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báo cáo hóa học:" Gene therapy with tumor-specific promoter mediated suicide gene plus IL-12 gene enhanced tumor inhibition and prolonged host survival in a murine model of Lewis lung carcinoma"

Tuyển tập các báo cáo nghiên cứu về hóa học được đăng trên tạp chí sinh học đề tài : Gene therapy with tumor-specific promoter mediated suicide gene plus IL-12 gene enhanced tumor inhibition and prolonged host survival in a murine model of Lewis lung carcinoma | Xu et al. Journal of Translational Medicine 2011 9 39 http www.translational-medicine.eom content 9 1 39 JOURNAL OF TRANSLATIONAL MEDICINE RESEARCH Open Access Gene therapy with tumor-specific promoter mediated suicide gene plus IL-12 gene enhanced tumor inhibition and prolonged host survival in a murine model of Lewis lung carcinoma x 1.2 2 3 1.2 1.2 1.2 1.2 1.2 Yu Xu Jinxuan Hou Zhengchun Liu Haijun Yu Wenjie Sun Jie Xiong Zhengkai Liao Fuxiang Zhou1 2 Conghua Xie1 2 and Yunfeng Zhou1 2 Abstract Background Gene therapy is a promising therapeutic approach for cancer. Targeted expression of desired therapeutic proteins within the tumor is the best approach to reduce toxicity and improve survival. This study is to establish a more effective and less toxic gene therapy of cancer. Methods Combined gene therapy strategy with recombinant adenovirus expressing horseradish peroxidase HRP mediated by human telomerase reverse transcriptase hTERT promoter AdhTERTHRP and murine interleukin-12 mIL-12 under the control of Cytomegalovirus CMV promoter AdCMVmIL-12 was developed and evaluated against Lewis lung carcinoma LLC both in vivo and in vitro. The mechanism of action and systemic toxicities were also investigated. Results The combination of AdhTERTHRP indole-3-acetic acid IAA treatment and AdCMVmIL-12 resulted in significant tumor growth inhibition and survival improvement compared with AdhTERTHRP IAA alone tumor volume 427.4 48.7 mm3 vs 581.9 46.9 mm3 p 0.005 on day 15 median overall survival OS 51 d vs 33 d or AdCMVmIL-12 alone tumor volume 362.2 33.8 mm3 vs 494.4 70.2 mm3 p 0.046 on day 12 median OS 51 d vs 36 d . The combination treatment stimulated more CD4 and CD8 T lymphocyte infiltration in tumors compared with either AdCMVmIL-12 alone 1.3-fold increase for CD4 T cells and 1.2-fold increase for CD8 T cells P 0.01 or AdhTERTHRP alone 2.1-fold increase for CD4 T cells and 2.2-fold increase for CD8 T cells P 0.01 . The apoptotic cells in combination group were .