claudin-3.claudin-4在结直肠腺瘤和结直肠癌中的表达

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1、授予单位代码10089学号或申请号11219HebeiMedicalUniversity硕士学位论文在职科学学位claudin-3.claudin-4在结直肠腺瘤和结直肠癌中的表达作者姓名：马兰芳导师：王爱民教授专业：内科学二级学院：解放军252医院2015年03月河北医科大学学位论文使用授权及知识产权归属承诺本学位论文在导师（或指导小组）的指导下，由本人独立完成。本学位论文研究所获得的研究成果，其知识产权归河北医科大学所有。河北医科大学有权对本学位论文进行交流、公开和使用。凡发表与学位论文主要内容相关的论文，第一署名为单位河北医科大学，试验材料、原始数据、申报的

2、专利等知识产权均归河i匕医科大学所有。否法律责任。研究生签名:河北医科大学研究生学位论文独创性声明本论文是在导师指导下进行的研究工作及取得的研究成果，除了文中特别加以标注和致谢等内容外，文中不包含其他人己经发表或撰写的研究成果，指导教师对此进行了审定。本论文由本人独立撰写，文责自负。研究生签名:r年/月忡目录中文摘要·············································································1英文摘要············································

3、·································2研究论文claudin-3.claudin-4在结直肠腺瘤和结直肠癌中的表达前言·············································································6材料与方法····································································7结果·························································

4、····················10附图·············································································11附表·············································································14讨论·············································································16结论··················

5、···························································20参考文献·······································································21综述Claudin与胃肠道肿瘤····················································22致谢············································································

6、·······35个人简历·············································································36中文摘要Claudin-3和claudin-4在结直肠腺瘤和结直肠癌中的表达摘要目的：近年来，结肠癌的发病率和死亡率随着人们生活水平的提高和饮食习惯的改变有逐年上升的趋势，严重影响人们的身体健康，缩短平均寿命。目前认为结肠癌发生机制主要为：1.腺瘤癌变；2.溃疡性结肠炎-大肠癌通路；3.幼年性息肉病-癌途径。其中腺瘤癌变通路占绝大部分。正常黏膜由于APC突变导致细胞增生，DNA甲基化

7、异常促进腺瘤形成，再由于Ras突变及DCC丢失、P53突变形成腺癌。另外微卫星的不稳定性也是遗传性非息肉病性大肠癌的发病因素，无论何种原因，癌干细胞的形成无疑是癌发生的关键因素，上皮起源的癌干细胞可能经历上皮细胞到间充质的转变，导致间充质特征的癌干细胞产生，多种研究表明claudin是形成上皮-间充质-癌干细胞的关键因子。Claudin即闭锁蛋白是构成细胞间紧密连接的最重要的膜蛋白结构分子，紧密连接（tightjunctionTJ）是胃肠粘膜上皮细胞间最重要的细胞间连接,位于连接复合体上极，负责形成细胞间栅栏和屏障功能，紧密连接蛋白包括claudin、occlud

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