Experimental studies of the antitumor effect of TNP-470 on malignant brain tumors. Antitumor effect of TNP-470 on a human medulloblastoma xenograft line.

Abstract

It has been shown that angiogenesis plays an important role in pathological conditions including the growth of solid tumors. Furthermore, it is thought that anti-angiogenic agents might be clinically useful for therapy of these diseases. TNP-470 (TNP), a synthetic analog of fumagillin isolated from Aspergillus fumigatus, was used as an anti-angiogenic agent in this study in a nude mouse model with a subcutaneously implanted fragment of medulloblastoma. After treatment with this agent for 4 weeks, the inhibition rates of tumor growth were as follows: 15.9% in the group given 1 mg/kg, 16.9% with 10 mg/kg, 29.6% with 30 mg/kg, 49.9% with 50 mg/kg and 65.7% with 100 mg/kg. TNP inhibited the growth of brain tumor dose-dependently and induced various ischemic changes within the tumor tissue. Therefore, TNP may be effective for the treatment of malignant brain tumors such as medulloblastoma.