RV-HSV-TKc/GCV治疗脑胶质瘤效果及其影响因素  

Experimental therapeutic outcome and effective factors on RV-HSV-TKc/GCV gene therapy of malignant gliomas

作　　者：王伟民[1] 朱诚[2] 胡加飞[2] 张晓鹏[2] 蔡如珏[2] 袁国良[2] 卢亦成[2] 

机构地区：[1]广州军区广州总医院神经外科,广州510010 [2]第二军医大学长征医院神经外科,上海20003

出　　处：《中国微侵袭神经外科杂志》2001年第4期201-204,共4页Chinese Journal of Minimally Invasive Neurosurgery

基　　金：国家自然科学基金资助项目(No.39370688)

摘　　要：目的研究应用逆转录病毒介导中国单纯疱疹病毒TK基因治疗系统(RV-HSV-TKc/GCV)治疗脑胶质瘤的可行性及其影响因素。方法通过体外和大鼠实验,观察转TKc细胞在治疗中的量效关系;转基因方式对疗效的影响;基因治疗细胞在瘤内的分布;治疗动物的肿瘤免疫反应。结果①TKc胶质瘤细胞对GCV的敏感浓度>0.01μg/ml,PLCTKcSN细胞与胶质瘤细胞混合培养120h较混育24h的GCV敏感性高,在GVC有效杀伤范围内,基因治疗细胞与瘤细胞数量比值>1.0;②3种方式的体内治疗结果表明TKc/GCV具有一定抑制肿瘤生长作用;③接种后第5、10、15天的针道周围可见有大量TK表达阳性细胞,距针道5mm处TK阳性细胞则难以见到,与肿瘤交界的正常脑组织无TK阳性细胞;④治疗后长期生存大鼠5只再次接种瘤细胞28d后剖检,2只未见肿瘤生长,3只有肿瘤生长但明显小于对照组;实验组NK活性和ADCC效应高于对照组。结论在治疗细胞数量足够的前提下TKc/GCV基因治疗系统对大鼠脑胶质瘤有控制生长作用;该系统具有一定调节体内主动免疫效能。治疗细胞的基因转导能力,在瘤内的分布局限性,GCV局部浓度和机体的免疫状态是影响该基因治疗效果的主要因素。Objective To study and evaluate the therapeutic effect and influence factors of chemo -gene therapy with retroviral-mediated thymidine kinase gene of chinese herpes simplex virus and ganciclovir (RT-HSV-TKc /GCV)for potential clinical treatment of malignant gliomas.Method In vitro and vivo experiments,the therapeutic amount of TKc cells to glioma cells,the therapeutic efficacy relating to the ways of transfer TKc gene bearing the local distribution of virus produce cells in rat cerebral,and antitumor immunities in glioma bear-ing rats following treated with RT-HSV-TKc /GCV were observed respectively.Re sult①Agent TKc -glioma cell was sensitive to GCV when its concentration was over0.1μg/ml,and the sensitiviy was higher when the gliom a cells were co-cultured with PLCTKcSN cells for120hours than that for24hours;②TKc /GCV resulted in some inhibitiing effect to tumor growth in rat through three kinds of therapeatic way in vivo;③TKc + cells were found aroud channel tissues but not5mm outside of the center after5,10and15days following the cells im-plantation into cerebral tissue.No TK cell was seen between tumor and nomal tissue;④In5rats,which were cured by TKc /GCV result-ing in long survival,replanted with C6cells,2rats had not tumor regrowth and3had much small regrowth than the control group,after28days of glioma cells implanted into the opposite side of the brain.Both NK and ADCC activity in experimental group were higher than that in control.Con clusion TKc /GCV system have some cure effect on glioma under enough amount of treatment cells to brain tumor,and that may upregulate antitumor immunity.Gene therapy cells ability and it's distribution in the tumor,GCV dosage in tumor and immunal status of tumor host perhaps are factors that influence effectiveness gene therapy for gliomas.

关 键 词：脑胶质瘤 逆转录病毒 胸苷酸激酶 基因治疗 

分 类 号：R739.41[医药卫生—肿瘤]