ercc1基因多态性及蛋白表达与上皮性卵巢癌铂类化疗敏感性及预后关系的研究

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1、授予单位代码10089学号或申请号20122363HebeiMedicalUniversity硕士学位论文科学学位ERCC1基因多态性及蛋白表达与上皮性卵巢癌铂类化疗敏感性及预后关系的研究研究生：田美玲导师：康山教授专业：妇产科学二级学院：第四医院2015年3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，位论文在导师C或指导小纽)的指针卜，山本人独、本学位论文研究所获的研究成果，其知识产权归河』匕保和I'大,所千J。河北医科大学有权对本学位论文进行交流、公幵和使川。凡发及位论文主要内容相关的论文，第一署名单位为丨11丨〗^医科大学，试验材料、原

2、始数据、申报的专利等知识产权均归河北眩科大卞所竹。狐承担相应的法律责任。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见，除r文111特别加以标注和致谢等内容外，文屮不包含丨〔•他人匕经发^成撰‘1j的研究成，指分教帅对此班行j‘丨-i�XL�o本论义山木人独w丄丨、1^目录中文摘要·············································································1英文摘要···································

3、··········································4英文缩写·············································································8研究论文ERCC1基因多态性及蛋白表达与上皮性卵巢癌铂类化疗敏感性及预后关系的研究前言·············································································9材料与方法···························

4、·········································10结果·············································································15附图·············································································17附表·······································································

5、······20讨论·············································································25结论·············································································27参考文献·······································································28综述ERCC1基因与上皮性卵巢癌铂类耐药的研究进展······

6、·············32致谢···················································································41个人简历·············································································42中文摘要ERCC1基因多态性及蛋白表达与上皮性卵巢癌铂类化疗敏感性及预后关系的研究摘要目的：卵巢癌为女性生殖系统三大常见恶性肿瘤之一，死亡率居首，病因及发病机制至今并不明确。因起病隐匿、

7、缺乏早期诊断指标，多数确诊时已为晚期。5年生存率仍未超30%。卵巢上皮性癌（EpithelialOvarianCancer，EOC)占卵巢癌的85%～90%，是卵巢癌中最常见的一种类型。目前以铂类为基础的联合化疗是进展期卵巢癌肿瘤细胞减灭术后的一线治疗方案，而卵巢癌患者治疗的主要障碍就是铂类化疗药物的耐药。铂类化合物（卡铂或顺铂）的抗肿瘤效应是通过与DNA结合成链内和链间交联及Pt-DNA加合物。DNA加合物引起DNA结构改变，从而影响DNA复制和抑制DNA的合成。研究证实,肿瘤患者临床缓解率与血液循环中Pt-DNA加合物的水平相关,如果肿瘤细胞DN

8、A修复能力减低，就会导致Pt-DNA加合物清除减少,使患者对铂类药物的疗效提高，反之疗效则差。因此，DNA修