We established a mouse rising dbl quote, left (low)primary
tumor resection model" in which a transplanted
tumor was resected after an orthotopic
transplantation of
colorectal cancer tissue to estimate the
therapeutic effect of an
angiogenesis inhibitor on
metastasis. The
angiogenesis inhibitor FR-118487 is a member of the
fumagillin family. Here, 1 mg / kg / day of
FR-118487 was subcutaneously administered to nude mice for 1 week, 2 weeks, or 4 weeks through an osmotic pump. Liver
metastasis developed in 7 of 9 control mice, 2 of 6 mice that underwent the
tumor resection 2 weeks after
transplantation (early resection), and in all 7 of the mice that underwent the
tumor resection 4 weeks after
transplantation (late resection). In the short treatment trial, the
FR-118487 administration immediately after the early resection completely inhibited both hepatic and peritoneal
metastases, whereas its administration after the late resection had no effect on liver
metastasis. In the prolonged treatment trial, inhibitory effects of prolonged treatment with
FR-118487 on both hepatic and peritoneal
metastases after the late resection were clearly demonstrated. The mice of the resection-alone group all died within 106 days after
tumor inoculation, due to
metastases of colon
carcinoma. In contrast, half of the mice that underwent resection and then received antiangiogenic
therapy were alive at the end of the observation period (160 days after
transplantation). In conclusion, the combination of surgery and subsequent antiangiogenic
therapy may be useful to prevent the distant
metastasis of
colorectal cancer and to improve the prognosis of patients with
colorectal cancer.