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Science 17 March 1989:
Vol. 243. no. 4897, pp. 1490 - 1493
DOI: 10.1126/science.2467380
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Articles
Science, Vol 243, Issue 4897, 1490-1493
Copyright © 1989 by American Association for the Advancement of Science
Control of angiogenesis with synthetic heparin substitutes
J Folkman,
PB Weisz,
MM Joullie,
WW Li,
and
WR Ewing
Department of Surgery, Harvard Medical School, Boston, MA 02115.
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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