國立臺灣大學醫學院外科陳晉興2006-07-262018-07-112006-07-262018-07-112005-07-31http://ntur.lib.ntu.edu.tw//handle/246246/24549Non-small-cell lung cancer (NSCLC) is one of the leading causes of cancer death in Taiwan and numerous developed countries. No obvious improvement in survival can be achieved in recent years although various efforts have been made. As the pathogenesis and biology of tumors are becoming clear, gene therapy could be an attractive modality for the treatment of lung cancer. Most gene therapy approaches currently use nonspecific, nonselective prokaryotic promoters such as the CMV promoter that can be expressed at high levels in normal cells, potentially contributing to toxicity. An alternative approach would be to use a tissue- or tumor-specific promoter to limit the spectrum of cells that express the gene therapy construct. In the previous studies, we have shown in vitro and in vivo that the activation of the survivin promoter is lung cancer specific. In this study, we choose another promoter, the GRP-78 (glucose-regulated protein 78) promoter to evaluate its future application in lung cancer gene therapy. Our preliminary data showed that the GRP-78 promoter was cancer-specific in cell line studies. To enhance its activity, the CMV and GRP enhancers were added at the upstream of the GRP-78 promoter. It appeared that both the CMV enhancer and GRP enhancer could increase the activity of the GRP promoter, respectively, while the cancer-specificity remained unchanged. By using this modified GRP-78 promoter, we showed that the activity and cancer specificity of this promoter is better than the CMV promoter in both cell lines and xenograft animal studies. The promising results of this study indicate the potential use of the modified GRP-78 promoter in cancer gene therapy.application/pdf173293 bytesapplication/pdfzh-TW國立臺灣大學醫學院外科lung cancergene therapysurvivinGRPBIK[SDGs]SDG3reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/24549/1/932314B002237.pdf