title: Treatment of metastatic liver tumors by intermittent repetitive injection of an angiogenesis inhibitor using an implantable port system in a rabbit model.
abstract: Angiogenesis inhibitors are expected as a new type of anticancer drug, because they may prevent tumor neovascularization. Among several angiogenesis inhibitors, 6-o-(N-chloroacetylcarbamoyl)-fumagillol (TNP-470) is thought to inhibit the proliferation of migrating endothelial cells, as an aspect of angiogenesis, and attracts an attention for clinical application. We attempted to evaluate anticancer effects of intermittent repetitive intraportal injection of TNP-470 for metastatic liver tumor models and considered the usefulness and a role as an angiogenesis inhibitor, TNP-470, in the anti-cancer therapy using an implantable port system. We used 25 Japanese white rabbits with metastatic liver tumors made by intraportal injection of tumor cells (VX2-carcinoma), and divided those into five groups; group A was control group, group B was treated by repetitive subcutaneous injection of TNP-470 and group C, D, E was treated by repetitive intraportal injection of TNP-470, adriamycin, TNP-470 + adriamycin respectively 5 times at 2 or 3 days interval after tumor inoculation using implantable port systems. After 2 weeks, we evaluated anti-cancer effect of TNP-470 pathologically. In the number of grown tumors, there was no difference among five groups statisitically. But the mean tumor size of each group is smaller in order of group E, D, C, B, A and the differences were significant (P < 0.05) except between E and D group. And intratumoral neovascularization tended to be less in group B, C, E than in group A, D pathologically. We consider that intermittent repetitive injection of TNP-470 is more useful than systemic administration for metastatic liver tumors and the administration of angiogenesis inhibitor with other anti-cancer agents via an implantable port system will be one of the most effective therapeutic methods for them.
authors.affiliation: Department of Radiology, Kobe University School of Medicine.
authors.forename: Y
authors.initials: Y
authors.lastname: Kuwata
authors.forename: S
authors.initials: S
authors.lastname: Hirota
authors.forename: M
authors.initials: M
authors.lastname: Sako
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D006224:Cricetinae; D003510:Cyclohexanes; D004195:Disease Models, Animal; D004867:Equipment Design; D015918:Infusion Pumps, Implantable; D007275:Injections, Intravenous; D008099:Liver / Q000098:blood supply; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011817:Rabbits; D012717:Sesquiterpenes / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured; D019043:Vascular Neoplasms / Q000517:prevention & control* / Q000556:secondary*
chemical_list: D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol