INT95116

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Context Info
Confidence 0.57
First Reported 2001
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 24
Total Number 28
Disease Relevance 19.56
Pain Relevance 1.29

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

extracellular space (PDGFA) extracellular region (PDGFA) embryo development (PDGFA)
cell-cell signaling (PDGFA)
Anatomy Link Frequency
fibroblasts 3
platelet 3
lung 2
endothelial cells 1
osteoblasts 1
PDGFA (Homo sapiens)
Pain Link Frequency Relevance Heat
fibrosis 212 99.38 Very High Very High Very High
Potency 19 98.56 Very High Very High Very High
cytokine 114 97.18 Very High Very High Very High
Pain 28 89.16 High High
Inflammation 220 87.52 High High
Inflammatory mediators 3 77.84 Quite High
fluoxetine 1 60.72 Quite High
cva 50 60.28 Quite High
antidepressant 1 59.48 Quite High
Inflammatory response 64 44.64 Quite Low
Disease Link Frequency Relevance Heat
Carcinoma 211 99.62 Very High Very High Very High
Mesothelioma 47 99.44 Very High Very High Very High
Pulmonary Fibrosis 56 99.38 Very High Very High Very High
Hypophosphatemia 21 99.34 Very High Very High Very High
Fibromyalgia 7 98.98 Very High Very High Very High
Apoptosis 404 98.72 Very High Very High Very High
Liver Cancer 3 98.64 Very High Very High Very High
Hypercalcemia 21 98.56 Very High Very High Very High
Gynecomastia 25 98.42 Very High Very High Very High
Renal Cell Carcinoma 67 98.32 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Imatinib mesylate (IM), is a selective and competitive inhibitor of tyrosine kinases, including BCR-ABL, ABL, KIT, and the platelet-derived growth factor receptors (PDGF-R).
Negative_regulation (inhibitor) of platelet-derived growth factor in platelet
1) Confidence 0.57 Published 2003 Journal J. Exp. Clin. Cancer Res. Section Abstract Doc Link 16767900 Disease Relevance 0.84 Pain Relevance 0
The mechanism of action of the mTOR inhibitors is quite distinct from those of drugs inhibiting VEGFR/PDGFR.
Negative_regulation (inhibiting) of PDGF
2) Confidence 0.57 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004583 Disease Relevance 0.77 Pain Relevance 0
Sunitinib has been identified as an inhibitor of various RTKs including PDGFR?
Negative_regulation (inhibitor) of PDGF
3) Confidence 0.42 Published 2010 Journal OncoTargets and therapy Section Body Doc Link PMC2895781 Disease Relevance 1.24 Pain Relevance 0.07
Sorafenib is also an inhibitor of VEGFR2 and 3, PDGFR-?
Negative_regulation (inhibitor) of PDGF
4) Confidence 0.42 Published 2010 Journal OncoTargets and therapy Section Body Doc Link PMC2895781 Disease Relevance 0.91 Pain Relevance 0.05
Functional proliferation and clonogenic assays were performed (i) to assess PDGFR-mediated survival and proliferation in fibroblasts and endothelial cells after SU9518 (small molecule inhibitor of PDGF receptor tyrosine kinase); (ii) to test the potency und selectivity of the PDGF RTK inhibitor after stimulation with PDGF isoforms (-AB, -AA, -BB) and VEGF+bFGF.
Negative_regulation (inhibitor) of PDGF receptor in endothelial cells associated with potency
5) Confidence 0.40 Published 2006 Journal BMC Cancer Section Abstract Doc Link PMC1458351 Disease Relevance 0.14 Pain Relevance 0.09
We showed previously that PDGF signaling inhibition attenuates radiation-induced lung fibrosis in a mouse model.
Negative_regulation (inhibition) of PDGF in lung associated with fibrosis and pulmonary fibrosis
6) Confidence 0.40 Published 2006 Journal BMC Cancer Section Abstract Doc Link PMC1458351 Disease Relevance 0.19 Pain Relevance 0.05
Recently, we have demonstrated this concept in vivo in a radiation-induced lung fibrosis model in mice by showing that inhibition of PDGF signaling functionally attenuates pulmonary fibrosis [13].
Negative_regulation (inhibition) of PDGF in lung associated with fibrosis and pulmonary fibrosis
7) Confidence 0.39 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1458351 Disease Relevance 0.56 Pain Relevance 0.25
Inhibition of PDGF signaling by SU9518 reduced the clonogenic survival fraction of fibroblasts.
Negative_regulation (Inhibition) of PDGF in fibroblasts
8) Confidence 0.39 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1458351 Disease Relevance 0 Pain Relevance 0
In our fibroblast clonogenic and proliferation assays, inhibition of PDGF signaling by SU9518 significantly reduced the clonogenic survival fraction and the proliferation of fibroblasts, thus supporting the important role of PDGF signaling for fibroblasts survival.
Negative_regulation (inhibition) of PDGF in fibroblasts
9) Confidence 0.39 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1458351 Disease Relevance 0.38 Pain Relevance 0.07
Increased levels of cGMP indirectly lead to increased levels of cAMP which may suppress transcription of DNA, activate anti-proliferative protein kinases, and inhibit PDGF activity (Tantini et al 2005).
