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沙利度胺是一种血管生成抑制剂。

Thalidomide is an inhibitor of angiogenesis.

作者信息

D'Amato R J, Loughnan M S, Flynn E, Folkman J

机构信息

Department of Surgery, Children's Hospital, Harvard Medical School, Boston 02115.

出版信息

Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4082-5. doi: 10.1073/pnas.91.9.4082.

Abstract

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.

摘要

沙利度胺是一种强效致畸剂,可导致人类肢体发育不全(肢体生长发育迟缓)。我们已经证明,在兔角膜微袋试验中,口服沙利度胺可抑制碱性成纤维细胞生长因子诱导的血管生成。包括对沙利度胺类似物分析在内的实验表明,其抗血管生成活性与致畸性相关,但与沙利度胺的镇静或轻度免疫抑制特性无关。对经沙利度胺治疗的兔子角膜新生血管进行电子显微镜检查发现,其具有特定的超微结构变化,类似于在经沙利度胺治疗的胚胎畸形肢芽脉管系统中所见的变化。这些实验揭示了沙利度胺致畸性的机制,并为沙利度胺作为口服药物治疗多种依赖血管生成的疾病的潜在用途带来了希望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86f3/43727/9383c4da3018/pnas01131-0615-a.jpg

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