ANGIOGENESIS INHIBITOR TNP-470 SUPPRESSES TUMORIGENESIS IN RAT URINARY-BLADDER

Purpose: The efficacy of the anti-angiogenic factor TNP-470, an analog ue of fumagillin, in controlling the development of bladder tumors was investigated. Materials and Methods: The anti-angiogenic activity of TNP-470 was evaluated in vitro by its capacity to suppress the growth and migration of bovine capillary endothelial cells. To investigate it s effect in vivo on the development of tumors, we instilled 0.5 mu g. of TNP-470 dissolved in rat urine into heterotopically transplanted ra t urinary bladders in which carcinogenesis had been initiated by N-met hyl-N-nitrosourea. Results: In vitro, TNP-470 selectively inhibited th e growth and migration of endothelial cells. Instillation of TNP-470 s hortly after treatment with carcinogen reduced the tumor incidence sig nificantly (p < 0.05) as compared with that in control animals receivi ng urine only. Conclusions: TNP-470 suppresses the development of blad der tumors when the treatment is started at an early stage of neoplasi a. It may be useful in preventing recurrences or new growth of bladder tumors.