siMUC1")
:mod (p / parent)))))
:ARG1-of (d2 / describe-01
:ARG0 (a2 / and
:op1 (f / figure :mod "6a")
:op2 (f2 / figure :mod "6b"))))
# ::id pmid_1684_6534.164 ::date 2015-08-15T13:15:30 ::annotator SDL-AMR-09 ::preferred
# ::snt The difference in the amount of MUC1 knockdown between 468.Neo and 468.MUC1Δ8 is highlighted by the purple shading in Figure 6b.
# ::save-date Wed Aug 19, 2015 ::file pmid_1684_6534_164.txt
(h / highlight-01
:ARG0 (s / shade-01
:ARG0 (p / purple))
:ARG1 (d / differ-02
:ARG1 (a / amount-01)
:ARG2 (c2 / cell-line :name (n3 / name :op1 "468.MUC1Δ8"))
:ARG3 (k / knock-down-02
:ARG1 (p2 / protein :name (n / name :op1 "MUC1")))
:ARG1 (c / cell-line :name (n2 / name :op1 "468.Neo")))
:medium (f / figure :mod "6b"))
# ::id pmid_1684_6534.165 ::date 2015-08-15T13:21:59 ::annotator SDL-AMR-09 ::preferred
# ::snt BrdU incorporation (Figure 6c) indicates that 468.Neo show decreased nucleotide incorporation after MUC1 siRNA compared to control (3.3% versus 25.0%, respectively); this is not seen in 468.MUC1Δ8 cells, which show similar levels of BrdU incorporation regardless of the siRNA used (21.5% for luciferase, 23.9% for MUC1).
# ::save-date Thu Jan 7, 2016 ::file pmid_1684_6534_165.txt
(m / multi-sentence
:snt1 (i / indicate-01
:ARG0 (i3 / incorporate-02
:ARG1 (s5 / small-molecule :name (n4 / name :op1 "BrdU")))
:ARG1 (s3 / show-01
:ARG0 (c2 / cell-line :name (n5 / name :op1 "468.Neo"))
:ARG1 (i4 / incorporate-02
:ARG1 (n6 / nucleotide)
:ARG1-of (d / decrease-01
:compared-to (c3 / control
:ARG1-of (m2 / mean-01
:ARG2 (v / versus
:op1 (p / percentage-entity :value 3.3)
:op2 (p2 / percentage-entity :value 25.0))))))
:time (a / after
:op1 (n10 / nucleic-acid :name (n7 / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (p7 / protein :name (n8 / name :op1 "MUC1"))))))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod "6c")))
:snt2 (s / see-01 :polarity -
:ARG1 (t / this)
:location (c / cell-line :name (n / name :op1 "468.MUC1Δ8")
:ARG0-of (s2 / show-01
:ARG1 (l / level
:ARG1-of (r2 / resemble-01)
:degree-of (i2 / incorporate-02
:ARG1 (s4 / small-molecule :name (n2 / name :op1 "BrdU"))))
:ARG1-of (r / regardless-91
:ARG2 (n11 / nucleic-acid :name (n3 / name :op1 "siRNA")
:ARG1-of (u / use-01)
:ARG1-of (m3 / mean-01
:ARG2 (a2 / and
:op1 (p3 / percentage-entity :value 21.5
:prep-for (l2 / luciferase))
:op2 (p4 / percentage-entity :value 23.9
:quant-of (p8 / protein :name (n9 / name :op1 "MUC1")))))))))))
# ::id pmid_1684_6534.166 ::date 2015-08-16T04:04:39 ::annotator SDL-AMR-09 ::preferred
# ::snt 468.Neo cells display a more dramatic decrease in BrdU incorporation after MUC1 siRNA than what is seen in parental 468.siMUC1 cells, which may reflect the additional stress of being maintained in G418-containing medium.
# ::save-date Sun Jan 17, 2016 ::file pmid_1684_6534_166.txt
(d / display-01
:ARG0 (c / cell-line :name (n5 / name :op1 "468.Neo"))
:ARG1 (d2 / decrease-01
:ARG1 (i / incorporate-02
:ARG1 (s3 / small-molecule :name (n / name :op1 "BrdU")))
:ARG2 (d3 / dramatic
:degree (m / more))
:compared-to (t / thing
:ARG1-of (s / see-01
:location (c2 / cell-line :name (n4 / name :op1 "468.siMUC1")
:mod (p2 / parent)))
:ARG1-of (r2 / reflect-01
:ARG2 (s2 / stress-01
:ARG0 (m2 / maintain-01
:location (m3 / medium
:ARG0-of (c3 / contain-01
:ARG1 (s4 / small-molecule :name (n6 / name :op1 "G418")))))
:mod (a2 / additional))
:ARG1-of (p / possible-01))))
:time (a / after
:op1 (n7 / nucleic-acid :name (n2 / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (p4 / protein :name (n3 / name :op1 "MUC1"))))))
# ::id pmid_1684_6534.167 ::date 2015-08-16T04:16:52 ::annotator SDL-AMR-09 ::preferred
# ::snt Similarly, analysis of apoptosis in trypsinized cells indicates that the increased apoptosis seen in parental 468.siMUC1 cells is also present in the 468.Neo line after MUC1 siRNA (Figure 6d; 43.6% in control versus 59.6% in MUC1 siRNA).
# ::save-date Sun Jan 17, 2016 ::file pmid_1684_6534_167.txt
(i / indicate-01
:ARG0 (a / analyze-01
:ARG1 (a2 / apoptosis
:ARG1-of (p5 / present-02
:ARG2 (c / cell
:ARG1-of (t / trypsinize-00)))))
:ARG1 (p6 / present-02
:ARG1 (a3 / apoptosis
:ARG1-of (s / see-01
:location (c2 / cell-line :name (n / name :op1 "468.siMUC1")
:mod (p3 / parent)))
:ARG1-of (i2 / increase-01))
:ARG2 (c3 / cell-line :name (n2 / name :op1 "468.Neo"))
:mod (a4 / also)
:time (a5 / after
:op1 n5)
:mod (c4 / control-01
:location (n5 / nucleic-acid :name (n3 / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (p4 / protein :name (n4 / name :op1 "MUC1")))))
:ARG1-of (m / mean-01
:ARG2 (p / percentage-entity :value 43.6
:compared-to (p2 / percentage-entity :value 59.6))))
:ARG1-of (r / resemble-01)
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "6d")))
# ::id pmid_1684_6534.168 ::date 2015-08-16T04:33:41 ::annotator SDL-AMR-09 ::preferred
# ::snt However, in 468.MUC1Δ8 cells, the level of apoptosis after luciferase siRNA (34.1%) is lower than that in 468.Neo cells; MUC1 siRNA increases the amount of apoptosis slightly (42.8%), restoring it to a level similar to that seen in luciferase siRNA-treated 468.Neo cells.
# ::save-date Mon Aug 24, 2015 ::file pmid_1684_6534_168.txt
(m2 / multi-sentence
:snt1 (h / have-concession-91
:ARG1 (l2 / low-04
:ARG1 (l3 / level
:quant-of (a / apoptosis)
:location (c2 / cell-line :name (n2 / name :op1 "468.MUC1Δ8"))
:ARG1-of (m3 / mean-01
:ARG2 (p / percentage-entity :value 34.1)))
:time (a2 / after
:op1 (n8 / nucleic-acid :name (n / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (l4 / luciferase))))
:compared-to (l5 / level
:quant-of a
:location (c4 / cell-line :name (n3 / name :op1 "468.Neo")))
:degree (m / more)))
:snt2 (i / increase-01
:ARG0 (n9 / nucleic-acid :name (n5 / name :op1 "siRNA")
:ARG0-of (e2 / encode-01
:ARG1 (p3 / protein :name (n4 / name :op1 "MUC1"))))
:ARG1 (a3 / amount
:quant-of (a4 / apoptosis)
:ARG1-of (m4 / mean-01
:ARG2 (p2 / percentage-entity :value 42.8)))
:ARG2 (s / slight)
:ARG0-of (r / restore-02
:ARG1 a3
:ARG2 (l / level
:ARG1-of (r4 / resemble-01
:ARG2 (l6 / level
:ARG1-of (s2 / see-01
:location (c3 / cell-line :name (n6 / name :op1 "468.Neo")
:ARG1-of (t / treat-04
:ARG2 (n10 / nucleic-acid :name (n7 / name :op1 "siRNA")
:ARG0-of (e3 / encode-01
:ARG1 (l7 / luciferase))))))))))))
# ::id pmid_1684_6534.169 ::date 2015-08-15T13:24:41 ::annotator SDL-AMR-09 ::preferred
# ::snt Together, these studies suggest that the above-described results are specific to MUC1, as stable transfection of an siRNA-resistant MUC1 rescues the phenotype seen in 468.siMUC1 cells.
# ::save-date Sun Jan 17, 2016 ::file pmid_1684_6534_169.txt
(s / suggest-01
:ARG0 (s7 / study-01
:mod (t3 / together)
:mod (t / this))
:ARG1 (c / cause-01
:ARG0 (r / rescue-01
:ARG0 (t4 / transfect-01
:ARG2 (p3 / protein :name (n2 / name :op1 "MUC1")
:ARG0-of (r2 / resist-01
:ARG1 (n5 / nucleic-acid :name (n3 / name :op1 "siRNA"))))
:ARG1-of (s6 / stable-03))
:ARG1 (p / phenotype
:ARG1-of (s5 / see-01
:location (c2 / cell-line :name (n4 / name :op1 "468.siMUC1")))))
:ARG1 (s3 / specific-02
:ARG1 (t2 / thing
:ARG2-of (r4 / result-01)
:ARG1-of (d / describe-01
:location (a / above)))
:ARG2 (p2 / protein :name (n / name :op1 "MUC1")))))
# ::id pmid_1901_8267.1 ::date 2015-07-09T12:02:58 ::annotator SDL-AMR-09 ::preferred
# ::snt KRAS or BRAF mutation status is a useful predictor of sensitivity to MEK inhibition in ovarian cancer (PMID:19018267)
# ::save-date Thu Dec 10, 2015 ::file pmid_1901_8267_1.txt
(u / useful-05
:ARG1 (o / or
:op1 (s / status
:mod (m / mutate-01
:ARG1 (g2 / gene :name (n4 / name :op1 "KRAS"))))
:op2 (s2 / status
:mod (m2 / mutate-01
:ARG1 (g / gene :name (n3 / name :op1 "BRAF")))))
:ARG2 (p / predict-01
:ARG0 o
:ARG1 (s3 / sensitive-03
:ARG1 (i / inhibit-01
:ARG1 (e / enzyme :name (n / name :op1 "MEK"))
:location (d / disease :wiki "Ovarian_cancer" :name (n2 / name :op1 "ovarian" :op2 "cancer")))))
:ARG1-of (d2 / describe-01
:ARG0 (p2 / publication-91
:ARG8 "PMID19018267")))
# ::id pmid_1901_8267.119 ::date 2015-07-09T12:47:35 ::annotator SDL-AMR-09 ::preferred
# ::snt Results
# ::save-date Wed Jul 22, 2015 ::file pmid_1901_8267_119.txt
(t / thing
:ARG2-of (r / result-01))
# ::id pmid_1901_8267.120 ::date 2015-07-09T12:48:36 ::annotator SDL-AMR-09 ::preferred
# ::snt Identification of KRAS and BRAF mutations
# ::save-date Wed Jul 22, 2015 ::file pmid_1901_8267_120.txt
(i / identify-01
:ARG1 (a2 / and
:op1 (m2 / mutate-01
:ARG1 (g / gene :name (n / name :op1 "KRAS")))
:op2 (m / mutate-01
:ARG1 (g2 / gene :name (n2 / name :op1 "BRAF")))))
# ::id pmid_1901_8267.121 ::date 2015-07-09T12:49:58 ::annotator SDL-AMR-09 ::preferred
# ::snt The mutational status of KRAS and BRAF in all 45 ovarian carcinomas is summarised in Table 1.
# ::save-date Wed Jul 22, 2015 ::file pmid_1901_8267_121.txt
(s / summarize-01
:ARG1 (s2 / status
:mod (m / mutate-01)
:poss (a / and
:op1 (g / gene :name (n / name :op1 "KRAS"))
:op2 (g2 / gene :name (n2 / name :op1 "BRAF")))
:location (c / carcinoma :quant 45
:mod (o / ovary)
:mod (a2 / all)))
:location (t / table :mod 1))
# ::id pmid_1901_8267.122 ::date 2015-07-09T13:02:24 ::annotator SDL-AMR-09 ::preferred
# ::snt Somatic mutations of KRAS were identified in 8 (13.7%) out of 58 ovarian carcinomas.
# ::save-date Sat Jul 11, 2015 ::file pmid_1901_8267_122.txt
(i / identify-01
:ARG1 (m / mutate-01
:ARG1 (g / gene :name (n / name :op1 "KRAS"))
:mod (s / somatic))
:location (c / carcinoma :quant 8
:ARG1-of (i2 / include-91
:ARG2 (c2 / carcinoma :quant 58
:mod (o / ovary))
:ARG3 (p / percentage-entity :value 13.7))))
# ::id pmid_1901_8267.123 ::date 2015-07-09T13:06:40 ::annotator SDL-AMR-09 ::preferred
# ::snt In contrast, somatic mutations of BRAF were identified in 5 (8.6%) out of 58 ovarian carcinomas.
# ::save-date Thu Jul 9, 2015 ::file pmid_1901_8267_123.txt
(c / contrast-01
:ARG2 (i / identify-01
:ARG1 (m / mutate-01
:ARG1 (g / gene :name (n / name :op1 "BRAF"))
:mod (s / somatic))
:location (c2 / carcinoma :quant 5
:ARG1-of (i2 / include-91
:ARG2 (c3 / carcinoma :quant 58
:mod (o / ovary))
:ARG3 (p / percentage-entity :value 8.6)))))
# ::id pmid_1901_8267.124 ::date 2015-07-09T13:09:29 ::annotator SDL-AMR-09 ::preferred
# ::snt Somatic mutations of either KRAS or BRAF were identified in 12 (20.6%) out of 58 ovarian carcinomas.
# ::save-date Thu Jul 9, 2015 ::file pmid_1901_8267_124.txt
(i / identify-01
:ARG1 (m / mutate-01
:ARG1 (o / or
:op1 (g / gene :name (n / name :op1 "KRAS"))
:op2 (g2 / gene :name (n2 / name :op1 "BRAF")))
:mod (s / somatic))
:location (c / carcinoma :quant 12
:ARG1-of (i2 / include-91
:ARG2 (c2 / carcinoma :quant 58
:mod (o2 / ovary))
:ARG3 (p / percentage-entity :value 20.6))))
# ::id pmid_1901_8267.125 ::date 2015-07-09T13:13:40 ::annotator SDL-AMR-09 ::preferred
# ::snt Most KRAS mutations were located at codon 12 and all BRAF mutations at codon 600.
# ::save-date Thu Jul 9, 2015 ::file pmid_1901_8267_125.txt
(a / and
:op1 (b / be-located-at-91
:ARG1 (m / mutate-01
:ARG1 (g / gene :name (n / name :op1 "KRAS"))
:mod (m2 / most))
:ARG2 (c / codon :mod 12))
:op2 (b2 / be-located-at-91
:ARG1 (m3 / mutate-01
:ARG1 (g2 / gene :name (n2 / name :op1 "BRAF"))
:mod (a2 / all))
:ARG2 (c2 / codon :mod 600)))
# ::id pmid_1901_8267.126 ::date 2015-07-09T13:19:54 ::annotator SDL-AMR-09 ::preferred
# ::snt Both of these codons are mutation hot spots.
# ::save-date Mon Dec 21, 2015 ::file pmid_1901_8267_126.txt
(s / spot
:ARG1-of (h / hot-03)
:location-of (m / mutate-01)
:domain (c / codon
:mod (t / this)
:mod (b / both)))
# ::id pmid_1901_8267.127 ::date 2015-07-09T13:22:58 ::annotator SDL-AMR-09 ::preferred
# ::snt Interestingly, simultaneous mutations of KRAS and BRAF did not occur in the tested ovarian carcinomas with the exception of one mucinous case.
# ::save-date Sat Jan 30, 2016 ::file pmid_1901_8267_127.txt
(b / be-located-at-91 :polarity -
:ARG1 (a / and
:op1 (m / mutate-01
:ARG1 (g / gene :name (n / name :op1 "KRAS")))
:op2 (m2 / mutate-01
:ARG1 (g2 / gene :name (n2 / name :op1 "BRAF")))
:mod (s / simultaneous))
:ARG2 (c / carcinoma
:ARG1-of (t / test-01)
:mod (o / ovary))
:ARG2-of (e / except-01
:ARG1 (c2 / case-04
:ARG1 (m3 / mucin)))
:ARG2-of (i / interest-01))
# ::id pmid_1901_8267.128 ::date 2015-07-09T13:53:31 ::annotator SDL-AMR-09 ::preferred
# ::snt A panel of ovarian cancer cell lines and primary cultures was first analysed for tumour mutation status in the KRAS and BRAF genes.
# ::save-date Wed Dec 9, 2015 ::file pmid_1901_8267_128.txt
(a / analyze-01
:ARG1 (p / panel
:consist-of (a2 / and
:op1 (c / cell-line
:mod (d / disease :wiki "Ovarian_cancer" :name (n / name :op1 "ovarian" :op2 "cancer")))
:op2 (t2 / thing
:ARG1-of (c3 / culture-01)
:mod (p2 / primary))))
:time (f / first)
:purpose (s / status
:mod (m / mutate-01
:ARG1 (t / tumor))
:location (a3 / and
:op1 (g / gene :name (n2 / name :op1 "KRAS"))
:op2 (g2 / gene :name (n3 / name :op1 "BRAF")))))
# ::id pmid_1901_8267.129 ::date 2015-07-09T14:01:29 ::annotator SDL-AMR-09 ::preferred
# ::snt As shown in Figure 1, three ovarian cancer cell lines harboured either KRAS or BRAF mutations.
# ::save-date Wed Dec 9, 2015 ::file pmid_1901_8267_129.txt
(h / harbor-01
:ARG0 (c / cell-line :quant 3
:mod (d / disease :wiki "Ovarian_cancer" :name (n / name :op1 "ovarian" :op2 "cancer")))
:ARG1 (o2 / or
:op1 (m / mutate-01
:ARG1 (g / gene :name (n2 / name :op1 "KRAS")))
:op2 (m2 / mutate-01
:ARG1 (g2 / gene :name (n3 / name :op1 "BRAF"))))
:ARG1-of (s / show-01
:ARG0 (f / figure :mod 1)))
# ::id pmid_1901_8267.130 ::date 2015-07-09T14:06:45 ::annotator SDL-AMR-09 ::preferred
# ::snt The frequency of either KRAS or BRAF mutations in conventional serous high-grade carcinomas (4.0% : 1/25) was significantly lower than in the other histological type (32.2% : 10/31).
# ::save-date Mon Dec 21, 2015 ::file pmid_1901_8267_130.txt
(l2 / low-04
:ARG1 (o3 / or
:op1 (h3 / have-frequency-91
:ARG1 (m2 / mutate-01
:ARG1 (g / gene :name (n / name :op1 "KRAS"))))
:op2 (h4 / have-frequency-91
:ARG1 (m3 / mutate-01
:ARG1 (g2 / gene :name (n2 / name :op1 "BRAF"))))
:location (c / carcinoma :quant 1
:ARG1-of (i / include-91
:ARG2 (c3 / carcinoma :quant 25
:mod (g3 / grade
:ARG1-of (h / high-02))
:mod (s / serum
:mod (c2 / conventional)))
:ARG3 (p / percentage-entity :value 4)))
:compared-to (t / type :quant 10
:ARG1-of (i2 / include-91
:ARG2 (t2 / type :quant 31
:mod (h2 / histology)
:mod (o2 / other))
:ARG3 (p2 / percentage-entity :value 32.2))))
:degree (m / more))
# ::id pmid_1901_8267.131 ::date 2015-07-09T14:20:08 ::annotator SDL-AMR-09 ::preferred
# ::snt Relationship between KRAS/BRAF mutations and p-ERK1/2 expression or clinicopathological factors
# ::save-date Wed Jul 22, 2015 ::file pmid_1901_8267_131.txt
(r / relation-03
:ARG0 (m / mutate-01
:ARG1 (s / slash
:op1 (g / gene :name (n / name :op1 "KRAS"))
:op2 (g2 / gene :name (n2 / name :op1 "BRAF"))))
:ARG2 (o / or
:op1 (e / express-03
:ARG2 (e2 / enzyme :name (n3 / name :op1 "ERK1/2")
:ARG3-of (p / phosphorylate-01)))
:op2 (f / factor
:mod (c / clinicopathologic))))
# ::id pmid_1901_8267.132 ::date 2015-07-09T14:24:53 ::annotator SDL-AMR-09 ::preferred
# ::snt The immunoreactivity of active p-ERK1/2 was detected in both the nucleus and the cytoplasm of the tumour cells (Figure 2).
# ::save-date Wed Nov 11, 2015 ::file pmid_1901_8267_132.txt
(d / detect-01
:ARG1 (i / immunoreact-00
:ARG1 (e / enzyme :name (n / name :op1 "ERK1/2")
:ARG3-of (p / phosphorylate-01)
:ARG1-of (a / activate-01)))
:location (a2 / and
:op1 (n2 / nucleus
:part-of (c / cell
:mod (t / tumor)))
:op2 (c2 / cytoplasm
:part-of c))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod 2)))
# ::id pmid_1901_8267.133 ::date 2015-07-09T14:28:12 ::annotator SDL-AMR-09 ::preferred
# ::snt This is consistent with an earlier report (Mizumoto et al, 2007).
# ::save-date Thu Jul 9, 2015 ::file pmid_1901_8267_133.txt
(c / consistent-01
:ARG1 (t / this)
:ARG2 (r / report-01
:time (e2 / early
:degree (m / more)))
:ARG1-of (d / describe-01
:ARG0 (p / publication-91
:ARG0 (a / and
:op1 (p2 / person :name (n / name :op1 "Mizumoto"))
:op2 (p3 / person
:mod (o / other)))
:time (d2 / date-entity :year 2007))))
# ::id pmid_1901_8267.134 ::date 2015-07-10T11:50:58 ::annotator SDL-AMR-09 ::preferred
# ::snt Positive active p-ERK1/2 was identified in 27 (46.6%) out of 58 ovarian carcinomas.
# ::save-date Wed Jul 22, 2015 ::file pmid_1901_8267_134.txt
(i / identify-01
:ARG1 (e / enzyme :name (n / name :op1 "ERK1/2")
:ARG3-of (p / phosphorylate-01)
:ARG1-of (a / activate-01)
:mod (p2 / positive))
:location (c / carcinoma :quant 27
:ARG1-of (i2 / include-91
:ARG2 (c2 / carcinoma :quant 58
:mod (o / ovary))
:ARG3 (p3 / percentage-entity :value 46.6))))
# ::id pmid_1901_8267.135 ::date 2015-07-10T11:53:27 ::annotator SDL-AMR-09 ::preferred
# ::snt The patients were stratified into two groups depending on the mutational status of KRAS/BRAF.
# ::save-date Thu Dec 10, 2015 ::file pmid_1901_8267_135.txt
(s / stratify-01
:ARG1 (p2 / person
:ARG0-of (h / have-rel-role-91
:ARG2 (p / patient)))
:manner (g / group :quant 2)
:ARG0-of (d / depend-01
:ARG1 (s2 / status
:mod (m / mutate-01)
:poss (s3 / slash
:op1 (g2 / gene :name (n / name :op1 "KRAS"))
:op2 (g3 / gene :name (n2 / name :op1 "BRAF"))))))
# ::id pmid_1901_8267.136 ::date 2015-07-10T11:56:44 ::annotator SDL-AMR-09 ::preferred
# ::snt The relationships between KRAS/BRAF mutations and clinicopathological factors, including p-ERK1/2 expression are shown in Table 2.
# ::save-date Wed Jul 22, 2015 ::file pmid_1901_8267_136.txt
(s / show-01
:ARG0 (t / table :mod 2)
:ARG1 (a2 / and
:op1 (r / relation-03
:ARG0 (m / mutate-01
:ARG1 (s2 / slash
:op1 (g / gene :name (n / name :op1 "KRAS"))
:op2 (g2 / gene :name (n2 / name :op1 "BRAF"))))
:ARG2 (f / factor
:mod (c / clinicopathologic)
:ARG2-of (i / include-01
:ARG1 (e / express-03
:ARG2 (e2 / enzyme :name (n3 / name :op1 "ERK1/2")
:ARG3-of (p / phosphorylate-01))))))))
# ::id pmid_1901_8267.137 ::date 2015-07-10T12:02:59 ::annotator SDL-AMR-09 ::preferred
# ::snt There was no significant correlation between KRAS/BRAF mutations and the patient's age.
# ::save-date Fri Dec 18, 2015 ::file pmid_1901_8267_137.txt
(c / correlate-01 :polarity -
:ARG1 (m / mutate-01
:ARG1 (s2 / slash
:op1 (g / gene :name (n / name :op1 "KRAS"))
:op2 (g2 / gene :name (n2 / name :op1 "BRAF"))))
:ARG2 (a / age-01
:ARG1 (p2 / person
:ARG0-of (h / have-rel-role-91
:ARG2 (p / patient))))
:ARG1-of (s / significant-02))
# ::id pmid_1901_8267.138 ::date 2015-07-10T12:05:31 ::annotator SDL-AMR-09 ::preferred
# ::snt The results in Table 2 show that KRAS/BRAF mutation is correlated significantly with FIGO stage I, II (P<0.001), and p-ERK1/2 (P<0.001).
# ::save-date Wed Dec 30, 2015 ::file pmid_1901_8267_138.txt
(s / show-01
:ARG0 (t2 / thing
:ARG2-of (r / result-01
:location (t / table :mod 2)))
:ARG1 (a / and
:op1 (c / correlate-01
:ARG1 (m / mutate-01
:ARG1 (s5 / slash
:op1 (g / gene :name (n / name :op1 "KRAS"))
:op2 (g2 / gene :name (n2 / name :op1 "BRAF"))))
:ARG2 (a3 / and
:op1 (s3 / stage :mod "I")
:op2 (s4 / stage :mod "II")
:mod (o / organization :name (n3 / name :op1 "FIGO")))
:ARG1-of (s6 / statistical-test-91
:ARG2 (l / less-than :op1 0.001)))
:op2 (c2 / correlate-01
:ARG1 m
:ARG2 (e / enzyme :name (n4 / name :op1 "ERK1/2")
:ARG3-of (p2 / phosphorylate-01))
:ARG1-of (s7 / statistical-test-91
:ARG2 l))
:ARG1-of (s2 / significant-02)))
# ::id pmid_1901_8267.139 ::date 2015-07-10T12:14:33 ::annotator SDL-AMR-09 ::preferred
# ::snt In addition, there were significant correlations between KRAS/BRAF mutations and pathological grade (P=0.004), and histological subtype (P=0.014).
# ::save-date Tue Dec 15, 2015 ::file pmid_1901_8267_139.txt
(a / and
:op2 (a2 / and
:op1 (c / correlate-01
:ARG1 (m / mutate-01
:ARG1 (s3 / slash
:op1 (g / gene :name (n / name :op1 "KRAS"))
:op2 (g2 / gene :name (n2 / name :op1 "BRAF"))))
:ARG2 (g3 / grade
:mod (p / pathology))
:ARG1-of (s4 / statistical-test-91
:ARG2 0.004))
:op2 (c2 / correlate-01
:ARG1 m
:ARG2 (s2 / subtype
:mod (h / histology))
:ARG1-of (s5 / statistical-test-91
:ARG2 0.014))
:ARG1-of (s / significant-02)))
# ::id pmid_1901_8267.140 ::date 2015-07-10T12:20:39 ::annotator SDL-AMR-09 ::preferred
# ::snt Effect of KRAS/BRAF mutations or p-ERK1/2 on the prognosis of ovarian carcinomas
# ::save-date Wed Jul 22, 2015 ::file pmid_1901_8267_140.txt
(a / affect-01
:ARG0 (o / or
:op1 (m / mutate-01
:ARG1 (s / slash
:op1 (g / gene :name (n / name :op1 "KRAS"))
:op2 (g2 / gene :name (n2 / name :op1 "BRAF"))))
:op2 (e / enzyme :name (n3 / name :op1 "ERK1/2")
:ARG3-of (p2 / phosphorylate-01)))
:ARG1 (p / prognosis
:mod (c / carcinoma
:mod (o2 / ovary))))
# ::id pmid_1901_8267.141 ::date 2015-07-10T12:28:43 ::annotator SDL-AMR-09 ::preferred
# ::snt Next, we examined the prognostic effect of KRAS/BRAF mutations and p-ERK1/2 expression.
# ::save-date Wed Jul 22, 2015 ::file pmid_1901_8267_141.txt
(e / examine-01
:ARG0 (w / we)
:ARG1 (a / affect-01
:ARG0 (a2 / and
:op1 (m / mutate-01
:ARG1 (s / slash
:op1 (g / gene :name (n / name :op1 "KRAS"))
:op2 (g2 / gene :name (n2 / name :op1 "BRAF"))))
:op2 (e2 / express-03
:ARG2 (e3 / enzyme :name (n3 / name :op1 "ERK1/2")
:ARG3-of (p2 / phosphorylate-01))))
:mod (p / prognostic))
:time (n4 / next))
# ::id pmid_1901_8267.142 ::date 2015-07-10T12:37:05 ::annotator SDL-AMR-09 ::preferred
# ::snt Out of the 58 samples that we examined, 45 were available for prognostic analysis.
# ::save-date Sun Dec 20, 2015 ::file pmid_1901_8267_142.txt
(a / available-02
:ARG1 (a2 / analyze-01
:mod (p / prognostic))
:ARG2 (t / thing :quant 45
:ARG1-of (i / include-91
:ARG2 (t2 / thing :quant 58
:ARG2-of (s2 / sample-01)
:ARG1-of (e / examine-01
:ARG0 (w / we))))))
# ::id pmid_1901_8267.143 ::date 2015-07-10T12:40:50 ::annotator SDL-AMR-09 ::preferred
# ::snt Kaplan–Meier estimates of overall survival are plotted in Figure 3.
# ::save-date Fri Dec 18, 2015 ::file pmid_1901_8267_143.txt
(p / plot-01
:ARG1 (e / estimate-01
:ARG1 (s / survive-01
:mod (o / overall))
:instrument (t / thing :name (n / name :op1 "Kaplan–Meier")))
:medium (f / figure :mod 3))
# ::id pmid_1901_8267.144 ::date 2015-07-10T12:45:52 ::annotator SDL-AMR-09 ::preferred
# ::snt There was no significant relationship between KRAS/BRAF mutations or p-ERK1/2 expression and overall survival in patients with ovarian carcinoma (P=0.2460, P=0.9339, respectively).
# ::save-date Tue Dec 15, 2015 ::file pmid_1901_8267_144.txt
(r / relation-03 :polarity -
:ARG0 (o4 / or
:op1 (m / mutate-01
:ARG1 (s3 / slash
:op1 (g / gene :name (n / name :op1 "KRAS"))
:op2 (g2 / gene :name (n2 / name :op1 "BRAF"))))
:op2 (e / express-03
:ARG2 (e2 / enzyme :name (n3 / name :op1 "ERK1/2")
:ARG3-of (p / phosphorylate-01)))
:mod (r2 / respective)
:ARG1-of (s4 / statistical-test-91
:ARG2 0.2460))
:ARG2 (s2 / survive-01
:ARG0 (p5 / person
:ARG0-of (h / have-rel-role-91
:ARG2 (p2 / patient))
:ARG0-of (h2 / have-03
:ARG1 (c / carcinoma
:mod (o3 / ovary))))
:mod (o2 / overall)
:ARG1-of (s5 / statistical-test-91
:ARG2 0.9339))
:ARG1-of (s / significant-02))
# ::id pmid_1901_8267.145 ::date 2015-07-10T12:52:48 ::annotator SDL-AMR-09 ::preferred
# ::snt Univariate analysis showed that only FIGO stage III, IV affected the overall survival of patients with ovarian carcinoma significantly(P=0.014).
# ::save-date Tue Dec 15, 2015 ::file pmid_1901_8267_145.txt
(s / show-01
:ARG0 (a / analyze-01
:mod (u / univariate))
:ARG1 (a2 / affect-01
:ARG0 (a3 / and
:op1 (s2 / stage :mod "III")
:op2 (s3 / stage :mod "IV")
:mod (o / organization :name (n / name :op1 "FIGO"))
:mod (o4 / only))
:ARG1 (s4 / survive-01
:ARG0 (p3 / person
:ARG0-of (h2 / have-rel-role-91
:ARG2 (p / patient))
:ARG0-of (h / have-03
:ARG1 (c / carcinoma
:mod (o3 / ovary))))
:mod (o2 / overall))
:ARG1-of (s5 / significant-02)
:ARG1-of (s6 / statistical-test-91
:ARG2 0.014)))
# ::id pmid_1901_8267.146 ::date 2015-07-10T12:59:27 ::annotator SDL-AMR-09 ::preferred
# ::snt Effects of ERK1/2 inactivation on ovarian carcinoma in vitro
# ::save-date Fri Jul 10, 2015 ::file pmid_1901_8267_146.txt
(a / affect-01
:ARG0 (a2 / activate-01 :polarity -
:ARG1 (e / enzyme :name (n / name :op1 "ERK1/2")))
:ARG1 (c / carcinoma
:mod (o / ovary))
:manner (i / in-vitro))
# ::id pmid_1901_8267.147 ::date 2015-07-10T13:04:45 ::annotator SDL-AMR-09 ::preferred
# ::snt A panel of ovarian cancer cell lines and primary cultures of ovarian cancer were first analysed for KRAS and BRAF gene mutation status.
# ::save-date Wed Dec 9, 2015 ::file pmid_1901_8267_147.txt
(a / analyze-01
:ARG1 (a2 / and
:op1 (p / panel
:consist-of (c / cell-line
:mod (d / disease :wiki "Ovarian_cancer" :name (n / name :op1 "ovarian" :op2 "cancer"))))
:op2 (c3 / culture-01
:ARG1 (d2 / disease :wiki "Cancer" :name (n4 / name :op1 "cancer"))
:mod (p2 / primary)))
:time (f / first)
:purpose (s / status
:mod (m / mutate-01
:ARG1 (a4 / and
:op1 (g / gene :name (n2 / name :op1 "KRAS"))
:op2 (g2 / gene :name (n3 / name :op1 "BRAF"))))))
# ::id pmid_1901_8267.148 ::date 2015-07-10T13:09:35 ::annotator SDL-AMR-09 ::preferred
# ::snt Mutational status was correlated with growth inhibition and apoptosis induction by the MEK inhibitor CI-1040 that prevented activation of the downstream target, ERK1/2.
# ::save-date Sat Jan 16, 2016 ::file pmid_1901_8267_148.txt
(c / correlate-01
:ARG0 (s2 / small-molecule :name (n2 / name :op1 "CI-1040")
:ARG0-of (i / inhibit-01
:ARG1 (p2 / protein-family :name (n / name :op1 "MEK")))
:ARG0-of (p / prevent-01
:ARG1 (a3 / activate-01
:ARG1 (t2 / target
:ARG1-of (m2 / mean-01
:ARG2 (e2 / enzyme :name (n3 / name :op1 "ERK1/2")))
:location (d / downstream)))))
:ARG1 (s / status
:mod (m / mutate-01))
:ARG2 (a / and
:op1 (i2 / inhibit-01
:ARG1 (g / grow-01))
:op2 (i3 / induce-01
:ARG2 (a2 / apoptosis))))
# ::id pmid_1901_8267.149 ::date 2015-07-11T01:55:31 ::annotator SDL-AMR-09 ::preferred
# ::snt Western blot analysis showed a dose-dependent effect on the expression of active ERK1/2 in ES2 cells, and active ERK1/2 was not detectable 6 h after treating the cells with CI-1040 at a concentration of 5 μM (Figure 4).
# ::save-date Fri Jan 15, 2016 ::file pmid_1901_8267_149.txt
(a / and
:op1 (s / show-01
:ARG0 (a2 / analyze-01
:manner (i / immunoblot-01))
:ARG1 (a3 / affect-01
:ARG1 (e / express-03
:ARG2 (e2 / enzyme :name (n3 / name :op1 "ERK1/2")
:ARG1-of (a4 / activate-01)
:location (c / cell-line :name (n4 / name :op1 "ES2"))))
:ARG0-of (d / depend-01
:ARG1 (d2 / dose))))
:op2 (p / possible-01 :polarity -
:ARG1 (d3 / detect-01
:ARG1 e2
:time (a5 / after
:op1 (t3 / treat-04
:ARG1 c
:ARG2 (s2 / small-molecule :name (n5 / name :op1 "CI-1040")
:quant (c3 / concentration-quantity :quant 5
:unit (m / micromolar))))
:quant (t2 / temporal-quantity :quant 6
:unit (h / hour)))))
:ARG1-of (d4 / describe-01
:ARG0 (f / figure :mod 4)))
# ::id pmid_1901_8267.150 ::date 2015-07-11T02:05:12 ::annotator SDL-AMR-09 ::preferred
# ::snt As shown in Figure 5, four of the tumours harbouring either KRAS or BRAF mutations showed a marked reduction (<50% of DMSO control) in the cell number in the CI-1040-treated group as compared with the other 14 tumours containing wild-type KRAS and BRAF (P<0.001).
# ::save-date Tue Dec 15, 2015 ::file pmid_1901_8267_150.txt
(s / show-01
:ARG0 (t / tumor :quant 4
:ARG1-of (i / include-01
:ARG2 (t2 / tumor
:ARG0-of (h / harbor-01
:ARG1 (o / or
:op1 (m / mutate-01
:ARG1 (g / gene :name (n / name :op1 "KRAS")))
:op2 (m2 / mutate-01
:ARG1 (g2 / gene :name (n2 / name :op1 "BRAF"))))))))
:ARG1 (r / reduce-01
:ARG1 (n4 / number
:quant-of (c2 / cell))
:ARG2 (l / less-than
:op1 (p / percentage-entity :value 50
:quant-of (c / control
:mod (s4 / small-molecule :name (n3 / name :op1 "DMSO")))))
:ARG1-of (m3 / mark-01)
:location (g3 / group
:ARG1-of (t3 / treat-04
:ARG2 (s2 / small-molecule :name (n5 / name :op1 "CI-1040"))))
:compared-to (t4 / tumor :quant 14
:mod (o2 / other)
:ARG0-of (c3 / contain-01
:ARG1 (a / and
:op1 (g4 / gene :name (n6 / name :op1 "KRAS")
:mod (w / wild-type))
:op2 (g5 / gene :name (n7 / name :op1 "BRAF")
:mod w)))))
:ARG1-of (s3 / show-01
:ARG0 (f / figure :mod 5))
:ARG1-of (s5 / statistical-test-91
:ARG2 (l2 / less-than :op1 0.001)))
# ::id pmid_1901_8267.151 ::date 2015-07-11T02:22:17 ::annotator SDL-AMR-09 ::preferred
# ::snt CI-1040 had no significant effect on the growth of normal cells, including the OSE cells.
# ::save-date Mon Dec 21, 2015 ::file pmid_1901_8267_151.txt
(a / affect-01 :polarity -
:ARG0 (s2 / small-molecule :name (n / name :op1 "CI-1040"))
:ARG1 (g / grow-01
:ARG1 (c / cell
:ARG1-of (n2 / normal-02)
:ARG2-of (i / include-01
:ARG1 (c2 / cell
:source (e / epithelium
:location (s3 / surface)
:part-of (o / ovary))))))
:ARG1-of (s / significant-02))
# ::id pmid_1901_8267.152 ::date 2015-07-11T02:26:44 ::annotator SDL-AMR-09 ::preferred
# ::snt It is likely that KRAS/BRAF mutation is not the only determinant for activating ERK1/2.
# ::save-date Wed Jul 22, 2015 ::file pmid_1901_8267_152.txt
(l / likely-01
:ARG1 (d / determine-01 :polarity -
:ARG0 (m / mutate-01
:ARG1 (s / slash
:op1 (g / gene :name (n / name :op1 "KRAS"))
:op2 (g2 / gene :name (n2 / name :op1 "BRAF"))))
:ARG1 (a / activate-01
:ARG1 (e / enzyme :name (n3 / name :op1 "ERK1/2")))
:mod (o / only)))
# ::id pmid_1901_8267.153 ::date 2015-07-11T02:33:19 ::annotator SDL-AMR-09 ::preferred
# ::snt Therefore, we analysed p-ERK1/2 expression in each of the cell lines listed in Figure 5.
# ::save-date Wed Jul 22, 2015 ::file pmid_1901_8267_153.txt
(c / cause-01
:ARG1 (a / analyze-01
:ARG0 (w / we)
:ARG1 (e / express-03
:ARG2 (e2 / enzyme :name (n / name :op1 "ERK1/2")
:ARG3-of (p / phosphorylate-01))
:ARG3 (c2 / cell-line
:mod (e3 / each)
:ARG1-of (l / list-01
:ARG2 (f / figure :mod 5))))))
# ::id pmid_1901_8267.154 ::date 2015-07-11T02:40:40 ::annotator SDL-AMR-09 ::preferred
# ::snt Only four of these cell lines, MDAH2774, ES2, MPSC1, and POC1, strongly expressed p-ERK1/2.
# ::save-date Wed Jul 22, 2015 ::file pmid_1901_8267_154.txt
(e / express-03
:ARG2 (e2 / enzyme :name (n5 / name :op1 "ERK1/2")
:ARG3-of (p / phosphorylate-01))
:ARG3 (c / cell-line :quant 4
:mod (o / only)
:ARG1-of (i / include-91
:ARG2 (c2 / cell-line
:mod (t / this)))
:ARG1-of (m / mean-01
:ARG2 (a / and
:op1 (c3 / cell-line :name (n / name :op1 "MDAH2774"))
:op2 (c4 / cell-line :name (n2 / name :op1 "ES2"))
:op3 (c5 / cell-line :name (n3 / name :op1 "MPSC1"))
:op4 (c6 / cell-line :name (n4 / name :op1 "POC1")))))
:ARG1-of (s / strong-02))
# ::id pmid_1901_8267.155 ::date 2015-07-11T12:38:54 ::annotator SDL-AMR-09 ::preferred
# ::snt SKOV3 and A2780 showed weak expression of ERK1/2.These results suggest that activation of ERK1/2 may depend on KRAS/BRAF mutation in ovarian cancer cells.
# ::save-date Wed Dec 9, 2015 ::file pmid_1901_8267_155.txt
(m / multi-sentence
:snt1 (s / show-01
:ARG0 (a / and
:op1 (c / cell-line :name (n2 / name :op1 "SKOV3"))
:op2 (c2 / cell-line :name (n3 / name :op1 "A2780")))
:ARG1 (e / express-03
:ARG2 (e2 / enzyme :name (n4 / name :op1 "ERK1/2"))
:ARG1-of (w / weak-02)))
:snt2 (s2 / suggest-01
:ARG0 (t2 / thing
:ARG2-of (r / result-01)
:mod (t / this))
:ARG1 (p / possible-01
:ARG1 (d2 / depend-01
:ARG0 (a2 / activate-01
:ARG1 (e3 / enzyme :name (n5 / name :op1 "ERK1/2")))
:ARG1 (m2 / mutate-01
:ARG1 (s3 / slash
:op1 (g / gene :name (n6 / name :op1 "KRAS"))
:op2 (g2 / gene :name (n7 / name :op1 "BRAF")))
:location (c3 / cell
:mod (d / disease :wiki "Ovarian_cancer" :name (n / name :op1 "ovarian" :op2 "cancer"))))))))
# ::id pmid_1901_8267.156 ::date 2015-07-11T12:46:17 ::annotator SDL-AMR-09 ::preferred
# ::snt To assess the mechanisms underlying growth inhibition by CI-1040, we measured the percentages of BrdUrd-labelled cells and Annexin V-labelled cells to estimate proliferation and apoptosis, respectively.
# ::save-date Sun Jan 17, 2016 ::file pmid_1901_8267_156.txt
(m / measure-01
:ARG0 (w / we)
:ARG1 (a / and
:op1 (p / percentage
:ARG3-of (i3 / include-91
:ARG1 (c / cell
:ARG1-of (l / label-01
:ARG0 (s2 / small-molecule :name (n / name :op1 "BrdUrd"))))))
:op2 (p2 / percentage
:ARG3-of (i2 / include-91
:ARG1 (c2 / cell
:ARG1-of (l2 / label-01
:ARG0 (p4 / protein :name (n2 / name :op1 "Annexin" :op2 "V")))))))
:purpose (e / estimate-01
:ARG0 w
:ARG1 (a2 / and
:op1 (p3 / proliferate-01)
:op2 (a3 / apoptosis)
:mod (r / respective)))
:purpose (a4 / assess-01
:ARG0 w
:ARG1 (m4 / mechanism
:ARG0-of (u / underlie-01
:ARG1 (i / inhibit-01
:ARG0 (s / small-molecule :name (n3 / name :op1 "CI-1040"))
:ARG1 (g / grow-01))))))
# ::id pmid_1901_8267.157 ::date 2015-07-11T12:55:02 ::annotator SDL-AMR-09 ::preferred
# ::snt We found that CI-1040 significantly reduced cellular proliferation and induced apoptosis in cell lines with either KRAS or BRAF mutations in comparison with cell lines with wild-type sequences (Figure 6, Supplementary Figure 1).
# ::save-date Sun Dec 20, 2015 ::file pmid_1901_8267_157.txt
(f / find-01
:ARG0 (w / we)
:ARG1 (a2 / and
:op1 (r / reduce-01
:ARG0 (s / small-molecule :name (n / name :op1 "CI-1040"))
:ARG1 (p / proliferate-01
:ARG0 (c / cell))
:ARG2 (s2 / significant-02))
:op2 (i / induce-01
:ARG0 s
:ARG2 (a / apoptosis))
:location (c2 / cell-line
:ARG0-of (h / have-03
:ARG1 (o / or
:op1 (m / mutate-01
:ARG1 (g / gene :name (n2 / name :op1 "KRAS")))
:op2 (m2 / mutate-01
:ARG1 (g2 / gene :name (n3 / name :op1 "BRAF")))))
:compared-to (c3 / cell-line
:ARG0-of (h2 / have-03
:ARG1 (s3 / sequence
:mod (w2 / wild-type))))))
:ARG1-of (d / describe-01
:ARG0 (a3 / and
:op1 (f2 / figure :mod 6)
:op2 (f3 / figure :mod 1
:ARG1-of (s4 / supplement-01)))))
# ::id pmid_1901_8267.158 ::date 2015-07-11T13:02:40 ::annotator SDL-AMR-09 ::preferred
# ::snt Effects of CI-1040 ERK1/2 inactivation on ovarian carcinomas in vivo
# ::save-date Wed Jul 22, 2015 ::file pmid_1901_8267_158.txt
(a / affect-01
:ARG0 (a2 / activate-01 :polarity -
:ARG0 (s / small-molecule :name (n2 / name :op1 "CI-1040"))
:ARG1 (e / enzyme :name (n / name :op1 "ERK1/2")))
:ARG1 (c / carcinoma
:mod (o / ovary))
:manner (i / in-vivo))
# ::id pmid_1901_8267.159 ::date 2015-07-11T13:10:17 ::annotator SDL-AMR-09 ::preferred
# ::snt On the basis of the above findings, we investigated whether CI-1040 had a growth-inhibitory effect on tumour formation and development in vivo.
# ::save-date Wed Nov 11, 2015 ::file pmid_1901_8267_159.txt
(i / investigate-01
:ARG0 (w / we)
:ARG1 (a / affect-01 :mode interrogative
:ARG0 (s / small-molecule :name (n / name :op1 "CI-1040"))
:ARG1 (a2 / and
:op1 (f / form-01
:ARG1 (t / tumor))
:op2 (d / develop-01
:ARG2 t))
:ARG2 (i3 / inhibit-01
:ARG0 s
:ARG1 (g / grow-01))
:manner (i2 / in-vivo))
:ARG1-of (b / base-02
:ARG0 (t2 / thing
:ARG1-of (f2 / find-01)
:mod (a3 / above))))
# ::id pmid_1901_8267.160 ::date 2015-07-11T13:17:34 ::annotator SDL-AMR-09 ::preferred
# ::snt Tumour xenografts from both MDAH2774 (KRAS mutant) and SKOV3 (wild type of KRAS and BRAF) cell lines were established in a nu/nu mouse model.
# ::save-date Wed Nov 11, 2015 ::file pmid_1901_8267_160.txt
(e / establish-01
:ARG1 (a2 / and
:op1 (x / xenograft
:mod (t / tumor)
:source (c / cell-line :name (n / name :op1 "MDAH2774")
:ARG1-of (m4 / mean-01
:ARG2 (g / gene :name (n2 / name :op1 "KRAS")
:ARG2-of (m / mutate-01)))))
:op2 (x2 / xenograft
:mod t
:source (c2 / cell-line :name (n3 / name :op1 "SKOV3")
:ARG1-of (m5 / mean-01
:ARG2 (a / and
:op1 (g2 / gene :name (n4 / name :op1 "KRAS")
:mod (w / wild-type))
:op2 (g3 / gene :name (n5 / name :op1 "BRAF")
:mod w))))))
:location (m2 / model
:mod (m3 / mouse
:mod (n6 / nude))))
# ::id pmid_1901_8267.161 ::date 2015-07-11T13:26:20 ::annotator SDL-AMR-09 ::preferred
# ::snt All mice injected with CI-1040 developed significantly smaller intra-abdominal xenograft tumours than the mice carrying diluent control cells of the KRAS mutant cell line MADH2774 (Figure 7A).
# ::save-date Wed Nov 11, 2015 ::file pmid_1901_8267_161.txt
(d / develop-01
:ARG1 (m / mouse
:mod (a / all)
:ARG2-of (i / inject-01
:ARG1 (s / small-molecule :name (n / name :op1 "CI-1040"))))
:ARG2 (t / tumor
:mod (x / xenograft)
:mod (i2 / intra-abdominal)
:mod (s2 / small
:degree (m2 / more))
:ARG1-of (s3 / significant-02))
:compared-to (m3 / mouse
:ARG0-of (c / carry-01
:ARG1 (c2 / cell
:mod (c3 / control)
:mod (d2 / diluent)
:poss (c4 / cell-line :name (n2 / name :op1 "MADH2774")
:mod (g / gene :name (n3 / name :op1 "KRAS")
:ARG2-of (m4 / mutate-01))))))
:ARG1-of (d3 / describe-01
:ARG0 (f / figure :mod "7A")))
# ::id pmid_1901_8267.162 ::date 2015-07-11T13:33:49 ::annotator SDL-AMR-09 ::preferred
# ::snt There were no differences in intra-abdominal xenograft tumour weights between the CI-1040-treated group and control groups transplanted with the wild-type KRAS/BRAF cell line SKOV3 (Figure 7B).
# ::save-date Wed Nov 11, 2015 ::file pmid_1901_8267_162.txt
(d / differ-02 :polarity -
:ARG1 (g / group
:ARG1-of (t / treat-04
:ARG2 (s / small-molecule :wiki -
:name (n / name :op1 "CI-1040"))))
:ARG2 (g2 / group
:mod (c / control)
:ARG2-of (t2 / transplant-01
:ARG1 (c2 / cell-line :wiki -
:name (n2 / name :op1 "SKOV3")
:mod (g5 / gene
:mod (s2 / slash
:op1 (g3 / gene :wiki -
:name (n3 / name :op1 "KRAS")
:mod (w / wild-type))
:op2 (g4 / gene :wiki "BRAF_(gene)"
:name (n4 / name :op1 "BRAF")
:mod w))))))
:ARG3 (w2 / weight-01
:ARG1 (t3 / tumor
:mod (x / xenograft)
:mod (i / intra-abdominal)))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod "7B")))
# ::id pmid_1901_8267.163 ::date 2015-07-11T13:43:37 ::annotator SDL-AMR-09 ::preferred
# ::snt Histological examination of the tumours after CI-1040 treatment showed inactivation of p-ERK1/2 in tumour cells based on immunohistochemistry (Figure 7C and D).
# ::save-date Wed Nov 11, 2015 ::file pmid_1901_8267_163.txt
(s / show-01
:ARG0 (e / examine-01
:ARG1 (t / tumor)
:mod (h / histologic)
:time (a / after
:op1 (t2 / treat-04
:ARG2 (s2 / small-molecule :name (n / name :op1 "CI-1040")))))
:ARG1 (a2 / activate-01 :polarity -
:ARG1 (e2 / enzyme :name (n2 / name :op1 "ERK1/2")
:ARG3-of (p / phosphorylate-01))
:location (c / cell
:mod t)
:ARG1-of (b / base-02
:ARG2 (i / immunohistochemistry)))
:ARG1-of (d / describe-01
:ARG0 (a3 / and
:op1 (f / figure :mod "7C")
:op2 (f2 / figure :mod "7D"))))
# ::id pmid_1956_8237.1 ::date 2015-08-15T04:21:12 ::annotator SDL-AMR-09 ::preferred
# ::snt Episodic Src activation in uveal melanoma revealed by kinase activity profiling (PMID:19568237)
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_1.txt
(a / activate-01
:ARG1 (p / protein :name (n / name :op1 "Src"))
:location (m / medical-condition :name (n2 / name :op1 "melanoma")
:mod (u / uveal))
:ARG1-of (r / reveal-01
:ARG0 (p2 / profile-01
:ARG1 (a2 / activity-06
:ARG0 (k / kinase))))
:ARG1-of (d2 / describe-01
:ARG0 (p3 / publication-91
:ARG8 "PMID19568237"))
:mod (e / episodic))
# ::id pmid_1956_8237.8 ::date 2015-08-15T07:27:16 ::annotator SDL-AMR-09 ::preferred
# ::snt Results:
# ::save-date Sat Aug 15, 2015 ::file pmid_1956_8237_8.txt
(t / thing
:ARG2-of (r / result-01))
# ::id pmid_1956_8237.9 ::date 2015-08-15T07:27:39 ::annotator SDL-AMR-09 ::preferred
# ::snt We identified Src as a kinase that is associated with ERK1/2 activation in UM.
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_9.txt
(i / identify-01
:ARG0 (w / we)
:ARG1 (p / protein :name (n / name :op1 "Src"))
:ARG2 (k / kinase
:ARG1-of (a / associate-01
:ARG2 (a2 / activate-01
:ARG1 (e / enzyme :name (n2 / name :op1 "ERK1/2"))
:location (m / medical-condition :name (n3 / name :op1 "melanoma")
:mod (u / uveal))))))
# ::id pmid_1956_8237.10 ::date 2015-08-15T07:30:45 ::annotator SDL-AMR-09 ::preferred
# ::snt However, low Src levels and reduced ERK1/2 activation in metastatic cell lines suggest that proliferation in metastases can become independent of Src and RAS/RAF/MEK/ERK signalling.
# ::save-date Tue Sep 1, 2015 ::file pmid_1956_8237_10.txt
(h / have-concession-91
:ARG1 (s / suggest-01
:ARG0 (a / and
:op1 (l / level
:ARG1-of (l2 / low-04)
:quant-of (p / protein :name (n / name :op1 "Src")))
:op2 (a4 / activate-01
:ARG1 (e / enzyme :name (n2 / name :op1 "ERK1/2"))
:ARG1-of (r / reduce-01))
:location (c / cell-line
:ARG1-of (m / metastasize-101)))
:ARG1 (p2 / possible-01
:ARG1 (b / become-01
:ARG1 (p3 / proliferate-01
:location m)
:ARG2 (d / depend-01 :polarity -
:ARG0 p3
:ARG1 (a3 / and
:op1 p
:op2 (s2 / signal-07
:ARG0 (p4 / pathway :name (n3 / name :op1 "RAS/RAF/MEK/ERK")))))))))
# ::id pmid_1956_8237.11 ::date 2015-08-15T07:42:29 ::annotator SDL-AMR-09 ::preferred
# ::snt Inhibition of Src led to the growth reduction of primary UM cultures and cell lines, whereas metastatic cell line growth was only slightly reduced.
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_11.txt
(c / contrast-01
:ARG1 (l / lead-03
:ARG0 (i / inhibit-01
:ARG1 (p / protein :name (n / name :op1 "Src")))
:ARG2 (r / reduce-01
:ARG1 (g / grow-01
:ARG1 (a / and
:op1 (c2 / cell-line
:mod (m2 / medical-condition :name (n2 / name :op1 "melanoma")
:mod (u / uveal))
:mod (p2 / primary))
:op2 (c3 / culture-01
:mod m2
:mod p2)))))
:ARG2 (r2 / reduce-01
:ARG1 (g2 / grow-01
:ARG1 (c4 / cell-line
:ARG1-of (m / metastasize-101)))
:mod (o / only)
:degree (s / slight)))
# ::id pmid_1956_8237.92 ::date 2015-08-15T07:47:31 ::annotator SDL-AMR-09 ::preferred
# ::snt Results
# ::save-date Sat Aug 15, 2015 ::file pmid_1956_8237_92.txt
(t / thing
:ARG2-of (r / result-01))
# ::id pmid_1956_8237.93 ::date 2015-08-15T07:47:58 ::annotator SDL-AMR-09 ::preferred
# ::snt ERK1/2 activation in UM
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_93.txt
(a / activate-01
:ARG1 (e / enzyme :name (n / name :op1 "ERK1/2"))
:location (m / medical-condition :name (n2 / name :op1 "melanoma")
:mod (u / uveal)))
# ::id pmid_1956_8237.94 ::date 2015-08-15T07:48:49 ::annotator SDL-AMR-09 ::preferred
# ::snt An antibody array was applied to investigate the MAPK pathway in 10 UM cell lines, in three primary UM and three UM metastasis.
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_94.txt
(a / apply-03
:ARG1 (a2 / array-01
:ARG1 (a3 / antibody))
:purpose (i / investigate-01
:ARG1 (p / pathway :name (n / name :op1 "MAPK"))
:location (a4 / and
:op1 (c / cell-line :quant 10
:mod (m2 / medical-condition :name (n2 / name :op1 "melanoma")
:mod (u / uveal)))
:op2 (m3 / medical-condition :quant 3 :name (n3 / name :op1 "melanoma")
:mod u
:mod (p2 / primary))
:op3 (m / metastasize-101 :quant 3
:mod m2))))
# ::id pmid_1956_8237.95 ::date 2015-08-15T07:56:17 ::annotator SDL-AMR-09 ::preferred
# ::snt We observed a uniform HSP27 phosphorylation, with the exception of in three UM cell lines (OCM1, -3, -8).
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_95.txt
(o / observe-01
:ARG0 (w / we)
:ARG1 (p / phosphorylate-01
:ARG1 (p2 / protein :name (n / name :op1 "HSP27"))
:ARG1-of (u / uniform-02)
:ARG2-of (e / except-01
:ARG1 (p3 / phosphorylate-01
:ARG1 p2
:location (c / cell-line :quant 3
:mod (m2 / medical-condition :name (n2 / name :op1 "melanoma")
:mod (u2 / uveal))
:ARG1-of (m / mean-01
:ARG2 (a / and
:op1 (c2 / cell-line :name (n3 / name :op1 "OCM1"))
:op2 (c3 / cell-line :name (n4 / name :op1 "OCM3"))
:op3 (c4 / cell-line :name (n5 / name :op1 "OCM8")))))))))
# ::id pmid_1956_8237.96 ::date 2015-08-15T08:02:04 ::annotator SDL-AMR-09 ::preferred
# ::snt UMs displaying activated ERK1/2 as well as phosphorylated HSP27 were most common, whereas signals for phosphorylated ERK1/2 were low in metastasis tissue (MET1-3) and metastatic UM cell lines (OMM1, OMM2.3 and OMM2.5) (Figure 1).
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_96.txt
(c / contrast-01
:ARG1 (c2 / common
:domain (m4 / medical-condition :name (n / name :op1 "melanoma")
:mod (u / uveal)
:ARG0-of (d2 / display-01
:ARG1 (a / and
:op1 (e / enzyme :name (n2 / name :op1 "ERK1/2")
:ARG1-of (a2 / activate-01))
:op2 (p2 / protein :name (n3 / name :op1 "HSP27")
:ARG3-of (p / phosphorylate-01)))))
:degree (m / most))
:ARG2 (l / low-04
:ARG1 (s / signal-07
:beneficiary (e2 / enzyme :name (n4 / name :op1 "ERK1/2")
:ARG3-of (p3 / phosphorylate-01)))
:location (a3 / and
:op1 (t / tissue
:ARG1-of (m2 / metastasize-101)
:ARG1-of (l2 / label-01
:ARG2 (t2 / thing :name (n5 / name :op1 "MET")
:value (v / value-interval :op1 1 :op2 3))))
:op2 (c3 / cell-line
:mod m4
:mod m2
:ARG1-of (m3 / mean-01
:ARG2 (a4 / and
:op1 (c4 / cell-line :name (n6 / name :op1 "OMM1"))
:op2 (c5 / cell-line :name (n7 / name :op1 "OMM2.3"))
:op3 (c6 / cell-line :name (n8 / name :op1 "OMM2.5")))))))
:ARG1-of (d3 / describe-01
:ARG0 (f / figure :mod 1)))
# ::id pmid_1956_8237.97 ::date 2015-08-15T08:21:25 ::annotator SDL-AMR-09 ::preferred
# ::snt Remarkably, two of the metastatic cell lines (OMM2.3, OMM2.5) are derived from the same patient as cell line Mel270 but contained far less activated ERK1/2.
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_97.txt
(c / contrast-01
:ARG1 (d / derive-01
:ARG1 (c2 / cell-line :quant 2
:ARG1-of (m2 / mean-01
:ARG2 (a / and
:op1 (c4 / cell-line :name (n / name :op1 "OMM2.3"))
:op2 (c5 / cell-line :name (n2 / name :op1 "OMM2.5")))
:ARG1-of (m / metastasize-101))
:ARG1-of (i / include-91
:ARG2 (c3 / cell-line)))
:ARG2 (p / person
:ARG0-of (h / have-rel-role-91
:ARG2 (p2 / patient))
:ARG1-of (s / same-01))
:ARG4 (c6 / cell-line :name (n3 / name :op1 "Mel270")))
:ARG2 (c7 / contain-01
:ARG0 c2
:ARG1 (e / enzyme :name (n4 / name :op1 "ERK1/2")
:ARG1-of (a2 / activate-01)
:quant (l / less
:degree (f / far))))
:ARG1-of (r / remarkable-02))
# ::id pmid_1956_8237.98 ::date 2015-08-15T08:30:04 ::annotator SDL-AMR-09 ::preferred
# ::snt Differential kinase activity in UM
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_98.txt
(a / activity-06
:ARG0 (k / kinase)
:mod (d / differential)
:location (m / medical-condition :name (n / name :op1 "melanoma")
:mod (u / uveal)))
# ::id pmid_1956_8237.99 ::date 2015-08-15T08:32:15 ::annotator SDL-AMR-09 ::preferred
# ::snt Reduction of ERK1/2 activation in metastatic cell lines compared with that in primary UM cell lines provides a model to identify the underlying mechanism of ERK1/2 activation in the absence of BRAF and NRAS mutations.
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_99.txt
(p / provide-01
:ARG0 (r / reduce-01
:ARG1 (a / activate-01
:ARG1 (e / enzyme :name (n / name :op1 "ERK1/2"))
:location (c / cell-line
:ARG1-of (m / metastasize-101)))
:ARG1-of (c2 / compare-01
:ARG2 (r2 / reduce-01
:ARG1 a
:location (c3 / cell-line
:mod (m6 / medical-condition :name (n2 / name :op1 "melanoma")
:mod (u / uveal)
:mod (p2 / primary))))))
:ARG1 (m2 / model-01
:purpose (i / identify-01
:ARG1 (m3 / mechanism
:ARG1-of (u2 / underlie-01)
:mod (a2 / activate-01
:ARG1 e
:condition (a3 / absent-01
:ARG1 (a4 / and
:op1 (m4 / mutate-01
:ARG1 (g / gene :name (n3 / name :op1 "BRAF")))
:op2 (m5 / mutate-01
:ARG1 (g2 / gene :name (n4 / name :op1 "NRAS"))))))))))
# ::id pmid_1956_8237.100 ::date 2015-08-15T08:41:09 ::annotator SDL-AMR-09 ::preferred
# ::snt To investigate whether a kinase is differentially activated between primary UM cell lines and metastatic UM cell lines, we used peptide-based tyrosine kinase arrays (Lemeer et al, 2007).
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_100.txt
(u3 / use-01
:ARG0 (w / we)
:ARG1 (a3 / array-01
:ARG1 (e2 / enzyme :name (n5 / name :op1 "tyrosine" :op2 "kinase"))
:ARG1-of (b / base-02
:ARG2 (p2 / peptide))
:ARG1-of (d4 / describe-01
:ARG0 (p3 / publication-91
:ARG0 (a4 / and
:op1 (p4 / person :name (n4 / name :op1 "Lemeer"))
:op2 (p5 / person
:mod (o / other)))
:time (d5 / date-entity :year 2007))))
:ARG2 (i / investigate-01
:ARG0 w
:ARG1 (a / activate-01 :mode interrogative
:ARG1 (k / kinase)
:manner (d / differential)
:location (a2 / and
:op1 (c / cell-line
:mod (m2 / medical-condition :name (n / name :op1 "melanoma")
:mod (u / uveal)
:mod (p / primary)))
:op2 (c2 / cell-line
:mod (m3 / medical-condition :name (n2 / name :op1 "melanoma")
:mod u
:ARG1-of (m / metastasize-101)))))))
# ::id pmid_1956_8237.101 ::date 2015-08-15T08:52:19 ::annotator SDL-AMR-09 ::preferred
# ::snt The UM cell lines displayed a high kinase activity, whereas the metastatic UM cell lines displayed a low kinase activity, although the same amount of lysate was incubated (Figure 2A).
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_101.txt
(h2 / have-concession-91
:ARG1 (c / contrast-01
:ARG1 (d / display-01
:ARG0 (c2 / cell-line
:mod (m3 / medical-condition :name (n / name :op1 "melanoma")
:mod (u / uveal)))
:ARG1 (a / activity-06
:ARG0 (k / kinase)
:ARG1-of (h / high-02)))
:ARG2 (d3 / display-01
:ARG0 (c3 / cell-line
:mod (m2 / medical-condition :name (n2 / name :op1 "melanoma")
:ARG1-of (m / metastasize-101)))
:ARG1 (a2 / activity-06
:ARG0 k
:ARG1-of (l / low-04))))
:ARG2 (i / incubate-01
:ARG1 (a3 / amount
:quant-of (l2 / lysate)
:ARG1-of (s / same-01)))
:ARG1-of (d5 / describe-01
:ARG0 (f / figure :mod "2A")))
# ::id pmid_1956_8237.102 ::date 2015-08-15T08:59:57 ::annotator SDL-AMR-09 ::preferred
# ::snt After normalisation, we could analyse the kinase data and identify nine substrates that were significantly differentially phosphorylated between primary and metastatic UM cell lines (Figure 2B, Table 1).
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_102.txt
(p / possible-01
:ARG1 (a / and
:op1 (a2 / analyze-01
:ARG0 (w / we)
:ARG1 (d / data
:topic (k / kinase)))
:op2 (i / identify-01
:ARG0 w
:ARG1 (s / substrate :quant 9
:ARG3-of (p2 / phosphorylate-01
:ARG1-of (s2 / significant-02)
:manner (d2 / differential)
:location (a3 / and
:op1 (c / cell-line
:mod (m2 / medical-condition :name (n / name :op1 "melanoma")
:mod (u / uveal)
:mod (p3 / primary)))
:op2 (c2 / cell-line
:mod (m3 / medical-condition :name (n2 / name :op1 "melanoma")
:mod (u2 / uveal)
:ARG1-of (m / metastasize-101))))))))
:time (a4 / after
:op1 (n3 / normalize-01))
:ARG1-of (d5 / describe-01
:ARG0 (a5 / and
:op1 (f / figure :mod "2B")
:op2 (t / table :mod 1))))
# ::id pmid_1956_8237.103 ::date 2015-08-15T09:08:13 ::annotator SDL-AMR-09 ::preferred
# ::snt Primary UM and metastatic tissue also showed differential phosphorylation of these nine peptides, although not as clearly as observed in the cell lines (Figure 2C).
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_103.txt
(s / show-01
:ARG0 (a / and
:op1 (m2 / medical-condition :name (n / name :op1 "melanoma")
:mod (u / uveal)
:mod (p / primary))
:op2 (t / tissue
:ARG1-of (m / metastasize-101)))
:ARG1 (p2 / phosphorylate-01
:ARG1 (p3 / peptide :quant 9
:mod (t2 / this))
:mod (d2 / differential))
:concession (c / clear-06 :polarity -
:ARG1 s
:compared-to (p4 / phosphorylate-01
:ARG1-of (o / observe-01
:location (c2 / cell-line))))
:mod (a2 / also)
:ARG1-of (d3 / describe-01
:ARG0 (f / figure :mod "2C")))
# ::id pmid_1956_8237.104 ::date 2015-08-15T09:17:31 ::annotator SDL-AMR-09 ::preferred
# ::snt Candidate kinase: Src
# ::save-date Tue Sep 1, 2015 ::file pmid_1956_8237_104.txt
(p / protein
:domain (k / kinase :name (n / name :op1 "Src")
:mod (c / candidate)))
# ::id pmid_1956_8237.105 ::date 2015-08-15T09:18:54 ::annotator SDL-AMR-09 ::preferred
# ::snt We identified nine peptides derived from eight proteins that were differentially phosphorylated between primary and metastatic cell line lysates.
# ::save-date Tue Sep 1, 2015 ::file pmid_1956_8237_105.txt
(i / identify-01
:ARG0 (w / we)
:ARG1 (p / peptide :quant 9
:ARG1-of (d / derive-01
:ARG2 (p2 / protein :quant 8
:ARG3-of (p3 / phosphorylate-01
:manner (d2 / differential)
:location (a / and
:op1 (l / lysate
:mod (c / cell-line)
:mod (p4 / primary))
:op2 (l2 / lysate
:mod (c2 / cell-line)
:ARG1-of (m / metastasize-101))))))))
# ::id pmid_1956_8237.106 ::date 2015-08-15T09:22:18 ::annotator SDL-AMR-09 ::preferred
# ::snt On the basis of a literature search, we identified candidate tyrosine kinases for eight out of nine peptides (Table 1) (Cooper et al, 1983; Thomas and Brugge, 1997; Koike et al, 2003; Diella et al, 2004).
# ::save-date Fri Nov 20, 2015 ::file pmid_1956_8237_106.txt
(i / identify-01
:ARG0 (w / we)
:ARG1 (e / enzyme :name (n7 / name :op1 "tyrosine" :op2 "kinase")
:mod (c / candidate))
:beneficiary (p / peptide :quant 8
:ARG1-of (i2 / include-91
:ARG2 (p2 / peptide :quant 9)))
:ARG1-of (d5 / describe-01
:ARG0 (t / table :mod 1))
:ARG1-of (b / base-02
:ARG2 (s / search-01
:ARG1 (l / literature
:ARG2-of (i3 / include-91
:ARG1 (a / and
:op1 (p3 / publication-91
:ARG0 (a2 / and
:op1 (p4 / person :name (n2 / name :op1 "Cooper"))
:op2 (p5 / person
:mod (o / other)))
:time (d / date-entity :year 1983))
:op2 (p6 / publication-91
:ARG0 (a3 / and
:op1 (p7 / person :name (n3 / name :op1 "Thomas"))
:op2 (p8 / person :name (n4 / name :op1 "Brugge")))
:time (d2 / date-entity :year 1997))
:op3 (p9 / publication-91
:ARG0 (a4 / and
:op1 (p10 / person :name (n5 / name :op1 "Koike"))
:op2 (p11 / person
:mod (o2 / other)))
:time (d3 / date-entity :year 2003))
:op4 (p12 / publication-91
:ARG0 (a5 / and
:op1 (p13 / person :name (n6 / name :op1 "Diella"))
:op2 (p14 / person
:mod (o3 / other)))
:time (d4 / date-entity :year 2004))))))))
# ::id pmid_1956_8237.107 ::date 2015-08-15T09:32:25 ::annotator SDL-AMR-09 ::preferred
# ::snt Among the candidates, Src and Src family members were most prominent.
# ::save-date Fri Jan 15, 2016 ::file pmid_1956_8237_107.txt
(p / prominent
:domain (a / and
:op1 (p2 / protein :name (n / name :op1 "Src"))
:op2 (m / member
:ARG1-of (i2 / include-91
:ARG2 (p3 / protein-family :name (n2 / name :op1 "Src"))))
:ARG1-of (i / include-91
:ARG2 (c / candidate)))
:degree (m2 / most))
# ::id pmid_1956_8237.108 ::date 2015-08-15T09:36:03 ::annotator SDL-AMR-09 ::preferred
# ::snt To validate the candidacy of Src, we performed in vitro inhibition experiments with the Src-kinase-specific inhibitors PP1 and the PP1 analogue, PP2.
# ::save-date Sun Jan 17, 2016 ::file pmid_1956_8237_108.txt
(p / perform-02
:ARG0 (w / we)
:ARG1 (e / experiment-01
:ARG1 (i / inhibit-01)
:ARG2 (s / small-molecule
:ARG0-of (i3 / inhibit-01)
:ARG1-of (s2 / specific-02
:ARG2 (k / kinase :name (n / name :op1 "Src")))
:ARG1-of (m / mean-01
:ARG2 (a / and
:op1 (p2 / protein :name (n2 / name :op1 "PP1"))
:op2 (p3 / protein :name (n3 / name :op1 "PP2")
:mod (a2 / analogue
:mod p2)))))
:manner (i2 / in-vitro))
:purpose (v / validate-01
:ARG0 w
:ARG1 (c / candidacy
:mod k)))
# ::id pmid_1956_8237.109 ::date 2015-08-15T09:46:46 ::annotator SDL-AMR-09 ::preferred
# ::snt We added PP1 and PP2 (10 μM) to lysates of primary UM tissue and of a primary UM cell line and measured the inhibitory effect of these Src inhibitors using kinase array (Figure 3A).
# ::save-date Sun Jan 17, 2016 ::file pmid_1956_8237_109.txt
(a / and
:op1 (a2 / add-02
:ARG0 (w / we)
:ARG1 (a3 / and
:op1 (s / small-molecule)
:op2 (s2 / small-molecule)
:quant (c2 / concentration-quantity :quant 10
:unit (m / micromolar)))
:ARG2 (a7 / and
:op1 (l / lysate
:source (t / tissue
:mod (m3 / medical-condition :name (n3 / name :op1 "melanoma")
:mod (u / uveal)
:mod (p / primary))))
:op1 (l2 / lysate
:source (c / cell-line
:mod m3))))
:op2 (m2 / measure-01
:ARG0 w
:ARG1 (a5 / affect-01
:ARG0 (s3 / small-molecule
:ARG0-of (i2 / inhibit-01
:ARG1 (p2 / protein-family :name (n4 / name :op1 "Src"))))
:ARG2 (i / inhibit-01))
:instrument (a6 / array-01
:ARG1 (k / kinase)))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod "3A")))
# ::id pmid_1956_8237.110 ::date 2015-08-15T09:55:58 ::annotator SDL-AMR-09 ::preferred
# ::snt A total of seven out of nine substrates that identified Src in the first screen displayed a significantly reduced phosphorylation when PP1 or PP2 were added to lysates of UM1 and Mel270 (Figure 3A).
# ::save-date Sun Jan 17, 2016 ::file pmid_1956_8237_110.txt
(d / display-01
:ARG0 (s / substrate :quant 7
:ARG1-of (i2 / include-91
:ARG2 (s3 / substrate :quant 9
:ARG0-of (i / identify-01
:ARG1 (p / protein :name (n / name :op1 "Src"))
:location (s2 / screen
:ord (o / ordinal-entity :value 1)))))
:ARG1-of (t / total-01))
:ARG1 (p2 / phosphorylate-01
:ARG1-of (r / reduce-01
:ARG2 (s4 / significant-02)))
:time (a / add-02
:ARG1 (o2 / or
:op1 (p3 / protein :name (n2 / name :op1 "PP1"))
:op2 (p4 / protein :name (n3 / name :op1 "PP2")))
:ARG2 (a3 / and
:op1 (l / lysate
:source (t2 / thing :name (n4 / name :op1 "UM1")))
:op2 (l2 / lysate
:source (c / cell-line :name (n5 / name :op1 "Mel270")))))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod "3A")))
# ::id pmid_1956_8237.111 ::date 2015-08-15T10:06:58 ::annotator SDL-AMR-09 ::preferred
# ::snt The PLCG1 peptide and one of the PAX1 (Y31) substrates did not reach significance but were still phosphorylated at a reduced level after PP1 and PP2 treatments.
# ::save-date Sun Jan 17, 2016 ::file pmid_1956_8237_111.txt
(c / contrast-01
:ARG1 (r / reach-01 :polarity -
:ARG0 (a / and
:op1 (p / peptide :name (n / name :op1 "PLCG1"))
:op1 (s / substrate :name (n2 / name :op1 "Y31")
:ARG1-of (i / include-91
:ARG2 (s2 / substrate :name (n3 / name :op1 "PAX1")))))
:ARG1 (s3 / significance))
:ARG2 (p2 / phosphorylate-01
:ARG1 a
:degree (l / level
:ARG1-of (r2 / reduce-01))
:time (a2 / after
:op1 (t / treat-04
:ARG2 (a3 / and
:op1 (p3 / protein :name (n4 / name :op1 "PP1"))
:op2 (p4 / protein :name (n5 / name :op1 "PP2")))))
:mod (s6 / still)))
# ::id pmid_1956_8237.112 ::date 2015-08-15T10:14:03 ::annotator SDL-AMR-09 ::preferred
# ::snt The peptide representing FAK1 Y576/Y577 is a genuine substrate for Src, which was not detected in the UM cell line comparison, but phosphorylation was significantly downregulated by PP1 and PP2 treatments.
# ::save-date Sun Jan 17, 2016 ::file pmid_1956_8237_112.txt
(c / contrast-01
:ARG1 (s / substrate
:mod (g / genuine)
:domain (p / peptide
:ARG0-of (r / represent-01
:ARG1 (o / or
:op1 (a / amino-acid :mod 576 :name (n / name :op1 "tyrosine"))
:op2 (a2 / amino-acid :mod 577 :name (n2 / name :op1 "tyrosine"))
:part-of (e / enzyme :mod 1 :name (n3 / name :op1 "FAK")))))
:beneficiary (p2 / protein :name (n4 / name :op1 "Src"))
:ARG1-of (d / detect-01 :polarity -
:time (c2 / compare-01
:ARG1 (c3 / cell-line
:mod (m / medical-condition :name (n5 / name :op1 "melanoma")
:mod (u / uveal))))))
:ARG2 (d3 / downregulate-01
:ARG1 (p3 / phosphorylate-01)
:ARG2 (t / treat-04
:ARG2 (a3 / and
:op1 (p4 / protein :name (n6 / name :op1 "PP1"))
:op2 (p5 / protein :name (n7 / name :op1 "PP2"))))
:ARG1-of (s4 / significant-02)))
# ::id pmid_1956_8237.113 ::date 2015-08-15T12:22:11 ::annotator SDL-AMR-09 ::preferred
# ::snt In the control experiment, in which we added the inactive analogue of PP1 (PP3) to cell lysates, we did not observe a loss of kinase activity (not shown).
# ::save-date Sun Jan 17, 2016 ::file pmid_1956_8237_113.txt
(o / observe-01 :polarity -
:ARG0 (w / we)
:ARG1 (l / lose-02
:ARG1 (a / activity-06
:ARG0 (k / kinase))
:ARG1-of (s2 / show-01 :polarity -))
:location (e / experiment-01
:mod (c / control)
:location-of (a2 / add-02
:ARG0 w
:ARG1 (a3 / analogue :name (n2 / name :op1 "PP3")
:ARG0-of (a4 / activity-06 :polarity -)
:poss (p / protein :name (n / name :op1 "PP1")))
:ARG2 (l2 / lysate
:mod (c2 / cell)))))
# ::id pmid_1956_8237.114 ::date 2015-08-15T12:29:33 ::annotator SDL-AMR-09 ::preferred
# ::snt The kinase activity of metastasis tissue and UM tissue differed marginally (Figure 2C), and incubation with PP1 (10 μM) resulted in a decimation of kinase activity similar to the inhibition that we observed in UM tissue (Figure 3B).
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_114.txt
(a / and
:op1 (d / differ-02
:ARG1 (t2 / tissue
:mod (m4 / medical-condition :name (n / name :op1 "melanoma")
:mod (u / uveal)))
:ARG2 (t / tissue
:ARG1-of (m / metastasize-101))
:ARG3 (a2 / activity-06
:mod (k / kinase))
:ARG1-of (m2 / marginal-02)
:ARG1-of (d3 / describe-01
:ARG0 (f / figure :mod "2C")))
:op2 (r / result-01
:ARG1 (i / incubate-01
:ARG2 (s / small-molecule
:quant (c / concentration-quantity :quant 10
:unit (m3 / micromolar))))
:ARG2 (d4 / decimate-01
:ARG1 (a4 / activity-06
:mod (k2 / kinase)
:ARG1-of (r2 / resemble-01
:ARG2 (i2 / inhibit-01
:ARG1-of (o / observe-01
:ARG0 (w / we)
:location t2)))))
:ARG1-of (d5 / describe-01
:ARG0 (f2 / figure :mod "3B"))))
# ::id pmid_1956_8237.115 ::date 2015-08-15T12:36:16 ::annotator SDL-AMR-09 ::preferred
# ::snt To validate Src activity, Mel270 was transfected with two siRNA constructs that target Src and reduced kinase activity (Figure 3B).
# ::save-date Sat Aug 15, 2015 ::file pmid_1956_8237_115.txt
(a / and
:op1 (t / transfect-01
:ARG1 (c / cell-line :name (n / name :op1 "Mel270"))
:ARG2 (c2 / construct :quant 2
:mod (n4 / nucleic-acid :name (n2 / name :op1 "siRNA"))
:ARG0-of (t2 / target-01
:ARG1 (p / protein :name (n3 / name :op1 "Src")))))
:op2 (r2 / reduce-01
:ARG1 (a2 / activity-06
:mod (k / kinase)))
:purpose (v / validate-01
:ARG1 (a3 / activity-06
:ARG0 p))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "3B")))
# ::id pmid_1956_8237.116 ::date 2015-08-15T12:48:53 ::annotator SDL-AMR-09 ::preferred
# ::snt Regulation of ERK1/2 and growth
# ::save-date Sat Aug 15, 2015 ::file pmid_1956_8237_116.txt
(a / and
:op1 (r / regulate-01
:ARG1 (e / enzyme :name (n / name :op1 "ERK1/2")))
:op2 (g / grow-01))
# ::id pmid_1956_8237.117 ::date 2015-08-15T12:49:54 ::annotator SDL-AMR-09 ::preferred
# ::snt To investigate whether Src contributes to ERK1/2 activation in Mel270, we analysed the two Src siRNA-transfected cell cultures with the MAPK antibody array.
# ::save-date Sun Jan 17, 2016 ::file pmid_1956_8237_117.txt
(a / analyze-01
:ARG0 (w / we)
:ARG1 (c / culture :quant 2
:mod (c2 / cell)
:ARG1-of (t / transfect-01
:ARG2 (n6 / nucleic-acid :name (n / name :op1 "siRNA")))
:mod (p2 / protein :name (n3 / name :op1 "Src")))
:instrument (a2 / array-01
:ARG1 (a3 / antibody
:ARG0-of (c5 / counter-01
:ARG1 (e2 / enzyme :name (n2 / name :op1 "MAPK")))))
:purpose (i / investigate-01
:ARG0 w
:ARG1 (c3 / contribute-01 :mode interrogative
:ARG0 p2
:ARG1 (a4 / activate-01
:ARG1 (e / enzyme :name (n4 / name :op1 "ERK1/2"))
:location (c4 / cell-line :name (n5 / name :op1 "Mel270"))))))
# ::id pmid_1956_8237.118 ::date 2015-08-15T12:54:56 ::annotator SDL-AMR-09 ::preferred
# ::snt At 24 and 48 h after transfection with Src siRNA, we observed a reduced ERK1 phosphorylation, whereas ERK2 phosphorylation was minimally affected (Figure 4).
# ::save-date Sat Aug 15, 2015 ::file pmid_1956_8237_118.txt
(c / contrast-01
:ARG1 (o / observe-01
:ARG0 (w / we)
:ARG1 (p / phosphorylate-01
:ARG1 (e / enzyme :name (n / name :op1 "ERK1"))
:ARG1-of (r / reduce-01)))
:ARG2 (a / affect-01
:ARG1 (p2 / phosphorylate-01
:ARG1 (e2 / enzyme :name (n2 / name :op1 "ERK2")))
:ARG1-of (m / minimal-02))
:time (a2 / after
:op1 (t / transfect-01
:ARG2 (n5 / nucleic-acid :name (n3 / name :op1 "siRNA")
:mod (p3 / protein :name (n4 / name :op1 "Src"))))
:quant (a3 / and
:op1 (t2 / temporal-quantity :quant 24
:unit (h / hour))
:op2 (t3 / temporal-quantity :quant 48
:unit (h2 / hour))))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod 4)))
# ::id pmid_1956_8237.119 ::date 2015-08-15T13:02:49 ::annotator SDL-AMR-09 ::preferred
# ::snt Whether Src inhibition and consequently a lowered ERK activation in UM cell lines is associated with a reduced growth was investigated with the WST-1 viability assay (Figure 5).
