Treatment of murine hemangioendotheliomas with the angiogenesis inhibitor AGM-1470.
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.
O'Reilly
M S
MS
Department of Surgery, Children's Hospital, Boston, MA 02115, USA.
Brem
H
H
Folkman
J
J
D000818:Animals; D003510:Cyclohexanes; D006390:Hemangioendothelioma / Q000628:therapy*; D006391:Hemangioma / Q000628:therapy; D051379:Mice; D009374:Neoplasms, Experimental / Q000628:therapy*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol