Department of Radiation Oncology, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China.
Cancer Gene Ther. 2013 Jun;20(6):358-65. doi: 10.1038/cgt.2013.28. Epub 2013 May 31.
Gene-directed enzyme prodrug therapy (GDEPT), or suicide gene therapy, has shown promise in clinical trials. In this preclinical study using stable cell lines and xenograft tumor models, we show that a triple-suicide-gene GDEPT approach produce enhanced therapeutic efficacy over previous methods. Importantly, all the three genes (thymidine kinase, cytosine deaminase and uracil phosphoribosyltransferase) function simultaneously as effectors for GDEPT and markers for multimodality molecular imaging (MMI), using positron emission tomography, magnetic resonance spectroscopy and optical (fluorescent and bioluminescent) techniques. It was demonstrated that MMI can evaluate the distribution and function/activity of the triple suicide gene. The concomitant expression of these genes significantly enhances prodrug cytotoxicity and radiosensitivity in vitro and in vivo.
基因导向酶前药治疗（GDEPT）或自杀基因治疗在临床试验中显示出前景。在本研究中使用稳定细胞系和异种移植肿瘤模型，我们表明三重自杀基因 GDEPT 方法比以前的方法产生增强的治疗效果。重要的是，所有三种基因（胸苷激酶、胞嘧啶脱氨酶和尿嘧啶磷酸核糖基转移酶）同时作为 GDEPT 的效应物和多模态分子成像（MMI）的标志物，使用正电子发射断层扫描、磁共振波谱和光学（荧光和生物发光）技术。已经证明 MMI 可以评估三重自杀基因的分布和功能/活性。这些基因的同时表达显著增强了体外和体内前药细胞毒性和放射敏感性。
