LZTS2抑癌基因与肿瘤相关性的研究进展

亮氨酸拉链肿瘤抑制因子2（leucine zipper tumor suppressor 2,LZTS2）是一种新的肿瘤抑制基因,近年受到越来越多的关注。目前许多研究表明,LZTS2与多种肿瘤的发生和细胞异常增殖等多个环节密切相关,是重要的候选肿瘤抑制基因,可为肿瘤的治疗提供新的思路。      

作用于血管生成的抗肿瘤药物进展

肿瘤生长转移具有血管依赖性，肿瘤血管生成抑制药物能破坏或抑制血管生成，有效阻止肿瘤的生长、转移和复发，是近年来肿瘤研究的新热点之一，也是肿瘤防治的一条新途径。本文对肿瘤血管生成抑制药物的种类，临床研究的新进展作一综述。     

白藜芦醇抗肿瘤血管生成机制

白藜芦醇是一种多酚类化合物,能通过多种途径抑制肿瘤的起始、促进和发展3个阶段,具有抑制血管生成的作用。现就白藜芦醇抑制肿瘤新生血管的生成和生长的机制作一综述。     

肺癌抑制基因1与鼻咽癌

新近发现的肺癌抑制基因1是一种肿瘤抑制基因,位于染色体11q23.2,多项研究表明肺癌肿瘤抑制基因1的低表达与肿瘤侵袭转移及患者预后密切相关.研究表明该基因在鼻咽癌中表达下降或消失,是一种鼻咽癌侯选肿瘤抑制基因.该基因的失活与其启动子区甲基化和杂合子缺失有关,但其在鼻咽癌中发挥抑癌作用的分子机制和细胞内外信号传导通路还有待进一步研究.     

肿瘤转移抑制基因BRMS1的研究进展

肿瘤转移抑制基因是指抑制肿瘤细胞转移而不影响原发肿瘤生长的基因。乳腺癌转移抑制基因1（BRMS1）是在2000年新发现的转移抑制基因,现已发现它能抑制多种肿瘤细胞的转移。本文就BRMS1的基因结构、生物学功能及与多种肿瘤的关系、作用机制及其临床意义作一综述。     

凋亡抑制因子Survivin的研究进展

Survivin是近来新发现的一种凋亡抑制因子,主要通过抑制Caspase-3、Caspase-7而阻断细胞凋亡过程,是凋亡抑制蛋白家族成员之一;主要分布于胚胎及分化未成熟的组织,同时高表达于多数肿瘤组织.研究表明,Survivin可能是一种癌基因,参与肿瘤的发生发展,是一个有潜在价值的肿瘤标志,与肿瘤预后密切相关,也可作为肿瘤治疗的新靶点.此外,Survivin在血管发育的中间环节可能具有重要作用.     

肿瘤放射免疫联合治疗新策略有望抑制转移

<正>如何在有效清除原发性肿瘤的同时,抑制肿瘤转移甚至预防肿瘤复发?苏州大学的校科研团队发现了一种基于生物材料的放射免疫联合治疗新策略,将有望成为抑制肿瘤转移与复发的"突破口"。该成果近日发表在《自然-生物医学工程》上。在肿瘤治疗研究领域,清除原发性肿瘤的同时,抑制肿     

三氧化二砷抑制肿瘤血管形成的研究进展

三氧化二砷(As2O3)是一种致癌剂,其适当剂量对肿瘤疗效明显.近年来,越来越多的证据表明三氧化二砷可通过各种机制抑制新生血管形成,使肿瘤细胞生长受到抑制,渐被广泛用于治疗血液系统肿瘤和实体瘤.现就As2O3抑制肿瘤新生血管形成的研究进展作一综述.     

