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Control of Angiogenesis with Synthetic Heparin Substitutes

Judah Folkman, Paul B. Weisz, Madeleine M. Joullié, William W. Li and William R. Ewing
Science
New Series, Vol. 243, No. 4897 (Mar. 17, 1989), pp. 1490-1493
Stable URL: http://www.jstor.org/stable/1703142
Page Count: 4
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Control of Angiogenesis with Synthetic Heparin Substitutes
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Abstract

Many diseases are dominated by persistent growth of capillary blood vessels. Tumor growth is also angiogenesis-dependent. Safe and effective angiogenesis inhibitors are needed to determine whether control of angiogenesis would be therapeutic. Heparin and certain steroids, administered together, can inhibit angiogenesis in a synergistic manner. This ``pair'' effect suggested that specific hydrophilic cycloamyloses may be suitable heparin substitutes. $\beta $-Cyclodextrin tetradecasulfate administered with a steroid inhibits angiogenesis at 100 to 1000 times the effectiveness of heparin in the chick embryo bioassay. This cyclic oligosaccharide also augments the anti-angiogenic effect of angiostatic steroids against corneal neovascularization in rabbits when $\beta $-cyclodextrin tetradecasulfate and a steroid are inserted into the cornea or applied topically as eyedrops.

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