Thalidomide is an inhibitor of angiogenesis

Thalidomide is an inhibitor of angiogenesis

April 1994 | ROBERT J. D'AMATO*, MICHAEL S. LOUGHAN, EVELYN FLYNN, AND JUDAH FOLKMAN
Thalidomide is a potent teratogen that causes limb malformations in humans. It has been shown to inhibit angiogenesis, the process of forming new blood vessels, in a rabbit cornea micropocket assay when administered orally. This inhibition was observed in the presence of basic fibroblast growth factor (bFGF), a key angiogenic factor. Thalidomide's antiangiogenic activity correlates with its teratogenic effects but not with its sedative or mild immunosuppressive properties. Electron microscopic analysis revealed structural changes in the corneal neovascularization of thalidomide-treated rabbits that resembled those in deformed limb buds of embryos. These findings suggest that thalidomide's teratogenicity may result from its ability to inhibit blood vessel growth in the developing limb bud. Thalidomide was developed in the 1950s as a sedative but was later found to cause severe birth defects. Despite its teratogenic effects, it was not shown to have similar effects in rodents. Experiments in rabbits showed that thalidomide could induce limb defects when administered to pregnant females. The mechanism of thalidomide's teratogenicity is not fully understood, but it is hypothesized that it inhibits blood vessel growth in the developing limb bud. This hypothesis is supported by experiments showing that thalidomide inhibits angiogenesis in the rabbit cornea and chicken chorioallantoic membrane models. Thalidomide's antiangiogenic activity was tested in various models, including the rabbit cornea and chicken chorioallantoic membrane. It was found to inhibit angiogenesis induced by bFGF, with a median inhibition of 36% in three experiments. Thalidomide also inhibited angiogenesis in immunosuppressed animals, suggesting a direct effect on angiogenesis. Electron microscopic examination of thalidomide-treated rabbits revealed ultrastructural changes in the corneal neovascularization that were similar to those seen in deformed limb buds of embryos. These findings support the hypothesis that thalidomide inhibits angiogenesis and may be used to treat diseases involving abnormal angiogenesis, such as diabetic retinopathy and solid tumors.Thalidomide is a potent teratogen that causes limb malformations in humans. It has been shown to inhibit angiogenesis, the process of forming new blood vessels, in a rabbit cornea micropocket assay when administered orally. This inhibition was observed in the presence of basic fibroblast growth factor (bFGF), a key angiogenic factor. Thalidomide's antiangiogenic activity correlates with its teratogenic effects but not with its sedative or mild immunosuppressive properties. Electron microscopic analysis revealed structural changes in the corneal neovascularization of thalidomide-treated rabbits that resembled those in deformed limb buds of embryos. These findings suggest that thalidomide's teratogenicity may result from its ability to inhibit blood vessel growth in the developing limb bud. Thalidomide was developed in the 1950s as a sedative but was later found to cause severe birth defects. Despite its teratogenic effects, it was not shown to have similar effects in rodents. Experiments in rabbits showed that thalidomide could induce limb defects when administered to pregnant females. The mechanism of thalidomide's teratogenicity is not fully understood, but it is hypothesized that it inhibits blood vessel growth in the developing limb bud. This hypothesis is supported by experiments showing that thalidomide inhibits angiogenesis in the rabbit cornea and chicken chorioallantoic membrane models. Thalidomide's antiangiogenic activity was tested in various models, including the rabbit cornea and chicken chorioallantoic membrane. It was found to inhibit angiogenesis induced by bFGF, with a median inhibition of 36% in three experiments. Thalidomide also inhibited angiogenesis in immunosuppressed animals, suggesting a direct effect on angiogenesis. Electron microscopic examination of thalidomide-treated rabbits revealed ultrastructural changes in the corneal neovascularization that were similar to those seen in deformed limb buds of embryos. These findings support the hypothesis that thalidomide inhibits angiogenesis and may be used to treat diseases involving abnormal angiogenesis, such as diabetic retinopathy and solid tumors.
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