Negative_regulation (inhibit) of PDGF
10) Confidence 0.32 Published 2006 Journal Vascular Health and Risk Management Section Body Doc Link PMC1994020 Disease Relevance 0.61 Pain Relevance 0
Sorafenib is a small molecular inhibitor of Raf kinase, PDGF (platelet-derived growth factor), VEGF receptor 2 & 3 kinases and c-Kit, the receptor for stem cell factor.
Negative_regulation (inhibitor) of PDGF in stem cell
11) Confidence 0.24 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2855702 Disease Relevance 0.93 Pain Relevance 0.12
Similarly, preclinical data suggested a key role for platelet-derived growth factor (PDGF) in mesothelioma, yet imatinib, a selective inhibitor of the PDGF receptor tyrosine kinase, failed to achieve any responses in 4 phase II trials [42].Vascular endothelial growth factor signaling may have an important role in the biology of mesothelioma.
Negative_regulation (inhibitor) of PDGF in platelet associated with mesothelioma
12) Confidence 0.23 Published 2008 Journal Curr Treat Options Oncol Section Body Doc Link PMC2782121 Disease Relevance 0.89 Pain Relevance 0
In this study, Mcl-1 knockdown sensitized HCC cells to the VEGF/PDGF inhibitor SU5614.
Negative_regulation (inhibitor) of PDGF associated with carcinoma
13) Confidence 0.18 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1601962 Disease Relevance 1.21 Pain Relevance 0
A second phase 1/2 trial employed combined VEGF, EGFR and PDGF-R blockade, and utilized combined bevacizumab 10 mg/kg IV every 2 weeks, erlotinib 150 mg by mouth daily, and imatinib 400 mg by mouth daily.40 The investigators reported a 9% response rate with 61% disease stabilization by RECIST criteria.
Negative_regulation (blockade) of PDGF in mouth associated with disease
14) Confidence 0.17 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004565 Disease Relevance 1.35 Pain Relevance 0
In addition, Mcl-1 downregulation also increased apoptosis rates after treatment with PI3K inhibitors and, to a lower extent, after treatment with mTOR, Raf I and VEGF/PDGF kinase inhibitors.
Negative_regulation (inhibitors) of PDGF associated with apoptosis
15) Confidence 0.16 Published 2006 Journal BMC Cancer Section Abstract Doc Link PMC1601962 Disease Relevance 1.42 Pain Relevance 0
In view of the several off-target kinases that IM and other TKIs inhibit, such as c-kit and PDGF-R, which play a normal physiological role in immune responses, it has been speculated that these drugs will probably have an impact on the immune responses of patients.
Negative_regulation (inhibit) of PDGF-R
16) Confidence 0.16 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC3010822 Disease Relevance 0.89 Pain Relevance 0
IM can decrease testosterone production by the inhibition of these receptors.35 Decreased testosterone production over time can lead to gynecomastia, which has been noted with long-term IM exposure and is possibly secondary to inhibition of c-kit and PDGF-R.
Negative_regulation (inhibition) of PDGF-R associated with gynecomastia
17) Confidence 0.16 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC3010822 Disease Relevance 0.90 Pain Relevance 0
Functional proliferation and clonogenic assays were performed (i) to assess PDGFR-mediated survival and proliferation in fibroblasts and endothelial cells after SU9518 (small molecule inhibitor of PDGF receptor tyrosine kinase); (ii) to test the potency und selectivity of the PDGF RTK inhibitor after stimulation with PDGF isoforms (-AB, -AA, -BB) and VEGF+bFGF.
Negative_regulation (inhibitor) of PDGF receptor in fibroblasts associated with potency
18) Confidence 0.13 Published 2006 Journal BMC Cancer Section Abstract Doc Link PMC1458351 Disease Relevance 0.14 Pain Relevance 0.09
They speculated that IM restrains bone resorption (by inhibiting c-Fms on osteoclasts) and stimulates bone formation (by inhibiting PDGF-R on osteoblasts), thus sequestrating both calcium and phosphate in bone.
Negative_regulation (inhibiting) of PDGF-R in osteoblasts associated with fibromyalgia and hypercalcemia
19) Confidence 0.12 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC3010822 Disease Relevance 0.64 Pain Relevance 0
Imatinib mesylate (IM) (Gleevec®, Novartis), a 2-phenylaminopyrimidine derivative, is a potent inhibitor of targeted protein tyrosine kinases, including BCR-ABL, c-kit, and platelet-derived growth factor receptor (PDGF-R), and was developed in the mid-1990s against a background of some uncertainty.1–3 The drug appears to work principally by occupying the ATP binding site of the BCR-ABL oncoprotein and thereby preventing phosphorylation of the substrate and interrupting contact with the effector protein.
Negative_regulation (inhibitor) of PDGF-R in platelet
20) Confidence 0.12 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC3010822 Disease Relevance 0.27 Pain Relevance 0

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