EFFECT OF ANGIOGENESIS INHIBITOR TNP-470 ON THE PROGRESSION OF HUMAN GASTRIC CANCER XENOTRANSPLANTED INTO NUDE MICE

The effect of an angiogenesis inhibitor, TNP-470, on pri-mary tumor growth, liver metastasis and peritoneal dissemi-nation of gastric cancer was investigated by means of an orthotopic xenotransplanted model of 2 human gastric can-cers, MT-2 andMT-5. TNP-470 showed a significant inhibitory effect on the growth of primary tumors after orthotopic transplantation of both xenografts when given at a dose of 30 mg/kg on alternate days from day 7 after transplantation (early treatment). However, growth of the MT-2 primary tumor was not inhibited by administration from day 14 after transplantation (late treatment). Liver metastasis was pre-vented significantly by early treatment of TNP-470. In particu-lar, early treatment ofMT-2 completely inhibited the develop-ment of macroscopic foci in the liver and was significantly more effective than late treatment. Peritoneal dissemination also was inhibited. Thus, TNP-470 was revealed to have strong inhibitory activity not only on primary tumors and liver metastases but also against peritoneal dissemination. These results suggest that this agent may provide a new approach to the treatment of gastric cancer. Int. J. Cance