# ::save-date Sat Jan 16, 2016 ::file pmid_1956_8237_119.txt
(i / investigate-01
:ARG1 (a / associate-01 :mode interrogative
:ARG1 (a2 / and
:op1 (i2 / inhibit-01
:ARG1 (p / protein :name (n / name :op1 "Src")))
:op2 (a3 / activate-01
:ARG1 (e / enzyme :name (n2 / name :op1 "ERK"))
:ARG1-of (l / lower-05)
:location (c / cell-line
:mod (m / medical-condition :name (n3 / name :op1 "melanoma")
:mod (u / uveal)))
:manner (c2 / consequent)))
:ARG2 (g / grow-01
:ARG1-of (r / reduce-01)))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod 5))
:instrument (a4 / assay-01
:mod (v / viable)
:mod (t / thing :name (n4 / name :op1 "WST-1"))))
# ::id pmid_1956_8237.120 ::date 2015-08-15T13:10:11 ::annotator SDL-AMR-09 ::preferred
# ::snt All UM cell lines showed a PP1-dose and time (1–6 days)-dependent reduction in cell viability but the magnitude of the response differed widely.
# ::save-date Sun Jan 17, 2016 ::file pmid_1956_8237_120.txt
(c / contrast-01
:ARG1 (s / show-01
:ARG0 (c2 / cell-line
:mod (m2 / medical-condition :name (n / name :op1 "melanoma")
:mod (u / uveal))
:mod (a / all))
:ARG1 (r / reduce-01
:ARG1 (v / viable
:mod (c3 / cell))
:ARG0-of (d3 / depend-01
:ARG1 (a2 / and
:op1 (d4 / dose-01
:ARG2 (p / protein :name (n2 / name :op1 "PP1")))
:op2 (t / time
:quant (b / between
:op1 (t2 / temporal-quantity :quant 1
:unit (d5 / day))
:op2 (t3 / temporal-quantity :quant 6
:unit d5)))))))
:ARG2 (d2 / differ-02
:ARG1 (m / magnitude
:mod (r2 / respond-01))
:ARG2-of (w / wide-02)))
# ::id pmid_1956_8237.121 ::date 2015-08-15T13:19:50 ::annotator SDL-AMR-09 ::preferred
# ::snt In general, the metastatic UM cell lines were less affected by PP1.
# ::save-date Sun Jan 17, 2016 ::file pmid_1956_8237_121.txt
(a / affect-01
:ARG0 (p / protein :name (n2 / name :op1 "PP1"))
:ARG1 (c / cell-line
:mod (m2 / medical-condition :name (n / name :op1 "melanoma")
:mod (u / uveal)
:ARG1-of (m / metastasize-101)))
:degree (l / less)
:ARG1-of (g / general-02))
# ::id pmid_1956_8237.122 ::date 2015-08-15T13:22:34 ::annotator SDL-AMR-09 ::preferred
# ::snt We also determined the growth inhibition rate of PP1 in cultures of five primary UM cell cultures and observed an increased sensitivity to PP1 treatment compared with the cell lines.
# ::save-date Sun Jan 17, 2016 ::file pmid_1956_8237_122.txt
(a / and
:op1 (d / determine-01
:ARG0 (w / we)
:ARG1 (r / rate
:degree-of (i / inhibit-01
:ARG0 (p2 / protein :name (n / name :op1 "PP1"))
:ARG1 (g / grow-01))
:location (c / culture
:ARG1-of (i2 / include-91
:ARG2 (c2 / culture :quant 5
:mod (c3 / cell)
:mod (m / medical-condition :name (n2 / name :op1 "melanoma")
:mod (u / uveal)
:mod (p / primary))))))
:mod (a2 / also))
:op2 (o / observe-01
:ARG0 w
:ARG1 (s2 / sensitive-03
:ARG1 (t / treat-04
:ARG2 p2)
:ARG1-of (i3 / increase-01)
:compared-to (c4 / cell-line))))
# ::id pmid_1956_8237.123 ::date 2015-08-15T13:29:10 ::annotator SDL-AMR-09 ::preferred
# ::snt We had to take samples at day 3 of PP1 treatment because, thereafter, massive cell death occurred (Figure 5B).
# ::save-date Sun Jan 17, 2016 ::file pmid_1956_8237_123.txt
(o / obligate-01
:ARG1 (w / we)
:ARG2 (t / take-01
:ARG0 w
:ARG1 (t4 / thing
:ARG1-of (s / sample-01))
:time (a / after
:op1 (t2 / treat-04
:ARG2 (p / protein :name (n / name :op1 "PP1")))
:quant (t3 / temporal-quantity :quant 3
:unit (d / day))))
:ARG1-of (c / cause-01
:ARG0 (d2 / die-01
:ARG1 (c2 / cell)
:mod (m / massive)
:time (a2 / after
:op1 a)))
:ARG1-of (d3 / describe-01
:ARG0 (f / figure :mod "5B")))
# ::id pmid_1956_8237.124 ::date 2015-08-15T13:35:53 ::annotator SDL-AMR-09 ::preferred
# ::snt Src protein is reduced in metastasis cell line
# ::save-date Tue Sep 1, 2015 ::file pmid_1956_8237_124.txt
(r / reduce-01
:ARG1 (p / protein :name (n / name :op1 "Src"))
:location (c / cell-line
:ARG1-of (m / metastasize-101)))
# ::id pmid_1956_8237.125 ::date 2015-08-15T13:36:45 ::annotator SDL-AMR-09 ::preferred
# ::snt Src is regulated by the phosphorylation of tyrosine residues at position 416 (Y416) and 527 (Y527).
# ::save-date Tue Sep 1, 2015 ::file pmid_1956_8237_125.txt
(r / regulate-01
:ARG0 (p2 / phosphorylate-01
:ARG1 (a3 / and
:op1 (r2 / residue
:mod (a / amino-acid :mod 416 :name (n2 / name :op1 "tyrosine")))
:op2 (r3 / residue
:mod (a4 / amino-acid :mod 527 :name (n3 / name :op1 "tyrosine")))))
:ARG1 (p / protein :name (n / name :op1 "Src")))
# ::id pmid_1956_8237.126 ::date 2015-08-15T13:43:45 ::annotator SDL-AMR-09 ::preferred
# ::snt The expression of phosphorylated Src Y416, which is associated with an active conformation, was low in the metastatic UM cell lines (Figure 6A).
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_126.txt
(l / low-04
:ARG1 (e / express-03
:ARG2 (a3 / amino-acid :mod 416 :name (n3 / name :op1 "tyrosine")
:part-of (p2 / protein :name (n / name :op1 "Src")
:ARG3-of (p3 / phosphorylate-01)))
:ARG1-of (a / associate-01
:ARG2 (c / conformation
:ARG0-of (a2 / activity-06))))
:location (c2 / cell-line
:mod (m2 / medical-condition :name (n2 / name :op1 "melanoma")
:mod (u / uveal)
:ARG1-of (m / metastasize-101)))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod "6A")))
# ::id pmid_1956_8237.127 ::date 2015-08-15T13:49:40 ::annotator SDL-AMR-09 ::preferred
# ::snt Surprisingly, the phosphorylation of Y527, which is associated with an inactive conformation, was also low, and a subsequent analysis indicated that Src expression is low in metastatic UM cell lines.
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_127.txt
(a / and
:op1 (l / low-04
:ARG1 (p / phosphorylate-01
:ARG1 (a2 / amino-acid :mod 527 :name (n / name :op1 "tyrosine"))
:ARG1-of (a3 / associate-01
:ARG2 (c / conformation
:ARG0-of (a4 / activity-06 :polarity -))))
:mod (a5 / also)
:manner (s2 / surprise-01))
:op2 (i / indicate-01
:ARG0 (a6 / analyze-01
:time (s / subsequent))
:ARG1 (l2 / low-04
:ARG1 (e / express-03
:ARG2 (p3 / protein :name (n2 / name :op1 "Src"))
:ARG3 (c2 / cell-line
:mod (m2 / medical-condition :name (n3 / name :op1 "melanoma")
:mod (u / uveal)
:ARG1-of (m / metastasize-101)))))))
# ::id pmid_1956_8237.128 ::date 2015-08-15T13:55:18 ::annotator SDL-AMR-09 ::preferred
# ::snt Therefore, the difference between kinase activity in metastatic cell lines (OMM1, OMM2.3 and OMM2.5) and UM cell lines (OCM1, OCM3, OCM8, Mel202, Mel270, Mel285, Mel290 and 92.1) seems to be the result of a difference in Src expression.
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_128.txt
(c14 / cause-01
:ARG1 (s / seem-01
:ARG1 (t / thing
:ARG2-of (r / result-01
:ARG1 (d / differ-02
:ARG3 (e / express-03
:ARG2 (p / protein :name (n / name :op1 "Src")))))
:domain (d2 / differ-02
:ARG1 (c / cell-line
:ARG1-of (m / metastasize-101)
:ARG2-of (i / include-91
:ARG1 (a2 / and
:op1 (c2 / cell-line :name (n2 / name :op1 "OMM1"))
:op2 (c3 / cell-line :name (n3 / name :op1 "OMM2.3"))
:op3 (c4 / cell-line :name (n4 / name :op1 "OMM2.5")))))
:ARG2 (c5 / cell-line
:mod (m3 / medical-condition :name (n5 / name :op1 "melanoma")
:mod (u / uveal))
:ARG1-of (m2 / mean-01
:ARG2 (a3 / and
:op1 (c6 / cell-line :name (n6 / name :op1 "OCM1"))
:op2 (c7 / cell-line :name (n7 / name :op1 "OCM3"))
:op3 (c8 / cell-line :name (n8 / name :op1 "OCM8"))
:op4 (c9 / cell-line :name (n9 / name :op1 "Mel202"))
:op5 (c10 / cell-line :name (n10 / name :op1 "Mel270"))
:op6 (c11 / cell-line :name (n11 / name :op1 "Mel285"))
:op7 (c12 / cell-line :name (n12 / name :op1 "Mel290"))
:op8 (c13 / cell-line :name (n13 / name :op1 "Mel292.1")))))
:ARG3 (a / activity-06
:ARG0 (k / kinase))))))
# ::id pmid_1956_8237.129 ::date 2015-08-15T14:08:25 ::annotator SDL-AMR-09 ::preferred
# ::snt To investigate the origin of a lowered Src expression, we performed a gene expression analysis (Figure 6B).
# ::save-date Tue Sep 1, 2015 ::file pmid_1956_8237_129.txt
(p / perform-02
:ARG0 (w / we)
:ARG1 (a / analyze-01
:ARG0 w
:ARG1 (e / express-03
:ARG2 (g / gene)))
:purpose (i / investigate-01
:ARG0 w
:ARG1 (o / originate-01
:ARG1 (e2 / express-03
:ARG2 (p2 / protein :name (n / name :op1 "Src"))
:ARG1-of (l / lower-05))))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "6B")))
# ::id pmid_1956_8237.130 ::date 2015-08-15T14:11:06 ::annotator SDL-AMR-09 ::preferred
# ::snt Src gene expression varied widely in the cell lines and in the metastatic cell lines, but a correlation between protein and gene expression was not observed in UM cell lines.
# ::save-date Thu Dec 10, 2015 ::file pmid_1956_8237_130.txt
(c / contrast-01
:ARG1 (v / vary-01
:ARG0 (e / express-03
:ARG2 (g / gene :wiki -
:name (n / name :op1 "Src"))
:ARG3 (a / and
:op1 (c2 / cell-line)
:op2 (c3 / cell-line
:ARG1-of (m / metastasize-101))))
:ARG1-of (w / wide-02))
:ARG2 (o / observe-01 :polarity -
:ARG1 (c4 / correlate-01
:ARG1 (e2 / express-03
:ARG2 (p / protein)
:ARG3 (c5 / cell-line
:mod (m2 / medical-condition :wiki "Melanoma"
:name (n2 / name :op1 "melanoma")
:mod (u / uveal))))
:ARG2 (e3 / express-03
:ARG2 (g2 / gene)
:ARG3 c5))))
# ::id pmid_1956_8237.131 ::date 2015-08-15T14:19:02 ::annotator SDL-AMR-09 ::preferred
# ::snt A western analysis of Src expression in UM and metastasis tissue revealed a very high Src expression in only one out of three primary UM, whereas all three metastasis tissues displayed medium expression of Src protein (Figure 6C).
# ::save-date Wed Dec 30, 2015 ::file pmid_1956_8237_131.txt
(c / contrast-01
:ARG1 (r / reveal-01
:ARG0 (a / analyze-01
:ARG1 (e / express-03
:ARG2 (p / protein :name (n2 / name :op1 "Src"))
:ARG3 (a2 / and
:op1 (m6 / medical-condition :name (n3 / name :op1 "melanoma")
:mod (u / uveal))
:op2 (t / tissue
:mod (m / metastasis))))
:mod (w / western))
:ARG1 (e2 / express-03
:ARG2 p
:ARG3 (m4 / medical-condition :quant 1 :name (n4 / name :op1 "melanoma")
:ARG1-of (i / include-91
:ARG2 (m5 / medical-condition :quant 3 :name (n5 / name :op1 "melanoma")
:mod (p2 / primary)
:mod u))
:mod u)
:ARG1-of (h / high-02
:degree (v / very))
:mod (o / only)))
:ARG2 (d4 / display-01
:ARG0 (t2 / tissue :quant 3
:ARG1-of (m2 / metastasize-101)
:mod (a3 / all))
:ARG1 (e3 / express-03
:ARG2 p
:degree (m3 / medium)))
:ARG1-of (d5 / describe-01
:ARG0 (f / figure :mod "6C")))
# ::id pmid_1991_9690.1 ::date 2015-08-13T06:32:51 ::annotator SDL-AMR-09 ::preferred
# ::snt Expression and function of hypoxia inducible factor-1 alpha in human melanoma under non-hypoxic conditions (PMID:19919690)
# ::save-date Thu Dec 10, 2015 ::file pmid_1991_9690_1.txt
(a / and
:op1 (e / express-03
:ARG2 (p / protein :name (n / name :op1 "hypoxia" :op2 "inducible" :op3 "factor-1" :op4 "alpha")))
:op2 (f / function-01
:ARG0 p)
:location (m / medical-condition :name (n2 / name :op1 "melanoma")
:mod (h / human))
:ARG1-of (d2 / describe-01
:ARG0 (p2 / publication-91
:ARG8 "PMID19919690"))
:ARG1-of (c / condition-01
:ARG2 (h2 / hypoxia :polarity -)))
# ::id pmid_1991_9690.6 ::date 2015-08-13T09:35:46 ::annotator SDL-AMR-09 ::preferred
# ::snt Results
# ::save-date Thu Aug 13, 2015 ::file pmid_1991_9690_6.txt
(t / thing
:ARG2-of (r / result-01))
# ::id pmid_1991_9690.7 ::date 2015-08-13T09:51:45 ::annotator SDL-AMR-09 ::preferred
# ::snt HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines.
# ::save-date Wed Dec 30, 2015 ::file pmid_1991_9690_7.txt
(i / increase-01
:ARG1 (a / and
:op1 (n3 / nucleic-acid :name (n / name :op1 "mRNA")
:ARG0-of (e / encode-01
:ARG1 (p / protein :name (n2 / name :op1 "HIF-1α"))))
:op2 p)
:location (a2 / and
:op1 (c / contrast-01
:ARG1 (c2 / cell-line
:mod (m / medical-condition :name (n6 / name :op1 "melanoma"))
:mod (p2 / phase
:mod (g / grow-01
:manner (r2 / radius))))
:ARG2 (m3 / melanocyte
:mod m))
:op2 (c4 / contrast-01
:ARG1 (c5 / cell-line
:mod m
:mod (p3 / phase
:mod (g2 / grow-01
:manner (v / vertical))))
:ARG2 c2)
:op3 (c7 / contrast-01
:ARG1 (c6 / cell-line
:mod m
:ARG1-of (m2 / metastasize-101))
:ARG2 c5)))
# ::id pmid_1991_9690.8 ::date 2015-08-13T10:05:00 ::annotator SDL-AMR-09 ::preferred
# ::snt We also detected expression of a HIF-1α mRNA splice variant that lacks part of the oxygen-dependent regulation domain in WM1366 and WM9 melanoma cells.
# ::save-date Thu Dec 10, 2015 ::file pmid_1991_9690_8.txt
(d / detect-01
:ARG0 (w / we)
:ARG1 (e / express-03
:ARG2 (v / variant
:ARG1-of (s / splice-01)
:mod (n6 / nucleic-acid :name (n / name :op1 "mRNA")
:ARG0-of (e2 / encode-01
:ARG1 (p / protein :name (n2 / name :op1 "HIF-1α"))))
:ARG0-of (l / lack-01
:ARG1 (t / thing
:part-of (d2 / domain
:ARG0-of (r2 / regulate-01)
:ARG0-of (d3 / depend-01
:ARG1 (o / oxygen))))
:location (a2 / and
:op1 (c / cell-line :name (n3 / name :op1 "WM1366")
:mod (m / medical-condition :name (n4 / name :op1 "melanoma")))
:op2 (c2 / cell-line :name (n5 / name :op1 "WM9")
:mod m)))))
:mod (a / also))
# ::id pmid_1991_9690.9 ::date 2015-08-13T14:08:13 ::annotator SDL-AMR-09 ::preferred
# ::snt Over-expression of HIF-1α and its splice variant in the RGP cell line SbCl2 resulted in a small increase in soft agar colony formation and a large increase in matrigel invasion relative to control transfected cells.
# ::save-date Sun Aug 16, 2015 ::file pmid_1991_9690_9.txt
(r / result-01
:ARG1 (o / overexpress-01
:ARG1 (a2 / and
:op1 (p / protein :name (n / name :op1 "HIF-1α"))
:op2 (v / variant
:ARG1-of (s / splice-01)
:poss p))
:location (c / cell-line :name (n2 / name :op1 "SbCl2")
:mod (p3 / phase
:mod (g / grow-01
:manner (r3 / radius)))))
:ARG2 (a / and
:op1 (i / increase-01
:ARG1 (f / form-01
:ARG1 (c2 / colony
:mod (a3 / agar
:ARG1-of (s3 / soft-02))))
:mod (s2 / small))
:op2 (i2 / increase-01
:ARG1 (i3 / invade-01
:ARG0 (p2 / protein :name (n4 / name :op1 "matrigel")))
:mod (l / large))
:ARG1-of (r2 / relative-05
:ARG3 (c3 / cell
:mod (c4 / control)
:ARG1-of (t2 / transfect-01)))))
# ::id pmid_1991_9690.10 ::date 2015-08-13T14:19:28 ::annotator SDL-AMR-09 ::preferred
# ::snt Knockdown of HIF-1α expression by siRNA in the MET WM9 melanoma cell line resulted in a large decrease in both soft agar colony formation and matrigel invasion relative to cells treated with non-specific siRNA.
# ::save-date Thu Dec 10, 2015 ::file pmid_1991_9690_10.txt
(r / result-01
:ARG1 (k / knock-down-02
:ARG0 (n5 / nucleic-acid :name (n2 / name :op1 "siRNA"))
:ARG1 (e / express-03
:ARG2 (p / protein :name (n / name :op1 "HIF-1α"))
:ARG3 (c / cell-line :name (n3 / name :op1 "WM9")
:mod (m / medical-condition :name (n4 / name :op1 "melanoma"))
:ARG1-of (m2 / metastasize-101))))
:ARG2 (d2 / decrease-01
:ARG1 (a / and
:op1 (f / form-01
:ARG1 (c2 / colony
:mod (a2 / agar
:ARG1-of (s / soft-02))))
:op2 (i / invade-01
:ARG0 (p2 / protein :name (n6 / name :op1 "matrigel"))))
:ARG1-of (r3 / relative-05
:ARG3 (c3 / cell
:ARG1-of (t2 / treat-04
:ARG2 (n8 / nucleic-acid :name (n7 / name :op1 "siRNA")
:ARG1-of (s2 / specific-02 :polarity -)))))
:mod (l / large)))
# ::id pmid_1991_9690.11 ::date 2015-08-14T06:57:56 ::annotator SDL-AMR-09 ::preferred
# ::snt There is a high level of ERK1/2 phosphorylation in WM9 cells, indicating an activated Ras-Raf-MEK-ERK1/2 MAPK pathway.
# ::save-date Fri Aug 14, 2015 ::file pmid_1991_9690_11.txt
(l2 / level
:ARG1-of (h / high-02)
:quant-of (p / phosphorylate-01
:ARG1 (e / enzyme :name (n2 / name :op1 "ERK1/2"))
:location (c / cell-line :name (n3 / name :op1 "WM9")))
:ARG0-of (i / indicate-01
:ARG1 (p3 / pathway :name (n4 / name :op1 "Ras-Raf-MEK-ERK1/2" :op2 "MAPK")
:ARG1-of (a / activate-01))))
# ::id pmid_1991_9690.12 ::date 2015-08-14T07:11:55 ::annotator SDL-AMR-09 ::preferred
# ::snt Treatment of WM9 cells with 30 μM U0126 MEK inhibitor, decreased ERK1/2 phosphorylation and resulted in a decrease in HIF-1α expression.
# ::save-date Sat Jan 16, 2016 ::file pmid_1991_9690_12.txt
(a / and
:op1 (d / decrease-01
:ARG0 (t2 / treat-04
:ARG1 (c / cell-line :name (n3 / name :op1 "WM9"))
:ARG2 (s2 / small-molecule :name (n4 / name :op1 "U0126")
:ARG0-of (i2 / inhibit-01
:ARG1 (p / protein-family :name (n5 / name :op1 "MEK")))
:quant (c2 / concentration-quantity :quant 30
:unit (m / micromolar))))
:ARG1 (p2 / phosphorylate-01
:ARG1 (e2 / enzyme :name (n6 / name :op1 "ERK1/2"))))
:op2 (r / result-01
:ARG1 t2
:ARG2 (d2 / decrease-01
:ARG1 (e3 / express-03
:ARG2 (p3 / protein :name (n7 / name :op1 "HIF-1α"))))))
# ::id pmid_1991_9690.13 ::date 2015-08-14T07:17:27 ::annotator SDL-AMR-09 ::preferred
# ::snt However, a 24 h treatment with 10 μM U0126 totally eliminated Erk1/2 phosphorylation, but did not change HIF-1alpha levels.
# ::save-date Fri Aug 14, 2015 ::file pmid_1991_9690_13.txt
(c / contrast-01
:ARG2 (c2 / contrast-01
:ARG1 (e / eliminate-01
:ARG0 (t / treat-04
:ARG2 (s / small-molecule :name (n / name :op1 "U0126")
:quant (c3 / concentration-quantity :quant 10
:unit (m / micromolar)))
:duration (t2 / temporal-quantity :quant 24
:unit (h / hour)))
:ARG1 (p / phosphorylate-01
:ARG1 (e2 / enzyme :name (n2 / name :op1 "ERK1/2")))
:degree (t3 / total))
:ARG2 (c4 / change-01 :polarity -
:ARG0 t
:ARG1 (l / level
:quant-of (p2 / protein :name (n3 / name :op1 "HIF-1alpha"))))))
# ::id pmid_1991_9690.14 ::date 2015-08-14T07:25:55 ::annotator SDL-AMR-09 ::preferred
# ::snt Furthermore, siRNA knockdown of MEK siRNA did not change HIF-1alpha levels.
# ::save-date Fri Aug 14, 2015 ::file pmid_1991_9690_14.txt
(a / and
:op2 (c / change-01 :polarity -
:ARG0 (k / knock-down-02
:ARG0 (n / nucleic-acid :name (n2 / name :op1 "siRNA"))
:ARG1 (n6 / nucleic-acid :name (n3 / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (e2 / enzyme :name (n4 / name :op1 "MEK")))))
:ARG1 (l / level
:quant-of (p2 / protein :name (n5 / name :op1 "HIF-1alpha")))))
# ::id pmid_1991_9690.47 ::date 2015-08-14T07:58:59 ::annotator SDL-AMR-09 ::preferred
# ::snt Results
# ::save-date Fri Aug 14, 2015 ::file pmid_1991_9690_47.txt
(t / thing
:ARG2-of (r / result-01))
# ::id pmid_1991_9690.48 ::date 2015-08-14T08:04:21 ::annotator SDL-AMR-09 ::preferred
# ::snt Expression of HIF-1α in human melanoma cells
# ::save-date Thu Dec 10, 2015 ::file pmid_1991_9690_48.txt
(e / express-03
:ARG2 (p / protein :name (n / name :op1 "HIF-1α"))
:ARG3 (c / cell
:mod (m / medical-condition :name (n2 / name :op1 "melanoma"))
:mod (h / human)))
# ::id pmid_1991_9690.49 ::date 2015-08-14T08:12:39 ::annotator SDL-AMR-09 ::preferred
# ::snt In addition to the well known pathway of HIF-1alpha protein stabilization under hpoxic conditions, it has been established that many oncoproteins and growth factor signaling pathways up-regulate HIF-1α expression under normoxic conditions [18,19].
# ::save-date Wed Feb 24, 2016 ::file pmid_1991_9690_49.txt
(e / establish-01
:ARG1 (a / and
:op1 (o / oncoprotein
:quant (m / many))
:op2 (p / pathway
:ARG0-of (s2 / signal-07)
:ARG0-of (u / upregulate-01
:ARG1 (e2 / express-03
:ARG2 (p2 / protein :name (n2 / name :op1 "HIF-1α")))
:ARG1-of (c / condition-01
:ARG2 (n3 / normoxia)))
:mod (g / growth-factor)))
:ARG1-of (a2 / add-02
:ARG2 (k / know-01
:ARG1 (p3 / pathway
:ARG0-of (s3 / stabilize-01
:ARG1 p2
:ARG1-of (c2 / condition-01
:ARG2 (h / hypoxia))))
:ARG1-of (w / well-09)))
:ARG1-of (d / describe-01
:ARG0 (p4 / publication
:ARG1-of (c3 / cite-01
:ARG2 (a3 / and :op1 18 :op2 19)))))
# ::id pmid_1991_9690.50 ::date 2015-08-14T08:51:55 ::annotator SDL-AMR-09 ::preferred
# ::snt However, there are few investigations into the normoxic expression of HIF-1α in human melanoma and its role in the malignant progression of this disease.
# ::save-date Thu Dec 10, 2015 ::file pmid_1991_9690_50.txt
(c / contrast-01
:ARG2 (i / investigate-01
:ARG1 (a / and
:op1 (e / express-03
:ARG2 (p / protein :name (n / name :op1 "HIF-1α"))
:ARG3 (m2 / medical-condition :name (n2 / name :op1 "melanoma")
:mod (h / human))
:mod (n3 / normoxia))
:op2 (r / role
:poss e
:topic (p2 / progress-01
:ARG1 m2
:ARG1-of (m / malignant-02))))
:quant (f / few)))
# ::id pmid_1991_9690.51 ::date 2015-08-14T08:57:27 ::annotator SDL-AMR-09 ::preferred
# ::snt Here, we show that in human melanoma cells, the oxygen-labile HIF-1α protein as well as its mRNA is expressed endogenously under normoxic conditions.
# ::save-date Thu Dec 10, 2015 ::file pmid_1991_9690_51.txt
(s / show-01
:ARG0 (w / we)
:ARG1 (e / express-03
:ARG2 (a / and
:op1 (p / protein :name (n2 / name :op1 "HIF-1α")
:mod (l2 / labile
:topic (o / oxygen)))
:op2 (n5 / nucleic-acid :name (n3 / name :op1 "mRNA")
:ARG0-of (e2 / encode-01
:ARG1 p)))
:ARG3 (c / cell
:mod (m / medical-condition :name (n / name :op1 "melanoma"))
:mod (h / human))
:manner (e3 / endogenous)
:ARG1-of (c2 / condition-01
:ARG2 (n4 / normoxic)))
:medium (h2 / here))
# ::id pmid_1991_9690.52 ::date 2015-08-14T09:07:06 ::annotator SDL-AMR-09 ::preferred
# ::snt Figure 1A shows that HIF-1α protein is highly expressed in WM9 cells relative to normal human melanocyte (HEMn-LP), but radial growth phase (SbCl2), and vertical growth phase (WM1366) also express a higher amount of HIF-1α protein relative to human melanocytes.
