Control of angiogenesis with synthetic heparin substitutes.
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.
Folkman
J
J
Department of Surgery, Harvard Medical School, Boston, MA 02115.
Weisz
P B
PB
Joullié
M M
MM
Li
W W
WW
Ewing
W R
WR
D000818:Animals; D003505:Cyclodextrins / Q000494:pharmacology*; D003912:Dextrins / Q000494:pharmacology*; D006493:Heparin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006497:Heparan Sulfate / Q000031:analogs & derivatives / Q000494:pharmacology; D009389:Neovascularization, Pathologic; D011817:Rabbits; D013213:Starch / Q000494:pharmacology*; D013256:Steroids / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D003505:Cyclodextrins; D003912:Dextrins; D006493:Heparin; D006497:Heparan Sulfate; D013213:Starch; D013256:Steroids