柯萨奇病毒腺病毒受体的表达对基因工程腺病毒抗瘤活性的影响  

Effect of Expression of Coxsackie and Adenovirus Receptor on Antitumor Activity of Genetically Modified Adenovirus

作　　者：袁中玉[1] 管忠震[1] 张力[1] 徐瑞华[1] 

机构地区：[1]中山大学肿瘤防治中心内科,广东广州510060

出　　处：《癌症》2005年第4期502-505,共4页Chinese Journal of Cancer

基　　金：国家"863"高科技项目(No.2002AA2Z3304)~~

摘　　要：背景与目的:腺病毒是研究最多的一种溶瘤病毒,也是基因治疗最常用的一种载体,但作为溶瘤病毒或载体,其治疗恶性肿瘤的疗效很大程度上受到组织器官表达柯萨奇病毒腺病毒受体(Coxsackieandadenovirusreceptor,CAR)的影响。本研究旨在观察CAR表达对腺病毒感染力及临床疗效的影响。方法:收集29例基因工程腺病毒(H101)临床试验患者的病理标本,用免疫组织化学法检测CAR表达,分析CAR表达与临床疗效的关系。体外通过流式细胞仪检测不同肿瘤细胞表面CAR表达,用MTT法测定病毒对不同细胞的抑制率,以观察CAR表达与H101感染力的关系。结果:29例恶性肿瘤患者中,10例有效病例CAR阳性表达者7例(70.0%),19例无效病例CAR阳性表达仅6例(31.6%),CAR表达与临床疗效呈显著性相关(P=0.048)。体外实验结果显示,不同肿瘤细胞株CAR的表达存在差异,其表达量与H101对细胞的感染力(病毒对肿瘤细胞抑制率)呈正相关(r=0.986)。结论:CAR的表达与腺病毒的感染力及临床疗效密切相关,CAR高表达的肿瘤对腺病毒治疗的疗效较低表达者明显为好。BACKGROUND & OBJECTIVE: The effect of adenovirus, a kind of oncolyti c virus and a kind of carrier in gene therapy, depends on the expression of Coxs ackie and adenovirus receptor (CAR) on cell surface to a large degree. This stud y was to evaluate relationship of CAR expression to infectivity and efficacy of adenovirus. METHODS:Pathologic specimens from 29 patients in a clinical trial of genetically modified adenovirus (H101) were collected. Expression of CAR in can cer tissues was detected by immuohistochemistry. Expression of CAR on cancer cel l membrane was detected by flow cytometry (FCM). Inhibitory effect of H101 on ce lls was assessed by MTT assay. RESULTS: Positive rate of CAR was significantly h igher in patients achieved complete remission (CR) or partial remission (PR) tha n in patients had stable disease (SD) or progressive disease (PD) <70.0% (7/10) vs. 31.6% (6/19), P=0.048>. CAR expression on different cells was different, and the amount of CAR was positively related to virus infectivity, presented as the inhibitory rate of H101-infected cells (r=0.986). CONCLUSIONS: The expression o f CAR closely relates to antitumor activity and efficacy of adenovirus. Also, th e efficacy of adenovirus is higher on cancers with increased CAR expression than on those with decreased CAR expression.

关 键 词：CAR受体 腺病毒 疗效 感染力 肿瘤 

分 类 号：R73-3[医药卫生—肿瘤]