Gene Therapy for Bladder Tumor using HSV-tk/GCV System

使用 HSV-tk/GCV 系统进行膀胱肿瘤的基因治疗

基本信息

批准号：
07557364
负责人：
AKIMOTO Masao
金额：
$ 2.18万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

Cancer gene therapy is extensively studied in both basic and clinical field. We examined efficacy of adenoviral gene therapy using BBN induced rat bladder tumor. Instillation of adenoviral vector carrying lacZ gene to rat bladder showed preferential gene transfer to tumor. Normal bladder showed only small blue spots after X-gal staining. Diffuse and strong blue staining was observed in bladder tumor. We speculated glycosaminoglycan (GAG) might respond to this preferential gene transfer. To remove GAG on bladder mucosa, we wash bladder with Hcl. Then we instilled adeno viral vector (Ad. CAG.lacZ). After washing bladder with HCl, normal bladder was stained blue strongly like as tumor. Alsian blue staining which could detect GAG revealed rack of GAG on both tumor and HCl washed normal bladder surface. These data indicated that rack of GAG on tumor surface induced preferential gene transfer by instillation of adenoviral vector.We next induced HSV-tk gene to bladder tumor using same method. Sequential treatment with ganciclovir caused marked size reduction of tumor compare to control group. BBN induced rat bladder tumor is very resemble to human superficial bladder tumor. Our experiments showed preferential in vivo gene transfer simple instillation of adenoviral vector. HSV-tk/GCV experiments showed marked anti tumor effect due to growth inhibition or size reduction of tumors. These data were very important to human clinical trial.

癌症基因治疗在基本和临床领域进行了广泛的研究。我们使用BBN诱导的大鼠膀胱肿瘤检查了腺病毒基因治疗的功效。向大鼠膀胱的载腺病毒载体滴注显示出优先的基因转移到肿瘤中。 X-GAL染色后，正常膀胱仅显示出小蓝色斑点。在膀胱肿瘤中观察到弥漫性和强蓝色染色。我们推测糖胺聚糖（GAG）可能会对这种优先基因转移做出反应。要去除膀胱粘膜上的插科打术，我们用HCl洗涤膀胱。然后，我们向Adeno病毒载体（ad Cag.lacz）灌输。用HCL洗涤膀胱后，正常膀胱被强烈染色，就像肿瘤一样。可以检测到插科打ga的阿尔西亚蓝色染色显示肿瘤上的堵塞架和HCL洗涤了正常的膀胱表面。这些数据表明，肿瘤表面的堵塞架通过滴注腺病毒载体引起的优先基因转移。接下来，我们使用相同的方法将HSV-TK基因诱导至膀胱肿瘤。 ganciclovir的顺序处理导致肿瘤与对照组的显着减小。 BBN诱导的大鼠膀胱肿瘤非常类似于人类浅膀胱肿瘤。我们的实验表明，体内基因转移的优先滴入腺病毒载体。 HSV-TK/GCV实验显示，由于肿瘤的生长抑制作用或尺寸减少，抗肿瘤作用明显。这些数据对人类临床试验非常重要。