# ::save-date Tue Aug 18, 2015 ::file pmid_1991_9690_52.txt
(s / show-01
:ARG0 (f / figure :mod "1A")
:ARG1 (c / contrast-01
:ARG1 (e / express-03
:ARG2 (p / protein :name (n / name :op1 "HIF-1α"))
:ARG3 (c2 / cell-line :name (n2 / name :op1 "WM9"))
:ARG1-of (h2 / high-02)
:ARG1-of (r / relative-05
:ARG3 (m3 / melanocyte
:ARG1-of (n9 / normal-02)
:mod (h3 / human)
:ARG1-of (m2 / mean-01
:ARG2 (c7 / cell-line :name (n8 / name :op1 "HEMn-LP"))))))
:ARG2 (e2 / express-03
:ARG2 (a3 / amount-01
:ARG1 p
:ARG1-of (h / high-02
:degree (m / more)))
:ARG3 (a / and
:op1 (p2 / phase
:mod (g / grow-01
:manner (r2 / radius))
:example (c4 / cell-line :name (n5 / name :op1 "SbCI2")))
:op2 (p3 / phase
:mod (g2 / grow-01
:manner (v / vertical))
:example (c5 / cell-line :name (n6 / name :op1 "WM1366"))))
:mod (a2 / also)
:ARG1-of (r3 / relative-05
:mod (m4 / melanocyte
:mod h3)))))
# ::id pmid_1991_9690.53 ::date 2015-08-14T10:16:13 ::annotator SDL-AMR-09 ::preferred
# ::snt Similar results are seen in second set of RGP, VGP and MET melanoma cell lines (Fig. 1B).
# ::save-date Thu Dec 10, 2015 ::file pmid_1991_9690_53.txt
(s / see-01
:ARG1 (t / thing
:ARG2-of (r2 / result-01)
:ARG1-of (r / resemble-01))
:location (s2 / set
:ord (o / ordinal-entity :value 2)
:consist-of (a / and
:op1 (c / cell-line
:mod (p / phase
:mod (g / grow-01
:manner (r3 / radius))))
:op2 (c2 / cell-line
:mod (p2 / phase
:mod (g2 / grow-01
:manner (v / vertical))))
:op3 (c3 / cell-line
:ARG1-of (m2 / metastasize-101))
:mod (m / medical-condition :name (n / name :op1 "melanoma"))))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod "1B")))
# ::id pmid_1991_9690.54 ::date 2015-08-14T10:37:38 ::annotator SDL-AMR-09 ::preferred
# ::snt HIF-1α was detected as 120 kD protein in nuclear extracts while no protein was detected in cytoplasmic extracts (data not shown).
# ::save-date Fri Aug 14, 2015 ::file pmid_1991_9690_54.txt
(c / contrast-01
:ARG1 (d / detect-01
:ARG1 (p / protein :name (n / name :op1 "HIF-1α")
:quant (m / mass-quantity :quant 120
:unit (k / kilodalton)))
:location (t / thing
:ARG1-of (e / extract-01)
:mod (n2 / nucleus)))
:ARG2 (d2 / detect-01 :polarity -
:ARG1 (p2 / protein)
:location (t2 / thing
:ARG1-of (e2 / extract-01)
:mod (c2 / cytoplasm)))
:ARG1-of (d3 / describe-01
:ARG0 (d4 / data
:ARG1-of (s / show-01 :polarity -))))
# ::id pmid_1991_9690.55 ::date 2015-08-14T11:12:27 ::annotator SDL-AMR-09 ::preferred
# ::snt Hypoxic stabilization of HIF-1α occurs at the protein level [3].
# ::save-date Tue Aug 18, 2015 ::file pmid_1991_9690_55.txt
(s / stabilize-01
:ARG1 (p / protein :name (n / name :op1 "HIF-1α"))
:ARG2 (l / level
:quant-of (p2 / protein))
:mod (h / hypoxia)
:ARG1-of (d / describe-01
:ARG0 (p3 / publication
:ARG1-of (c / cite-01
:ARG2 3))))
# ::id pmid_1991_9690.56 ::date 2015-08-14T11:15:07 ::annotator SDL-AMR-09 ::preferred
# ::snt Since HIF-1α protein was increased in human melanoma cells under normoxic conditions, we determined whether this increase might be due to increased HIF-1α mRNA levels.
# ::save-date Thu Dec 10, 2015 ::file pmid_1991_9690_56.txt
(d / determine-01
:ARG0 (w / we)
:ARG1 (p2 / possible-01 :mode interrogative
:ARG1 (c / cause-01
:ARG0 (l / level
:quant-of (n5 / nucleic-acid :name (n / name :op1 "mRNA")
:ARG0-of (e / encode-01
:ARG1 (p3 / protein :name (n2 / name :op1 "HIF-1α"))))
:ARG1-of (i3 / increase-01))
:ARG1 (i / increase-01
:mod (t / this))))
:ARG1-of (c4 / cause-01
:ARG0 (i2 / increase-01
:ARG1 p3
:location (c2 / cell
:mod (m / medical-condition :name (n3 / name :op1 "melanoma"))
:mod (h / human)
:ARG1-of (c3 / condition-01
:ARG2 (n4 / normoxia))))))
# ::id pmid_1991_9690.57 ::date 2015-08-14T12:05:32 ::annotator SDL-AMR-09 ::preferred
# ::snt Initially we used semi-quantitative RT-PCR to assess expression of HIF-1α full length (FL) and a splice variant HIF-1α785 that is missing the acetylation site lys532 due to lack of exon 11 (Fig. 2A).
# ::save-date Sun Jan 17, 2016 ::file pmid_1991_9690_57.txt
(u / use-01
:ARG0 (w / we)
:ARG1 (t / thing :name (n / name :op1 "RT-PCR")
:mod (q / quantitative
:degree (s / semi)))
:ARG2 (a / assess-01
:ARG0 w
:ARG1 (a2 / and
:op1 (e / express-03
:ARG2 (p / protein :name (n2 / name :op1 "HIF-1α"))
:ARG1-of (l / long-03
:degree (f / full)))
:op2 (v / variant
:ARG1-of (s2 / splice-01)
:ARG1-of (m2 / mean-01
:ARG2 (p2 / protein :name (n4 / name :op1 "HIF-1α785")))
:ARG0-of (m / miss-01
:ARG1 (s3 / site-01
:ARG0-of (a4 / acetylate-01)
:mod (a3 / amino-acid :mod 532 :name (n3 / name :op1 "lysine")))
:ARG1-of (c / cause-01
:ARG0 (l2 / lack-01
:ARG1 (e2 / exon :mod 11)))))))
:time (i / initial)
:ARG1-of (d / describe-01
:ARG0 (f2 / figure :mod "2A")))
# ::id pmid_1991_9690.58 ::date 2015-08-15T02:35:20 ::annotator SDL-AMR-09 ::preferred
# ::snt This splice variant encodes HIF-1α protein that has been reported to be stable under normoxic conditions [17,20].
# ::save-date Tue Aug 18, 2015 ::file pmid_1991_9690_58.txt
(e / encode-01
:ARG0 (v / variant
:ARG1-of (s / splice-01)
:mod (t / this))
:ARG1 (p / protein :name (n / name :op1 "HIF-1α")
:ARG1-of (s2 / stable-03
:ARG1-of (c / condition-01
:ARG2 (n2 / normoxia))
:ARG1-of (r / report-01)))
:ARG1-of (d / describe-01
:ARG0 (p2 / publication
:ARG1-of (c2 / cite-01
:ARG2 (a / and :op1 17 :op2 20)))))
# ::id pmid_1991_9690.59 ::date 2015-08-15T02:46:07 ::annotator SDL-AMR-09 ::preferred
# ::snt Primers were designed so that full length HIF-1α would exclude HIF-1α785 by targeting exon 11, which is absent in HIF-1α785.
# ::save-date Fri Nov 20, 2015 ::file pmid_1991_9690_59.txt
(d / design-01
:ARG1 (p3 / primer)
:ARG3 (e / exclude-01
:ARG0 (p / protein :name (n2 / name :op1 "HIF-1α")
:ARG1-of (l2 / long-03
:degree (f / full)))
:ARG1 (p2 / protein :name (n3 / name :op1 "HIF-1α785"))
:manner (t / target-01
:ARG0 p
:ARG1 (e2 / exon :mod 11
:ARG1-of (a / absent-01
:ARG2 p2)))))
# ::id pmid_1991_9690.60 ::date 2015-08-15T03:01:12 ::annotator SDL-AMR-09 ::preferred
# ::snt Primers for HIF-1α785 excluded HIF-1α by targeting the exon 10:12 boundary only present in HIF-1α785.
# ::save-date Fri Nov 20, 2015 ::file pmid_1991_9690_60.txt
(e / exclude-01
:ARG0 (p4 / primer
:beneficiary (p / protein :name (n2 / name :op1 "HIF-1α758")))
:ARG1 (p2 / protein :name (n3 / name :op1 "HIF-1α"))
:manner (t / target-01
:ARG0 p4
:ARG1 (b / boundary
:ARG1-of (p3 / present-02
:ARG2 p
:mod (o / only))
:mod (b2 / between
:op1 (e2 / exon :mod 10)
:op2 (e3 / exon :mod 12)))))
# ::id pmid_1991_9690.61 ::date 2015-08-15T03:08:45 ::annotator SDL-AMR-09 ::preferred
# ::snt Fig. 2B shows that human melanoma cell lines express both full-length and the 785 splice variant HIF-1α mRNA at a level that appeared to be higher than normal human melanocytes.
# ::save-date Sun Jan 17, 2016 ::file pmid_1991_9690_61.txt
(s / show-01
:ARG0 (f / figure :mod "2B")
:ARG1 (e / express-03
:ARG2 (a / and
:op1 (n6 / nucleic-acid :name (n2 / name :op1 "mRNA")
:ARG0-of (e2 / encode-01
:ARG1 (p / protein :name (n3 / name :op1 "HIF-1α")
:ARG1-of (l3 / long-03
:degree (f2 / full)))))
:op2 (n7 / nucleic-acid :name (n4 / name :op1 "mRNA")
:ARG0-of (e3 / encode-01
:ARG1 (v / variant
:ARG1-of (s2 / splice-01)
:ARG1-of (m2 / mean-01
:ARG2 (p2 / protein :name (n5 / name :op1 "HIF-1α785")))))))
:ARG3 (c / cell-line
:mod (m4 / medical-condition :name (n / name :op1 "melanoma"))
:mod (h2 / human))
:manner (l2 / level
:ARG1-of (a2 / appear-01)
:ARG1-of (h / high-02
:degree (m / more)
:compared-to (m3 / melanocyte
:ARG1-of (n8 / normal-02)
:mod (h3 / human))))))
# ::id pmid_1991_9690.62 ::date 2015-08-15T03:20:33 ::annotator SDL-AMR-09 ::preferred
# ::snt These findings were verified by qRT-PCR measurement of full-length and HIF-1α785 mRNA levels (Fig. 3).
# ::save-date Tue Aug 18, 2015 ::file pmid_1991_9690_62.txt
(v / verify-01
:ARG0 (m / measure-01
:ARG1 (a / and
:op1 (l / level
:quant-of (n3 / nucleic-acid :name (n2 / name :op1 "mRNA")
:ARG1-of (l4 / long-03
:degree (f2 / full))))
:op2 (l3 / level
:quant-of (n6 / nucleic-acid :name (n4 / name :op1 "mRNA")
:ARG0-of (e2 / encode-01
:ARG1 (p2 / protein-segment :name (n5 / name :op1 "HIF-1α785"))))))
:mod (t3 / thing :name (n / name :op1 "RT-PCR")
:mod (q / quantitative)))
:ARG1 (t / thing
:ARG1-of (f / find-01)
:mod (t2 / this))
:ARG1-of (d / describe-01
:ARG0 (f3 / figure :mod 3)))
# ::id pmid_1991_9690.63 ::date 2015-08-15T03:57:36 ::annotator SDL-AMR-09 ::preferred
# ::snt All melanoma cell lines had increased expression of HIF-1α mRNA relative to normal human melanocytes.
# ::save-date Thu Dec 10, 2015 ::file pmid_1991_9690_63.txt
(i / increase-01
:ARG1 (e / express-03
:ARG2 (n4 / nucleic-acid :name (n2 / name :op1 "mRNA")
:ARG0-of (e2 / encode-01
:ARG1 (p / protein :name (n3 / name :op1 "HIF-1α"))))
:ARG3 (c / cell-line
:mod (m2 / medical-condition :name (n / name :op1 "melanoma"))
:mod (a / all))
:ARG1-of (r2 / relative-05
:ARG3 (m / melanocyte
:ARG1-of (n6 / normal-02)
:mod (h / human)))))
# ::id pmid_1991_9690.64 ::date 2015-08-15T04:02:27 ::annotator SDL-AMR-09 ::preferred
# ::snt In addition VGP and MET cell lines expressed more of the 785 HIF-1α mRNA than full length HIF-1α mRNA.
# ::save-date Sun Jan 17, 2016 ::file pmid_1991_9690_64.txt
(a / and
:op2 (e / express-03
:ARG2 (n / nucleic-acid :name (n3 / name :op1 "mRNA")
:ARG0-of (e2 / encode-01
:ARG1 (p / protein :name (n4 / name :op1 "HIF-1α785"))))
:ARG3 (a2 / and
:op1 (c / cell-line
:mod (p3 / phase
:mod (g / grow-01
:manner (v / vertical))))
:op2 (c2 / cell-line
:mod (m2 / metastasis)))
:compared-to (e3 / express-03
:ARG2 (n2 / nucleic-acid :name (n5 / name :op1 "mRNA")
:ARG0-of (e4 / encode-01
:ARG1 (p2 / protein :name (n6 / name :op1 "HIF-1α")
:ARG1-of (l2 / long-03
:degree (f / full)))))
:ARG3 a2)
:degree (m / more)))
# ::id pmid_1991_9690.65 ::date 2015-08-15T04:13:53 ::annotator SDL-AMR-09 ::preferred
# ::snt Overall the WM9 metastatic melanoma expressed the highest amount of 785 HIF-1α mRNA (~79× higher than normal human melanocytes).
# ::save-date Thu Dec 10, 2015 ::file pmid_1991_9690_65.txt
(e / express-03
:ARG2 (a / amount-01
:ARG1 (n5 / nucleic-acid :name (n3 / name :op1 "mRNA")
:ARG0-of (e2 / encode-01
:ARG1 (p / protein-segment :name (n4 / name :op1 "HIF-1α785"))))
:ARG2 (h2 / high-02
:degree (m2 / more)
:mod (a2 / approximately
:op1 (p2 / product-of :op1 79))
:compared-to (m3 / melanocyte
:ARG1-of (n7 / normal-02)
:mod (h3 / human)))
:ARG1-of (h / high-02
:degree (m / most)))
:ARG3 (c / cell-line :name (n / name :op1 "WM9")
:mod (m5 / medical-condition :name (n2 / name :op1 "melanoma")
:ARG1-of (m4 / metastasize-101)))
:mod (o / overall))
# ::id pmid_1991_9690.66 ::date 2015-08-15T04:31:21 ::annotator SDL-AMR-09 ::preferred
# ::snt HIFαFL and HIF-1α785 gain-of-function in radial growth phase SbCl2 cells
# ::save-date Tue Aug 18, 2015 ::file pmid_1991_9690_66.txt
(m / mutate-01
:ARG1 (a / and
:op1 (p / protein :name (n / name :op1 "HIFα")
:ARG1-of (l2 / long-03
:degree (f / full)))
:op2 (p2 / protein-segment :name (n2 / name :op1 "HIF-1α785")))
:location (c / cell-line :name (n3 / name :op1 "SbCl2")
:mod (p3 / phase
:mod (g2 / grow-01
:manner (r / radius))))
:manner (g3 / gain-02
:ARG0 a
:ARG1 (f2 / function-01)))
# ::id pmid_1991_9690.67 ::date 2015-08-15T04:58:43 ::annotator SDL-AMR-09 ::preferred
# ::snt The level of HIF-1α protein is low in the radial growth phase SbCl2 cells relative to VGP or MET cell lines.
# ::save-date Wed Aug 19, 2015 ::file pmid_1991_9690_67.txt
(l / low-04
:ARG1 (l2 / level
:quant-of (p / protein :name (n / name :op1 "HIF-1α")))
:location (c / cell-line :name (n2 / name :op1 "SbCl2")
:mod (p2 / phase
:mod (g / grow-01
:manner (r / radius))))
:ARG1-of (r2 / relative-05
:ARG3 (a / and
:op1 (c2 / cell-line
:mod (p3 / phase
:mod (g2 / grow-01
:manner (v / vertical))))
:op2 (c3 / cell-line
:ARG1-of (m / metastasize-101)))))
# ::id pmid_1991_9690.68 ::date 2015-08-15T05:31:43 ::annotator SDL-AMR-09 ::preferred
# ::snt We determined the effect of HIF-1αFL or HIF-1α785 overexpression on SbCl2 anchorage-independent growth and Matrigel invasion.
# ::save-date Sun Jan 17, 2016 ::file pmid_1991_9690_68.txt
(d / determine-01
:ARG0 (w / we)
:ARG1 (a / affect-01
:ARG0 (o / overexpress-01
:ARG1 (o2 / or
:op1 (p / protein :wiki "HIF1A" :name (n / name :op1 "HIF-1α")
:ARG1-of (l2 / long-03
:degree (f / full)))
:op2 (p2 / protein :wiki - :name (n2 / name :op1 "HIF-1α785")))
:location (c / cell-line :wiki - :name (n4 / name :op1 "SbCl2")))
:ARG1 (a2 / and
:op1 (g / grow-01
:ARG0-of (d2 / depend-01 :polarity -
:ARG1 (a3 / anchorage)))
:op2 (i / invade-01
:ARG0 (p3 / protein :wiki "Matrigel" :name (n3 / name :op1 "Matrigel"))))))
# ::id pmid_1991_9690.69 ::date 2015-08-15T05:40:38 ::annotator SDL-AMR-09 ::preferred
# ::snt HIF-1αFL and HIF-1α785 were cloned into the pLenti-V5-D-TOPO vector and transiently overexpressed in SbCl2 cells (Fig. 4A).
# ::save-date Sun Jan 17, 2016 ::file pmid_1991_9690_69.txt
(a / and
:op1 (c / clone-01
:ARG1 (a2 / and
:op1 (p / protein :name (n / name :op1 "HIF-1α")
:ARG1-of (l2 / long-03
:degree (f3 / full)))
:op2 (p2 / protein :name (n2 / name :op1 "HIF-1α785")))
:instrument (v / vector :name (n3 / name :op1 "pLenti-V5-D-TOPO")))
:op2 (o / overexpress-01
:ARG1 a2
:ARG1-of (t / transient-02)
:location (c2 / cell-line :name (n4 / name :op1 "SbCl2")))
:ARG1-of (d / describe-01
:ARG0 (f2 / figure :mod "4A")))
# ::id pmid_1991_9690.70 ::date 2015-08-15T06:25:07 ::annotator SDL-AMR-09 ::preferred
# ::snt HIF-1α785 overexpression resulted in a small, but statistically significant increase in anchorage-independent growth, relative to mock or lacz transfected cells (Fig. 4C and 4D).
# ::save-date Fri Nov 20, 2015 ::file pmid_1991_9690_70.txt
(r / result-01
:ARG1 (o / overexpress-01
:ARG1 (p / protein :name (n / name :op1 "HIF-1α785")))
:ARG2 (i2 / increase-01
:ARG1 (g / grow-01
:ARG0-of (d / depend-01
:ARG1 (a / anchorage)))
:mod (s / small
:ARG1-of (c / contrast-01
:ARG2 (s2 / significant-02
:mod (s3 / statistics)))
:ARG1-of (r2 / relative-05
:ARG3 (o2 / or
:op1 (c4 / cell
:ARG1-of (t2 / transfect-01
:mod (m / mock)))
:op2 (c2 / cell
:ARG1-of (t / transfect-01
:ARG2 (p2 / protein :name (n3 / name :op1 "lacz"))))))))
:ARG1-of (d2 / describe-01
:ARG0 (a2 / and
:op1 (f / figure :mod "4C")
:op2 (f2 / figure :mod "4D"))))
# ::id pmid_1991_9690.71 ::date 2015-08-16T03:28:58 ::annotator SDL-AMR-09 ::preferred
# ::snt In contrast overexpression of both HIF-1αFL and HIF-α785 in SbCl2 resulted in a large and significant 3-fold increase in Matrigel invasion relative to mock or Lacz transfected cells (Fig. 4B).
# ::save-date Fri Nov 20, 2015 ::file pmid_1991_9690_71.txt
(c / contrast-01
:ARG2 (r / result-01
:ARG1 (o / overexpress-01
:ARG1 (a / and
:op1 (p / protein :name (n / name :op1 "HIF-1α")
:ARG1-of (l4 / long-03
:degree (f / full)))
:op2 (p2 / protein :name (n2 / name :op1 "HIF-1α785")))
:location (c2 / cell-line :name (n3 / name :op1 "SbCl2")))
:ARG2 (i / increase-01
:ARG1 (i2 / invade-01
:ARG0 (p4 / protein :name (n4 / name :op1 "matrigel")))
:ARG2 (p3 / product-of :op1 3)
:mod (l3 / large)
:ARG1-of (s / significant-02)
:ARG1-of (r2 / relative-05
:ARG3 (t2 / transfect-01
:ARG1 (c5 / cell)
:ARG2 (o3 / or
:op1 (v / vector
:mod (m / mock))
:op2 (p5 / protein :name (n6 / name :op1 "lacz")))))))
:ARG1-of (d / describe-01
:ARG0 (f2 / figure :mod "4B")))
# ::id pmid_1991_9690.72 ::date 2015-08-16T04:26:12 ::annotator SDL-AMR-09 ::preferred
# ::snt HIF-1α loss-of-function in human metastatic melanoma WM9 cells
# ::save-date Thu Dec 10, 2015 ::file pmid_1991_9690_72.txt
(l2 / lose-02
:ARG0 (p / protein :name (n / name :op1 "HIF-1α")
:mod (l / lose-01))
:ARG1 (f / function-01)
:location (c / cell-line :name (n2 / name :op1 "WM9")
:mod (h / human)
:mod (m / medical-condition :name (n3 / name :op1 "melanoma"))
:ARG1-of (m2 / metastasize-101)))
# ::id pmid_1991_9690.73 ::date 2015-08-16T04:31:24 ::annotator SDL-AMR-09 ::preferred
# ::snt HIF-1α protein is highly expressed under normoxic conditions in the WM9 human metastatic melanoma cell line.
# ::save-date Thu Dec 10, 2015 ::file pmid_1991_9690_73.txt
(e / express-03
:ARG2 (p / protein :name (n / name :op1 "HIF-1α"))
:ARG3 (c / cell-line :name (n2 / name :op1 "WM9")
:mod (h / human)
:mod (m / medical-condition :name (n3 / name :op1 "melanoma"))
:ARG1-of (m2 / metastasize-101))
:ARG1-of (c2 / condition-01
:ARG2 (n4 / normoxia))
:ARG1-of (h2 / high-02))
# ::id pmid_1991_9690.74 ::date 2015-08-16T04:35:16 ::annotator SDL-AMR-09 ::preferred
# ::snt To determine whether HIF-1α could be contributing to the malignant characteristics of these cells, we knocked down its expression and examine how this affected anchorage independent growth and Matrigel invasion.
# ::save-date Wed Aug 19, 2015 ::file pmid_1991_9690_74.txt
(a / and
:op1 (k / knock-down-02
:ARG0 (w / we)
:ARG1 (e / express-03
:ARG2 (p2 / protein :name (n / name :op1 "HIF-1α"))))
:op2 (e2 / examine-01
:ARG0 w
:ARG1 (t2 / thing
:manner-of (a2 / affect-01
:ARG0 k
:ARG1 (a3 / and
:op1 (g / grow-01
:ARG0-of (d / depend-01 :polarity -
:ARG1 (a4 / anchorage)))
:op2 (i / invade-01
:ARG0 (p3 / protein :name (n2 / name :op1 "matrigel")))))))
:purpose (d2 / determine-01
:ARG0 w
:ARG1 (p / possible-01 :mode interrogative
:ARG1 (c / contribute-01
:ARG0 p2
:ARG1 (c2 / characteristic-02
:ARG1 (c3 / cell
:mod (t / this))
:ARG2 (m / malignant-02))))))
# ::id pmid_1991_9690.75 ::date 2015-08-16T04:43:42 ::annotator SDL-AMR-09 ::preferred
# ::snt WM9 cells were treated with 100 nM siRNA targeting HIF-1α (Dharmacon) which consistently decreased its expression by ~75-85% (Fig. 5A).
# ::save-date Mon Feb 1, 2016 ::file pmid_1991_9690_75.txt
(t / treat-04
:ARG1 (c / cell-line :name (n / name :op1 "WM9"))
:ARG2 (n5 / nucleic-acid :name (n2 / name :op1 "siRNA")
:ARG0-of (t2 / target-01
:ARG1 (p / protein :name (n3 / name :op1 "HIF-1α")))
:quant (c2 / concentration-quantity :quant 100
:unit (n4 / nanomolar))
:source (c4 / company :name (n6 / name :op1 "Dharmacon")))
:ARG0-of (d / decrease-01
:ARG1 (e / express-03
:ARG2 p)
:ARG2 (a / approximately
:op1 (v / value-interval
:op1 (p2 / percentage-entity :value 75)
:op2 (p3 / percentage-entity :value 85)))
:manner (c3 / consistent-02))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod "5A")))
# ::id pmid_1991_9690.76 ::date 2015-08-16T04:54:11 ::annotator SDL-AMR-09 ::preferred
# ::snt Colony formation after 5 days in soft agarose was inhibited by 70% in HIF-1α-siRNA transfected WM9 cells in comparison to cells transfected with control siRNA (Fig. 5B).
# ::save-date Sat Feb 13, 2016 ::file pmid_1991_9690_76.txt
(i / inhibit-01
:ARG1 (f / form-01
:ARG1 (c / colony)
:time (a / after
:quant (t2 / temporal-quantity :quant 5
:unit (d2 / day)))
:location (a2 / agarose
:ARG1-of (s / soft-02)))
:quant (p / percentage-entity :value 70)
:location (c2 / cell-line :name (n2 / name :op1 "WM9")
:ARG1-of (t3 / transfect-01
:ARG2 (n6 / nucleic-acid :name (n3 / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (p2 / protein :name (n4 / name :op1 "HIF-1α"))))))
:compared-to (c3 / cell
:ARG1-of (t4 / transfect-01
:ARG2 (n7 / nucleic-acid :name (n5 / name :op1 "siRNA")
:mod (c4 / control))))
:ARG1-of (d3 / describe-01
:ARG0 (f2 / figure :mod "5B")))
# ::id pmid_1991_9690.77 ::date 2015-08-16T05:04:33 ::annotator SDL-AMR-09 ::preferred
# ::snt A photo (Fig. 5C) of the colonies formed at this time point in control vs. HIF-1α transfected cells verifies this decrease in soft agar colony formation.
# ::save-date Wed Aug 19, 2015 ::file pmid_1991_9690_77.txt
(v / verify-01
:ARG0 (p / photograph-01
:ARG1 (c / colony
:ARG1-of (f / form-01
:time (p2 / point)
:location (c2 / contrast-01
:ARG1 (c3 / cell
:ARG1-of (t / transfect-01
:ARG2 (p3 / protein :name (n / name :op1 "HIF-1α"))))
:ARG2 (c4 / cell
:mod (c5 / control)
:ARG1-of (t2 / transfect-01)))))
:ARG1-of (d2 / describe-01
:ARG0 (f3 / figure :mod "5C")))
:ARG1 (d / decrease-01
:ARG1 (f2 / form-01
:ARG1 (c6 / colony
:location (a / agar
:ARG1-of (s / soft-02))))
:mod (t3 / this)))
# ::id pmid_1991_9690.78 ::date 2015-08-16T05:16:14 ::annotator SDL-AMR-09 ::preferred
# ::snt Matrigel invasion was also significantly decreased in HIF-1α-siRNA transfected WM9 cells compared to control siRNA transfected WM9 cells (Fig. 5D).
# ::save-date Sun Aug 16, 2015 ::file pmid_1991_9690_78.txt
(d / decrease-01
:ARG1 (i / invade-01
:ARG0 (p / protein :name (n / name :op1 "matrigel")))
:mod (a / also)
:ARG1-of (s / significant-02)
:location (c / cell-line :name (n2 / name :op1 "WM9")
:ARG1-of (t / transfect-01
:ARG2 (n7 / nucleic-acid :name (n3 / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (p2 / protein :name (n4 / name :op1 "HIF-1α"))))))
:compared-to (c2 / cell-line :name (n5 / name :op1 "WM9")
:ARG1-of (t2 / transfect-01
:ARG2 (n8 / nucleic-acid :name (n6 / name :op1 "siRNA")
:mod (c3 / control))))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod "5D")))
# ::id pmid_1991_9690.79 ::date 2015-08-16T05:23:15 ::annotator SDL-AMR-09 ::preferred
# ::snt Measurement of cell viability in the Matrigel chambers shows no difference between control vs. HIF-1α siRNA transfected cells (Fig. 5E).
