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
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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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    ABSTRACT: T regulatory cells;interleukin 2;peptide vaccination
    British Journal of Haematology 08/2015; DOI:10.1111/bjh.13657 · 4.71 Impact Factor
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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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    ABSTRACT: Background Thalidomide is a known teratogen and it is estimated that more than ten thousand babies were affected by thalidomide embryopathy (TE), which is characterized mainly by limb defects, but can involve many organs and systems. Most people with TE were only evaluated at birth and it is not well established if thalidomide exposure during embryonic development leads to later effects. We analyzed the clinical history of adults with TE to better understand this gap in the clinical findings of TE.Methods Brazilian individuals with TE were invited to answer a clinical questionnaire which considered family history, social information, medical history, and current clinical and psychological health status. A clinical examination was also performed, including on the infant subjects to evaluate congenital anomalies. The characterization of the features was analyzed using descriptive statistics and Chi-square or Fisher's exact test.ResultsThe congenital anomalies caused by thalidomide were reviewed in 28 Brazilian individuals, and the questionnaire was applied to the 23 adult subjects with TE (aged 19 to 55). Progressive deafness and dental loss were reported. From the comparison of TE individuals with the general Brazilian population, the early onset of cardiovascular diseases (p = 0.009) and a higher frequency of psychological disorders (p = 0.011) were observed.Conclusion Although there is no sufficient evidence that thalidomide exposure caused or worsened the described events, this approach helps to better understand the TE phenotype, improves the clinical diagnosis, and can lead to adequate health support for these individuals. Birth Defects Research (Part A), 2015. © 2015 Wiley Periodicals, Inc.
    Birth Defects Research Part A Clinical and Molecular Teratology 06/2015; 103(9). DOI:10.1002/bdra.23376 · 2.09 Impact Factor
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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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    ABSTRACT: Drug repositioning (also referred to as drug repurposing), the process of finding new uses of existing drugs, has been gaining popularity in recent years. The availability of several established clinical drug libraries and rapid advances in disease biology, genomics and bioinformatics has accelerated the pace of both activity-based and in silico drug repositioning. Drug repositioning has attracted particular attention from the communities engaged in anticancer drug discovery due to the combination of great demand for new anticancer drugs and the availability of a wide variety of cell- and target-based screening assays. With the successful clinical introduction of a number of non-cancer drugs for cancer treatment, drug repositioning now became a powerful alternative strategy to discover and develop novel anticancer drug candidates from the existing drug space. In this review, recent successful examples of drug repositioning for anticancer drug discovery from non-cancer drugs will be discussed.
    International journal of biological sciences 06/2014; 10(7):654-663. DOI:10.7150/ijbs.9224 · 4.51 Impact Factor
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