[Therapeutic effect of angiogenesis inhibitors on liver metastases of human colorectal carcinoma]

Nihon Geka Gakkai Zasshi. 1998 Jul;99(7):441-5.
[Article in Japanese]

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / therapeutic use*
  • Antibodies / therapeutic use*
  • Colorectal Neoplasms / pathology*
  • Cyclohexanes
  • Disease Models, Animal
  • Endothelial Growth Factors / immunology*
  • Humans
  • Liver Neoplasms / blood supply*
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / secondary*
  • Lymphokines / immunology*
  • Mice
  • Neovascularization, Pathologic*
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Sesquiterpenes / therapeutic use*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Antibiotics, Antineoplastic
  • Antibodies
  • Cyclohexanes
  • Endothelial Growth Factors
  • Lymphokines
  • Sesquiterpenes
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • O-(Chloroacetylcarbamoyl)fumagillol