# ::save-date Wed Aug 19, 2015 ::file pmid_1991_9690_79.txt
(s / show-01
:ARG0 (m / measure-01
:ARG1 (v / viable
:domain (c / cell))
:location (c2 / chamber
:mod (p / protein :name (n / name :op1 "matrigel"))))
:ARG1 (d / differ-02 :polarity -
:ARG1 (c4 / cell
:ARG1-of (t / transfect-01
:ARG2 (n5 / nucleic-acid :name (n2 / name :op1 "siRNA")
:mod (c5 / control))))
:ARG2 (c6 / cell
:ARG1-of (t2 / transfect-01
:ARG2 (n6 / nucleic-acid :name (n3 / name :op1 "siRNA")
:ARG0-of (e / encode-01
:ARG1 (p2 / protein :name (n4 / name :op1 "HIF-1α")))))))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod "5E")))
# ::id pmid_1991_9690.80 ::date 2015-08-16T06:02:49 ::annotator SDL-AMR-09 ::preferred
# ::snt These knock down studies suggest that increased non-hypoxic expression of HIF-1α plays an important role in key malignant properties exhibited by these human melanoma cells.
# ::save-date Wed Dec 30, 2015 ::file pmid_1991_9690_80.txt
(s / suggest-01
:ARG0 (s2 / study-01
:ARG1 (k / knock-down-02)
:mod (t / this))
:ARG1 (p / play-02
:ARG0 (e / express-03
:ARG2 (p2 / protein :wiki "HIF1A"
:name (n / name :op1 "HIF-1α"))
:mod (h / hypoxic :polarity -)
:ARG1-of (i / increase-01))
:ARG1 (r / role
:mod (i2 / important)
:topic (p3 / property
:ARG1-of (m / malignant-02)
:ARG1-of (k2 / key-02)
:ARG1-of (e2 / exhibit-01
:ARG0 (c / cell
:mod (m2 / medical-condition :wiki "Melanoma"
:name (n2 / name :op1 "melanoma"))
:mod (h2 / human)
:mod (t2 / this)))))))
# ::id pmid_1991_9690.81 ::date 2015-08-16T06:26:20 ::annotator SDL-AMR-09 ::preferred
# ::snt Regulation of HIF-1α expression in human melanoma by the ERK1/2 MAPK pathway
# ::save-date Thu Dec 10, 2015 ::file pmid_1991_9690_81.txt
(r / regulate-01
:ARG0 (p2 / pathway :name (n2 / name :op1 "ERK1/2" :op2 "MAPK"))
:ARG1 (e / express-03
:ARG2 (p3 / protein :name (n3 / name :op1 "HIF-1α"))
:ARG3 (m / medical-condition :name (n4 / name :op1 "melanoma")
:mod (h / human))))
# ::id pmid_1991_9690.82 ::date 2015-08-16T06:28:49 ::annotator SDL-AMR-09 ::preferred
# ::snt Hypoxia independent expression of HIF-1α is thought to be regulated by growth signaling pathways [18,19] and the majority of melanomas have constitutively active ERK1/2 MAPK pathway due to BRAF or N-Ras mutations [14,15].
# ::save-date Thu Dec 10, 2015 ::file pmid_1991_9690_82.txt
(a2 / and
:op1 (t / think-01
:ARG1 (r / regulate-01
:ARG0 (p3 / pathway
:ARG0-of (s / signal-07
:ARG1 (g / grow-01)))
:ARG1 (e / express-03
:ARG2 (p2 / protein :name (n2 / name :op1 "HIF-1α"))
:ARG0-of (d / depend-01 :polarity -
:ARG1 (h / hypoxia))))
:ARG1-of (d2 / describe-01
:ARG0 (p4 / publication
:ARG1-of (c / cite-01
:ARG2 (a / and :op1 18 :op2 19)))))
:op2 (h2 / have-03
:ARG0 (m4 / medical-condition :name (n3 / name :op1 "melanoma")
:quant (m / majority)
:ARG1-of (i / include-91
:ARG2 (m5 / medical-condition :name (n4 / name :op1 "melanoma"))))
:ARG1 (p5 / pathway :name (n5 / name :op1 "ERK1/2" :op2 "MAPK")
:mod (c2 / constitutive)
:ARG1-of (c3 / cause-01
:ARG0 (o / or
:op1 (m2 / mutate-01
:ARG1 (e2 / enzyme :name (n6 / name :op1 "BRAF")))
:op2 (m3 / mutate-01
:ARG1 (e3 / enzyme :name (n7 / name :op1 "N-Ras")))))
:ARG0-of (a5 / activity-06))
:ARG1-of (d5 / describe-01
:ARG0 (p6 / publication
:ARG1-of (c4 / cite-01
:ARG2 (a4 / and :op1 14 :op2 15))))))
# ::id pmid_1991_9690.83 ::date 2015-08-16T06:54:04 ::annotator SDL-AMR-09 ::preferred
# ::snt Therefore, we determined whether HIF-1α expression in human metastatic melanoma WM9 cells was dependent on activation of ERK1/2 MAPK signaling.
# ::save-date Thu Dec 10, 2015 ::file pmid_1991_9690_83.txt
(c / cause-01
:ARG1 (d / determine-01
:ARG0 (w / we)
:ARG1 (d2 / depend-01 :mode interrogative
:ARG0 (e / express-03
:ARG2 (p2 / protein :name (n2 / name :op1 "HIF-1α"))
:ARG3 (c2 / cell-line :name (n3 / name :op1 "WM9")
:mod (m / medical-condition :name (n4 / name :op1 "melanoma"))
:mod (h / human)
:ARG1-of (m2 / metastasize-101)))
:ARG1 (a / activate-01
:ARG1 (s / signal-07
:ARG0 (p3 / pathway :name (n5 / name :op1 "ERK1/2" :op2 "MAPK")))))))
# ::id pmid_1991_9690.84 ::date 2015-08-16T07:07:13 ::annotator SDL-AMR-09 ::preferred
# ::snt These cells have an active ERK1/2 MAPK pathway as evidenced by the high phosphorylation of ERK (Fig. 6A).
# ::save-date Sat Jan 16, 2016 ::file pmid_1991_9690_84.txt
(h / have-03
:ARG0 (c / cell
:mod (t / this))
:ARG1 (p4 / pathway :name (n3 / name :op1 "ERK1/2" :op2 "MAPK")
:ARG0-of (a2 / activity-06))
:ARG1-of (e / evidence-01
:ARG0 (p2 / phosphorylate-01
:ARG1 (e2 / enzyme :name (n2 / name :op1 "ERK"))
:ARG1-of (h2 / high-02)))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "6A")))
# ::id pmid_1991_9690.85 ::date 2015-08-16T07:40:03 ::annotator SDL-AMR-09 ::preferred
# ::snt Treatment of WM9 cells with 30 μM U0126, a selective U0126 MEK inhibitor, decreased ERK1/2 phosphorylation and led to a time-dependent decrease in HIF-1α protein expression (Fig. 6A).
# ::save-date Tue Dec 15, 2015 ::file pmid_1991_9690_85.txt
(a / and
:op1 (d / decrease-01
:ARG0 (t2 / treat-04
:ARG1 (c / cell-line :name (n3 / name :op1 "WM9"))
:ARG2 (s2 / small-molecule :name (n4 / name :op1 "U0126")
:quant (c2 / concentration-quantity :quant 30
:unit (m / micromolar))
:ARG1-of (m2 / mean-01
:ARG2 (s3 / small-molecule :name (n5 / name :op1 "U0126")
:ARG0-of (i / inhibit-01
:ARG1 (p / protein-family :name (n2 / name :op1 "MEK")))
:ARG0-of (s / select-01)))))
:ARG1 (p2 / phosphorylate-01
:ARG1 (e / enzyme :name (n6 / name :op1 "ERK1/2"))))
:op2 (l / lead-03
:ARG1 t2
:ARG2 (d2 / decrease-01
:ARG1 (e2 / express-03
:ARG2 (p3 / protein :name (n7 / name :op1 "HIF-1α")))
:ARG0-of (d3 / depend-01
:ARG1 (t3 / time))))
:ARG1-of (d4 / describe-01
:ARG0 (f / figure :mod "6A")))
# ::id pmid_1991_9690.86 ::date 2015-08-16T08:00:17 ::annotator SDL-AMR-09 ::preferred
# ::snt Although 30 μM U0126 has been used in published studies to selectively inhibit MEK [16,21], the original paper describing this inhibitor [22] used much lower concentrations to achieve high selectivity.
# ::save-date Fri Feb 5, 2016 ::file pmid_1991_9690_86.txt
(h / have-concession-91
:ARG1 (u2 / use-01
:ARG0 (p4 / paper
:mod (o / original)
:ARG0-of (d2 / describe-01
:ARG1 s
:ARG1-of (d3 / describe-01
:ARG0 (p5 / publication
:ARG1-of (c3 / cite-01
:ARG2 22)))))
:ARG1 (c4 / concentrate-02
:ARG1-of (l / low-04
:degree (m / more
:degree (m3 / much))))
:ARG2 (a2 / achieve-01
:ARG0 p4
:ARG1 (s4 / select-01
:ARG1-of (h2 / high-02))))
:ARG2 (u / use-01
:ARG1 (s / small-molecule :name (n / name :op1 "U0126")
:quant (c / concentration-quantity :quant 30
:unit (m2 / micromolar)))
:ARG2 (i2 / inhibit-01
:ARG0 s
:ARG1 (e / enzyme :name (n2 / name :op1 "MEK"))
:ARG0-of (s5 / select-01))
:ARG1-of (d / describe-01
:ARG0 (p3 / publication
:ARG1-of (c2 / cite-01
:ARG2 (a / and :op1 16 :op2 21))))
:location (s2 / study-01
:ARG1-of (p2 / publish-01))))
# ::id pmid_1991_9690.87 ::date 2015-08-16T08:20:18 ::annotator SDL-AMR-09 ::preferred
# ::snt Therefore we repeated this experiment using 10 μM U0126 (Fig. 6B).
# ::save-date Wed Aug 19, 2015 ::file pmid_1991_9690_87.txt
(c / cause-01
:ARG1 (r / repeat-01
:ARG0 (w / we)
:ARG1 (e / experiment-01
:mod (t / this))
:manner (u / use-01
:ARG0 w
:ARG1 (s / small-molecule :name (n / name :op1 "U0126")
:quant (c2 / concentration-quantity :quant 10
:unit (m / micromolar)))))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "6B")))
# ::id pmid_1991_9690.88 ::date 2015-08-16T08:26:49 ::annotator SDL-AMR-09 ::preferred
# ::snt At 24 h of treatment, 10 μM U0126 completely suppressed the phosphorylation of ERK1/2, yet there was minimal change in the level of HIF-1α relative to control cells.
# ::save-date Wed Aug 19, 2015 ::file pmid_1991_9690_88.txt
(s2 / suppress-01
:ARG0 (s / small-molecule :name (n / name :op1 "U0126")
:quant (c / concentration-quantity :quant 10
:unit (m / micromolar)))
:ARG1 (p / phosphorylate-01
:ARG1 (e / enzyme :name (n2 / name :op1 "ERK1/2")))
:ARG1-of (c2 / complete-02)
:ARG1-of (c3 / contrast-01
:ARG2 (c4 / charge-03
:ARG1 (l / level
:quant-of (p2 / protein :name (n3 / name :op1 "HIF-1α")))
:ARG1-of (m2 / minimal-02)
:ARG1-of (r / relative-05
:ARG3 (c5 / cell
:mod (c6 / control)))))
:time (a / after
:op1 (t / treat-04)
:quant (t2 / temporal-quantity :quant 24
:unit (h / hour))))
# ::id pmid_1991_9690.89 ::date 2015-08-16T08:34:36 ::annotator SDL-AMR-09 ::preferred
# ::snt With further time of inhibitor treatment, phosphorylation of ERK was not totally suppressed, but HIF-1α levels decreased.
# ::save-date Sat Jan 16, 2016 ::file pmid_1991_9690_89.txt
(s / suppress-01
:ARG1 (p / phosphorylate-01
:ARG1 (e / enzyme :name (n / name :op1 "ERK")))
:ARG1-of (c / contrast-01
:ARG2 (d / decrease-01
:ARG1 (l / level
:quant-of (p3 / protein :name (n2 / name :op1 "HIF-1α")))))
:degree (t / total :polarity -)
:condition (t4 / time
:mod (f / further)
:duration-of (t3 / treat-04
:ARG2 (s2 / small-molecule
:ARG0-of (i / inhibit-01)))))
# ::id pmid_1991_9690.90 ::date 2015-08-16T08:42:33 ::annotator SDL-AMR-09 ::preferred
# ::snt We also used siRNA specifically targeting MEK1 and 2 in WM9 cells to inhibit ERK1/2 phosphorylation.
# ::save-date Fri Feb 5, 2016 ::file pmid_1991_9690_90.txt
(u / use-01
:ARG0 (w / we)
:ARG1 (n6 / nucleic-acid :name (n / name :op1 "siRNA")
:ARG0-of (t / target-01
:ARG1 (a2 / and
:op1 (e / enzyme :name (n2 / name :op1 "MEK1"))
:op2 (e2 / enzyme :name (n3 / name :op1 "MEK2")))
:location (c / cell-line :name (n4 / name :op1 "WM9"))
:manner (s / specific-02)))
:ARG2 (i / inhibit-01
:ARG0 n6
:ARG1 (p / phosphorylate-01
:ARG1 (e3 / enzyme :name (n5 / name :op1 "ERK1/2"))))
:mod (a / also))
# ::id pmid_1991_9690.91 ::date 2015-08-16T08:53:11 ::annotator SDL-AMR-09 ::preferred
# ::snt Treatment of WM9 cells with siRNA targeting MEK1 and 2 consistently decreased its expression by greater than 90% and also decreased ERK1/2 phosphorylation.
# ::save-date Mon Feb 1, 2016 ::file pmid_1991_9690_91.txt
(a / and
:op1 (d / decrease-01
:ARG0 (t / treat-04
:ARG1 (c / cell-line :name (n / name :op1 "WM9"))
:ARG2 (n6 / nucleic-acid :name (n2 / name :op1 "siRNA")
:ARG0-of (t2 / target-01
:ARG1 (a2 / and
:op1 (e / enzyme :name (n3 / name :op1 "MEK1"))
:op2 (e2 / enzyme :name (n4 / name :op1 "MEK2"))))))
:ARG1 (e3 / express-03
:ARG3 c)
:ARG2 (m / more-than
:op1 (p / percentage-entity :value 90))
:manner (c2 / consistent-02))
:op2 (d2 / decrease-01
:ARG0 t
:ARG1 (p2 / phosphorylate-01
:ARG1 (e4 / enzyme :name (n5 / name :op1 "ERK1/2")))
:mod (a3 / also)))
# ::id pmid_1991_9690.92 ::date 2015-08-16T09:00:08 ::annotator SDL-AMR-09 ::preferred
# ::snt However, knockdown of MEK1 and 2 did not decrease the normoxic expression of HIF-1α protein in human metastatic melanoma WM9 cells (Fig. 6C).
# ::save-date Thu Dec 10, 2015 ::file pmid_1991_9690_92.txt
(c / contrast-01
:ARG2 (d / decrease-01 :polarity -
:ARG0 (k / knock-down-02
:ARG1 (a / and
:op1 (e / enzyme :name (n / name :op1 "MEK1"))
:op2 (e2 / enzyme :name (n2 / name :op1 "MEK2"))))
:ARG1 (e3 / express-03
:ARG2 (p / protein :name (n4 / name :op1 "HIF-1α"))
:ARG3 (c2 / cell-line :name (n5 / name :op1 "WM9")
:mod (m / medical-condition :name (n6 / name :op1 "melanoma"))
:mod (h / human)
:ARG1-of (m2 / metastasize-101))
:mod (n3 / normoxia)))
:ARG1-of (d3 / describe-01
:ARG0 (f / figure :mod "6C")))
# ::id pmid_2000_3375.1 ::date 2015-06-19T16:50:37 ::annotator SDL-AMR-09 ::preferred
# ::snt Aurora-A overexpression enhances cell-aggregation of Ha-ras transformants through the MEK/ERK signaling pathway (PMID:20003375)
# ::save-date Sat Jan 16, 2016 ::file pmid_2000_3375_1.txt
(e / enhance-01
:ARG0 (o / overexpress-01
:ARG1 (e2 / enzyme :name (n / name :op1 "Aurora-A")))
:ARG1 (a / aggregate-01
:ARG1 (c3 / cell
:ARG2-of (t / transform-01
:ARG0 (g / gene :name (n2 / name :op1 "Ha-ras")))))
:manner (s / signal-07
:ARG0 (p / pathway :name (n3 / name :op1 "MEK/ERK")))
:ARG1-of (d / describe-01
:ARG0 (p2 / publication-91
:ARG8 "PMID20003375")))
# ::id pmid_2000_3375.12 ::date 2015-06-19T17:20:43 ::annotator SDL-AMR-09 ::preferred
# ::snt Results
# ::save-date Tue Jun 30, 2015 ::file pmid_2000_3375_12.txt
(t / thing
:ARG2-of (r / result-01))
# ::id pmid_2000_3375.13 ::date 2015-06-19T18:45:48 ::annotator SDL-AMR-09 ::preferred
# ::snt Overexpression of wild-type Aurora-A and mutation of RasV12 were detected in human bladder and colon cancer tissues.
# ::save-date Thu Dec 10, 2015 ::file pmid_2000_3375_13.txt
(d / detect-01
:ARG1 (a / and
:op1 (o / overexpress-01
:ARG1 (e / enzyme :name (n / name :op1 "Aurora-A")
:mod (w / wild-type)))
:op2 (m / mutate-01 :value "V12"
:ARG2 (e2 / enzyme :name (n2 / name :op1 "Ras"))))
:location (a3 / and
:op1 (t / tissue
:mod (h / human)
:mod (d4 / disease :wiki "Cancer" :name (n5 / name :op1 "cancer")
:mod (b / bladder)))
:op2 (t2 / tissue
:mod h
:mod (d2 / disease :wiki "Colorectal_cancer" :name (n3 / name :op1 "colon" :op2 "cancer")))))
# ::id pmid_2000_3375.14 ::date 2015-06-19T18:52:24 ::annotator SDL-AMR-09 ::preferred
# ::snt Wild-type Aurora-A induces focus formation and aggregation of the RasV12 transformants.
# ::save-date Sun Jul 19, 2015 ::file pmid_2000_3375_14.txt
(i / induce-01
:ARG0 (e / enzyme :name (n / name :op1 "Aurora-A")
:mod (w / wild-type))
:ARG2 (a / and
:op1 (f / form-01
:ARG1 (f2 / focus))
:op2 (a2 / aggregate-01
:ARG1 (c / cell
:ARG2-of (t / transform-01
:ARG0 (e2 / enzyme :name (n2 / name :op1 "Ras")
:ARG2-of (m / mutate-01 :value "V12")))))))
# ::id pmid_2000_3375.15 ::date 2015-06-19T18:57:07 ::annotator SDL-AMR-09 ::preferred
# ::snt Aurora-A activates Ral A and the phosphorylation of AKT as well as enhances the phosphorylation of MEK, ERK of WT cells.
# ::save-date Sat Jan 16, 2016 ::file pmid_2000_3375_15.txt
(a / and
:op1 (a2 / activate-01
:ARG0 (e / enzyme :name (n / name :op1 "Aurora-A"))
:ARG1 (a3 / and
:op1 (e5 / enzyme :name (n2 / name :op1 "Ral" :op2 "A"))
:op2 (p2 / phosphorylate-01
:ARG1 (e2 / enzyme :name (n3 / name :op1 "AKT")))))
:op2 (e3 / enhance-01
:ARG0 e
:ARG1 (p3 / phosphorylate-01
:ARG1 (a4 / and
:op1 (e4 / enzyme :name (n4 / name :op1 "MEK"))
:op2 (e6 / enzyme :name (n5 / name :op1 "ERK"))
:part-of (c / cell
:mod (w / wild-type))))))
# ::id pmid_2000_3375.16 ::date 2015-06-20T16:51:14 ::annotator SDL-AMR-09 ::preferred
# ::snt Finally, the Ras/MEK/ERK signaling pathway is responsible for Aurora-A induced aggregation of the RasV12 transformants.
# ::save-date Fri Oct 23, 2015 ::file pmid_2000_3375_16.txt
(r / responsible-01 :li "-1"
:ARG0 (p / pathway :name (n / name :op1 "Ras/MEK/ERK")
:ARG0-of (s / signal-07))
:ARG1 (a / aggregate-01
:ARG1 (c / cell
:ARG1-of (t / transform-01
:ARG0 (e2 / enzyme :name (n3 / name :op1 "Ras")
:ARG2-of (m / mutate-01 :value "V12"))))
:ARG2-of (i / induce-01
:ARG0 (e / enzyme :name (n2 / name :op1 "Aurora-A")))))
# ::id pmid_2000_3375.109 ::date 2015-06-20T16:51:44 ::annotator SDL-AMR-09 ::preferred
# ::snt Results
# ::save-date Wed Jul 1, 2015 ::file pmid_2000_3375_109.txt
(t / thing
:ARG2-of (r / result-01))
# ::id pmid_2000_3375.110 ::date 2015-06-20T17:22:15 ::annotator SDL-AMR-09 ::preferred
# ::snt Detection of Aurora-A overexpression accompanied with Ha-ras mutation in bladder cancers
# ::save-date Sat Jun 20, 2015 ::file pmid_2000_3375_110.txt
(d / detect-01
:ARG1 (a / accompany-01
:ARG0 (m / mutate-01
:ARG1 (g / gene
:name (n2 / name :op1 "Ha-ras")))
:ARG1 (o / overexpress-01
:ARG1 (e / enzyme
:name (n / name :op1 "Aurora-A"))))
:location (d2 / disease :wiki "Cancer"
:name (n3 / name :op1 "cancer")
:mod (b / bladder)))
# ::id pmid_2000_3375.111 ::date 2015-06-20T17:28:55 ::annotator SDL-AMR-09 ::preferred
# ::snt Aurora-A overexpression accompanied with Ha-ras codon 12 mutation has been reported in bladder cancers [41].
# ::save-date Mon Jul 20, 2015 ::file pmid_2000_3375_111.txt
(r / report-01
:ARG1 (a / accompany-01
:ARG0 (m / mutate-01
:ARG1 (c2 / codon :mod 12
:part-of (g / gene
:name (n3 / name :op1 "Ha-ras"))))
:ARG1 (o / overexpress-01
:ARG1 (e / enzyme
:name (n / name :op1 "Aurora-A")))
:location (d / disease :wiki "Cancer"
:name (n4 / name :op1 "cancer")
:mod (b / bladder)))
:ARG1-of (d2 / describe-01
:ARG0 (p / publication-91
:ARG1-of (c / cite-01 :ARG2 41))))
# ::id pmid_2000_3375.112 ::date 2015-06-20T17:42:56 ::annotator SDL-AMR-09 ::preferred
# ::snt In this study, Ha-rasV12 mutation was detected in the tumour part of the bladder cancer specimen by SNP-real-time PCR and verified by sequence analysis (Figure 1A, Gly12 -> Val 12).
# ::save-date Sat Jan 2, 2016 ::file pmid_2000_3375_112.txt
(a2 / and
:op1 (d3 / detect-01
:ARG1 (m2 / mutate-01 :value "V12"
:ARG2 (e / enzyme :name (n3 / name :op1 "Ha-ras")))
:ARG2 (p / polymorphism
:mod (n2 / nucleotide
:ARG1-of (s / single-02))
:ARG1-of (a / analyze-01
:manner (r / real-time)
:mod (r2 / react-01
:ARG0 (p2 / polymerase)
:mod (c / chain)
:subevent (t / transcribe-01
:ARG1-of (r3 / reverse-01)))))
:location (t2 / tumor
:part-of (s2 / specimen
:mod (d4 / disease :wiki "Cancer" :name (n4 / name :op1 "cancer")
:mod (b2 / bladder)))))
:op2 (v / verify-01
:ARG1 m2
:manner (a3 / analyze-01
:mod (s3 / sequence)))
:medium (s4 / study-01
:mod (t3 / this))
:ARG1-of (d5 / describe-01
:ARG0 (f / figure :mod "1A")
:ARG2 (m3 / mutate-01
:ARG1 (a4 / amino-acid :mod 12 :name (n5 / name :op1 "glycine"))
:ARG2 (a5 / amino-acid :mod 12 :name (n6 / name :op1 "valine")))))
# ::id pmid_2000_3375.113 ::date 2015-06-20T18:08:32 ::annotator SDL-AMR-09 ::preferred
# ::snt The Aurora-A protein overexpression was detected in the same cancer part of the bladder tissue compared to the normal part by IHC staining (Figure 1B, T vs. N).
# ::save-date Sun Jan 17, 2016 ::file pmid_2000_3375_113.txt
(d / detect-01
:ARG1 (o / overexpress-01
:ARG1 (e / enzyme :name (n / name :op1 "Aurora-A")))
:manner (s2 / stain-01
:ARG2 (i / immunohistochemistry))
:ARG1-of (d3 / describe-01
:ARG0 (f2 / figure :mod "1B"))
:location (p2 / part
:part-of (t / tissue
:mod (b / bladder))
:ARG1-of (c2 / compare-01
:ARG2 (p4 / part
:ARG1-of (n4 / normal-02)))
:ARG1-of (s / same-01)
:mod (d2 / disease :wiki "Cancer" :name (n2 / name :op1 "cancer"))))
# ::id pmid_2000_3375.114 ::date 2015-06-20T18:24:07 ::annotator SDL-AMR-09 ::preferred
# ::snt Similarly, Ki-ras codon 12 mutation and higher expression level of Aurora-A were only detected in the cancer part of the colon tissue (Figure 1C and 1D).
# ::save-date Mon Dec 21, 2015 ::file pmid_2000_3375_114.txt
(r / resemble-01
:ARG2 (d / detect-01
:ARG1 (a / and
:op1 (m / mutate-01
:ARG1 (c3 / codon :mod 12
:part-of (g / gene :name (n2 / name :op1 "Ki-ras"))))
:op2 (l / level
:degree-of (e / express-03
:ARG2 (e2 / enzyme :name (n3 / name :op1 "Aurora-A")))
:ARG1-of (h / high-02
:degree (m2 / more))))
:location (p / part
:mod (d2 / disease :wiki "Cancer" :name (n4 / name :op1 "cancer"))
:part-of (t / tissue
:mod (c2 / colon)))
:manner (o / only)
:ARG1-of (d3 / describe-01
:ARG0 (a3 / and
:op1 (f / figure :mod "1C")
:op2 (f2 / figure :mod "1D")))))
# ::id pmid_2000_3375.115 ::date 2015-06-20T18:25:36 ::annotator SDL-AMR-09 ::preferred
# ::snt Taken together, despite of the difference in transformation of NIH3T3 cells by Ki-ras and Ha-ras, overexpression of Aurora-A and RasV12 (Ki- or Ha-) mutations are simultaneously detected in various cancers including bladder and colon.
# ::save-date Sat Jan 16, 2016 ::file pmid_2000_3375_115.txt
(d / detect-01
:ARG1 (a / and
:op1 (o / overexpress-01
:ARG1 (e / enzyme :name (n / name :op1 "Aurora-A")))
:op2 (m / mutate-01 :value "V12"
:ARG1 (o2 / or
:op1 (e2 / enzyme :name (n2 / name :op1 "Ki-Ras"))
:op2 (e3 / enzyme :name (n3 / name :op1 "Ha-Ras"))))
:ARG1-of (t3 / take-01
:mod (t2 / together)))
:manner (s / simultaneous)
:concession (d2 / differ-02
:ARG1 e2
:ARG2 e3
:ARG3 (t / transform-01
:ARG1 (c / cell-line :name (n4 / name :op1 "NIH3T3"))))
:location (d6 / disease :wiki "Cancer" :name (n5 / name :op1 "cancer")
:mod (v / various)
:ARG1-of (i / include-91
:ARG2 (a2 / and
:op1 (d3 / disease :wiki "Cancer" :name (n6 / name :op1 "cancer")
:mod (b / bladder))
:op2 (d4 / disease :wiki "Colorectal_cancer" :name (n7 / name :op1 "colon" :op2 "cancer"))))))
# ::id pmid_2000_3375.116 ::date 2015-06-20T18:55:05 ::annotator SDL-AMR-09 ::preferred
# ::snt Establishment of stable cell lines over-expressing Aurora-A and mutant RasV12
# ::save-date Mon Jul 20, 2015 ::file pmid_2000_3375_116.txt
(e / establish-01
:ARG1 (c / cell-line
:ARG1-of (s / stable-03)
:ARG0-of (o / overexpress-01
:ARG1 (a / and
:op1 (e2 / enzyme :name (n / name :op1 "Aurora-A"))
:op2 (e3 / enzyme :name (n2 / name :op1 "Ras")
:ARG2-of (m / mutate-01 :value "V12"))))))
# ::id pmid_2000_3375.117 ::date 2015-06-20T19:01:09 ::annotator SDL-AMR-09 ::preferred
# ::snt It is intriguing to unravel the combined effects of Aurora-A and mutant RasV12 on the morphological change and tumorigenesis of the cells.
