The effect of angiogenesis inhibitor TNP-470 against postoperative lung metastasis following removal of orthotopic transplanted human colon cancer: an experimental study.
We have investigated the antimetastatic effect of TNP-470 against postoperative lung metastasis following the removal of human colon cancer xenotransplanted into nude rat. The KM12SM human colon cells were injected into the cecal wall. At 5 weeks after the injection, the cecum was removed including the tumor. Then, TNP-470 was administered continuously by subcutaneous injection pump at a dosage of 30 mg/kg/week. The Control Group received no administration of TNP-470. Group A and Group B received administration of TNP-470 just after the cecal removal for 4 and 2 weeks, respectively. Group C received 2 weeks' administration of TNP-470 from week 3 after the removal. The survival rate of each group was calculated, and any lung metastasis was evaluated macro and microscopically. At 7 weeks after the removal, lung metastasis was detected in all rats of the Control Group, and in 4 of 8 rats in Group C. In Groups A and Group B, only one rat developed lung metastasis. The 30 week-survival rate in Group A and that in Group B was significantly higher than that in the Control Group or Group C. Moreover, the incidence of lung metastasis at the time of death or 30 weeks after the removal in Group A, and in Group B, was lower than that in Control Group or Group C. The angiogenesis inhibitor, TNP-470 showed an excellent antimetastatic effect against postoperative lung metastasis from transplanted human colon cancer.
Oda
H
H
Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
Ogata
Y
Y
Shirouzu
K
K
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003510:Cyclohexanes; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D008297:Male; D009368:Neoplasm Transplantation; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D051381:Rats; D011916:Rats, Inbred F344; D012717:Sesquiterpenes / Q000627:therapeutic use*; D015996:Survival Rate; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol