INT164756

Context Info Confidence 0.57 First Reported 2006 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 32 Total Number 32 Disease Relevance 21.69 Pain Relevance 0.72

signal transduction (PDGFRB) cytoplasmic membrane-bounded vesicle (PDGFRB) plasma membrane (PDGFRB) nucleus (PDGFRB) cytoplasm (PDGFRB) signal transducer activity (PDGFRB)

Anatomy Link Frequency platelet 4 fibroblast 3 endothelial cells 2 seams 1 3G3 1 PDGFRB (Homo sapiens)

Pain Link Frequency Relevance Heat Bioavailability 2 100.00 fibrosis 162 97.60 palliative 13 94.92 cytokine 50 87.52 nud 6 82.00 positron emission tomography 14 63.84 metalloproteinase 11 60.44 Potency 19 57.20 addiction 12 44.64 Piles 1 25.00

Disease Link Frequency Relevance Heat Breast Cancer 547 99.98 Ovarian Cancer 457 99.96 Reprotox - General 1 106 99.24 Fibromyalgia 11 98.92 Glioblastoma 55 98.76 Solid Tumor 97 98.64 Cancer 811 98.52 Pulmonary Fibrosis 54 97.60 Leukemia 22 97.28 Gastrointestinal Stromal Tumor 116 96.64

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

On the other hand, imatinib mesylate, a tyrosine kinase inhibitor of PDGFRs has clinical activity in DFSP, as will be discussed later.

Negative_regulation (inhibitor) of PDGFR

1) Confidence 0.57 Published 2007 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721290 Disease Relevance 0.39 Pain Relevance 0

Sorafanib has the potential for both antiangiogenic effects, via inhibition of VEGFR and platelet-derived growth factor receptor (PDGFR), as well as antiproliferative effects, via Raf kinase inhibition.

Negative_regulation (inhibition) of platelet-derived growth factor receptor in platelet

2) Confidence 0.50 Published 2007 Journal Breast Cancer Res Section Body Doc Link PMC2242654 Disease Relevance 0.62 Pain Relevance 0

Sorafanib has the potential for both antiangiogenic effects, via inhibition of VEGFR and platelet-derived growth factor receptor (PDGFR), as well as antiproliferative effects, via Raf kinase inhibition.

Negative_regulation (inhibition) of PDGFR in platelet

3) Confidence 0.50 Published 2007 Journal Breast Cancer Res Section Body Doc Link PMC2242654 Disease Relevance 0.62 Pain Relevance 0

For this reason a diminished IFP due to imatinib mediated PDGFR inhibition could be another mechanism to alter the effects of irradiation.

Negative_regulation (inhibition) of PDGFR

4) Confidence 0.49 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2925350 Disease Relevance 0.75 Pain Relevance 0

Additionally an imatinib related inhibition of PDGFR ?

Negative_regulation (inhibition) of PDGFR

5) Confidence 0.49 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2925350 Disease Relevance 1.36 Pain Relevance 0

Here we investigate effects of SU9518, a PDGFR inhibitor combined with ionizing radiation in human primary fibroblasts and endothelial cells in vitro, with a view on utilizing RTKI for antifibrotic therapy.

Negative_regulation (inhibitor) of PDGFR in endothelial cells

6) Confidence 0.40 Published 2006 Journal BMC Cancer Section Abstract Doc Link PMC1458351 Disease Relevance 0.18 Pain Relevance 0.08

For example Imatinib/Gleevec (primarily a bcr/abl kinase inhibitor) or SU11248 (mainly a VEGFR inhibitor) are also potent inhibitors of PDGFR and other kinases.

Negative_regulation (inhibitors) of PDGFR

7) Confidence 0.40 Published 2006 Journal BMC Cancer Section Abstract Doc Link PMC1458351 Disease Relevance 0.18 Pain Relevance 0.05

PDGFR tyrosine kinase inhibition reduces radiation-induced fibroblast activation.

Negative_regulation (inhibition) of PDGFR in fibroblast

8) Confidence 0.40 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1458351 Disease Relevance 0.40 Pain Relevance 0.16

SU9518, a PDGFR tyrosine kinase inhibitor, reduces radiation-induced fibroblast and endothelial cell activation.

Negative_regulation (inhibitor) of PDGFR in endothelial cell

9) Confidence 0.40 Published 2006 Journal BMC Cancer Section Abstract Doc Link PMC1458351 Disease Relevance 0 Pain Relevance 0.03

In murine breast tumours inhibition of activated PDGFR ß by imatinib leads to reduction in tumour cell growth [20].

Negative_regulation (inhibition) of PDGFR associated with cancer and breast cancer

10) Confidence 0.36 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2925350 Disease Relevance 1.37 Pain Relevance 0

In contrast to these results imatinib is able to inhibit PDGFR ?

Negative_regulation (inhibit) of PDGFR

11) Confidence 0.36 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2925350 Disease Relevance 0.24 Pain Relevance 0

activity in glioblastoma cells, whereas a direct correlation between imatinib induced inhibition of PDGFR ?

Negative_regulation (inhibition) of PDGFR associated with glioblastoma

12) Confidence 0.36 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2925350 Disease Relevance 0.72 Pain Relevance 0

In combination with doxorubicin an increase in chemosensitivity due to the potential of imatinib to inhibit PDGFR ?

Negative_regulation (inhibit) of PDGFR

13) Confidence 0.36 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2925350 Disease Relevance 0.67 Pain Relevance 0.09

Imatinib mesylate (Gleevec®; Novartis Oncology) is an oral, small molecule tyrosine kinase inhibitor with good oral bioavailability.11 Imatinib exhibits potent inhibitory activity against KIT, platelet-derived growth factor receptor (PDGFR), ABL kinase and the chimeric BCR-ABL fusion oncoprotein of chronic myeloid leukemia.

Negative_regulation (inhibitor) of platelet-derived growth factor receptor in platelet associated with leukemia and bioavailability

14) Confidence 0.34 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2819895 Disease Relevance 1.44 Pain Relevance 0.05

SU11248 (sunitinib malate) is an inhibitor of receptor tyrosine kinases for VEGFR1, VEGFR2, PDGFR, c-kit, and Flt-3.

Negative_regulation (inhibitor) of PDGFR

15) Confidence 0.33 Published 2007 Journal Breast Cancer Res Section Body Doc Link PMC2246178 Disease Relevance 0.69 Pain Relevance 0.03

Imatinib mesylate is a potent, selective inhibitor of PDGFR alpha (PDGFRa), PDGFR beta (PDGFRb), BCR-abl, KIT, ARG and c-FMS protein-tyrosine kinases [12,14].

Negative_regulation (inhibitor) of PDGFRb associated with fibromyalgia

16) Confidence 0.33 Published 2010 Journal World J Surg Oncol Section Body Doc Link PMC2892497 Disease Relevance 0.31 Pain Relevance 0

A possible explanation for this enhanced radio- and chemosensitivity seams to be the imatinib mediated inhibition of the PDGFR ?

Negative_regulation (inhibition) of PDGFR in seams

17) Confidence 0.32 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2925350 Disease Relevance 0.60 Pain Relevance 0

It is certain that inhibition of the PDGFR ?

Negative_regulation (inhibition) of PDGFR

18) Confidence 0.32 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2925350 Disease Relevance 0.68 Pain Relevance 0

Modulation and inhibition of the PDGFR ?

Negative_regulation (inhibition) of PDGFR

19) Confidence 0.32 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2925350 Disease Relevance 0.10 Pain Relevance 0

There are various reasons for the ineffectiveness of imatinib monotherapy in ovarian cancer: downregulation of c-kit and PDGFR may lead to induction of VEGF, inhibition of a single tyrosine kinase might be insufficient to impact downstream signaling cascades, and the molecular targets of imatinib might not be relevant in the occurrence of ovarian cancer in comparison with gastrointestinal stromal tumor or chronic myeloid leukemia where a single specific mutation or a translocation, respectively, can be responsible for the genesis of these two cancers [62].

Negative_regulation (downregulation) of PDGFR associated with leukemia, cancer, ovarian cancer and gastrointestinal stromal tumor

20) Confidence 0.29 Published 2010 Journal Journal of Oncology Section Body Doc Link PMC2804796 Disease Relevance 1.08 Pain Relevance 0

General Comments

This test has worked.