新型酪氨酸激酶抑制剂PTK787/ZK222584的研究进展

PTK787/ZK222584是一种新型血管内皮生长因子受体酪氨酸激酶抑制剂,通过抑制酪氨酸激酶的磷酸化,阻断信号传导,抑制肿瘤新生血管的形成从而抑制肿瘤的生长。临床前研究和临床试验研究显示该药对多种肿瘤有抗肿瘤活性,不良反应较轻。     

白藜芦醇抗肿瘤血管生成机制

白藜芦醇是一种多酚类化合物，能通过多种途径抑制肿瘤的起始、促进和发展3个阶段，具有抑制血管生成的作用。现就白藜芦醇抑制肿瘤新生血管的生成和生长的机制作一综述。     

乳腺癌患者外周血清中APC基因启动子甲基化异常的检测及其意义

背景与目的:检测肿瘤患者外周血中肿瘤相关标志物是当前肿瘤研究的热点之一,恶性肿瘤患者外周血中存在游离的肿瘤相关DNA已引起肿瘤学界的极大关注,人们曾在多种肿瘤患者血清中发现与原发肿瘤相同的DNA变异.本研究以APC(adenomatous polyposis coli)基因启动子甲基化作为肿瘤标志物,探讨乳腺癌患者外周血清中游离的肿瘤相关DNA与肿瘤组织及临床病理参数的相关性.方法:采用甲基化特异性PCR(methylation specific-PCR,MSP)方法,分别检测84例乳腺癌组织、癌旁正常腺体组织及外周血清中游离DNA APC基因启动子甲基化状况.结果:84例乳腺癌组织APC基因启动子甲基化频率为45.2%(38/84),相应外周血清中同样DNA变异阳性检出率为31.0%(26/84).外周血清中DNA甲基化变异与肿瘤组织的甲基化状况显著相关(r=0.977,P=0.002).检测外周血清中APC基因甲基化的敏感性为68.4%,特异性为97.8%.肿瘤组织及外周血清中游离DNA甲基化异常与临床分期、病理类型、肿块大小及受体状况无相关性(P＞0.05).肿瘤组织未检测到甲基化患者的血清中及健康人血清中均未检测到该基因甲基化变异.结论:乳腺癌患者外周血清中肿瘤相关DNA甲基化与肿瘤组织中相同基因的变异显著相关.     

自杀基因治疗恶性肿瘤的研究现状及展望

肿瘤的自杀基因疗法是近年来肿瘤基因治疗的研究热点,是一种具有潜在临床应用前景的新的肿瘤基因治疗策略。本文就近年来自杀基因疗法在肿瘤治疗中取得的研究进展,分别从作用机制、自杀基因系统、旁观者效应、自杀基因的转导以及联合基因治疗等几个方面进行综述。     

Tumor suppressor gene: implication in the clinical medicine

Several genetic events are necessary for a cell to become malignant. Some of these events are activation of proto-oncogenes, and other events are loss of normal function of tumor suppressor gene(s). Two or more different tumor suppressor genes may be inactivated in some tumors, and the same suppressor gene may be involved in different types of tumors. Loss of constitutional heterozygosity (LOH) in the tumor suggests that a certain tumor suppressor gene may reside near the locus of the probe by which the LOH was demonstrated. However, LOH is not necessarily found when a tumor suppressor gene is inactivated. The frequency of LOH found by a probe depends upon the distance between the probe and the tumor suppressor gene. Moreover, inactivation of the suppressor gene by point mutation or very small deletion does not cause any change in electrophoretic mobility of the DNA fragment detected by the probe. Treatment of a cancer by tumor suppressor gene(s) is not possible until a technique by which we can introduce the gene into all the tumor cells is established. At present, clinicians should cooperate with basic scientists in the search for tumor suppressor genes. The comparison of clinical features and the genetic alterations in the tumor will shed light on the malignant behavior of the tumor cells such as rapid growth and/or tendency to metastasis.     

