【作者】 王斌；

【导师】 傅庆诏；

【作者基本信息】 山东大学 ， 妇产科学， 2006， 博士

【摘要】 卵巢癌是女性生殖系统三大恶性肿瘤之一，死亡率高居妇科恶性肿瘤之首，其远期生存率仅为30％～40％。由于起病隐匿，70％以上的患者就诊时已属晚期。虽然在接受传统方法治疗初期会有反应，多数患者终将复发或对化学治疗药物产生耐药。因此，探索新的治疗方法对于改善卵巢癌患者临床结局具有重要意义。 随着基础研究的不断深入，包括免疫治疗和基因治疗的卵巢癌生物治疗作为肿瘤治疗的第四种模式日益受到重视，成为传统手术治疗和化疗的有力补充，显现出极具潜力的发展前景。分子生物学和免疫学的进展为卵巢癌的基因治疗研究提供了理论基础和技术方法，近年来采用的基因治疗策略主要包括分子化学治疗(如HSVtk／GCV自杀基因治疗)、纠错性基因治疗(导入野生型p53等抑癌基因)、免疫增强性基因治疗(导入各种细胞因子)等。但是，基因治疗存在目的基因导入肿瘤细胞的效率较低、靶向性不高等不足，这些问题的解决将有力的促进基因治疗的广泛应用。目前常用的基因治疗载体系统有逆转录病毒、腺病毒、腺相关病毒等病毒载体，以及脂质体、裸DNA、各种微粒或聚合物包裹等非病毒载体系统。早期的基因治疗研究多采用逆转录病毒作为载体，尽管可以持久整合到宿主细胞DNA，但由于可携带的基因片段有限，易被补体灭活以及整合到宿主细胞所带来的安全性等问题，其应用受到限制。由于对腺病毒的生物学功能已很明确，近年来重组腺病毒载体的靶向性成为基因治疗的研究热点。腺病毒载体具有转染效率高、可转染非分裂细胞等优点，通过对腺病毒基因组E1区和纤毛的改造，可使其以不依赖柯萨奇腺病毒受体的方式进入细胞，并选择性地在p53缺陷的肿瘤细胞中复制，有效地提高了治疗的靶向性。腺相关病毒则具有无致病作用，可更多还原

【Abstract】 Being one of the most harmful genital malignant tumors, ovarian cancer has posed us many problems concerning diagnosis and treatment. Because it is hidden when the disease arises, over 70% of the patients have reached later period when seeing a doctor. Although in initial stage traditional treatments take effect, most ovarian cancers will recurred or are drug-resistant. Therefore, it is very important to look for new treatment methods to improve the patients’ ending.Recently, biological therapy for ovarian cancer including immunization therapy and gene therapy has been paid more attention as the fourth therapeutic patttern, and showed infinite prospect. The development of molecular biology and immunology provides theoretical principle and technology for the gene therapy of the ovarian cancer. In rescent years strategies mainly include molecular chemical therapy, error checking gene therapy, immunopotentiation therapy and so on. But in the present time there are some problems in gene therapy such as low efficiency in transferring target genes to tumor cells and lacking accurate directivity. The staple carrier system includes viral carriers such as retrovirus, adenovirus, gland-related virus and non-viral-carriers such as lipidosome, bare DNA or diversified particulates .The early gene therapy studies used to make retrovirus as a carrier. Because of carrying fewer gene segments and easily inactivated by complement and doing harm to parasitifer cells, its application was restricted significantly. The biological effect of adenovirus更多还原