Tslcl基因与肿瘤

Tslcl在多种恶性肿瘤中都有不同程度的表达缺失或低表达,提示其与肿瘤的发生相关。进一步研究发现Tslcl的失活与肿瘤细胞的浸润及转移有关,同时证明Tslcl可以作为独立因素参与肿瘤的早期诊断及预后评价,并可能成为新的治疗靶点。     

肿瘤干细胞和肿瘤关系的研究进展

肿瘤干细胞在维持肿瘤细胞的分化、增殖及凋亡中发挥着重要作用.大量研究表明,肿瘤的发生、转移和复发与肿瘤干细胞的异常表达密切相关,这也许会成为肿瘤治疗的新靶点.因此研究肿瘤干细胞的起源及其与肿瘤的发生关系,成为当前研究和治疗肿瘤领域的新热点.本文就肿瘤干细胞与肿瘤发生的关系作简要的综述.     

胰腺癌组织Six1表达及其临床意义的研究

目的:研究Six1在胰腺癌组织及胰腺炎、良性腺瘤和癌旁组织中的表达情况,探讨Six1与胰腺癌的关系及其临床生物学意义.方法:采用蛋白质印迹法及免疫组织化学技术,检测Six1在4株胰腺癌细胞系及3T3细胞系的表达和其在胰腺癌、良性腺瘤、胰腺炎及癌旁组织中的表达.结果:蛋白质印迹法结果显示,Six1在Bxpc-3和CFPAC-1细胞株中的表达明显增强;并且在胰腺癌组织和良性腺瘤组织的表达也显著高于癌旁组织.免疫组化结果显示,34例(85.0%)胰腺癌组织、3例(75.0%)良性腺瘤组织、6例(60.0%)胰腺炎和癌旁组织中Six1表达阳性;其阳性表达与肿瘤大小和远处转移显著相关(P＜0.05).结论:Six1表达是胰腺癌发生的早期事件,可能导致肿瘤向恶性发展;其表达水平与肿瘤大小及远处转移有关.     

P-糖蛋白与CD44在肿瘤中表达的相关性

P-糖蛋白(P-gp)是最重要的肿瘤多药耐药蛋白之一;CD44分子异常表达与肿瘤的侵袭和转移密切相关.近年来的研究发现,P-gp和CD44分子在肿瘤中的表达具有某种相关性,即肿瘤多药耐药与侵袭转移之间可能存在着某种关联.探讨两者可能存在的相关性及深入了解两者之间的内在联系,对肿瘤治疗具有重要的指导意义.     

紧密连接蛋白Claudins与胃肠道肿瘤

Claudins是一种表达于上皮细胞和内皮细胞的紧密连接蛋白,研究发现其异常表达与胃肠道肿瘤的发生及转移有关.Claudim对胃肠道肿瘤的诊断、治疗及预后评估有着广阔的应用前景.     

ABH(O)血型抗原与恶性肿瘤相关性研究

目的　找出恶性肿瘤ABH(O)血型抗原 (Bloodgroupantigens,以下简称BGA)的丢失与恶性肿瘤的发病特点及相互关系。方法　采用免疫组化方法检测 70例恶性肿瘤患者BGA表达情况 ,分析BGA的表达与肿瘤淋巴结转移、血行转移的关系 ,从而找出相互规律 .结果　 70例恶性肿瘤标本中 ,肿瘤BGA表达阳性者 39例 (5 5 .7% ) ;肿瘤BGA表达阴性者 31例 (44 .3% ) ,BGA表达与肿瘤分化程度及有无淋巴结或血行转移之间有显著差异 (P〈0 .0 1或 0 .0 0 5 )。结论　肿瘤ABH(O)抗原的异常表达与肿瘤的转移、复发和预后有密切的关系。     

肿瘤标志物M2-PK的生物学特性和临床应用

在实体肿瘤诊治过程中,肿瘤标志物的监测对于肿瘤的诊断、分型和监测治疗效果及判断预后有极其重要的临床价值.近年来肿瘤标志物M2-PK与肿瘤的关系成为研究的热点,其血清表达水平与乳腺癌、肺癌、胃肠道肿瘤、肾细胞癌和胰腺癌的病理生理学发展过程密切相关,现对这一领域的研究进展作一综述.     

子宫内膜癌中PTEN蛋白、P-AKT蛋白的表达及意义

目的:检测子宫内膜癌组织中PTEN蛋白及P-AKT蛋白表达并探讨其意义.方法:采用免疫组织化学法检测66例子宫内膜癌、28例正常子宫内膜组织中PTEN蛋白及P-AKT的表达.结果:子宫内膜癌组织中PTEN蛋白为缺失表达,高于正常子宫内膜组织(P＜0.05),而且PTEN表达在G1级肿瘤高于G2、G3级(P＜0.05),PTEN蛋白缺失率与肿瘤组织类型有关(P＜0.05),与肌层浸润、淋巴结转移及病理分期无明显关系(P＞0.05).子宫内膜癌组织中P-AKT蛋白表达为高表达,P-AKT的表达与肿瘤组织学分级、病理学分期、有无淋巴结转移以及肿瘤浸润子宫肌层深度显著相关(P＜0.05),其表达与组织学类型无关(P＞0.05).P-AKT与PTEN的表达呈明显负相关.结论:PTEN表达缺失与临床病理参数无关,蛋白表达缺失常发生细胞分化较差的子宫内膜癌.PTEN蛋白表达缺失与P-AKT表达水平有关.     

GST-π在大肠癌中的表达和临床意义

目的探讨GST-π蛋白与大肠癌病理学特征之间,耐药之间的关系.方法分别用兔抗人GST-π抗体对60例大肠癌石蜡标本进行免疫组化研究.结果1.GST-π蛋白的表达和性别,肿瘤大小、部位及类型无关(P＞0.05);但与肿瘤的分化程度、Dukes分期,TNM分期,临床分期、淋巴结转移有统计学差异(P＜0.001).2.GST-π在癌灶及癌旁组织中的表达意义不同,在肿瘤组织中低分化组高表达而在癌旁组织中则低表达,二者有统计学差异(P＜0.001).结论1.GST-π在瘤组织中的表达,强度及在癌旁组织中的表达和肠癌生物学特性密切相关,与肿瘤的分化及临床分期、淋巴结转移有关,可做为衡量恶性程度,耐药性及预后的指标之一.     

Wnt信号通路关键蛋白与上皮性卵巢癌间的关系

目的:探讨正常卵巢组织,良性、交界性及恶性卵巢肿瘤组织中Wnt信号通路关键蛋白β-catenin及APC的表达及与临床病理特征间的相关性.方法:采用免疫组织化学SP法检测8例正常卵巢组织,15例卵巢良性上皮性肿瘤,14例卵巢交界性上皮肿瘤及69例上皮性卵巢癌中β-catenin和APC蛋白的表达情况.结果:β-catenin在细胞膜上的表达降低及在胞浆中的表达升高,与肿瘤的恶性程度、临床分期、病理学类型及分化相关,并在转移灶中细胞膜上的表达高于原发灶;APC蛋白的表达与肿瘤的恶性程度、临床分期相关.二者均与淋巴结、大网膜的转移、腹水的有无、腹水细胞学的阳性与否及预后无关,β-catenin与APC之间无统计学上的相关性.结论:β-catenin与APC在卵巢上皮性肿瘤的发生、发展过程中起重要作用.     

Microbubble-enhanced ultrasound-mediated gene transfer--towards the development of targeted gene therapy for cancer

Ultrasound-mediated gene transfer is emerging as a possible alternative to viral gene transfer, and pre-clinical data suggest that it may play a significant role in gene therapy-based approaches to the treatment of disease. As an extracorporeal stimulus, ultrasound can non-invasively and transiently compromise cell membrane permeability (sonoporation), thereby offering the promise of delivering either genes or oligonucleotide-based therapeutics to cells and tissues in a site-specific manner. The membrane-permeabilising effects of ultrasound can be greatly enhanced using microbubble preparations, many of which have, in the past, found application as ultrasound contrast agents. Because these ultrasound-responsive agents are highly amenable to surface modification it has been suggested that they may be exploited as ultrasound-responsive nucleic acid delivery vehicles. In this article we seek to explore the potential role ultrasound, in combination with microbubble-based agents, may play in providing site-specific gene therapy-based approaches for the treatment of cancer.     

Microbubble-enhanced ultrasound-mediated gene transfer – Towards the development of targeted gene therapy for cancer

Ultrasound-mediated gene transfer is emerging as a possible alternative to viral gene transfer, and pre-clinical data suggest that it may play a significant role in gene therapy-based approaches to the treatment of disease. As an extracorporeal stimulus, ultrasound can non-invasively and transiently compromise cell membrane permeability (sonoporation), thereby offering the promise of delivering either genes or oligonucleotide-based therapeutics to cells and tissues in a site-specific manner. The membrane-permeabilising effects of ultrasound can be greatly enhanced using microbubble preparations, many of which have, in the past, found application as ultrasound contrast agents. Because these ultrasound-responsive agents are highly amenable to surface modification it has been suggested that they may be exploited as ultrasound-responsive nucleic acid delivery vehicles. In this article we seek to explore the potential role ultrasound, in combination with microbubble-based agents, may play in providing site-specific gene therapy-based approaches for the treatment of cancer.     