# ::save-date Thu Sep 24, 2015 ::file pmid_2000_3375_117.txt
(i / intrigue-01
:ARG0 (u / unravel-01
:ARG1 (a / affect-01
:ARG0 (a2 / and
:op1 (e / enzyme :name (n / name :op1 "Aurora-A"))
:op2 (e2 / enzyme :name (n2 / name :op1 "Ras")
:ARG2-of (m / mutate-01 :value "V12")))
:ARG1 (a3 / and
:op1 (c2 / change-01
:ARG1 c3
:mod (m2 / morphology))
:op2 (c4 / create-01
:ARG1 (t / tumor
:mod (c3 / cell))))
:ARG1-of (c / combine-01))))
# ::id pmid_2000_3375.118 ::date 2015-06-21T16:11:15 ::annotator SDL-AMR-09 ::preferred
# ::snt Stable cell lines were established by transfecting Vector DNA, wild-type Aurora-A or kinase-inactivated Aurora-A into 7-4 cells, which was derived from NIH/3T3 cells harboring the inducible Ha-rasV12 oncogene [23], designated Vector, WT and KD cell line, respectively.
# ::save-date Wed Jan 13, 2016 ::file pmid_2000_3375_118.txt
(e / establish-01
:ARG1 (c / cell-line
:ARG1-of (s / stable-03))
:manner (t / transfect-01
:ARG1 (c2 / cell
:mod (b / between :op1 7 :op2 4)
:ARG1-of (d3 / derive-01
:ARG2 (c3 / cell-line :name (n3 / name :op1 "NIH/3T3")
:ARG0-of (h / harbor-01
:ARG1 (a / and
:op1 (g / gene :name (n5 / name :op1 "Ha-ras")
:ARG1-of (d4 / describe-01
:ARG0 (p / publication-91
:ARG1-of (c4 / cite-01
:ARG2 23)))
:ARG2-of (m / mutate-01 :value "V12")
:ARG2-of (i / induce-01
:ARG1-of (p2 / possible-01))
:ARG0-of (c7 / cause-01
:ARG1 (d / disease :wiki "Cancer" :name (n7 / name :op1 "cancer"))))
:op2 (d5 / designate-01
:ARG1 (v2 / vector))
:op3 (a2 / and
:op1 (c5 / cell-line
:mod (w3 / wild-type))
:op2 (c6 / cell-line
:mod (k3 / knock-down-02))))
:manner (r / respective)))))
:ARG2 (o / or
:op1 (n4 / nucleic-acid :wiki "DNA" :name (n6 / name :op1 "DNA")
:mod (v / vector))
:op2 (e2 / enzyme :name (n / name :op1 "Aurora-A")
:mod (w / wild-type))
:op3 (e3 / enzyme :name (n2 / name :op1 "Aurora-A")
:ARG1-of (d2 / deactivate-01
:ARG0 (k / kinase))))))
# ::id pmid_2000_3375.119 ::date 2015-06-21T16:42:04 ::annotator SDL-AMR-09 ::preferred
# ::snt The expression levels of Ha-rasV12 in Vector, WT and KD cells in the presence of IPTG were much higher compared to the cells without IPTG (Figure 2A).
# ::save-date Sat Jan 16, 2016 ::file pmid_2000_3375_119.txt
(h / high-02
:ARG1 (l / level
:degree-of (e / express-03
:ARG2 (g / gene :name (n / name :op1 "Ha-ras")
:ARG2-of (m3 / mutate-01 :value "V12"))
:ARG3 (a2 / and
:op1 (c / cell
:mod (v / vector))
:op2 (c2 / cell
:mod (w / wild-type))
:op3 (c3 / cell
:mod (k / knock-down-02))))
:condition (s2 / small-molecule :name (n2 / name :op1 "IPTG")))
:degree (m / more
:degree (m2 / much))
:compared-to (l2 / level
:degree-of (e3 / express-03
:ARG3 (c4 / cell
:ARG0-of (l3 / lack-01
:ARG1 s2))))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "2A")))
# ::id pmid_2000_3375.120 ::date 2015-06-21T17:25:40 ::annotator SDL-AMR-09 ::preferred
# ::snt Aurora-A can physically interact with the tail of Histone H3 (H3) and efficiently phosphorylates H3 at serine10 [45-48].
# ::save-date Sun Dec 20, 2015 ::file pmid_2000_3375_120.txt
(a / and
:op1 (p / possible-01
:ARG1 (i / interact-01
:ARG0 (e / enzyme :name (n / name :op1 "Aurora-A"))
:ARG1 (t / tail
:part-of (p2 / protein :name (n2 / name :op1 "Histone" :op2 "H3")))
:ARG2 (p5 / physical)))
:op2 (p3 / phosphorylate-01
:ARG1 (a3 / amino-acid :mod 10 :name (n3 / name :op1 "serine")
:part-of p2)
:ARG2 e
:ARG2-of (e2 / efficient-01))
:ARG1-of (d / describe-01
:ARG0 (p4 / publication-91
:ARG1-of (c / cite-01
:ARG2 (v / value-interval :op1 45 :op2 48)))))
# ::id pmid_2000_3375.121 ::date 2015-06-21T17:33:42 ::annotator SDL-AMR-09 ::preferred
# ::snt In addition, activation of ERK pathway in Ha-ras transformed mouse fibroblasts increases the level of p-H3S10.
# ::save-date Fri Sep 18, 2015 ::file pmid_2000_3375_121.txt
(a / and
:op2 (i / increase-01
:ARG0 (a2 / activate-01
:ARG1 (p / pathway :name (n / name :op1 "ERK"))
:location (f / fibroblast
:source (m / mouse)
:ARG1-of (t / transform-01
:ARG0 (g / gene :name (n2 / name :op1 "Ha-ras")))))
:ARG1 (l / level
:quant-of (a4 / amino-acid :mod 10 :name (n5 / name :op1 "serine")
:part-of (p2 / protein :name (n4 / name :op1 "H3"))
:ARG3-of (p3 / phosphorylate-01)))))
# ::id pmid_2000_3375.122 ::date 2015-06-21T17:42:59 ::annotator SDL-AMR-09 ::preferred
# ::snt Consistently, our data showed the level of phosphorylated H3S10 (p-H3S10 detected by anti-p-H3S10 antibody) in WT cells (Figure 2A, lane 2, 1.8 fold) was higher than in Vector cells (Figure 2A, lane 1, 1.0 fold) and KD cells (Figure 2A, lane 3, 0.9 fold) in the absent of IPTG where Ras was not overexpressed.
# ::save-date Mon Feb 1, 2016 ::file pmid_2000_3375_122.txt
(s / show-01
:ARG0 (d / data
:poss (w / we))
:ARG1 (h / high-02
:ARG1 (l / level
:quant-of (a5 / amino-acid :mod 10 :name (n / name :op1 "serine")
:ARG3-of (p2 / phosphorylate-01)
:ARG1-of (d2 / detect-01
:ARG0 (a / antibody
:ARG0-of (c5 / counter-01
:ARG1 a5)))
:part-of (p / protein :name (n5 / name :op1 "H3")))
:ARG1-of (d3 / describe-01
:part-of (l2 / lane :mod 2
:part-of (f2 / figure :mod "2A"))
:quant (p4 / product-of :op1 1.8))
:location (c / cell
:mod (w2 / wild-type)))
:degree (m / more)
:compared-to (a3 / and
:op1 (c2 / cell
:mod (v / vector)
:ARG1-of (d4 / describe-01
:part-of (l3 / lane :mod 1
:part-of f2)
:quant (p5 / product-of :op1 1.0)))
:op2 (c3 / cell
:mod (k / knock-down-02)
:ARG1-of (d5 / describe-01
:part-of (l4 / lane :mod 3
:part-of f2)
:quant (p6 / product-of :op1 0.9))))
:condition (a6 / and
:op1 (a7 / absent-01
:ARG1 (s2 / small-molecule :name (n3 / name :op1 "IPTG")))
:op2 (o / overexpress-01 :polarity -
:ARG1 (e2 / enzyme :name (n4 / name :op1 "Ras")))))
:manner (c4 / consistent-02))
# ::id pmid_2000_3375.123 ::date 2015-06-21T18:08:24 ::annotator SDL-AMR-09 ::preferred
# ::snt Our data showed that the Aurora-A overexpressed in WT cells is functional.
# ::save-date Sun Jul 19, 2015 ::file pmid_2000_3375_123.txt
(s / show-01
:ARG0 (d / data
:poss (w / we))
:ARG1 (f / function-01
:ARG0 (e / enzyme :name (n / name :op1 "Aurora-A")
:ARG1-of (o / overexpress-01
:location (c / cell
:mod (w2 / wild-type))))))
# ::id pmid_2000_3375.124 ::date 2015-06-21T18:10:28 ::annotator SDL-AMR-09 ::preferred
# ::snt In the presence of IPTG, where RasV12 protein was overexpressed, the level of phosphorylated H3S10 was increased both in Vector (Figure 2A, lane 4, 2.8 fold), WT (Figure 2A, lane 5, 3.8 fold) and KD (Figure 2A, lane 6, 2.8 fold) cells.
# ::save-date Sat Jan 16, 2016 ::file pmid_2000_3375_124.txt
(i / increase-01
:ARG1 (l / level
:quant-of (a3 / amino-acid :mod 10 :name (n / name :op1 "serine")
:ARG3-of (p2 / phosphorylate-01)
:part-of (p / protein :name (n4 / name :op1 "H3"))))
:location (a4 / and
:op1 (c / cell
:mod (v / vector
:ARG1-of (d / describe-01
:ARG0 (l2 / lane :mod 4
:part-of (f2 / figure :mod "2A"))
:quant (p4 / product-of :op1 2.8))))
:op2 (c2 / cell
:mod (w / wild-type
:ARG1-of (d2 / describe-01
:ARG0 (l3 / lane :mod 5
:part-of f2)
:quant (p5 / product-of :op1 3.8))))
:op3 (c3 / cell
:mod (k / knock-down-02
:ARG1-of (d3 / describe-01
:ARG0 (l4 / lane :mod 6
:part-of f2)
:quant (p6 / product-of :op1 2.8)))))
:condition (a5 / and
:op1 (s / small-molecule :name (n2 / name :op1 "IPTG"))
:op2 (o / overexpress-01
:ARG1 (e / enzyme :name (n3 / name :op1 "Ras")
:ARG2-of (m / mutate-01 :value "V12")))))
# ::id pmid_2000_3375.125 ::date 2015-06-21T18:22:43 ::annotator SDL-AMR-09 ::preferred
# ::snt Biological activity analysis showed that WT cells over-expressing wild-type Aurora-A became rounded and formed aggregates in the presence of IPTG compared to the Vector cells and KD cells (Figure 2B).
# ::save-date Mon Dec 21, 2015 ::file pmid_2000_3375_125.txt
(s / show-01
:ARG0 (a / analyze-01
:ARG1 (a2 / activity-06
:mod (b / biology)))
:ARG1 (a3 / and
:op1 (r / round-04
:ARG1 (c / cell
:mod (w / wild-type)
:ARG0-of (o / overexpress-01
:ARG1 (e / enzyme :name (n / name :op1 "Aurora-A")
:mod (w2 / wild-type)))
:compared-to (a5 / and
:op1 (c2 / cell
:mod (v / vector))
:op2 (c3 / cell
:mod (k / knock-down-02)))))
:op2 (f / form-01
:ARG0 c
:ARG1 (a4 / aggregate-01))
:condition (s2 / small-molecule :name (n2 / name :op1 "IPTG")))
:ARG1-of (d / describe-01
:ARG0 (f2 / figure :mod "2B")))
# ::id pmid_2000_3375.126 ::date 2015-06-21T18:38:24 ::annotator SDL-AMR-09 ::preferred
# ::snt Transforming analysis showed that WT cells form more foci compared to Vector and KD cells (Figure 2C).
# ::save-date Thu Jul 9, 2015 ::file pmid_2000_3375_126.txt
(s / show-01
:ARG0 (a / analyze-01
:mod (t / transform-01))
:ARG1 (f / form-01
:ARG0 (c / cell
:mod (w / wild-type))
:ARG1 (f2 / focus
:mod (m / more))
:compared-to (a3 / and
:op1 (c2 / cell
:mod (v / vector))
:op2 (c3 / cell
:mod (k / knock-down-02))))
:ARG1-of (d / describe-01
:ARG0 (f3 / figure :mod "2C")))
# ::id pmid_2000_3375.127 ::date 2015-06-23T07:19:26 ::annotator SDL-AMR-09 ::preferred
# ::snt Despite the fact that focus numbers were also increased in the other two cell lines, a further increase of focus number in WT cells was observed after IPTG induction (Figure 2C).
# ::save-date Tue Jun 30, 2015 ::file pmid_2000_3375_127.txt
(o / observe-01
:ARG1 (i / increase-01
:ARG1 (n / number
:quant-of (f / focus))
:degree (f2 / further)
:location (c / cell
:mod (w / wild-type)))
:time (a / after
:op1 (i2 / induce-01
:ARG2 (s / small-molecule :name (n2 / name :op1 "IPTG"))))
:ARG1-of (d / describe-01
:ARG0 (f5 / figure :mod "2C"))
:concession (i3 / increase-01
:ARG1 n
:mod (a2 / also)
:location (c2 / cell-line :quant 2
:mod (o2 / other))))
# ::id pmid_2000_3375.128 ::date 2015-06-23T07:26:47 ::annotator SDL-AMR-09 ::preferred
# ::snt Taken together, both Aurora-A and mutant RasV12 overexpression can induce focus formation.
# ::save-date Tue Jun 30, 2015 ::file pmid_2000_3375_128.txt
(h / have-condition-91
:ARG1 (p / possible-01
:ARG1 (i / induce-01
:ARG0 (a / and
:op1 (o / overexpress-01
:ARG1 (e / enzyme :name (n / name :op1 "Aurora-A")))
:op2 (o2 / overexpress-01
:ARG1 (e2 / enzyme :name (n2 / name :op1 "Ras")
:ARG2-of (m / mutate-01 :value "V12"))))
:ARG2 (f / form-01
:ARG1 (f2 / focus))))
:ARG2 (t / take-01
:ARG1 a
:mod (t2 / together)))
# ::id pmid_2000_3375.129 ::date 2015-06-23T07:32:44 ::annotator SDL-AMR-09 ::preferred
# ::snt Further induction of focus formation was detected when these two genes were overexpressed simultaneously.
# ::save-date Fri Mar 4, 2016 ::file pmid_2000_3375_129.txt
(d / detect-01
:ARG1 (i / induce-01
:ARG2 (f2 / form-01
:ARG1 (f3 / focus))
:degree (f / further))
:condition (o / overexpress-01
:ARG1 (g / gene :quant 2
:mod (t / this))
:mod (s / simultaneous)))
# ::id pmid_2000_3375.130 ::date 2015-06-23T07:34:41 ::annotator SDL-AMR-09 ::preferred
# ::snt Cell proliferation analysis showed that WT cells grew slower than Vector and KD cells in the absence of IPTG.
# ::save-date Tue Dec 29, 2015 ::file pmid_2000_3375_130.txt
(s / show-01
:ARG0 (a / analyze-01
:ARG1 (p / proliferate-01
:ARG0 (c / cell)))
:ARG1 (g / grow-01
:ARG1 (c2 / cell
:mod (w / wild-type))
:ARG2 (s2 / slow-05
:degree (m / more)
:compared-to (a2 / and
:op1 (c3 / cell
:mod (v / vector))
:op2 (c4 / cell
:mod (k / knock-down-02))))
:condition (a3 / absent-01
:ARG1 (s3 / small-molecule :name (n / name :op1 "IPTG")))))
# ::id pmid_2000_3375.131 ::date 2015-06-23T07:42:00 ::annotator SDL-AMR-09 ::preferred
# ::snt Growth rate of Vector, WT and KD cells were decreased when mutant Ras was overexpressed (Fig. 2D).
# ::save-date Sat Jan 16, 2016 ::file pmid_2000_3375_131.txt
(d / decrease-01
:ARG1 (a / and
:op1 (r / rate
:degree-of (g / grow-01
:ARG1 (c / cell
:mod (v / vector))))
:op2 (r2 / rate
:degree-of (g2 / grow-01
:ARG1 (c2 / cell
:mod (w / wild-type))))
:op3 (r3 / rate
:degree-of (g3 / grow-01
:ARG1 (c3 / cell
:mod (k / knock-down-02)))))
:time (o / overexpress-01
:ARG1 (e / enzyme :name (n / name :op1 "Ras")
:ARG2-of (m / mutate-01)))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure :mod "2D")))
# ::id pmid_2000_3375.132 ::date 2015-06-23T07:45:33 ::annotator SDL-AMR-09 ::preferred
# ::snt The increase of cell aggregation of WT cells in the presence of IPTG was independent of cell growth rate.
# ::save-date Mon Dec 21, 2015 ::file pmid_2000_3375_132.txt
(d / depend-01 :polarity -
:ARG0 (i / increase-01
:ARG1 (a / aggregate-01
:ARG1 (c / cell
:mod (w / wild-type))
:mod (c2 / cell))
:condition (p / present-02
:ARG1 (s / small-molecule :name (n / name :op1 "IPTG"))))
:ARG1 (r / rate
:degree-of (g / grow-01
:ARG1 c)))
# ::id pmid_2000_3375.133 ::date 2015-06-23T07:52:55 ::annotator SDL-AMR-09 ::preferred
# ::snt Aurora-A overexpression increases phosphorylation status of MEK/ERK and AKT as well as the activity of RalA in the RasV12 transformants
# ::save-date Sun Jan 17, 2016 ::file pmid_2000_3375_133.txt
(i / increase-01
:ARG0 (o / overexpress-01
:ARG1 (e2 / enzyme :name (n / name :op1 "Aurora-A")))
:ARG1 (a2 / and
:op1 (s / status
:mod (p / phosphorylate-01)
:poss (a / and
:op1 (p2 / pathway :name (n2 / name :op1 "MEK/ERK"))
:op2 (p4 / pathway :name (n3 / name :op1 "AKT"))))
:op2 (a3 / activity-06
:ARG0 (p3 / protein :name (n4 / name :op1 "RalA"))
:location (e3 / enzyme :name (n5 / name :op1 "Ras")
:ARG2-of (t / transform-01 :value "V12")))))
# ::id pmid_2000_3375.134 ::date 2015-06-23T08:05:53 ::annotator SDL-AMR-09 ::preferred
# ::snt To clarify the effects of Aurora-A on the signaling pathways related to Ras overexpression, three downstream signaling pathways of Ras, Raf/MEK, PI3K/AKT and RalGDS/Ral A were investigated.
# ::save-date Tue Jun 30, 2015 ::file pmid_2000_3375_134.txt
(i / investigate-01
:ARG1 (p / pathway :quant 3
:location (d / downstream)
:ARG0-of (s / signal-07
:ARG1 (e / enzyme :name (n / name :op1 "Ras")))
:ARG1-of (m / mean-01
:ARG2 (a / and
:op1 (p2 / pathway :name (n2 / name :op1 "Raf/MEK"))
:op2 (p3 / pathway :name (n3 / name :op1 "PI3K/AKT"))
:op3 (p4 / pathway :name (n4 / name :op1 "RalGDS/RalA")))))
:ARG2 (c / clarify-10
:ARG1 (a2 / affect-01
:ARG0 (e2 / enzyme :name (n5 / name :op1 "Aurora-A"))
:ARG1 (p6 / pathway
:ARG0-of s
:ARG1-of (r / relate-01
:ARG2 (o / overexpress-01
:ARG2 e))))))
# ::id pmid_2000_3375.135 ::date 2015-06-23T08:16:40 ::annotator SDL-AMR-09 ::preferred
# ::snt The phosphorylation of MEK (p-MEK) was higher in WT cells (Figure 3A, lane 2, 1.7 fold) than that in Vector (Figure 3A, lane 1, 1.0 fold) and KD cells (Figure 3A, lane 3, 0.8 fold).
# ::save-date Tue Dec 29, 2015 ::file pmid_2000_3375_135.txt
(h / high-02
:ARG1 (p / phosphorylate-01
:ARG1 (e / enzyme :name (n / name :op1 "MEK")))
:degree (m / more)
:location (c / cell
:mod (w / wild-type)
:ARG1-of (d / describe-01
:ARG0 (l2 / lane :mod 2
:part-of (f / figure :mod "3A"))
:ARG2 (p3 / product-of :op1 1.7)))
:compared-to (p2 / phosphorylate-01
:ARG1 e
:location (a / and
:op1 (c2 / cell
:mod (v / vector)
:ARG1-of (d2 / describe-01
:ARG0 (l3 / lane :mod 1
:part-of f)
:ARG2 (p4 / product-of :op1 1.0)))
:op2 (c3 / cell
:mod (k / knock-down-02)
:ARG1-of (d3 / describe-01
:ARG0 (l4 / lane :mod 3
:part-of f)
:ARG2 (p5 / product-of :op1 0.8))))))
# ::id pmid_2000_3375.136 ::date 2015-06-23T08:25:44 ::annotator SDL-AMR-09 ::preferred
# ::snt P-MEK levels in each cell line were further increased after IPTG induction (RasV12 is over-expressed) (Figure 3A, lane 4, 5, and 6).
# ::save-date Tue Jun 30, 2015 ::file pmid_2000_3375_136.txt
(i / increase-01
:ARG1 (l / level
:location (c / cell-line
:mod (e2 / each))
:quant-of (e / enzyme :name (n / name :op1 "MEK")
:ARG3-of (p / phosphorylate-01)))
:degree (f / further)
:time (a / after
:op1 (i2 / induce-01
:ARG2 (s / small-molecule :name (n2 / name :op1 "IPTG"))))
:ARG1-of (m / mean-01
:ARG2 (o / overexpress-01
:ARG1 (e3 / enzyme :name (n3 / name :op1 "Ras")
:ARG2-of (m2 / mutate-01 :value "V12"))))
:ARG1-of (d / describe-01
:ARG0 (a2 / and
:op1 (l2 / lane :mod 4)
:op2 (l3 / lane :mod 5)
:op3 (l4 / lane :mod 6)
:part-of (f2 / figure :mod "3A"))))
# ::id pmid_2000_3375.137 ::date 2015-06-24T05:09:24 ::annotator SDL-AMR-09 ::preferred
# ::snt The same phenomenon was also been observed in p-ERK1/2 (Figure 3A).
# ::save-date Wed Nov 4, 2015 ::file pmid_2000_3375_137.txt
(o / observe-01
:ARG1 (p / phenomenon
:ARG1-of (s / same-01))
:mod (a / also)
:condition (s2 / slash
:op1 (e / enzyme :name (n / name :op1 "ERK1"))
:op2 (e2 / enzyme :name (n2 / name :op1 "ERK2"))
:ARG3-of (p2 / phosphorylate-01))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "3A")))
# ::id pmid_2000_3375.138 ::date 2015-06-24T05:12:44 ::annotator SDL-AMR-09 ::preferred
# ::snt These results indicated that Aurora-A may further increase Ras induced MEK/ERK phosphorylation.
# ::save-date Tue Jun 30, 2015 ::file pmid_2000_3375_138.txt
(i / indicate-01
:ARG0 (t / thing
:ARG2-of (r / result-01)
:mod (t2 / this))
:ARG1 (p3 / possible-01
:ARG1 (i2 / increase-01
:ARG0 (e2 / enzyme :name (n3 / name :op1 "Aurora-A"))
:ARG1 (p5 / phosphorylate-01
:ARG1 (p / pathway :name (n2 / name :op1 "MEK/ERK"))
:ARG2-of (i3 / induce-01
:ARG0 (e / enzyme :name (n / name :op1 "Ras"))))
:degree (f / further))))
# ::id pmid_2000_3375.139 ::date 2015-06-24T05:18:34 ::annotator SDL-AMR-09 ::preferred
# ::snt The effect of Aurora-A on the PI3K/AKT pathway was evaluated by detecting phosphorylation of AKT (p-AKT).
# ::save-date Tue Dec 29, 2015 ::file pmid_2000_3375_139.txt
(e / evaluate-01
:ARG1 (a / affect-01
:ARG0 (e3 / enzyme :name (n2 / name :op1 "Aurora-A"))
:ARG1 (p4 / pathway :name (n3 / name :op1 "PI3K/AKT")))
:manner (d / detect-01
:ARG1 (p2 / phosphorylate-01
:ARG1 (e2 / enzyme :name (n / name :op1 "AKT")))))
# ::id pmid_2000_3375.140 ::date 2015-06-24T05:21:51 ::annotator SDL-AMR-09 ::preferred
# ::snt The p-AKT level was also higher in WT cells (Figure 3A, lane 2, 2.1 fold) compared to Vector and KD cells (Figure 3A, lane 1, 1.0 fold and lane 3, 1.1 fold, respectively).
# ::save-date Tue Dec 29, 2015 ::file pmid_2000_3375_140.txt
(h / high-02
:ARG1 (l / level
:quant-of (e / enzyme :name (n / name :op1 "AKT")
:ARG3-of (p / phosphorylate-01)))
:degree (m / more)
:mod (a / also)
:location (c / cell
:mod (w / wild-type)
:ARG1-of (d / describe-01
:ARG0 (l2 / lane :mod 2
:part-of (f / figure :mod "3A"))
:ARG2 (p2 / product-of :op1 2.1)))
:compared-to (a2 / and
:op1 (c2 / cell
:mod (v / vector)
:ARG1-of (d2 / describe-01
:ARG0 (l3 / lane :mod 1
:part-of f)
:ARG2 (p3 / product-of :op1 1.0)))
:op2 (c3 / cell
:mod (k / knock-down-02)
:ARG1-of (d3 / describe-01
:ARG0 (l4 / lane :mod 3
:part-of f)
:ARG2 (p4 / product-of :op1 1.1)))))
# ::id pmid_2000_3375.141 ::date 2015-06-24T05:27:47 ::annotator SDL-AMR-09 ::preferred
# ::snt Upon IPTG induction, RasV12 overexpression increased the level of p-AKT in Vector and KD cells (Figure 3A, lane 4, 1.8 fold and lane 6, 2.1 fold, respectively).
# ::save-date Tue Dec 29, 2015 ::file pmid_2000_3375_141.txt
(i / increase-01
:ARG0 (o / overexpress-01
:ARG1 (e / enzyme :name (n / name :op1 "Ras")
:ARG2-of (m / mutate-01 :value "V12"))
:location (a / and
:op1 (c / cell
:mod (v / vector)
:ARG1-of (d / describe-01
:ARG0 (l2 / lane :mod 4
:part-of (f / figure :mod "3A"))
:ARG2 (p2 / product-of :op1 1.8)))
:op2 (c2 / cell
:mod (k / knock-down-02)
:ARG1-of (d2 / describe-01
:ARG0 (l3 / lane :mod 6
:part-of f)
:ARG2 (p3 / product-of :op1 2.1)))))
:ARG1 (l / level
:quant-of (e2 / enzyme :name (n2 / name :op1 "AKT")
:ARG3-of (p / phosphorylate-01)))
:condition (i2 / induce-01
:ARG2 (s / small-molecule :name (n3 / name :op1 "IPTG"))))
# ::id pmid_2000_3375.142 ::date 2015-06-24T06:10:24 ::annotator SDL-AMR-09 ::preferred
# ::snt Co-expression of RasV12 and wild-type Aurora-A in WT cells increases the level of p-AKT (Figure 3A, lane 5, 3.5 fold) as compared to RasV12overexpression alone (Figure 3A, lane 4, 1.8 fold).
