Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1522282 (EMT)
 2,868 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously demonstrated that vascular endothelial growth factor-165 (VEGF), a tumor-secreted angiogenic factor, can acutely and chronically induce fenestrations in microvascular endothelium (Cancer Res 1997, 57:765-772). Because the morphology and function of microvascular endothelium differs from tissue to tissue, we undertook studies to examine whether the neovasculature in tumors also differed depending upon tumor location. Four tumor types implanted in the brain or subcutis in nude mice were studied: a murine rhabdomyosarcoma (M1S), a murine mammary carcinoma (EMT), and two human glioblastomas (U87 and U251). In addition, we studied Chinese hamster ovary cells stably transfected with human VEGF165. As previously reported, tumors grown in the subcutaneous space had a microvasculature that was fenestrated and had open endothelial gaps. The identical tumors when grown in the brain also had fenestrated endothelium and vessels with open endothelial gaps, but they were drastically reduced in occurrence. Open endothelial gaps were not seen in all tumors implanted in the brain (EMT and M1S), although fenestrated endothelium was always seen. VEGF and VEGF receptors were measured in tumors from both locations by immunoblotting and competitive polymerase chain reaction, respectively. VEGF amount was not significantly different between the tumor locations. Interestingly, total tumor vascular mRNA expression of both Flk-1 and Flt-1 was greater in tumor vessels derived from the brain compared with tumor vessels derived from subcutaneous tissues. These results demonstrate that the host microvascular environment determines the morphology and function of the tumor vasculature and that endothelia from different tissues vary in their ability to express the VEGF receptors given identical stimuli.
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PMID:Host microvasculature influence on tumor vascular morphology and endothelial gene expression. 977 55

Heart valve malformations are one of the most common types of birth defects, illustrating the complex nature of valve development. Vascular endothelial growth factor (VEGF) signaling is one pathway implicated in valve formation, however its specific spatial and temporal roles remain poorly defined. To decipher these contributions, we use two inducible dominant negative approaches in mice to disrupt VEGF signaling at different stages of embryogenesis. At an early step in valve development, VEGF signals are required for the full transformation of endocardial cells to mesenchymal cells (EMT) at the outflow tract (OFT) but not atrioventricular canal (AVC) endocardial cushions. This role likely involves signaling mediated by VEGF receptor 1 (VEGFR1), which is highly expressed in early cushion endocardium before becoming downregulated after EMT. In contrast, VEGFR2 does not exhibit robust cushion endocardium expression until after EMT is complete. At this point, VEGF signaling acts through VEGFR2 to direct the morphogenesis of the AVC cushions into mature, elongated valve leaflets. This latter role of VEGF requires the VEGF-modulating microRNA, miR-126. Thus, VEGF roles in the developing valves are dynamic, transitioning from a differentiation role directed by VEGFR1 in the OFT to a morphogenetic role through VEGFR2 primarily in the AVC-derived valves.
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PMID:VEGF signaling has distinct spatiotemporal roles during heart valve development. 2081 97

Anacardic acid is a major constituent of nutshell of cashew. In this study, we have isolated it from the leaves of Anacardium Occidentale L. using polarity-based fractionation and confirmed the structure using GC-MS, NMR and FT-IR. The main focus of this study is to harness the molecular mechanism of anti-metastatic action of anacardic acid (A1). We have used MCF-7, a weak metastatic and U-87, a highly metastatic, breast and glioma cell lines respectively, for our study. We have shown that VEGF increases migration and invasion activities of MCF-7 cells, upon overexpression of Twist and Snail genes. It is observed from the current study that exposure of MCF-7 cells to A1 resulted in upregulation of epithelial marker E-cadherin with a concomitant decrease in the expression of mesenchymal markers Twist and Snail gene expression besides exhibiting a strong anti-migratory and anti-invasive activity. In metastatic U-87 glioma cells, treatment with A1 decreased the phosphorylation of MAP kinases, inhibited the translocation of Sp1 and down regulated VEGF and Flt-1 gene expression. Overall, the current findings demonstrate for the first time that anacardic acid functions as a potent EMT inhibitor by targeting VEGF signaling pathway, providing a novel template for drug discovery.
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PMID:Anti-metastatic action of anacardic acid targets VEGF-induced signalling pathways in epithelial to mesenchymal transition. 2578 52