Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice.

作者: Paul Perrotte , Hiroki Kuniyasu , Beryl Y. Eve , Daniel J. Hicklin , Keiji Inoue

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摘要: Epidermal growth factor receptor (EGFR) regulates the and progression of human transitional cell carcinoma (TCC) bladder. We have shown that therapy targeting EGFR inhibited TCC established orthotopically in nude mice. The purpose this study was to evaluate whether EGFR-directed affects angiogenesis associated with metastasis TCC. determined cytostatic effect on production angiogenic factors after vitro treatment line 253J B-V MAb C225, a chimerized monoclonal anti-EGFR antibody. cells were implanted into athymic mice, tumors (4 weeks) treated i.p. C225. Expression vascular endothelial (VEGF), interleukin-8 (IL-8), basic fibroblast (bFGF) evaluated by immunohistochemistry situ mRNA hybridization analyses correlated microvessel density immunohistochemical staining anti-CD31. In C225 protein VEGF, IL-8, bFGF dose-dependent manner. mice TCCs growing resulted inhibition compared controls (P <0.0005). expression significantly lower than controls. down-regulation these preceded involution blood vessels. These studies indicate has significant antitumor mediated, part, angiogenesis.

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