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

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.

• Authors: H Konno, T Tanaka, T Kanai, S Baba
• Journal: Nihon Geka Gakkai zasshi (Nihon Geka Gakkai Zasshi) Vol. 99 Issue 7 Pg. 441-5 (Jul 1998) ISSN: 0301-4894 [Print] Japan
• PMID: 9742525 (Publication Type: Journal Article, Review)

Chemical References

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

Topics

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