【作者】 张蓓；

【导师】 刘嘉茵； 胡刚；

【作者基本信息】 南京医科大学 ， 妇科肿瘤学， 2006， 博士

【摘要】 肿瘤基因治疗通常是指把外源性基因利用不同的方法导入患者体内，利用基因产物的功能杀死肿瘤细胞。在基因治疗的研究中，基因导入系统是最关键的技术，因此高效的载体表达系统是提高基因治疗效率的关键。腺病毒是基因治疗中最常用的载体，具有可插入大片断外源基因、可感染非分裂期细胞、转导效率高、培养物中可获高滴度的病毒产量以及不整合到宿主细胞基因组等优点。尽管腺病毒具有很多优点并广泛应用于基因治疗，但是依然存在缺乏特异性、肿瘤细胞靶向性及感染效率低下的缺陷。目前可以通过改造腺病毒提高效率，即在腺病毒的基因组内加入针对个别肿瘤特征的肿瘤特异性启动子，在转录水平使外源基因选择性地在肿瘤部位高表达，最大程度地提高基因治疗的高效性和安全性。 Survivin是新近发现的一种凋亡抑制基因，它在正常组织中不表达，而在各种肿瘤组织中高表达，与肿瘤的发生发展密切相关。有研究表明survivin基因在卵巢癌组织中高表达，而在卵巢正常组织及良性卵巢肿瘤组织中几乎不表达，因此可以作为卵巢肿瘤特异性启动子在肿瘤的基因治疗中发挥作用。本研究在此基础上构建了含Survivin启动子的新型腺病毒载体AdGL3BSurvivin及具有治疗作用的条件复制腺病毒(溶瘤病毒)CRAd-Survivin-RGD4C，经过包装，产出病毒，转染卵巢癌细胞，观察survivin基因作为卵巢癌特异性启动子及放化疗诱导型启动子的作用，并探讨应用更多还原

【Abstract】 BackgroundCurrently, surgery and chemotherapy are two most commonly used therapeutic modalities for ovarian cancers. Patients with ovarian carcinomas often suffer from regional relapse after primary surgery and platinum-based chemotherapy, 5- year survival was no more than 30%. Therefore, patients need novel locoregional therapies that are more effective and less toxic combination with platinum-based chemotherapy. Gene therapy represents one such modality, in which genes are delivered into cancer cells to destroy the tumor or to enhance the immune response against the cancer. Adenoviral vectors are widely used as gene transfer vectors in cancer therapy because of their ability to transfect a wide range of host tissues and their ability to infect both proliferating and nonproliferating cells. These advantages of adenoviral vectors, however, result in a lack of specificity in their infection pattern leading to transfection of normal host tissues with an unfortunate accompanying potential for toxicity. Altering the tropism of viral vectors to achieve the required levels of efficiency and utilizing tumor specific promoters to restrict transgene expression to tumor cells to enhance specificity are used in gene therapy in order to enhance the therapeutic index.Survivin is a member of the inhibitor of apoptosis protein family (IAP) and,更多还原