Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of oncogenesis is extremely complicated and controlled by various factors, most of which are based on cell proliferation, tumor invasion, neovascularization, and inhibition of apoptosis. We have investigated the relationship between thirty three oncogenes expression and histopathological prognostic factors of endometrial carcinomas, including clinical stage, histological grade, presence of invasion to greater than one-half the myometrium, clinical outcome, and survival rate. Scoring on the basis of the percentage of positive cells indicated that Plks, EphB4, ephrin-B2, Id1, CaMKIV, c-Ets1, Elf-1, and survivin expression were significantly associated with PCNA-labeling index, clinical stage, histological grade, the presence of invasion to greater than one-half the myometrium, and clinical outcome. Survival data were available for all patients, and univariate Cox regression analysis showed that Plks, CaMKIV, Elf-1, and survivin expression were significantly associated with poor prognosis. Our results demonstrate that some oncogenes expression in endometrial carcinoma correlate with the malignant potential of these tumors. Thus, in addition to being of diagnostic value, modulation of these oncogenes activity in the tumors by chemotherapeutic agents or gene therapy may prove to be of therapeutic value. In this review, we demonstrate the biologic behavior of seven novel molecules (Plks, Eph/ephrin, Id family, CaMK, c-Ets1, Elf-1, and survivin) in the endometrial carcinoma.
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PMID:The relationship between oncogene expression and clinical outcome in endometrial carcinoma. 1537 36

Almost all cancers show intrinsic and/or evasive resistance to vascular endothelial growth factor (VEGF) inhibitors by multiple mechanisms. Serum angiopoietin-2 (Ang2) level has been proposed as a potential biomarker of VEGF inhibitor response in several cancers. From these clinical observations, the Ang2 and Tie2 (its receptor) axis has been focused on as a promising target. Here, we show a novel strategy to circumvent the resistance by combining multi-tyrosine kinase inhibitors lenvatinib (VEGF receptor, fibroblast growth factor receptor, and RET inhibitor) and golvatinib (E7050; c-Met, Tie2, and EphB4 inhibitor). Tie2 identifies a highly pro-angiogenic macrophage subset, Tie2-expressing macrophages (TEM). Angi-Tie2 and EphB4-EphrinB2 signaling plays critical roles in pericyte-mediated vessel stabilization. In vitro analyses suggested that golvatinib combined with lenvatinib inhibited pericyte-mediated vessel stabilization and TEM differentiation. In thyroid and endometrial cancer models, golvatinib and lenvatinib inhibited pericyte network development and TEM infiltration, resulting in severe perfusion disorder and massive apoptosis. Body weight loss was tolerable, and no macroscopic change was observed. These preclinical studies suggest that modulation of the tumor microenvironment by a strategic and well-tolerated combination of multi-targeting tyrosine kinase inhibitors may sensitize cancer to VEGF inhibitors.
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PMID:Multitargeting strategy using lenvatinib and golvatinib: maximizing anti-angiogenesis activity in a preclinical cancer model. 2545 59