结直肠癌放射线联合CD基因治疗的研究进展

放疗联合基因治疗恶性肿瘤的研究正日益受到重视 ,实验显示放疗联合基因治疗肿瘤二者有明显的协同作用 ,能有效提高对肿瘤细胞的杀伤效能。本文对 CD基因的作用机理、CD基因的靶向转移、放射线联合 CD基因治疗结直肠癌等方面的研究进行综述     

结直肠癌放射线联合CD基因治疗的研究进展—（文献综述）

放疗联合基因治疗恶性肿瘤的研究正日益受到重视,实验显示放疗联合基因治疗肿瘤二者有明显的协同作用,能有效提高对肿瘤细胞的杀伤效能。本文对CD基因的作用机理、CD基因的靶向转移、放射线联合CD基因治疗结直肠癌等方面的研究进行综述。     

结直肠癌放射线联合CD基因治疗的研究进展(文献综述)

放疗联合基因治疗恶性肿瘤的研究正日益受到重视,实验显示放疗联合基因治疗肿瘤二者有明显的协同作用,能有效提高对肿瘤细胞的杀伤效能.本文对CD基因的作用机理、CD基因的靶向转移、放射线联合CD基因治疗结直肠癌等方面的研究进行综述.     

结直肠癌基因治疗策略临床进展

自1988年美国批准第一个向人体转入外源基因的申请后，肿瘤基因治疗作为一种新的治疗模式进入临床试验，并进行了深入策略研究。本文就近年来结直肠癌基因治疗策略研究进展作一综述。     

实验性结肠癌癌胚抗原特异性药物前体基因治疗的改进

结肠癌肝转移依然是转移性疾病最普遍的形式。尽管局部化疗、放疗和免疫治疗可以使肿瘤暂时缓解 ,进展期结直肠癌病人的预后并没有改善。因此 ,结肠癌肝转移的处理迫切需要新的治疗方法 ,基因治疗即是候选者之一。在不同的肿瘤基因治疗策略中 ,埃希氏大肠杆菌胞嘧啶脱氨酶 (CD) /5 氟胞嘧啶 ( 5 FC)系统是实验性治疗转移性结肠癌最适当的药物前体基因疗法之一 ,因为转入肿瘤细胞内的CD基因产物可以把无毒性的药物前体 5 FC转变成 5 氟尿嘧啶 ( 5 FU) ,后者广泛用于结直肠癌病人的治疗。在本研究中 ,我们检测是否Cre/loxP系统改良…     

结直肠癌肝转移的综合治疗

结直肠癌肝转移是影响结直肠癌预后的重要因素,治疗方案包括手术治疗、化疗(全身静脉化疗和介入治疗)、基因治疗和局部治疗(射频消融、激光消融、无水酒精注射和冷冻切除术)等,其中手术是目前唯一有效的治愈手段,手术死亡率为1%~2.8%,术后5年生存率为34%~38%,但仅有10%~25%结直肠癌肝转移患者确诊时适于手术切除,因此各种非手术治疗的作用正日益受到关注。本文就结直肠癌肝转移的综合治疗作一综述。     

结直肠癌基础领域热点问题研究进展

作为世界范围内发病率及死亡率逐年上升的消化道恶性肿瘤,结直肠癌的基础研究近年来备受关注.现就其中的热点问题如结直肠癌干细胞、结直肠癌表观遗传学、MicroRNA调控与结直肠癌、免疫炎症与结直肠癌、风险基因筛选与结直肠癌、结直肠癌治疗及预后敏感相关蛋白等研究做一述评.     

结直肠癌肝转移相关基因研究进展

肝脏是结直肠癌的主要远处转移器官．分期相同的结直肠癌．即使治疗措施完全相同．患者术后出现复发或转移的情况可能相去甚远。究其原因．可能是因为分子水平存在差异。随着分子生物学技术的迅速发展．通过对基因表达谱的研究．不断有新的基因被发现参与了结直肠癌肝转移。本文就近年来结直肠癌肝转移相关基因的研究热点与最新成果作一综述。     

GSE74602芯片数据中直肠癌关键基因与治疗药物的生物信息学筛选

目的:通过生物信息学方法探寻结直肠癌的诊断标志物及潜在的治疗靶点与治疗药物。方法:从美国国立生物技术信息中心(NCBI)公共数据平台基因表达大棚车(GEO)下载芯片数据GSE74602,包括60个样本,其中30例结直肠癌样本,30例正常结直肠组织样本。用R语言中的Limma包对正常组织和癌症组织进行差异表达分析,用DAVID在线数据库对筛选出来的差异表达基因进行基因本体论(GO)富集分析和京都基因与基因组百科(KEGG)信号通路分析,同时通过STRING在线数据库构建差异表达基因的蛋白互作网络,利用Cytoscape软件进行可视化编辑,并且通过MCODE插件进行子网络模块分析,筛选出结直肠癌发生过程中的核心基因。最后,用连通图数据库(c Map)分析具有潜在治疗结直肠癌的小分子药物。结果:总共筛选出231个差异表达基因,包括122个上调基因,109个下调基因。GO分析结果表明,表达上调的基因富集的生物学过程主要包括细胞周期、细胞分裂等,而表达下调的基因富集在免疫反应,细胞内信号级联和防御反应等生物学过程。KEGG通路分析发现表达上调的基因主要参与细胞中氮及矿物质的代谢和细胞中相关物质的分泌(胆汁、胰液)的信号通路,而表达下调的基因主要参与药物代谢、细胞循环以及p53信号传导通路。子网络模块分析发现了一些在结直肠癌发生的调控中起着重要作用的关键基因,如KIF20A、CENPF、NCAPG、PYY、IQGAP3;蛋白互作网络中的差异表达基因被映射到c Map上,筛选出若干个潜在治疗结直肠癌的小分子药物,如紫霉素、去甲骆驼蓬碱、斑鸠霉素等。结论:所发现的关键基因可能会成为诊断结直肠癌新的肿瘤标志物或者治疗结直肠癌的新的靶点;此外,筛选出的小分子药物有可能成为治疗结直肠癌的新型药物。     

不同种族人群的结直肠癌具有特定的遗传和后天特征

现已一致认为,结直肠癌的变异与种族相关,如在埃及,结直肠癌好发于年轻人,大多数为直肠癌且为晚期癌。Nieminen TT等标记了埃及的69例散发性结直肠癌的启动子甲基化有关的24个肿瘤抑制基因、微卫星不稳定、错配修复基因、P53、     

Gene therapy for gastrointestinal tract cancer: Prospects for combination treatment consisting of surgery and molecular surgery

Progress in understanding carcinogenesis has shown cancer to be a disease caused by gene abnormalities, and a variety of oncogenes and tumor suppressor genes have thus been identified. Advances in molecular biology have given us new tools for diagnosing, staging and predicting the outcome for cancer patients and gene therapy could therefore potentially revolutionize the treatment of gastrointestinal (GI) tract cancer. Progress has been made in several approaches related to genetic modification: (1) antisense oncogene and the restoration of tumor suppresor gene therapy; (2) suicide gene therapy; and (3) cancer immunotherapy. In situ in vivo gene transfer is a practical method of gene therapy for GI tract cancer. Although many hurdles need to be overcome to achieve effective gene transfer and targeting, our early results of in situ in vivo suicide gene therapy for canine gastric cancer are promising. The era of combined treatment consisting of surgery and molecular surgery for GI tract cancer is thus considered to soon be possible.     

Prostate cancer gene therapy: outcome of basic research and clinical trials

With the advances in genetic engineering, tumor biology, and immunology, gene therapy has been recognized as a promising new treatment option for cancer, including prostate cancer. Several clinical trials of prostate cancer gene therapy currently underway are using therapeutic genes, including suicide genes, immunomodulatory genes, tumor suppressor genes, and antioncogenes. Although gene therapy for prostate cancer as a clinical alternative is still at an early stage that requires several technological breakthroughs, information obtained from clinical trials indicates the full potential of prostate cancer gene therapy. Concordant progress in basic research and gene therapy technology will ready prostate cancer gene therapy for widescale use in the future. In this report, the general concept and current progress in prostate cancer gene therapy are summarized.     

The current state of cancer gene therapy and its application in esophageal carcinoma

Advances in molecular genetics have accelerated the understanding of the genetic basis of many diseases. This is particularly true for esophageal adenocarcinoma with its well-defined premalignant lesions. At the same time, remarkable progress in recombinant DNA technology has enabled the development of molecular treatments for inherited disorders, infectious diseases and cancer. In recent years, especially the development of gene therapy systems as new treatment or prevention strategies for various malignant diseases has been explored. The present article deals with the general principles of gene therapy and then focuses on how these principles can be applied to esophageal cancer. Subsequently, the scarcely available experimental data from the literature are briefly reviewed. Finally, we summarize our experimental work over the last few years. Our main goal has been to develop an efficient and selective gene delivery system in order to maximize the proportion of successfully transduced tumor cells while sparing normal cells. CONCLUSION: The field of cancer gene therapy has evolved tremendously, with promising developments especially in the field of targeting and novel therapeutic genes. However, substantial research is still needed before gene therapy can play a significant role in the management of esophageal cancer. The focus of this research should be on further developing adequate experimental models as well as on improving gene-delivering vectors. Although it is unlikely that cancer gene therapy will replace the conventional methods of treatment, selective and efficient vectors may be used for patients with Barrett's esophagus or as adjuvant therapy for patients with esophageal cancer in the future.     

Gene therapy for lung cancer

Over the past three decades, the molecular biology of lung cancer has been progressively delineated. Concurrently, gene therapy techniques have been developed that allow targeting or replacement of dysfunctional genes in cancer cells, such as activated tumor-promoting oncogenes, inactivated tumor-suppressing, or apoptosis-promoting genes. This article will review the therapeutic implications of molecular changes associated with non-small cell lung cancer and the status of gene therapy.     

