【作者】 千新来；

【导师】 赵清正；

【作者基本信息】 中国协和医科大学 ， 生物化学与分子生物学， 2005， 博士

【摘要】 肿瘤是多因素诱导、多基因参与、多阶段发生与演进的极其复杂的病理过程，是一种全身性疾病。近几十年以来，传统的肿瘤治疗方法(手术、放疗和化疗)虽已经取得了长足的进展，但对中晚期和／或复发转移患者的预后没有显著的改善。因此，寻找恶性肿瘤新的治疗措施以补充甚至代替现有的传统治疗方法是非常必要的。经过肿瘤学工作者多年的努力，包括肿瘤基因治疗和肿瘤免疫治疗在内的肿瘤生物治疗正逐渐成为具有挑战性但又颇有前景的肿瘤治疗方法。 1．腺病毒5型E1A下游基因c-101抗癌和化疗增敏作用及相关机理的初步研究 随着后基因组时代的到来，新基因的克隆和功能研究已成为生命科学研究的热点和阐明疾病机理、寻找新的疾病治疗方法的关键。肿瘤是一种基因病。对肿瘤生物学特性和肿瘤-宿主相互作用的深入研究，为肿瘤基因治疗提供了许多潜在的靶点和坚实的理论基础。腺病毒5型E1A基因能通过多种途径发挥抗癌作用。但E1A是一个外源性的病毒基因，其安全性引起了人们的质疑。因此，本研究对我们实验室克隆的一个E1A下游基因c-101在人类肿瘤细胞中的功能和相关机理进行了初步研究。 利用分子克隆技术，构建了c-101基因真核表达重组质粒pcDNA3.1-c-101，经脂质体介导将其转导入LN686细胞，建立了稳定高表达c-101基因的细胞系LN686-c-101。 生长速度、倍增时间、克隆形成率、裸鼠致瘤性、细胞周期分布和凋亡等是评价肿瘤恶性生物学行为的重要指标。本研究结果显示：c-101基因稳定高表达可以逆转LN686细胞的恶性表型，包括：生长速度减慢、倍增时间延长、克隆形成率降低、裸鼠致瘤性降低和细胞周期分析观察到了Sub-G1峰(凋亡峰)等。更多还原

【Abstract】 Tumorigenesis, which is related to induction of multifactor, participation of multigene, and development of multiphase, is a very complex pathologic process and also is a systemic disease. Advances in conventional cancer treatments (surgery, radiotherapy and chemotherapy) have failed to make a significant impact on the prognosis of the patients with late stage, recurrence, and/or metastasis in the last few decades. Therefore, there is a pressing need to develop novel cancer therapies that may complement or even replace current conventional treatment. Biotherapy, including cancer gene therapy (CGT) and immunotherapy, is gradually becoming a challenging and promising cancer therapy.Section one: Preliminarily studies on the effects and mechanisms of anti-cancer and chemosensitivity of c-101 geneWith the coming of post-genomic era, the cloning and function analysis of a novel gene is being the spotlight of life science and is the key to elucidate mechanisms or find new therapeutics of disease. Cancer is a genetic disease in which individual cells demonstrate mutations in genes related to growth control and apoptosis, and have functional alterations that support their ability to invade and metastasize. The interaction of cancer cells with their microenvironment, including extracellular matrix, cells of the immune system, and cells necessary for induction of angiogenesis to sustain tumor growth, is a critical component of tumor growth. Thus, there are many potential targets in which introduction of new genes, and inactivation更多还原