Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A

Department of Surgery, Children's Hospital, Harvard Medical School, Boston 02115.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 05/1994; 91(9):4082-5. DOI: 10.1097/00006982-199616030-00022
Source: PubMed


Thalidomide is a potent teratogen causing dysmelia (stunted limb growth) in humans. We have demonstrated that orally administered thalidomide is an inhibitor of angiogenesis induced by basic fibroblast growth factor in a rabbit cornea micropocket assay. Experiments including the analysis of thalidomide analogs revealed that the antiangiogenic activity correlated with the teratogenicity but not with the sedative or the mild immunosuppressive properties of thalidomide. Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of thalidomide-treated embryos. These experiments shed light on the mechanism of thalidomide's teratogenicity and hold promise for the potential use of thalidomide as an orally administered drug for the treatment of many diverse diseases dependent on angiogenesis.

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    • "No difference in the numbers of R3-specific CTLs with or without incubation with thalidomide (3Á5 vs. 2Á5) was observed. It was proved that thalidomide targets leukaemic cells in different indirect mechanisms, including modulation of the tumour microenvironment by inhibiting angiogenesis (D'Amato et al, 1994; Davies et al, 2001; Molica, 2007). The current study also showed that thalidomide is able to restore the immune response against R3 peptide following inhibition by Tregs in an in vitro system . "
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    • "Thalidomide has been used in Brazil to treat this condition since the second half of the 1960s (Oliveira et al., 1999; Paumgartten and Chahound , 2006). More recently, the drug has also been designated to treat other conditions, such as multiple myeloma, lupus erythematosus, idiopathic ulceration from AIDS, and graft versus host disease, due to its important immunomodulatory and antiangiogenesis properties (Sampaio et al., 1991; Moreira et al., 1993; D' Amato et al., 1994). Because of these properties, the use of thalidomide was increased in Brazil, but under restrict legislation (RDC no. "
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    • "In the ensuing decades, several research groups found that thalidomide possesses anticancer activity. It was found to inhibit angiogenesis in animal models by Robert D'Amato and Judah Folkman 6 and was subsequently shown to have promising therapeutic effect on refractory multiple myeloma and metastatic prostate cancer 7, 8. In 2006, thalidomide received US-FDA approval for the treatment of multiple myeloma in combination with dexamethasone. "
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