Chromosome abnormalities and tumor suppressor gene in childhood cancer

Retinoblastoma gene has been cloned, and gene product has been characterized precisely. Recently, Wilms' tumor gene has been cloned, and interestingly, its expression was found in genitourinary system, suggesting that anomaly of this system was due to WT gene itself. Molecular analysis performed in colon cancer suggested that several tumor suppressor genes were involved in carcinogenesis and progression of this tumor. These findings revealed that tumor suppressor genes were involved in the development of adult cancer as well as childhood embryonal tumors. Chromosome abnormalities and tumor suppressor gene in childhood cancer are reviewed and referred to future prospects.     

胆管癌p53-bax线粒体凋亡通路的甲基化研究

目的探讨胆管癌p53-bax线粒体凋亡通路中多个基因的甲基化状态及其在胆管癌发生过程中的意义。方法采用甲基化特异性聚合酶链反应（MSP），对胆管癌组织和癌旁组织中的p14^ARF、DAPK和TMS1／ASC基因启动子的甲基化状态进行检测，并对胆管癌组织中p53基因外显子5～8进行DNA序列分析。结果36例胆管癌组织标本中，有24例（66．7％）至少存在1个抑癌基因的甲基化，其中p14^ARF、DAPK和TMS1／ASC基因甲基化的比率分别为25．0％、30．6％和36．1％；癌旁组织中，有5例（13．9％）存在抑癌基因的甲基化，其中TMS1／ASC3例（8．3％），DAPK2例（5．6％）。36例胆管癌组织标本巾，有22例（61．1％）存在p53基因的突变。p53突变伴1个以上抑癌基因甲基化者共14例，占38．9％，其发生率与胆管癌的病理类型、分化程度和浸润深度有关（P〈0．05）。结论p53-bax线粒体凋亡通路中，DNA甲基化是胆管癌中常见的分子事件。癌旁组织中，DAPK和TMS1／ASC基因的甲基化率虽然较低，但可能有早期诊断意义。p53突变伴抑癌基因的甲基化与胆管癌的病理生物学行为有关，并趋向于较高的恶性程度。     

肿瘤基因治疗的研究进展

目的:综述分析国内外肿瘤基因治疗研究现状的文献,为基础与临床研究提供研究方向、思路和资料。方法:应用MEDLINE、CA、CBMdisc、CMCC、CJFD和CSTPCD等数据检索系统及数据库,以"肿瘤基因治疗"等为关键词,检索1998-01～2007-06与肿瘤基因治疗相关的文献。纳入标准:1)肿瘤基因治疗的动物及临床试验研究,包括方法、效果及进展;2)肿瘤基因治疗与其他生物疗法疗效、不良反应及优缺点的比较。根据纳入标准,粗选143篇文献,最后17篇文献纳入综述分析。结果:基因治疗作为肿瘤治疗的新手段是随着DNA重组技术的成熟而发展起来的,是以改变遗传物质为基础的生物医疗技术,它通过将正常基因或有治疗作用的基因导入靶细胞来纠正突变或有缺陷的基因,以达治疗目的。基因沉默疗法、自杀基因疗法、免疫基因疗法、基因替代疗法、反义基因疗法、多药耐药相关基因治疗、抗肿瘤新生血管治疗和抗端粒酶治疗等均取得显著进展。结论:不同的肿瘤基因治疗方法各有利弊,随着治疗方法与病毒载体的不断改造和完善,基因的转移率、靶向性与安全性不断提高。     

肿瘤基因治疗的靶向性策略

肿瘤基因治疗的靶向性问题直接关系到治疗的成败。这种靶向性的策略包括目的基因对肿瘤细胞的靶向转移，目的基因在肿瘤细胞中的特异表达，以及基因修饰细胞分泌的肿瘤靶向治疗分子。对现有病毒或非病毒载体进行改造，由与载体融合的抗体或配体与肿瘤表面抗原或受体的相互作用可以实现目的基因的靶向转移；肿瘤或组织特异性调控元件的应用，以及一些物化、生理因素的诱导则能使治疗基因特异地在肿瘤细胞中表达并发挥作用。     

