Midkine promoter-driven suicide gene expression and -mediated adenovirus replication produced cytotoxic effects to immortalised and tumour cells

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
L YuM Tagawa

Abstract

We examined possible application of a regulatory region of midkine (MK) gene, which is frequently upregulated in a number of human tumours but not in normal cells, to cancer gene therapy. We examined transcriptional activity of the MK genomic fragments in paired cell lines, immortalized cells and their parental normal fibroblasts, and found that the MK fragments activated a fused reporter or a suicide gene preferentially in the immortalized cells. Recombinant adenoviruses (Ad), in which the MK fragment was inserted upstream to the E1A gene (AdMK), replicated preferentially in the immortalized cells and were cytotoxie to them. Human hepatocellular carcinoma cells were significantly susceptible to AdMK compared with human normal fibroblasts in vitro and the replication of AdMK was less than that of wild-type Ad in the infected fibroblasts. Hepatocellular carcinoma cells infected with AdMK did not form tumours in immunocompromised mice and intratumoural injection of AdMK into the hepatocellular carcinoma developed in mice retarded the subsequent tumour growth. Expression of E1A and necrosis of tumours were detected in AdMK-injected but not control Ad-injected cases. The MK promoter-driven suicide gene therapy and -mediated replica...Continue Reading

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Citations

May 13, 2006·Cancer Immunology, Immunotherapy : CII·Masatoshi TagawaTakenori Ochiai
Jan 1, 1997·Journal of Neuroscience Methods·H J FederoffT Corden
Jun 12, 2001·Biochemical Systematics and Ecology·S D. SarkerM S.J. Simmonds
Dec 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Christopher M HineVera Gorbunova
Aug 23, 2008·Journal of Experimental & Clinical Cancer Research : CR·Eiji ToyodaShinji Uemoto
Jan 1, 2010·Cancers·Hirofumi Jono, Yukio Ando
Mar 20, 2018·Cell Death & Disease·Yu ChenZhiyong Mao
Jan 18, 2006·Reviews in Medical Virology·Adam M SonabendMaciej S Lesniak
Dec 6, 2019·Oncogene·Panagiota S FilippouAnastasia Constantinidou
Sep 19, 2006·World Journal of Gastroenterology : WJG·Tie-Jun LiAi-Long Huang
Feb 25, 2021·IUBMB Life·Arezoo Gowhari ShabgahJamshid Gholizadeh Navashenaq

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