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Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model

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World Journal of Gastroenterology 2004年第8期10卷 1191-1197页

作者： SungYiHong MyunHeeLee WooJinHyung SungHoonNoh SeungHoChoi Kyung Sup Kim hyuncheoljung JaeKyungRoh Department of Surgery Yonsei University College of MedicineSeoulKorea Institute of Genetic Science Department of Biochemistry and Molecular BiologyYonsei University College of MedicineSeoulKorea Oncology Internal MedicineCancer Metastasis Research CenterYonsei University College of Medicine

AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating ***, a sustained and high protein delivery is required to achieve the desired therapeutic *** evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell *** test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were *** biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in *** over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically *** animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated *** with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated ***,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.

关键词： Adenoviridae Animals Antineoplastic Agents Antineoplastic Agents, Phytogenic Camptothecin Carcinoma, Hepatocellular Cell Line, Tumor Combined Modality Therapy DNA Topoisomerases inhibitors Drug Synergism Endostatins Endothelium, Vascular Enzyme Inhibitors Etoposide Gene Expression Gene Therapy Humans Liver Neoplasms Mice Research Support, Non-U.S. Gov't Sarcoma Survival Rate Umbilical Veins

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