o-(chloroacetylcarbamoyl)fumagillol and Hemangioendothelioma

Endothelial malignancies, such as angiosarcoma and hemangioendothelioma, are often resistant to chemotherapy and surgery, and may result in death. Improved means of therapy are needed for these disorders.. We wanted to determine whether angiosarcoma can be treated with angiogenesis inhibitors in mice.. Mice were inoculated with a cell line that gives rise to angiosarcoma and were treated with the angiogenesis inhibitors 2-methoxyestradiol and TNP-470. Response to therapy was monitored by measurement of tumors.. TNP-470 caused an 84% reduction in tumor size, and 2-methoxyestradiol caused a 68% reduction in tumor size.. Angiogenesis inhibitors are highly effective in treatment of angiosarcoma in mice. Clinical trials of these agents in humans with angiosarcoma and hemangioendothelioma are warranted.

Topics: 2-Methoxyestradiol; Animals; Cyclohexanes; Endothelium, Vascular; Estradiol; Hemangioendothelioma; Hemangiosarcoma; Male; Mice; Mice, Nude; Neovascularization, Pathologic; O-(Chloroacetylcarbamoyl)fumagillol; Sesquiterpenes

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.

Topics: Animals; Cyclohexanes; Hemangioendothelioma; Hemangioma; Mice; Neoplasms, Experimental; O-(Chloroacetylcarbamoyl)fumagillol; Sesquiterpenes; Survival Rate; Tumor Cells, Cultured