ELIZA

return kwic search for suggest out of >500 occurrences
308129 occurrences (No.71 in the rank) during 5 years in the PubMed. [no cache] 500 found

470) Our data suggest for the first time that DCC-2701 may be superior to HGF antagonists that are in clinical trials and that pTyr(1349) levels might be a good indicator of c-MET activation and likely response to targeted therapy as a result of signals from the microenvironment.

--- ABSTRACT ---

PMID:24362531 DOI:10.1038/onc.2013.539

2015 Oncogene

* Effective inhibition of c-MET-mediated signaling, growth and migration of ovarian cancer cells is influenced by the ovarian tissue microenvironment.

- The signaling mediated by c-MET and its ligand, hepatocyte growth factor (HGF), has been implicated in malignant progression of cancer involving stimulation of proliferation, invasion and metastasis. We studied the c-MET/HGF axis as a mediator of tumor-stromal interaction in ovarian cancer and the value of targeting c-MET for the treatment of ovarian cancer. To assess c-MET signaling, we established in vitro models of the microenvironment using primary and immortalized human fibroblasts from normal ovary and tumor samples and epithelial ovarian cancer cell lines. We found that fibroblast from normal ovaries secreted high levels of HGF (1500-3800 pg/ml) as compared with tumor-derived fibroblasts (undetectable level) and could elicit cellular biological responses on c-MET-expressing ovarian cancer cells including increase of cell proliferation and migration (2- to 140-fold increase). HGF secreted by fibroblasts was also found sequestered within extracellular matrices (ECMs) and when degraded this ECM-derived HGF stimulated cancer cell migration (1.5- to 24-fold). In cells containing constitutive c-MET phosphorylation, recombinant HGF and fibroblast-derived HGF negligibly affect c-MET phosphorylation on Tyr(1234) and Tyr(1003). However, both sources of HGF increased the phosphorylation of c-MET on Tyr(1349), the multi-substrate docking site, by more than sixfold and led to activation of downstream signaling transducers. DCC-2701 (Deciphera Pharmaceuticals, LLC), a novel c-MET/TIE-2/VEGFR inhibitor was able to effectively reduce tumor burden in vivo and block c-MET pTyr(1349)-mediated signaling, cell growth and migration as compared with a HGF antagonist in vitro. Importantly, DCC-2701's anti-proliferative activity was dependent on c-MET activation induced by stromal human fibroblasts and to a lesser extent exogenous HGF. Our data suggest for the first time that DCC-2701 may be superior to HGF antagonists that are in clinical trials and that pTyr(1349) levels might be a good indicator of c-MET activation and likely response to targeted therapy as a result of signals from the microenvironment.

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(1)388 that	(3)16 the	(5)7 an	(7)3 possible
(2)23 a	(4)8 that,	(6)3 increased	(8)2 different

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--- WordNet output for suggest --- =>〜しようと提案する, を提案する, 示唆する, 暗示する, 提案する Overview of verb suggest The verb suggest has 5 senses (first 5 from tagged texts) 1. (57) propose, suggest, advise -- (make a proposal, declare a plan for something; "the senator proposed to abolish the sales tax") 2. (21) hint, suggest -- (drop a hint; intimate by a hint) 3. (19) suggest, intimate -- (imply as a possibility; "The evidence suggests a need for more clarification") 4. (14) indicate, suggest -- (suggest the necessity of an intervention; in medicine; "Tetracycline is indicated in such cases") 5. (12) suggest, evoke, paint a picture -- (call to mind; "this remark evoked sadness") --- WordNet end ---