Treatment of murine hemangioendotheliomas with the angiogenesis inhibitor AGM-1470

J Pediatr Surg. 1995 Feb;30(2):325-9; discussion 329-30. doi: 10.1016/0022-3468(95)90583-9.

Abstract

Hemangioma and other angiomatous diseases of childhood are common. Although most lesions are harmless and self-limiting, some are associated with significant morbidity and may be life-threatening. Interferon-alpha, a weak angiogenesis inhibitor, recently has been found to significantly reduce the mortality rate associated with life-threatening hemangiomas. The effectiveness of AGM-1470, a potent inhibitor of angiogenesis derived from the fungal product fumagillin, was tested in a mouse model of hemangioendothelioma. Thirty syngeneic mice were implanted with cells derived from a spontaneous mouse hemangioendothelioma. Tumors formed within 2 to 3 days, and the animals were then treated systemically with AGM-1470 or with saline and vehicle alone. After 22 days, the tumor volume in the saline-treated mice was 7368 +/- 2723 mm3, versus 709 +/- 73 mm3 in the mice that received AGM-1470 (P < .001). Survival was prolonged for the AGM-1470-treated mice, and there was no evidence of drug-related toxicity. All experiments were repeated. In this study, AGM-1470 was safe and highly effective in the treatment of hemangioendothelioma. AGM-1470, and other antiangiogenic agents, may provide safe and effective treatment for hemangioma and other angiomatous diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cyclohexanes
  • Hemangioendothelioma / therapy*
  • Hemangioma / therapy
  • Mice
  • Neoplasms, Experimental / therapy*
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Sesquiterpenes / adverse effects
  • Sesquiterpenes / therapeutic use*
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Cyclohexanes
  • Sesquiterpenes
  • O-(Chloroacetylcarbamoyl)fumagillol