Experimental studies of the antitumor effect of TNP-470 on malignant brain tumors. Antitumor effect of TNP-470 on a human medulloblastoma xenograft line.
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.
Isobe
N
N
Department of Neurosurgery, Hiroshima University School of Medicine, Japan.
Uozumi
T
T
Kurisu
K
K
Kawamoto
K
K
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002528:Cerebellar Neoplasms / Q000473:pathology*; D002648:Child; D003510:Cyclohexanes; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008527:Medulloblastoma / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol