Inhibition of lymphatic metastasis in a syngeneic rat fibrosarcoma model by an angiogenesis inhibitor, AGM-1470

Invasion Metastasis. 1996;16(2):73-82.

Abstract

We examined whether lymphatic metastasis was inhibited by the potent angiogenesis inhibitor AGM-1470 [O-(chloroacetyl-carbamoyl)fumagillol, TNP-470] using a rat lymphatic metastasis model. Clone A of the rat fibrosarcoma AS653HM, when inoculated into the footpads of syngeneic rats, highly and preferentially metastasized to lymph nodes. In contrast, when AGM-1470 was administered subcutaneously to rats bearing the tumor cells, the tumor growth and incidence of metastasis in the lymph nodes were reduced in a dose- and schedule-dependent manner. Similar inhibition of lymphatic metastasis was also observed in the rats in which treatment with AGM-1470 was initiated following resection of the primary tumor in the foot, indicating that the treatment with AGM-1470 inhibited the progression of lymphatic metastasis at the metastatic sites of the lymph nodes. These results suggest that AGM-1470 can be a potential agent to prevent lymphatic metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacology
  • Antibiotics, Antineoplastic / therapeutic use*
  • Cyclohexanes
  • Fibrosarcoma / pathology*
  • Fibrosarcoma / surgery
  • Injections, Subcutaneous
  • Lymphatic Metastasis / prevention & control*
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / drug therapy*
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Rats
  • Sesquiterpenes / administration & dosage
  • Sesquiterpenes / pharmacology
  • Sesquiterpenes / therapeutic use*
  • Tumor Cells, Cultured

Substances

  • Antibiotics, Antineoplastic
  • Cyclohexanes
  • Sesquiterpenes
  • O-(Chloroacetylcarbamoyl)fumagillol