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《Academic Journal of Second Military Medical University》 2004-07
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Combination of adenovirus-mediated endostatin gene and chemotherapy in treatment of Lewis lung cancer in mice

MA Ling-Yun,LI Qiang * ,LIU Zhong-Ling(Department of Respiratory Diseases,Changhai Hospital,Second Military Medical University,Shanghai200433,China)  
Objective:To study the antitumor effect of combination therapy with adenoviral transfer of mouse endostatin gene and cyclophosphamide chemotherapy on mouse Lewis lung cancer.Methods:Mouse endostatin gene was cloned into repli-cation-defective adenovirus by virus recombination technology to construct Ad-mES,adenovirus vector coding mouse endo-statin gene,and then its biological activities were surveyed in vivo.Animal models of mouse Lewis lung carcinoma in C57BL/6mice were established and randomly divided into4groups(n=10):including control,chemotherapy,gene therapy,and chemotherapy+gene therapy group.Mice received cyclophosphamide150mg/kg s.c.3times a day in a21-d cycle for chemotherapy;control group received0.9%normal saline100μl.Ad-mES(6×10 9 pfu/100μl)were administrated by multi-spots intra-tumor injection to every mouse in gene therapy group and combination therapy group.The tumor sizes were mea-sured at different times points.The expression of endostatin after transfer was detected by Western blot and the microvessel density(MVD)of tumor was measured by immunohistochemical examination.Results:Higher titers of recombinant aden-oviruses(Ad-mES)were constructed.Combination therapy with Ad-mES and cyclophosphamide inhibited tumor growth(P0.01)and prolonged mice survival time(P0.05)significantly.Conclusion:The recombinant adenovirus can effectively ex-press biologically active mEndostatin,which can inhibit tumor growth,decrease tumor micro-blood vessels and prolong sur-vival time.The gene therapy combined with the chemotherapy have synergistic effect,laying a foundation for the study of com-bination therapy of the solid tumor.
【Fund】: 上海市科委重点科研基金 ( 0 3 411982 8)
【CateGory Index】: R734.2
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【Co-references】
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【Secondary References】
Chinese Journal Full-text Database 1 Hits
1 LI Yao-Hui1,LIU Dong-Mei2,SHENG Ji-Wen1,YAN Fang1,ZHANG Shi-Zhuang31Department of Medical Chemistry,2Department of Pharmacy,Weifang Medical College,Weifang 261053,China,3Imaging Center,Affiliated Hospital,Weifang Medical College,Weifang 261031,China;Extraction of anti-neoplasm active component from Gekko swinhonis and its inhibitory effects on CT-26 murine colon carcinoma[J];Journal of the Fourth Military Medical University;2009-12
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