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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/21735


    標題: Tumor-targeting prodrug-activating bacteria for cancer therapy
    作者: C-M Cheng
    Y-L Lu
    K-H Chuang
    W-C Hung
    J Shiea
    Y-C Su
    C-H Kao
    B-M Chen
    S Roffler
    T-L Cheng
    貢獻者: 藥學系         
    關鍵字: non-invasive imaging
    b-glucuronidase
    glucuronide prodrug
    optical imaging
    luminescence
    prodrug-activating bacteria
    日期: 2008-03
    上傳時間: 2009-10-13 10:52:55 (UTC+8)
    摘要: Increasing the specificity of chemotherapy may improve the efficacy of cancer treatment. Toward this aim, we developed a strain of bacteria to express enzymes for selective prodrug activation and non-invasive imaging in tumors. -glucuronidase and the luxCDABE gene cluster were expressed in the DH5 strain of Escherichia coli to generate DH5-lux/G. These bacteria emitted light for imaging and hydrolyzed the glucuronide prodrug 9ACG to the topoisomerase I inhibitor 9-aminocamptothecin (9AC). By optical imaging, colony-forming units (CFUs) and staining for G activity, we found that DH5-lux/G preferentially localized and replicated within CL1-5 human lung tumors in mice. The intensity of luminescence, CFU and G activity increased with time, indicating bacterial replication occurred in tumors. In comparison with DH5-lux/G, 9AC or 9ACG treatment, combined systemic administration of DH5-lux/G followed by 9ACG prodrug treatment significantly (P<0.005) delayed the growth of CL1-5 tumors. Our results demonstrate that prodrug-activating bacteria may be useful for selective cancer chemotherapy.
    關聯: Cancer Gene Therapy 15:p.393-401
    Appears in Collections:[藥學系(所)] 期刊論文

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