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腺病毒介导的p53基因转染至原位和腹膜内小鼠膀胱癌

Adenoviral-p53 gene transfer to orthotopic and peritoneal murine bladder cancer.

作者信息

Werthman P E, Drazan K E, Rosenthal J T, Khalili R, Shaked A

机构信息

Department of Surgery, University of California at Los Angeles 90095, USA.

出版信息

J Urol. 1996 Feb;155(2):753-6.

PMID:8558719
Abstract

PURPOSE

This study was designed to examine the potential for adenoviral-mediated gene therapy in primary and metastatic bladder cancer.

MATERIALS AND METHODS

Orthotopic and intraperitoneal bladder tumors were established after delivery of 1 x 10(6) MBT-2 cells into syngeneic mice. Gene transfer was accomplished via intravesical or intraperitoneal instillation by using an E-1 deleted adenovirus encoding LacZ or human p53. Successful tumor transduction was confirmed in tumor DNA and mRNA by polymerase chain reaction. Detection of recombinant gene product was detected by histochemical staining (X-gal) and Western blot.

RESULTS

Palpable tumors developed 18 days following implantation. LacZ and p53 mRNA were present in tumor and adjacent normal tissue after bladder and intraperitoneal vector administration. Recombinant gene products were identified by histochemistry and Western blot.

CONCLUSION

Bladder tumor-directed gene transfer using adenoviral vectors is an efficient and powerful tool for evaluating the adjuvant role of therapeutic gene products.

摘要

目的

本研究旨在探讨腺病毒介导的基因治疗在原发性和转移性膀胱癌中的潜力。

材料与方法

将1×10⁶个MBT - 2细胞接种于同基因小鼠后,建立原位和腹腔内膀胱肿瘤模型。通过膀胱内或腹腔内滴注使用编码LacZ或人p53的E - 1缺失腺病毒来完成基因转移。通过聚合酶链反应在肿瘤DNA和mRNA中确认肿瘤成功转导。通过组织化学染色(X - gal)和蛋白质印迹法检测重组基因产物。

结果

植入后18天出现可触及的肿瘤。膀胱和腹腔内载体给药后,肿瘤和相邻正常组织中存在LacZ和p53 mRNA。通过组织化学和蛋白质印迹法鉴定重组基因产物。

结论

使用腺病毒载体进行膀胱肿瘤导向的基因转移是评估治疗性基因产物辅助作用的有效且强大的工具。

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