5—氟胞嘧啶对表达胞嘧啶脱氨酶的人肾母细胞瘤裸鼠异种移植瘤 …

OBJECTIVE: To study the effect of 5-fluorocytosine (5-FC) as prodrug in the treatment of Wilms' tumor xenografts transduced with cytosine deaminase (CD) gene. METHODS: An in vivo model of a poorly differentiated Wilms' tumor transplanted in nude mice was established. Expression adenoviral-vector of CD gene (Ad/CMV-CD) or lac gene (Ad/CMV-lac) was transduced to the tumor xenografts by intratumoral injections. Expression of the transduced genes were confirmed by RT-PCR. Mice with Wilms' tumor xenograft were treated with 5-FC (500 mg.kg-1.d-1 x 10 d). Tumor growth was monitored. RESULTS: The growth of tumor xenografts transduced with lac gene grew as quick as the untransduced ones. In contrast, the growth of the tumor xenografts transduced with CD gene was significantly inhibited as compared to untransduced and lac gene transduced xenografts. The average rate of inhibition was 65% according to the tumor weight at 8 wk. Cell necrosis was observed in the CD gene transduced tumors. CONCLUSION: Intratumoral cytosine deaminase gene transduction followed by systemic 5-fluorocytosine is effective in the treatment of Wilms' tumor.     

Tumor irradiation followed by intratumoral cytokine gene therapy for murine renal adenocarcinoma

To circumvent the toxicity caused by systemic injection of cytokines, cytokine cDNA genes encoding the human interleukin IL-2 cDNA (Ad-IL-2) and murine interferon IFN-gamma gene (Ad- IFN-gamma) were inserted into adenoviral vectors. These constructs were used for intratumoral gene therapy of murine renal adenocarcinoma Renca tumors. Treatment with three doses of Ad-IL-2 or Ad- IFN-gamma, given a day apart, was more effective than single-dose gene therapy. We found that tumor irradiation enhanced the therapeutic efficacy of Ad-IL-2 and Ad-IFN-gamma intratumoral gene therapy. Tumor irradiation, administered 1 day prior to three doses of Ad-IL-2 treatment, was more effective than radiation or Ad-IL-2 alone, resulting in tumor growth arrest in all mice, increased survival and a consistent increase in complete tumor regression response rate. Complete responders rejected Renca tumor challenge and demonstrated specific cytotoxic T-cell activity, indicative of specific tumor immunity. The effect of radiation combined with three doses of Ad-IFN-gamma was less pronounced and did not lead to tumor immunity. Histological observations showed that irradiation of the tumor prior to gene therapy increased tumor destruction and inflammatory infiltrates in the tumor nodules. These findings demonstrate that tumor irradiation improves the efficacy of Ad-IL-2 gene therapy for induction of antitumor immune response.     

腺病毒介导RA538基因转移及其对肿瘤的抑制作用

目的:RA538是从维甲酸诱导终末分化的人食管癌细胞系中分离出的一个与分化相关的基因,本研究探讨了其抗癌作用.方法:利用腺病毒介导基因转移观察对肿瘤细胞的抑制效应.结果:通过重组体腺病毒将RA538基因转导到人肺腺癌细胞系(GLC-82)和人结肠癌细胞系(HCY)中,获得较高的转导效率,显示出较明显的抑制肿瘤生长作用,抑制率分别为77.2%和77.9%,并能降低两细胞系体内肿瘤形成能力.流式细胞计数、DNA片段化分析及TUNEL检测证实RA538可诱导肿瘤细胞发生凋亡.Westem blot分析表明,RA538具有明显下调c-myc基因表达的作用,结论:研究结果提示,RA538是一个较广谱的抑癌基因,可以作为肿瘤基因治疗的一个新目的基因,具有良好的应用前景.