# ::save-date Tue Feb 2, 2016 ::file pmid_2000_3375_142.txt
(i / increase-01
:ARG0 (c / coexpress-01
:ARG2 (a / and
:op1 (e / enzyme :name (n / name :op1 "Ras")
:ARG2-of (m / mutate-01 :value "V12"))
:op2 (e3 / enzyme :name (n2 / name :op1 "Aurora-A")
:mod (w / wild-type)))
:ARG3 (c2 / cell
:mod w))
:ARG1 (l / level
:quant-of (e2 / enzyme :name (n3 / name :op1 "AKT")
:ARG3-of (p2 / phosphorylate-01))
:ARG1-of (d / describe-01
:ARG0 (l2 / lane :mod 5
:part-of (f / figure :mod "3A"))
:ARG2 (p3 / product-of :op1 3.5)))
:compared-to (o / overexpress-01
:ARG1 e
:mod (a2 / alone)
:ARG1-of (d2 / describe-01
:ARG0 (l3 / lane :mod 4
:part-of f)
:ARG2 (p4 / product-of :op1 1.8))))
# ::id pmid_2000_3375.143 ::date 2015-06-24T06:16:23 ::annotator SDL-AMR-09 ::preferred
# ::snt The RalGDS/RalA signaling pathway was determined by detecting the activity of RalA using GST-RalBD pull-down assay.
# ::save-date Mon Dec 21, 2015 ::file pmid_2000_3375_143.txt
(d / determine-01
:ARG1 (p / pathway :name (n / name :op1 "RalGDS/RalA")
:ARG0-of (s / signal-07))
:manner (d2 / detect-01
:ARG1 (a / activity-06
:ARG0 (p2 / protein :name (n2 / name :op1 "RalA")))
:manner (u / use-01
:ARG1 (a2 / assay-01
:manner (p3 / pull-down-08
:ARG3 (p4 / protein :name (n3 / name :op1 "GST-RalBD")))))))
# ::id pmid_2000_3375.144 ::date 2015-06-24T06:19:50 ::annotator SDL-AMR-09 ::preferred
# ::snt As shown in Figure 3A, Aurora-A overexpression alone activated RalA (Figure 3A, lane 2, 2.0 fold) as compared to the parental Vector cells (Figure 3A, lane 1, 1.0 fold).
# ::save-date Tue Jun 30, 2015 ::file pmid_2000_3375_144.txt
(a / activate-01
:ARG0 (o / overexpress-01
:ARG1 (e / enzyme :name (n / name :op1 "Aurora-A"))
:mod (a2 / alone))
:ARG1 (p2 / protein :name (n2 / name :op1 "RalA"))
:ARG1-of (d / describe-01
:ARG0 (l / lane :mod 2
:part-of (f / figure :mod "3A"))
:ARG2 (p3 / product-of :op1 2.0))
:compared-to (c / cell
:mod (p4 / parental)
:mod (v / vector)
:ARG1-of (d2 / describe-01
:ARG0 (l2 / lane :mod 1
:part-of f)
:ARG2 (p5 / product-of :mod 1.0)))
:ARG1-of (s / show-01
:medium f))
# ::id pmid_2000_3375.145 ::date 2015-06-24T06:24:16 ::annotator SDL-AMR-09 ::preferred
# ::snt After IPTG induction, The RalA activity was increased by RasV12 overexpression (Figure 3A, lane 4, 2.5 fold).
# ::save-date Mon Dec 21, 2015 ::file pmid_2000_3375_145.txt
(i / increase-01
:ARG0 (o / overexpress-01
:ARG1 (e / enzyme :name (n3 / name :op1 "Ras")
:ARG2-of (m / mutate-01 :value "V12")))
:ARG1 (a / activity-06
:ARG0 (p / protein :name (n2 / name :op1 "RalA")))
:time (a2 / after
:op1 (i2 / induce-01
:ARG2 (s / small-molecule :name (n / name :op1 "IPTG"))))
:ARG1-of (d / describe-01
:ARG0 (l / lane :mod 4
:part-of (f / figure :mod "3A"))
:ARG2 (p2 / product-of :op1 2.5)))
# ::id pmid_2000_3375.146 ::date 2015-06-24T06:27:58 ::annotator SDL-AMR-09 ::preferred
# ::snt Co-expression of RasV12 and wild-type Aurora-A in WT cells increase the activity of RalA of RasV12 (Figure 3A, lane 5, 3.7 fold).
# ::save-date Tue Feb 2, 2016 ::file pmid_2000_3375_146.txt
(i / increase-01
:ARG0 (c / coexpress-01
:ARG2 (a / and
:op1 (e / enzyme :name (n2 / name :op1 "Ras")
:ARG2-of (m / mutate-01 :value "V12"))
:op2 (e2 / enzyme :name (n3 / name :op1 "Aurora-A")
:mod w))
:ARG3 (c2 / cell
:mod (w / wild-type)))
:ARG1 (a2 / activity-06
:ARG0 (p2 / protein :name (n / name :op1 "RalA")
:location (c3 / cell
:mod e)))
:ARG1-of (d / describe-01
:ARG0 (l / lane :mod 5
:part-of (f / figure :mod "3A"))
:ARG2 (p3 / product-of :op1 3.7)))
# ::id pmid_2000_3375.147 ::date 2015-06-24T06:34:51 ::annotator SDL-AMR-09 ::preferred
# ::snt Taken together, both Aurora-A and RasV12 increased the levels of p-MEK, pERK1/2, and p-AKT and the activation of RalA.
# ::save-date Tue Jun 30, 2015 ::file pmid_2000_3375_147.txt
(h / have-condition-91
:ARG1 (i / increase-01
:ARG0 (a / and
:op1 (e / enzyme :name (n2 / name :op1 "Aurora-A"))
:op2 (e2 / enzyme :name (n3 / name :op1 "Ras")
:ARG2-of (m / mutate-01 :value "V12")))
:ARG1 (a2 / and
:op1 (l / level
:quant-of (e3 / enzyme :name (n4 / name :op1 "MEK")
:ARG3-of (p2 / phosphorylate-01)))
:op2 (l2 / level
:quant-of (s / slash
:op1 (e4 / enzyme :name (n5 / name :op1 "ERK1"))
:op2 (e5 / enzyme :name (n6 / name :op1 "ERK2"))
:ARG3-of p2))
:op3 (l3 / level
:quant-of (e6 / enzyme :name (n7 / name :op1 "AKT")
:ARG3-of p2))
:op4 (a3 / activate-01
:ARG1 (p3 / protein :name (n / name :op1 "RalA")))))
:ARG2 (t / take-01
:ARG1 a
:mod (t2 / together)))
# ::id pmid_2000_3375.148 ::date 2015-06-24T06:54:56 ::annotator SDL-AMR-09 ::preferred
# ::snt This induction was further enhanced when Aurora-A and RasV12 were overexpressed simultaneously.
# ::save-date Fri Mar 4, 2016 ::file pmid_2000_3375_148.txt
(e2 / enhance-01
:ARG1 (i / induce-01
:mod (t / this))
:degree (f / further)
:time (o / overexpress-01
:ARG1 (a / and
:op1 (e / enzyme :name (n2 / name :op1 "Aurora-A"))
:op2 (e3 / enzyme :name (n3 / name :op1 "Ras")
:ARG2-of (m / mutate-01 :value "V12")))
:mod (s / simultaneous)))
# ::id pmid_2000_3375.149 ::date 2015-06-24T06:57:48 ::annotator SDL-AMR-09 ::preferred
# ::snt To further confirm our results, Aurora-A specific small interference RNA (siRNA) was used.
# ::save-date Tue Dec 29, 2015 ::file pmid_2000_3375_149.txt
(u / use-01
:ARG1 (n3 / nucleic-acid :name (n / name :op1 "small" :op2 "interference" :op3 "RNA")
:ARG1-of (s / specific-02
:ARG2 (e / enzyme :name (n2 / name :op1 "Aurora-A"))))
:ARG2 (c / confirm-01
:ARG1 (t / thing
:ARG2-of (r2 / result-01)
:poss (w / we))
:degree (f / further)))
# ::id pmid_2000_3375.150 ::date 2015-06-24T07:01:06 ::annotator SDL-AMR-09 ::preferred
# ::snt As shown in Figure 3B, Aurora-A specific siRNA decreased the expression level of Aurora-A in WT cells.
# ::save-date Mon Dec 21, 2015 ::file pmid_2000_3375_150.txt
(d / decrease-01
:ARG0 (n3 / nucleic-acid :name (n / name :op1 "siRNA")
:ARG1-of (s / specific-02
:ARG2 (e2 / enzyme :name (n2 / name :op1 "Aurora-A"))))
:ARG1 (l / level
:degree-of (e / express-03
:ARG1 e2
:ARG3 (c / cell
:mod (w / wild-type))))
:ARG1-of (s2 / show-01
:medium (f / figure :mod "3B")))
# ::id pmid_2000_3375.151 ::date 2015-06-24T07:03:28 ::annotator SDL-AMR-09 ::preferred
# ::snt Accordingly, levels of p-MEK/p-ERK, p-AKT and activation of RalA were also decreased when Aurora-A siRNA was introduced into WT cells upon IPTG induction.
# ::save-date Tue Jun 30, 2015 ::file pmid_2000_3375_151.txt
(d / decrease-01
:ARG1 (a / and
:op1 (l / level
:quant-of (s / slash
:op1 (e / enzyme :name (n / name :op1 "MEK"))
:op2 (e2 / enzyme :name (n2 / name :op1 "ERK"))
:ARG3-of (p / phosphorylate-01)))
:op2 (l2 / level
:quant-of (e3 / enzyme :name (n3 / name :op1 "AKT")
:ARG3-of p))
:op3 (l3 / level
:degree-of (a2 / activate-01
:ARG1 (p2 / protein :name (n4 / name :op1 "RalA")))))
:mod (a3 / also)
:time (i / introduce-02
:ARG1 (n8 / nucleic-acid :name (n5 / name :op1 "siRNA")
:mod (e4 / enzyme :name (n6 / name :op1 "Aurora-A")))
:ARG2 (c / cell
:mod (w / wild-type))
:condition (i2 / induce-01
:ARG2 (s3 / small-molecule :name (n7 / name :op1 "IPTG"))))
:manner (a4 / accordingly))
# ::id pmid_2000_3375.152 ::date 2015-06-24T07:11:06 ::annotator SDL-AMR-09 ::preferred
# ::snt Our results confirmed that wild-type-Aurora-A enhance Ras downstream signaling pathways including MEK/ERK, AKT and RalA.
# ::save-date Sun Jan 17, 2016 ::file pmid_2000_3375_152.txt
(c / confirm-01
:ARG0 (t / thing
:poss (w / we)
:ARG2-of (r / result-01))
:ARG1 (e2 / enhance-01
:ARG0 (e4 / enzyme :name (n3 / name :op1 "Aurora-A")
:mod (w2 / wild-type))
:ARG1 (p3 / pathway
:location (d / downstream)
:ARG0-of (s / signal-07
:ARG1 (e / enzyme :name (n / name :op1 "Ras")))
:ARG2-of (i / include-91
:ARG1 (a / and
:op1 (p / pathway :name (n2 / name :op1 "MEK/ERK"))
:op2 (p2 / pathway :name (n4 / name :op1 "AKT"))
:op3 (p4 / pathway :name (n5 / name :op1 "RalA")))))))
# ::id pmid_2000_3375.153 ::date 2015-06-24T07:16:41 ::annotator SDL-AMR-09 ::preferred
# ::snt The MEK/ERK pathway is involved in WT cell aggregation
# ::save-date Wed Jun 24, 2015 ::file pmid_2000_3375_153.txt
(i / involve-01
:ARG1 (p / pathway :name (n / name :op1 "MEK/ERK"))
:ARG2 (a / aggregate-01
:ARG1 (c / cell
:mod (w / wild-type))))
# ::id pmid_2000_3375.154 ::date 2015-06-24T07:17:46 ::annotator SDL-AMR-09 ::preferred
# ::snt The involvement of MEK/ERK, PI3K/AKT and RalGDS/RalA signaling pathways in Aurora-A-related cell aggregation (Fig. 2B, WT + IPTG) was clarified by treatment of the cells with the following inhibitors: FTI-277, a farnesylation inhibitor of Ras; PD-98059, the inhibitor of MEK kinase and LY-294002, the inhibitor of PI3K kinase and RalASa94A, a mutant of Ral.
# ::save-date Sat Jan 16, 2016 ::file pmid_2000_3375_154.txt
(c / clarify-10
:ARG1 (i2 / involve-01
:ARG1 (a / and
:op1 (p / pathway :name (n / name :op1 "MEK/ERK"))
:op2 (p2 / pathway :name (n2 / name :op1 "PI3K/AKT"))
:op3 (p3 / pathway :name (n5 / name :op1 "RalGDS/RalA"))
:ARG0-of (s / signal-07))
:ARG2 (a2 / aggregate-01
:ARG1 (c2 / cell)
:ARG1-of (r / relate-01
:ARG2 (e2 / enzyme :name (n6 / name :op1 "Aurora-A"))))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "2B")))
:manner (t2 / treat-04
:ARG1 c2
:ARG2 (m / molecular-physical-entity
:ARG0-of (i3 / inhibit-01)
:ARG1-of (f2 / follow-01)
:ARG1-of (m2 / mean-01
:ARG2 (a3 / and
:op1 (s2 / small-molecule :name (n7 / name :op1 "FTI-277")
:ARG0-of (i4 / inhibit-01
:ARG1 (p4 / protein-family :name (n3 / name :op1 "Ras"))
:ARG2-of (f3 / farnesylate-01)))
:op2 (s3 / small-molecule :name (n8 / name :op1 "PD-98059")
:ARG0-of (i5 / inhibit-01
:ARG1 (k / kinase :name (n4 / name :op1 "MEK"))))
:op3 (s4 / small-molecule :name (n9 / name :op1 "LY-294002")
:ARG0-of (i6 / inhibit-01
:ARG1 (a4 / and
:op1 (k2 / kinase :name (n10 / name :op1 "PI3K"))
:op1 (p5 / protein :name (n11 / name :op1 "RalASa94A")
:ARG3-of (m6 / mutate-01
:ARG1 (p6 / protein :name (n12 / name :op1 "Ral"))))))))))))
# ::id pmid_2000_3375.155 ::date 2015-06-24T07:28:27 ::annotator SDL-AMR-09 ::preferred
# ::snt FTI-277 restrains Ras protein as a non-farnesylated form and inhibits p-ERK1/2 expression dose-dependently but had no effect on p-AKT (Figure 4A, lanes 2 and 3).
# ::save-date Sat Jan 16, 2016 ::file pmid_2000_3375_155.txt
(c / contrast-01
:ARG1 (a / and
:op1 (r / restrain-01
:ARG0 (s2 / small-molecule :name (n2 / name :op1 "FTI-277"))
:ARG1 (p / protein-family :name (n / name :op1 "Ras"))
:manner (f2 / form
:ARG1-of (f / farnesylate-01 :polarity -)))
:op2 (i / inhibit-01
:ARG0 s2
:ARG1 (e / express-03
:ARG2 (s / slash
:op1 (e2 / enzyme :name (n3 / name :op1 "ERK1"))
:op2 (e3 / enzyme :name (n4 / name :op1 "ERK2"))
:ARG3-of (p2 / phosphorylate-01)))
:manner (d / depend-01
:ARG1 (d2 / dose))))
:ARG2 (a2 / affect-01 :polarity -
:ARG0 s2
:ARG1 (e4 / enzyme :name (n5 / name :op1 "AKT")
:ARG3-of p2))
:ARG1-of (d3 / describe-01
:ARG0 (a3 / and
:op1 (l / lane :mod 2)
:op2 (l2 / lane :mod 3)
:part-of (f3 / figure :mod "4A"))))
# ::id pmid_2000_3375.156 ::date 2015-06-24T07:34:20 ::annotator SDL-AMR-09 ::preferred
# ::snt PD-98059 decreased the phosphorylation of ERK1/2 (p-ERK1/2) but had no effect on other signaling pathways (Figure 4A, lanes 4 and 5).
# ::save-date Tue Dec 29, 2015 ::file pmid_2000_3375_156.txt
(c / contrast-01
:ARG1 (d / decrease-01
:ARG0 (s3 / small-molecule :name (n / name :op1 "PD-98059"))
:ARG1 (p2 / phosphorylate-01
:ARG1 (s / slash
:op1 (e / enzyme :name (n2 / name :op1 "ERK1"))
:op2 (e2 / enzyme :name (n3 / name :op1 "ERK2")))))
:ARG2 (a / affect-01 :polarity -
:ARG0 s3
:ARG1 (p3 / pathway
:ARG0-of (s2 / signal-07)
:mod (o / other)))
:ARG1-of (d2 / describe-01
:ARG0 (a2 / and
:op1 (l2 / lane :mod 4)
:op2 (l3 / lane :mod 5)
:part-of (f / figure :mod "4A"))))
# ::id pmid_2000_3375.157 ::date 2015-06-24T07:41:01 ::annotator SDL-AMR-09 ::preferred
# ::snt LY-294002 reduced the phosphorylation of AKT (p-AKT) but had no effect on another signaling pathway (Figure 4A, lanes 6 and 7).
# ::save-date Tue Dec 29, 2015 ::file pmid_2000_3375_157.txt
(c / contrast-01
:ARG1 (r / reduce-01
:ARG0 (s2 / small-molecule :name (n / name :op1 "LY-294002"))
:ARG1 (p / phosphorylate-01
:ARG1 (e / enzyme :name (n2 / name :op1 "AKT"))))
:ARG2 (a / affect-01 :polarity -
:ARG0 s2
:ARG1 (p2 / pathway
:ARG0-of (s / signal-07)
:mod (o / other)))
:ARG1-of (d / describe-01
:ARG0 (a2 / and
:op1 (l2 / lane :mod 6)
:op2 (l3 / lane :mod 7)
:part-of (f / figure :mod "4A"))))
# ::id pmid_2000_3375.158 ::date 2015-06-24T07:43:38 ::annotator SDL-AMR-09 ::preferred
# ::snt In summary, in WT cells Aurora-A increases the expression of p-ERK1/2 in a Ras dependent manner.
# ::save-date Tue Jun 30, 2015 ::file pmid_2000_3375_158.txt
(i / increase-01
:ARG0 (e5 / enzyme :name (n2 / name :op1 "Aurora-A"))
:ARG1 (e2 / express-03
:ARG2 (s2 / slash
:op1 (e3 / enzyme :name (n3 / name :op1 "ERK1"))
:op2 (e4 / enzyme :name (n4 / name :op1 "ERK2"))
:ARG3-of (p2 / phosphorylate-01))
:ARG3 (c / cell
:mod (w / wild-type)))
:manner (d / depend-01
:ARG1 (e / enzyme :name (n / name :op1 "Ras")))
:ARG2-of (s / summarize-01))
# ::id pmid_2000_3375.159 ::date 2015-06-24T07:46:55 ::annotator SDL-AMR-09 ::preferred
# ::snt However, FTI-277 does not reduce the p-AKT in WT cells co-expressing RasV12 and wild-type Aurora-A. Wild-type Aurora-A activates RalA (Figure 3A and 3B) and phosphorylates RalA at serine194 to promote cellular transformation and migration [38].
# ::save-date Tue Feb 2, 2016 ::file pmid_2000_3375_159.txt
(m / multi-sentence
:snt1 (h / have-concession-91
:ARG1 (r / reduce-01 :polarity -
:ARG0 (s / small-molecule :name (n2 / name :op1 "FTI-277"))
:ARG1 (e2 / enzyme :name (n3 / name :op1 "AKT")
:ARG3-of (p / phosphorylate-01))
:location (c / cell
:mod (w / wild-type)
:ARG3-of (c2 / coexpress-01
:ARG2 (a / and
:op1 (e / enzyme :name (n / name :op1 "Ras")
:ARG2-of (m3 / mutate-01 :value "V12"))
:op2 (e3 / enzyme :name (n4 / name :op1 "Aurora-A")
:mod w))))))
:snt2 (a2 / and
:op1 (a3 / activate-01
:ARG0 (e4 / enzyme :name (n5 / name :op1 "Aurora-A"))
:ARG1 (p4 / protein :name (n6 / name :op1 "RalA"))
:ARG1-of (d / describe-01
:ARG0 (a4 / and
:op1 (f / figure :mod "3A")
:op2 (f2 / figure :mod "3B"))))
:op2 (p5 / phosphorylate-01
:ARG1 (a5 / amino-acid :mod 194 :name (n7 / name :op1 "serine")
:part-of p4)
:ARG2 e4
:purpose (p6 / promote-02
:ARG0 e4
:ARG1 (a6 / and
:op1 (t / transform-01
:ARG1 (c3 / cell))
:op2 (m4 / migrate-01
:ARG0 c3))))
:ARG1-of (d2 / describe-01
:ARG0 (p7 / publication
:ARG1-of (c4 / cite-01
:ARG2 38)))))
# ::id pmid_2000_3375.160 ::date 2015-06-24T07:54:16 ::annotator SDL-AMR-09 ::preferred
# ::snt To reveal the role of RalA phosphorylation at ser194 in Aurora-A induced RalA activation in WT cells, the mutants RalAS183A or RalAS194A were transiently transfected into WT cells and the RalA activity was evaluated.
# ::save-date Mon Dec 21, 2015 ::file pmid_2000_3375_160.txt
(a / and
:op1 (t / transfect-01
:ARG1 (c / cell
:mod (w / wild-type))
:ARG2 (o / or
:op1 (p2 / protein :name (n / name :op1 "RalAS183A"))
:op2 (p3 / protein :name (n2 / name :op1 "RalAS194A"))
:ARG2-of (m / mutate-01))
:ARG1-of (t2 / transient-02))
:op2 (e / evaluate-01
:ARG1 (a2 / activity-06
:ARG0 (p4 / protein :name (n3 / name :op1 "RalA"))))
:purpose (r / reveal-01
:ARG1 (p5 / play-08
:ARG0 (p / phosphorylate-01
:ARG1 (a3 / amino-acid :mod 194 :name (n4 / name :op1 "serine")
:part-of p4))
:ARG1 (a4 / activate-01
:ARG1 p4
:ARG2-of (i / induce-01
:ARG0 (e2 / enzyme :name (n5 / name :op1 "Aurora-A"))))
:location c)))
# ::id pmid_2000_3375.161 ::date 2015-06-24T08:02:31 ::annotator SDL-AMR-09 ::preferred
# ::snt Consistent with a previous report [38], only RalAS194A could reduce the Ral A activity (Figure 4B, lane 3).
# ::save-date Mon Dec 21, 2015 ::file pmid_2000_3375_161.txt
(c / consistent-01
:ARG1 (p2 / possible-01
:ARG1 (r / reduce-01
:ARG0 (p3 / protein :name (n / name :op1 "RalAS194A")
:mod (o / only))
:ARG1 (a / activity-06
:ARG0 (p4 / protein :name (n2 / name :op1 "RalA"))))
:ARG1-of (d2 / describe-01
:ARG0 (l / lane :mod 3
:part-of (f / figure :mod "4B"))))
:ARG2 (r2 / report
:time (p / previous)
:ARG1-of (d / describe-01
:ARG0 (p5 / publication
:ARG1-of (c2 / cite-01
:ARG2 38)))))
# ::id pmid_2000_3375.162 ::date 2015-06-24T08:06:08 ::annotator SDL-AMR-09 ::preferred
# ::snt To determine which signaling pathway is involved in the aggregation of WT cells during RasV12 overexpression, we first demonstrated that Aurora-A induced cell aggregation was blocked by Aurora-A specific small interfering RNA (Figure 4C).
# ::save-date Mon Dec 21, 2015 ::file pmid_2000_3375_162.txt
(d / demonstrate-01
:ARG0 (w / we)
:ARG1 (b / block-01
:ARG1 (a / aggregate-01
:ARG1 (c / cell)
:ARG2-of (i / induce-01
:ARG0 (e2 / enzyme :name (n2 / name :op1 "Aurora-A"))))
:ARG2 (n4 / nucleic-acid :name (n3 / name :op1 "small" :op2 "interfering" :op3 "RNA")
:ARG1-of (s / specific-02
:ARG2 e2)))
:time (f / first)
:purpose (d2 / determine-01
:ARG0 w
:ARG1 (i2 / involve-01 :mode interrogative
:ARG1 (p2 / pathway
:ARG0-of (s2 / signal-07))
:ARG2 (a2 / aggregate-01
:ARG1 (c2 / cell
:mod (w3 / wild-type)))
:time (o2 / overexpress-01
:ARG1 (e / enzyme :name (n / name :op1 "Ras")
:ARG2-of (m / mutate-01 :value "V12")))))
:ARG1-of (d3 / describe-01
:ARG0 (f2 / figure :mod "4C")))
# ::id pmid_2000_3375.163 ::date 2015-06-24T08:11:16 ::annotator SDL-AMR-09 ::preferred
# ::snt The WT cells were treated with FTI-277, PD-98059 or LY-294002 for 24 h and cell aggregation was observed.
# ::save-date Mon Jun 29, 2015 ::file pmid_2000_3375_163.txt
(a / and
:op1 (t / treat-04
:ARG1 (c / cell
:mod (w / wild-type))
:ARG2 (o / or
:op1 (s / small-molecule :name (n / name :op1 "FTI-277"))
:op2 (s2 / small-molecule :name (n2 / name :op1 "PD-98059"))
:op3 (s3 / small-molecule :name (n3 / name :op1 "LY-294002")))
:duration (t2 / temporal-quantity :quant 24
:unit (h / hour)))
:op2 (o2 / observe-01
:ARG1 (a2 / aggregate-01
:ARG1 c)))
# ::id pmid_2000_3375.164 ::date 2015-06-24T08:13:39 ::annotator SDL-AMR-09 ::preferred
# ::snt Both FTI-277 and PD98059 reversed the aggregation of WT cells, whereas LY-294002 showed no effect on cell aggregation (Figure 4C).
# ::save-date Mon Jun 29, 2015 ::file pmid_2000_3375_164.txt
(c / contrast-01
:ARG1 (r / reverse-01
:ARG0 (a / and
:op1 (s3 / small-molecule :name (n / name :op1 "FTI-277"))
:op2 (s4 / small-molecule :name (n2 / name :op1 "PD98059")))
:ARG1 (a2 / aggregate-01
:ARG1 (c2 / cell
:mod (w / wild-type))))
:ARG2 (s / show-01
:ARG0 (s2 / small-molecule :name (n3 / name :op1 "LY-294002"))
:ARG1 (a3 / affect-01 :polarity -
:ARG0 s2
:ARG1 a2))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "4C")))
# ::id pmid_2000_3375.165 ::date 2015-06-24T08:16:08 ::annotator SDL-AMR-09 ::preferred
# ::snt Because mutant RalAS194A was unable to block cell aggregation, its role in Aurora-A induced cell aggregation was excluded (Figure 4C).
# ::save-date Tue Jun 30, 2015 ::file pmid_2000_3375_165.txt
(e / exclude-01
:ARG1 (p / play-08
:ARG0 (p2 / protein :name (n / name :op1 "RalAS194A")
:ARG2-of (m / mutate-01))
:ARG1 (a / aggregate-01
:ARG1 (c / cell)
:ARG2-of (i / induce-01
:ARG0 (e2 / enzyme :name (n2 / name :op1 "Aurora-A")))))
:ARG1-of (c2 / cause-01
:ARG0 (c3 / capable-01 :polarity -
:ARG1 p2
:ARG2 (b / block-01
:ARG0 p2
:ARG1 a))))
# ::id pmid_2000_3375.166 ::date 2015-06-24T08:20:11 ::annotator SDL-AMR-09 ::preferred
# ::snt Taken together, the Ras/MEK/ERK signaling pathway but not the PI3K/AKT or RalGDS/RalA pathway is responsible for Aurora-A induced cell aggregation.
# ::save-date Tue Jun 30, 2015 ::file pmid_2000_3375_166.txt
(h / have-condition-91
:ARG1 (c / contrast-01
:ARG1 (r / responsible-01
:ARG0 (p2 / pathway :name (n2 / name :op1 "Ras/MEK/ERK")
:ARG0-of (s / signal-07))
:ARG1 (a / aggregate-01
:ARG1 (c2 / cell)
:ARG2-of (i / induce-01
:ARG0 (e / enzyme :name (n3 / name :op1 "Aurora-A")))))
:ARG2 (r2 / responsible-01 :polarity -
:ARG0 (o / or
:op1 (p / pathway :name (n / name :op1 "PI3K/AKT"))
:op2 (p4 / pathway :name (n4 / name :op1 "RalGDS/RalA")))
:ARG1 a))
:ARG2 (t / take-01
:ARG1 p2
:mod (t2 / together)))