大肠癌的基因治疗研究进展

大肠癌的基因治疗研究发展迅速，已出现多种治疗方案，包括通过自杀基因治疗、针对原癌基因和抑癌基因的治疗，通过增强机体免疫功能的免疫基因治疗途径和联合基因治疗的方法。其中有些方法已获准进入临床试验阶段。本文将对近年来大肠癌基因治疗研究的几个方面作简要综述。     

大肠癌基因治疗的现状和进展

大肠癌是世界范围内最常见的癌症之一，在西方社会其发病率排在肿瘤的第二位，在我国的消化道肿瘤中排第三位。尽管手术、放疗、化疗技术不断提高，但五年生存率只有50％左右。随着人类基因组工程的完成，基因治疗已成为大肠癌治疗的新热点。本文综述了大肠癌基因治疗的现状与研究进展。     

大肠癌的自杀基因治疗实验研究进展

自杀基因治疗恶性肿瘤是目前肿瘤基因治疗中的热点 ,但在治疗大肠癌方面却起步较晚。本文综述近几年自杀基因治疗大肠癌的实验研究进展。     

改变细胞膜脂肪酸组成防治大肠癌的基因治疗研究*

目的:利用脂肪酸去饱和酶基因fat- 1 改变细胞膜脂肪酸组成,进行大肠癌的基因治疗研究。方法:将fat- 1 基因插入腺病毒载体中,与骨架载体同源重组,构建腺病毒重组载体（Ad-GFP-fat1）,通过包装细胞系（293）产生的腺病毒,感染人大肠癌株HT- 29细胞。提取细胞的总RNA,以fat- 1 基因的反义mRNA 作探针,用Northern Blot检测fat- 1 基因在HT- 29细胞内的表达。以流式细胞仪对HT- 29细胞G0/G1 期、S 期、G2/M期所占比例进行检测,分析fat- 1 基因对HT- 29细胞增殖和凋亡的影响。以气相色谱分析仪分析fat- 1 基因对HT- 29细胞细胞膜n-6 PUFAs 和n-3 PUFAs 含量及n-6/n- 3PUFAs 比例的影响。将HT- 29细胞皮下接种于裸鼠右前肢腋下,建立裸鼠HT- 29大肠癌细胞皮下移植瘤模型。成瘤后进行治疗实验,经连续5 次治疗,于最后一次治疗后第3 天处死小鼠,取肿瘤称重。分析fat- 1 基因裸鼠体内抗肿瘤效果。结果:通过基因重组技术,得到高滴度的含fat- 1 基因的重组病毒;腺病毒介导的fat- 1 基因能够在HT- 29细胞中有效表达;fat- 1 基因的表达可降低HT- 29细胞膜n-6/n- 3PUFAs 的比例,有效抑制HT- 29细胞增殖,促进细胞凋亡并能抑制裸鼠移植瘤的发展。结论:fat- 1 基因的表达,可抑制HT- 29细胞的体内外增殖并诱导细胞凋亡,在大肠癌基因治疗中可能具有良好利用价值。      

组织特异性CD/5-FC系统对大肠癌的原位基因治疗

  目的 探讨癌胚抗原(carcinoembryonic antigen,CEA)组织特异性胞嘧啶脱氨基酶基因对不同分泌CEA大肠癌组织的靶向杀伤作用. 方法 脂质体法将CEA组织特异性逆转录病毒载体G1CEACDNa在PA317细胞中进行包装,大肠癌细胞LoVo和SW480分别接种到BALB/c裸鼠大腿皮下,成瘤2周后,瘤内多点注射法行原位基因转染,每天腹腔注射500mg/kg的5-FC(5-fluorocytosine),观察治疗效果. 结果 病毒滴度为5.6×106CFU/L.经多次注射法转染,目的基因在肿瘤组织中能有效表达,治疗21天后,基因治疗组有明显的抑瘤作用,但对LoVo细胞肿瘤的抑瘤作用明显大于对SW480细胞肿瘤. 结论 CEA组织特异性CD/5-FC系统对LoVo细胞肿瘤的抑瘤作用更明显.     

