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Treatment of murine hemangioendotheliomas with the angiogenesis inhibitor AGM-1470.

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.
AuthorsM S O'Reilly, H Brem, J Folkman
JournalJournal of pediatric surgery (J Pediatr Surg) Vol. 30 Issue 2 Pg. 325-9; discussion 329-30 (Feb 1995) ISSN: 0022-3468 [Print] United States
PMID7738759 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Cyclohexanes
  • Sesquiterpenes
  • O-(Chloroacetylcarbamoyl)fumagillol
Topics
  • Animals
  • Cyclohexanes
  • Hemangioendothelioma (therapy)
  • Hemangioma (therapy)
  • Mice
  • Neoplasms, Experimental (therapy)
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Sesquiterpenes (adverse effects, therapeutic use)
  • Survival Rate
  • Tumor Cells, Cultured

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