Molecular classification of head and neck squamous cell carcinoma using cDNA microarrays

Squamous cell carcinomas of the head and neck constitute an anatomically heterogeneous group of neoplasms that share in common a causal association with tobacco and alcohol exposure. The clinical course of these neoplasms is difficult to predict based on established prognostic clinicopathological criteria. Given the genetic complexity of head and neck cancers, it is not surprising that correlations with individual genetic abnormalities have also been disappointing. Several authors have suggested that global gene expression patterns can be used to subgroup patients with cancer. Here we report the use of cDNA microarrays containing 9216 clones to measure global patterns of gene expression in these neoplasms. We have used a statistical algorithm to identify 375 genes, which divide patients with head and neck tumors into two clinically distinct subgroups based on gene expression patterns. Our results demonstrate that gene expression profiling can be used as a predictor of outcome.     

Brain tumors

Brain tumors generally arise as the culmination of a multistep process that involves a variety of genetic abnormalities. Theoretically, replacement of abnormal genes with normal genes is essential to brain tumor treatment. However, it is very difficult to replace all damaged genes. Currently, most clinical protocols for gene therapy in brain tumors include transfer of a gene which can induce tumor cells to die or which can enhance the environment to generate a systemic immune response against the tumor. The former strategy includes suicide gene therapies, tumor suppressor gene therapy and oncolytic virus therapy. The latter adopts immunogene therapy. In this report, we also focus on other gene therapies, such as therapies to control the cell cycle or apoptosis, and promote antiangiogenesis. Gene therapy is generally accepted to be rather safe in recent years. In fact, the current single-gene therapies for brain tumor are limited and probably restricted to a few tumors. Several agents with different mechanisms of action would be necessary to kill heterogenously mixed tumor cells. Further molecular techniques and basic studies may overcome the malignancy of cancers.     

Bystander effect in herpes simplex virus-thymidine kinase/ganciclovir cancer gene therapy: role of gap-junctional intercellular communication

Antitumor suicide gene therapy is one of the emerging strategies against cancer. It consists of the introduction into cancer cells of a gene capable of converting a nontoxic prodrug into a cytotoxic drug. Because this therapeutic gene cannot be easily introduced into the whole cell population of a tumor, the successful eradication of tumors depends on a phenomenon called the "bystander effect," by which the introduced gene can affect even cells in which it is not itself present. From a therapeutic point of view, it may be crucial to enhance this phenomenon through various means to achieve tumor eradication. One such suicide gene, the thymidine kinase gene from the herpes simplex virus, in combination with the prodrug ganciclovir, has been extensively and successfully used in some animal models exhibiting a strong bystander effect. Among the mechanisms involved in this phenomenon, gap junctional intercellular communication (GJIC) is directly involved in the transfer of the toxic metabolites of ganciclovir, which pass directly from herpes simplex virus thymidine kinase-expressing cells to surrounding cells that do not express it. Because GJIC appears to be a mediator of the bystander effect both in vitro and in vivo, here we review possible molecular strategies for enhancing the extent of tumor cell death by increasing the intratumoral GJIC capacity.     

上皮-间质转化及其干性作用与肿瘤

上皮-间质转化（EMT）参与肿瘤转移过程,Twist作为关键调控因子在EMT中发挥重要作用,放疗、化疗和多种细胞因子均可诱导Twist介导的EMT。研究表明,肿瘤细胞可能通过EMT转变为肿瘤干细胞样细胞,并进一步导致放化疗抵抗、肿瘤血管形成及远处转移,对肿瘤的预后产生巨大影响,EMT有望成为肿瘤治疗的重要靶点。     

丝裂原活化蛋白激酶激酶4与肿瘤转移

丝裂原活化蛋白激酶激酶4(MKK4)是丝裂原活化蛋白激酶(MAPK)信号转导通路组成的成员之一.研究发现,MKK4与肿瘤的发生和转移密切相关,作用机制复杂,能抑制肿瘤发生,近5%不同组织来源的肿瘤均有MKK4基因的功能突变缺失.MKK4基因也是一个转移抑制基因,能抑制多种肿瘤的转移.     

The rel gene and its role in oncogenesis

The rel oncogene induces rapidly fatal lymphomas in birds. The mechanism by which this occurs is not clear, but investigations into the properties of rel have shown it to be an unusual protein. Unlike other 'nuclear' oncogenes described in this issue, v-rel can be found in both the cytoplasm and nucleus. In addition, it appears to transform avian lymphoid cells regardless of its localization. Interestingly, the rel gene is highly homologous to the Drosophila gene dorsal, which is involved in determination of dorsal-ventral polarity in the developing embryo. In this review, the biology of the virus containing the rel oncogene, REV-T, will be described. The structure of the gene and the properties of the rel protein will be examined. The rel protein will be compared to the Drosophila homolog, dorsal, both structurally and functionally.