Analysis of the Molecular Pathology for the Salidonmide Syndrome

沙利度胺是一种具有抗免疫和抗炎作用的药物。近年来，这种药物被用于治疗多种疾病。然而，它也是众所周知的，显示出强烈的致畸作用的胚胎，这是所谓的沙利度胺综合征，其机制仍不清楚。本研究旨在揭示沙利度胺致畸作用的机制。Roberts综合征是一种具有短肢畸形表型的人类遗传性疾病，与Salidomide综合征的肢体表型相似。我们利用培养的细胞系分析了沙立度胺死亡的可能靶基因的表达水平。我们发现ESCO2的表达受到抑制，这是Roberts综合征的缺陷，这可能提示了沙利度胺综合征的部分机制。其他研究工作证明了罗伯茨患者淋巴母细胞的细胞生物学特性。它们对丝裂霉素C的敏感性高于正常淋巴母细胞，且在纺锤体检查点上存在问题。这些结果可能有助于揭示沙利度胺的副作用，并提示抑制其致畸作用的治疗方法

Salidomide is a medicine which has anti-immune effect and anti-inflamation effect. Recently this medicine is applied for the treatment for several diseases. However it is also well-known to show the strong teratogenic effect for the embryo which is called Salidomide syndrome, which mechanism is still unclear. We planed the research to disclose the mechanism of the teratogenic effect of the salidomide. We have experience the molecular cloning of Roberts syndrome which is human genetic disease with phenotype of phocomelia, which resemble to the limb phenotype of salidomide syndrome. We analyze the salidomide died on the expression level of possible target genes using cultured cell line. We found suppressed expression of ESCO2 which is defect in Roberts syndrome which might suggest the part of mechanism of salidomide syndrome. Other research effort proved the cellular biological characteristics of Roberts patient lymphoblasts. They are sensitive to the mitomycine C than normal lymphoblast and has problem in spindle checkpoint. These result might lead the disclosure of salidomide side effect and suggest the treatment to inhibit the teratogenic effect