Abstract
Heat-induced therapeutic gene expression is highly desired for gene therapy to minimize side effects. Furthermore, if the gene expression is triggered by heat stress, combined therapeutic effects of hyperthermia and gene therapy may be possible. We combined TNF-α gene therapy driven by the stress-inducible promoter, gadd 153, with hyperthermia using magnetite cationic liposomes (MCLs). In nude mice, MCLs induced cell death throughout much of the tumor area on heating under an alternating magnetic field. This heat stress also resulted in a 3-fold increase in TNF-α gene expression driven by the gadd 153 promoter as compared with that of nonheated tumor. TNF-α gene expression was also observed in the peripheral area where the hyperthermic effect was not enough to cause cell death. The combined treatment strongly arrested tumor growth in nude mice over a 30-day period, suggesting potential for cancer treatment. Cancer Gene Therapy (2001) 8, 649–654.
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Acknowledgements
We are grateful to Nikki Holbrook (National Institute on Aging, Baltimore, MD) for providing the JymCAT0 plasmid including the gadd 153 promoter and Hirohumi Hamada (Cancer Chemotherapy Center, Japanese Foundation for Cancer Research) for providing the plasmid SKhTNF-α including the h TNF-α gene.
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This study was partially funded by a Grant-in-Aid for Scientific Research on Priority Areas (Nos. 10145104 and 11227202) and a Grant-in-Aid for JSPS Fellows (No. 12004238) from the Ministry of Education, Science, Sports and Culture of Japan.
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Ito, A., Shinkai, M., Honda, H. et al. Heat-inducible TNF-α gene therapy combined with hyperthermia using magnetic nanoparticles as a novel tumor-targeted therapy. Cancer Gene Ther 8, 649–654 (2001). https://doi.org/10.1038/sj.cgt.7700357
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DOI: https://doi.org/10.1038/sj.cgt.7700357
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