肿瘤基因治疗研究进展

肿瘤的基因治疗就是应用基因操作方法纠正肿瘤细胞基因的结构或功能缺陷，或通过增强危主对肿瘤的杀伤能力和机体的防御机能以治疗肿瘤。一、肿瘤基因治疗的策略肿瘤基因治疗的目的是消除肿瘤，为达到此目的有如下三种治疗策略。1．直接修复肿瘤细胞的基因缺陷，此时靶细胞为肿     

肿瘤自杀基因治疗研究进展

将某些细菌及病毒特有的药物敏感基因转导入肿瘤细胞,从而达到治疗肿瘤的目的,称为肿瘤的自杀基因治疗。自杀基因疗法因其独有的旁观者效应,可克服基因转导率低的缺陷,又可以和放疗、免疫基因治疗联合应用,是较为有效并具有临床应用前景的基因疗法。     

乳腺癌的自杀基因治疗研究进展

从自杀基因治疗乳腺癌的研究现状、自杀基因体系、旁观者效应、临床试验研究等方面综述了近几年自杀基因治疗乳腺癌的实验和临床研究的进展。     

胆管癌基因治疗研究进展

胆管癌的基因治疗研究日益受到人们的重视,并且目前亦取得了一定的进展.本文从抑癌基因治疗、自杀基因治疗、反义基因治疗等几个方面对胆管癌基因治疗研究进展作一简要综述.     

内皮抑素基因治疗的研究进展

内皮抑素是迄今为止所发现的最强的血管形成抑制因子,可抑制内皮细胞生长和迁移,在动物试验中能有效抑制多种恶性肿瘤生长和转移.主要介绍近年来有关内皮抑素基因治疗的研究新进展.     

肿瘤反基因治疗研究进展

寡聚核苷酸及其衍生物能选择性调节基因表达.在反义技术中,寡聚核苷酸可以mRNA的专一序列或双链DNA的特定序列为靶点,阻止遗传信息向蛋白质的流动;也可与双螺旋DNA专一序列结合形成三链DNA,阻止基因转录或DNA复制.反基因寡聚核苷酸以其独特的结构和优于反义RNA的技术特点,为恶性肿瘤的治疗提供了新的途径.     

TRAIL在肿瘤治疗中的研究进展

TRAIL是TNF家族的新成员,它通过与死亡受体结合,激活caspase通路传递和放大凋亡信号,从而诱导靶细胞发生快速、大量、高效的凋亡反应.TRAIL可以选择性地杀伤肿瘤细胞和病毒感染的细胞,而正常细胞则通过表达诱骗受体等方式逃逸其杀伤作用,这种特性使其具有在肿瘤治疗中应用的巨大潜力.     

Maintenance therapy in colon cancer

In the last decade dramatic improvements have been obtained in the treatment of metastatic colorectal cancer. Thanks to the introduction in the clinical practice of new drugs such as Irinotecan and Oxaliplatin, and modern biological drugs such as Bevacizumab and Cetuximab, the response rate, progression-free and overall survival are about 50-60%, 9-11 and 20-24 months respectively. Despite this progress, many questions remain unsolved especially those related to the optimal duration of treatment and the role of maintenance therapy. To treat until progression (or unacceptable toxicity) is the classical way but in the common clinical practice is frequent to perform an induction therapy (until the maximum response is obtained) followed by a complete stop and restart on progression, or by a maintenance without the drug/s responsible of the major cumulative toxicities. The following report focus on the role of different strategies respect to the classic "treatment until progression".     

