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端粒酶特异性溶瘤腺病毒在人类癌症中的诊疗应用

[Theranostic application of telomerase-specific oncolytic adenovirus for human cancer].

作者信息

Fujiwara Toshiyoshi, Tanaka Noriaki

机构信息

Center for Gene and Cell Therapy, Okayama University Hospital.

出版信息

Nihon Rinsho. 2007 Oct;65(10):1913-22.

Abstract

Replication-selective tumor-specific viruses present a novel approach for treatment of neoplastic disease. Telomerase activation is considered to be a critical step in carcinogenesis and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. We constructed an attenuated adenovirus 5 vector (Telomelysin, OBP-301), in which the hTERT promoter element drives expression of E1 genes. We further modified the E3 region of OBP-301 to contain green fluorescent protein (GFP) gene for monitoring viral replication (TelomeScan, OBP-401). When TelomeScan was intratumorally injected into human tumors orthotopically implanted into the rectum in mice, para-aortic lymph node metastasis could be visualized at laparotomy under a three-chip color cooled charged-coupled device camera. This article reviews recent highlights in this rapidly evolving field: cancer therapeutic and cancer diagnostic approaches using the telomerase-specific oncolytic adenoviruses.

摘要

复制选择性肿瘤特异性病毒为肿瘤疾病的治疗提供了一种新方法。端粒酶激活被认为是致癌过程中的关键步骤,其活性与人类端粒酶逆转录酶(hTERT)的表达密切相关。我们构建了一种减毒腺病毒5载体(Telomelysin,OBP - 301),其中hTERT启动子元件驱动E1基因的表达。我们进一步对OBP - 301的E3区域进行修饰,使其包含绿色荧光蛋白(GFP)基因以监测病毒复制(TelomeScan,OBP - 401)。当将TelomeScan瘤内注射到原位植入小鼠直肠的人类肿瘤中时,在开腹手术中使用三芯片彩色冷却电荷耦合器件相机可观察到腹主动脉旁淋巴结转移。本文综述了这一快速发展领域的近期亮点:使用端粒酶特异性溶瘤腺病毒的癌症治疗和癌症诊断方法。

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