[Therapeutic effect of angiogenesis inhibitors on liver metastases of human colorectal carcinoma].
Angiogenesis is essential for the growth of solid tumors. Antiangiogenic therapy has therefore attracted considerable interest as a novel therapy for various tumors including colorectal carcinoma. We experimentally investigated the therapeutic effect of TNP-470, a nonspecific inhibitor of angiogenic factors, and vascular endothelial growth factor (VEGF)-neutralizing antibody (VEGFAb), was a VEGF-specific inhibitor, on liver metastases of colon carcinoma using a murine orthotopic transplantation model. TK-4 and TK-13 are moderately differentiated adenocarcinoma strains established in our department which express VEGF mRNA and protein. Administration of TNP-470 30 mg/kg significantly inhibited the liver metastases of both strains, as did administration of VEGFAb 100 micrograms/mouse. The therapeutic effect on liver metastases was more dominant with antiangiogenic therapy than with chemotherapy (mitomycin C). Furthermore, the sustained effect of TNP-470 induced tumor dormancy and consequently improved the survival of the animals. These results suggest that antiangiogenic treatment will be a potent therapy for liver metastases of human colorectal carcinoma in the future.
Konno
H
H
Second Department of Surgery, Hamamatsu University School Medicine, Japan.
Tanaka
T
T
Kanai
T
T
Baba
S
S
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000906:Antibodies / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000473:pathology*; D003510:Cyclohexanes; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000276:immunology*; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000556:secondary*; D008222:Lymphokines / Q000276:immunology*; D051379:Mice; D009389:Neovascularization, Pathologic; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000903:Antibiotics, Antineoplastic; D000906:Antibodies; D003510:Cyclohexanes; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012717:Sesquiterpenes; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000077609:O-(Chloroacetylcarbamoyl)fumagillol