Adjuvant therapy in colon cancer

Huge advances have been made in the treatment of colon cancer over the last decade. Success has been most noticeable in stage IV disease - where careful selection of patients with small-volume disease for treatment with surgical resection ± perioperative chemotherapy has resulted in an improvement in survival of approximately 5-50%; and stage III - disease where the advent of 5-fluorouracil/oxaliplatin, as adjuvant treatment has also resulted in a significant prolongation in survival. Progression-free survival is now an established surrogate for overall survival, and has resulted in more timely reporting of adjuvant studies and therefore faster integration of promising agents into the clinic. Targeted agents, which have shown promise in the metastatic setting, are currently being examined in the adjuvant setting, although results so far are disappointing. Patients with high-risk stage II cancer remain a challenging group. They have a poorer prognosis than those with stage IIIA disease, and national and international guidance recommend offering chemotherapy after careful discussion of the pros and cons. Despite the fact that we have identified many of the biological features that make stage II disease higher risk, we still struggle to achieve the same improvement in survival for this subgroup compared with others. It may be that these patients required treatment with alternative regimens and predictive biomarkers would be particularly helpful.     

肝癌基因治疗给药途径的研究进展

目前肝癌基因治疗主要的给药方式有经静脉给药、选择性肝动脉给药、经门静脉给药、瘤内给药、脾内注射、逆行性内窥镜胆胰管造影(ERCP)给药等。本文就上述常用的几种给药途径进行了总结。     

Adjuvant therapy of colon cancer

The status of adjuvant therapy for colon cancer recently was clarified through the use of an innovative statistical evaluation of the existing published data. Even without including the NSABP results, meta-analysis formalized the long-held subjective impression that adjuvant treatment does not worsen patient outcome but, rather, consistently tends to improve it. It is important to recall that even small advantages for therapy of a common disease will have a major public health impact. A review of the results of adjuvant therapy in colon cancer thus far leads to suggestions for future directions, several of which already have been put into practice. Clearly, large-scale cooperative trials are necessary, not only to detect the subtle survival benefits of existing adjuvant therapies, but also to allow for meaningful subgroup analysis. Additional techniques for identifying and quantifying prognostic variables will aid in this latter effort. For example, flow cytometric DNA content analysis is currently in progress on patient specimens from several of the recently completed adjuvant trials, including those conducted by ECOG and NSABP. Not only will such analysis clarify the prognostic relevance of tumor ploidy and proliferative activity but, more importantly, it may identify subsets of patients who derive particular benefit from adjuvant treatment. Lastly, the need for more effective therapies is obvious. The current adjuvant trials employ agents or combinations of agents that hold some promise based on their activity in preliminary trials. However, significant progress will have to await the introduction of new agents with greater activity against colon cancer, and improvement in our understanding and use of specific immunotherapy.     

Adjuvant therapy of colon cancer

The primary curative therapy of colorectal cancer is surgical resection. However, within the last 15 years, prospectively randomized appropriately powered clinical trials have convincingly demonstrated that adjunctive postoperative adjuvant chemotherapy is of benefit to all patients with node-positive disease (stage III) and arguably to high-risk node-negative (stage II) cases. In the United States, the clinical trials encompassing greater than 5,000 cases have demonstrated that fluorouracil (5-FU)/leucovorin used in a variety of doses and schedules improves disease-free and overall survival in resected node-positive (stage III) colorectal cancer. The postoperative use of 5-FU/leucovorin for approximately 6 months represents standard of care for such patients. Current clinical trials are evaluating the role of nonfluorinated pyrimidine chemotherapeutic agents in adjuvant chemotherapy for resected large bowel cancer. 5-FU/leucovorin combined with irinotecan (CPT-11) versus 5-FU/leucovorin are being tested in a national intergroup clinical trial. Another trial is evaluating 5-FU/leucovorin plus oxaliplatin versus 5-FU/leucovorin alone. These clinical trials will be important in defining the appropriate standard of care for patients with resected colorectal cancer, since recent studies in advanced colorectal cancer in the United States and in Western Europe have demonstrated that combinations of 5-FU/leucovorin and CPT-11 or 5-FU/ leucovorin and oxaliplatin are superior to 5-FU/leucovorin alone.