Gene therapy for brain tumors: the fundamentals

BACKGROUND: Over the past two decades, significant advances have been made in the fields of virology and molecular biology, and in understanding the genetic alterations present in brain tumors. The knowledge gained has been exploited for use in gene therapy. OBJECTIVE: The purpose of this article is to present an introduction to the field of brain tumor gene therapy for the practicing clinician. RESULTS: A variety of gene therapy strategies have now been used in the laboratory and in clinical trials for brain tumors. They can be divided into five categories: 1) gene-directed enzyme prodrug ("suicide gene") therapy (GDEPT); 2) gene therapy designed to boost the activity of the immune system against cancer cells; 3) oncolytic virus therapy; 4) transfer of potentially therapeutic genes--such as tumor suppressor genes--into cancer cells; and 5) antisense therapy. GDEPT is the strategy that has been most extensively studied. CONCLUSIONS: To date, gene therapy has been found to be reasonably safe and concerns related to adverse events such as insertional mutagenesis have not been realized. Although patients have not been cured, the development of this therapy could still be considered to be at an early stage. Current research is addressing factors that could be limiting the successful clinical application of gene therapy, which remains an intriguing experimental option for patients with malignant brain tumors.     

Gene therapy for lung cancer: practice and promise

Gene therapy has emerged as an exciting and promising strategy of cancer therapy. Improved molecular biology techniques and a greater understanding of the mechanisms involved in lung cancer pathogenesis allowed a variety of genes to be validated as molecular targets for gene therapy. A variety of gene therapy strategy have been explored in the pre-clinical research. These include replacement of defective tumor suppressor genes, inactivating oncogenes, introducing suicide genes, immunogenic therapy, and antiangiogenesis-based approach. Clinical trials of gene therapy for lung cancer showed the feasibility of delivering a variety of agent as well as highlighted problems with the delivery of therapeutic constructs. Although some may consider the initial results of these novel therapies to be disappointing, they underscore the complexity of these approaches and the likelihood that these approaches will be effective only when used in a coordinated fashion in the proper clinical context. This review provides an update on our current understanding of lung cancer biology and examines several important issues in cancer gene therapy. In addition, recent results of clinical trials of gene therapy for lung cancer are presented.     

RNAi 在大肠癌基因治疗中的应用策略和展望

目的 探讨RNA干扰（RNA interference，RNAi）技术在大肠癌基因治疗研究中的应用。方法复习近几年的相关文献并进行综述。结果RNAi能够高效特异地沉默同源基因表达，可在大肠癌发生、发展多个环节发挥重要作用。结论RNAi技术为大肠癌基因治疗研究开辟了新的途径。     

Possibility and future problems of gene therapy for gastric cancer]

Recently, stage-oriented surgery has been performed for gastric cancer, but a new strategy is necessary for stage IV gastric cancer. The first target of gene therapy for gastric cancer was for stage IV patients with-widespread lymph node metastases and/or peritoneal dissemination. We reported on suicide gene therapy in experimental gastric cancer induced by ENNG in the dog, and the results showed that in situ gene transfer of a suicide gene (Ad. CAGHSV-TK) followed by prodrug (GCV) treatment may be applicable not only to the primary gastric tumor, but also to lymph node metastasis. Next, we assessed the efficacy of in situ gene therapy with Ad. CAGHSV-TK/GCV in gastric cancer induced by MNNG in rats, and followed the histopathological changes in the gastric cancer and HSV-TK gene in peripheral blood for 30 days. The results showed that: 1) apoptosis preceded tissue degeneration; 2) histopathological efficacy requires 30 days after suicide gene therapy; and 3) the HSV-TK gene persisted for 30 days. Based on these studies, we speculated that combination treatment with endoscopy is possible for all early gastric cancer, i.e., endoscopic mucosal resection of the primary tumor plus suicide gene therapy for sentinel lymph node metastasis. New possible strategies for peritoneal dissemination are: 1) tumor dormancy therapy with adeno-associated virus (AAV); and 2) combination gene therapy with suicide genes plus gene transfer to provide immunotherapy.     

自杀基因联合其他疗法治疗肿瘤的研究进展

肿瘤的基因治疗经多年研究已取得了许多令人瞩目的成就,其中自杀基因疗法的发展尤为迅速,是一种颇具临床应用前景的基因治疗策略。但是自杀基因治疗的单独应用仍有不少局限性,如转染效率低、诱导免疫反应能力弱、缺乏组织特异性、易引起肿瘤耐药性、对肿瘤细胞类型有依赖等。所以,研究自杀基因与其他肿瘤疗法的联合应用以及不同自杀基因之间协同作用以寻求更有效的抗肿瘤效应已逐渐成为非常有前景的治疗手段。本文就近几年自杀基因联合其他疗法治疗肿瘤的研究进展作综述。