Therapeutic effect of TNP-470 on spontaneous liver metastasis of colon tumors in the rabbit.
Even though angiogenesis inhibitor is thought to be one of the promising agents in tumor dormancy therapy, its optimal administration is still unknown. Therefore, the efficient protocol using TNP-470 was examined regarding its treatment affect against spontaneous liver metastases of colon tumors in the rabbit. A spontaneous liver metastases model was established in the rabbit by the inoculation of VX-2 tumors into the subserosal space of the colon. The therapeutic effect of TNP-470 was then investigated by monitoring both the number of metastatic nodules in the liver and the microvessel density (MVD) in the tumor by immunohistochemical staining using anti-CD31 monoclonal antibody. TNP-470 did not show any effect on the primary tumor. It was able to reduce the metastatic spread to liver when it was administered at the microscopic metastatic stage. Treatment at this stage, however, was not able to sufficiently control the disease. These results indicated that TNP-470 could efficiently cause the tumor to enter into a dormant state by inhibiting angiogenesis when it was used at the initial stage of the metastatic process in the liver. Regarding its clinical application, TNP-470 might be useful for preventing the metachronous liver metastases of colorectal cancer when it is administered as adjuvant therapy after curative surgery.
Sano
J
J
Second Department of Surgery, Gifu University School of Medicine, Gifu-city, Japan.
Sugiyama
Y
Y
Kunieda
K
K
Sano
B
B
Saji
S
S
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003110:Colonic Neoplasms / Q000473:pathology*; D003510:Cyclohexanes; D005260:Female; D007262:Infusions, Intravenous; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000556:secondary*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011817:Rabbits; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol