Antitumor effects of angiogenesis inhibitor 0-(chloroacetyl-carbamoyl) fumagillol (TNP-470) against murine renal cell carcinoma.
OBJECTIVE
The effect of 0-(chloroacetyl-carbamoyl) fumagillol (TNP-470) on tumor growth and metastasis is investigated.


METHODS
BALB/c mice were inoculated with Renca murine tumor and graded doses of TNP-470 were given subcutaneously every other day beginning on day 1 and ending on day 9. Tumor angiogenesis was measured quantitatively by a colorimetric assay.


RESULTS
TNP-470 inhibited tumor growth and prolonged the life span of Renca-bearing mice in a dose-dependent manner. Body weight-loss was not observed in the mice given less than 30 mg./kg./day. When the treatment was delayed on day 6, TNP-470 did not inhibit tumor growth, pointing to the importance of the timing of drug administration in relation to disease stage. Tumor angiogenesis was inhibited 33 to 62% of the control level by TNP-470. Furthermore, TNP-470 reduced pulmonary and hepatic metastatic foci of intravenously inoculated Renca and of the tumor inoculated in the spleen.


CONCLUSIONS
These data suggest that TNP-470 may be effective as a treatment of renal cell carcinoma, especially when micrometastases are involved.
Fujioka
T
T
Department of Urology, Iwate Medical University School of Medicine, Japan.
Hasegawa
M
M
Ogiu
K
K
Matsushita
Y
Y
Sato
M
M
Kubo
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000098:blood supply* / Q000188:drug therapy; D003510:Cyclohexanes; D005260:Female; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol