The antiangiogenic agents TNP-470 and 2-methoxyestradiol inhibit the growth of angiosarcoma in mice

J Am Acad Dermatol. 1999 Jun;40(6 Pt 1):925-9. doi: 10.1016/s0190-9622(99)70080-0.

Abstract

Background: 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.

Objective: We wanted to determine whether angiosarcoma can be treated with angiogenesis inhibitors in mice.

Methods: 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.

Results: TNP-470 caused an 84% reduction in tumor size, and 2-methoxyestradiol caused a 68% reduction in tumor size.

Conclusion: Angiogenesis inhibitors are highly effective in treatment of angiosarcoma in mice. Clinical trials of these agents in humans with angiosarcoma and hemangioendothelioma are warranted.

Publication types

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

MeSH terms

  • 2-Methoxyestradiol
  • Animals
  • Cyclohexanes
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / pathology
  • Estradiol / analogs & derivatives*
  • Estradiol / therapeutic use
  • Hemangioendothelioma / blood supply
  • Hemangioendothelioma / drug therapy
  • Hemangiosarcoma / blood supply*
  • Hemangiosarcoma / drug therapy*
  • Male
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / prevention & control*
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Sesquiterpenes / therapeutic use*

Substances

  • Cyclohexanes
  • Sesquiterpenes
  • Estradiol
  • 2-Methoxyestradiol
  • O-(Chloroacetylcarbamoyl)fumagillol