Angiogenesis inhibitor TNP-470 suppresses tumorigenesis in rat urinary bladder.
OBJECTIVE
The efficacy of the anti-angiogenic factor TNP-470, an analogue of fumagillin, in controlling the development of bladder tumors was investigated.


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 its effect in vivo on the development of tumors, we instilled 0.5 microgram of TNP-470 dissolved in rat urine into heterotopically transplanted rat urinary bladders in which carcinogenesis had been initiated by N-methyl-N-nitrosourea.


RESULTS
In vitro, TNP-470 selectively inhibited the growth and migration of endothelial cells. Instillation of TNP-470 shortly after treatment with carcinogen reduced the tumor incidence significantly (p < 0.05) as compared with that in control animals receiving urine only.


CONCLUSIONS
TNP-470 suppresses the development of bladder tumors when the treatment is started at an early stage of neoplasia. It may be useful in preventing recurrences or new growth of bladder tumors.
Tanaka
Y
Y
Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611-3008, USA.
Kawamata
H
H
Fujimoto
K
K
Oyasu
R
R
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D003510:Cyclohexanes; D004354:Drug Screening Assays, Antitumor; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D051381:Rats; D011916:Rats, Inbred F344; D012717:Sesquiterpenes / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D019459:Urothelium / Q000187:drug effects / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol