o-(chloroacetylcarbamoyl)fumagillol and Corneal-Diseases

A semi-synthetic analogue of fumagillin, TNP-470, has been shown to be a potent angiogenesis inhibitor. In this study, we evaluated the anti-tumor efficacy of TNP-470 on rabbits bearing VX2 carcinoma of the tongue, by comparison of topical, intra-tumor (i.t.) injection with systemic, intra-venous (i.v.) administration. The i.t. injection of the angiogenesis inhibitor produced much stronger anti-tumor effects, and almost complete tumor regression was achieved at doses of 10 mg/kg or 20 mg/kg. TNP-470 injected intra-tumorally significantly reduced expression of proliferating cell nuclear antigen (PCNA) and microvessel density in the VX2 carcinoma of the tongue. TNP-470 also halted the tumor-associated neovascularization in the rabbit cornea assay. These data suggest that i.t. injection of TNP-470 effectively inhibits tumor angiogenesis and disrupts microvasculature development, which may suppress tumor growth. In conclusion, the i.t. injection of TNP-470 provided remarkable anti-tumor effects on the VX2 carcinoma of the tongue and is expected to have promising therapeutic uses for oral cancer.

Topics: Animals; Antibiotics, Antineoplastic; Carcinoma; Corneal Diseases; Cyclohexanes; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Eye Neoplasms; Injections, Intralesional; Male; Neoplasm Transplantation; Neovascularization, Pathologic; O-(Chloroacetylcarbamoyl)fumagillol; Rabbits; Sesquiterpenes; Time Factors; Tongue Neoplasms