Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1658953 (tumor vasculature)
 2,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently shown that VEGF functions as a survival factor for newly formed vessels during developmental neovascularization, but is not required for maintenance of mature vessels. Reasoning that expanding tumors contain a significant fraction of newly formed and remodeling vessels, we examined whether abrupt withdrawal of VEGF will result in regression of preformed tumor vessels. Using a tetracycline-regulated VEGF expression system in xenografted C6 glioma cells, we showed that shutting off VEGF production leads to detachment of endothelial cells from the walls of preformed vessels and their subsequent death by apoptosis. Vascular collapse then leads to hemorrhages and extensive tumor necrosis. These results suggest that enforced withdrawal of vascular survival factors can be applied to target preformed tumor vasculature in established tumors. The system was also used to examine phenotypes resulting from over-expression of VEGF. When expression of the transfected VEGF cDNA was continuously "on," tumors became hyper-vascularized with abnormally large vessels, presumably arising from excessive fusions. Tumors were significantly less necrotic, suggesting that necrosis in these tumors is the result of insufficient angiogenesis.
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PMID:Conditional switching of vascular endothelial growth factor (VEGF) expression in tumors: induction of endothelial cell shedding and regression of hemangioblastoma-like vessels by VEGF withdrawal. 923 51

Vascular Endothelial Growth Factor (VEGF) functions as a key regulator in tumor angiogenesis. In addition, VEGF is an important survival factor for endothelial cells under chemical or physical stress. In our report, we show that treatment of endothelial cells with the chemotherapeutic agent carboplatin significantly increased the expression of VEGF. Furthermore, neutralization of secreted VEGF with specific polyclonal anti-VEGF antibodies or monoclonal antibody sensitized endothelial cells to carboplatin treatment and increased apoptosis several-fold. Interestingly, carboplatin treatment did not alter VEGF expression in tumor cells. Similarly, antibody to VEGF did not change the chemosensitivity of tumor cells to this drug. Most importantly, tumor-bearing animals treated with carboplatin showed an increase in VEGF immunoreactivity in the tumor vasculature, confirming the in vitro studies. Based on these observations, we determined whether neutralization of VEGF could enhance the anti-tumor activity of carboplatin in an in vivo ovarian cancer model system. A combination therapy consisting of a suboptimal dose of carboplatin (32.5 mg/kg/inj., q3d x 5; i.p.) and polyclonal anti-VEGF antibody (2 mg/inj., q3d x 10; i.p.) significantly enhanced solid tumor growth inhibition over individual monotherapies and included multiple complete responses. These findings suggest that VEGF is a critical endothelial cell specific survival factor that is induced by carboplatin and contributes to the protection of tumor vasculature during chemotherapy treatment. In addition, these results provide evidence for a potential mechanism that underlies enhanced anti-tumor activity achieved with chemotherapy and anti-VEGF antibody combination treatment regimens as recently reported in a number of clinical trials. We conclude that a similar type of combination therapy may be applicable to many types of malignancies since VEGF expression was differentially induced in the tumor host environment (i.e., tumor vasculature) and not in the tumor cells themselves; hence, this phenomenon may be independent of the type and origin of the primary cancer.
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PMID:Carboplatin selectively induces the VEGF stress response in endothelial cells: Potentiation of antitumor activity by combination treatment with antibody to VEGF. 1509 98