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P53 is a tumor suppressor gene with a pivotal role in regulating apoptosis. Introduction of the p53 gene into tumor cells has been shown to induce apoptosis. In most of the previous reports, p53 was transduced by adenovirus vectors. However, it is unclear whether the induction of apoptosis by adenovirus-mediated p53 gene therapy is due to p53 protein or adenovirus transduction. It is also unknown whether the same adenovirus vectors can be used for gene therapy of different human cancers in which different p53 mutations are present. Here we investigated whether adenovirus-mediated p53 gene therapy induces apoptosis in a number of cell types with different p53 gene mutations, and whether adenovirus-mediated p53 gene therapy can be used for the treatment of human cancer in vivo. Our results showed that p53-mediated apoptosis by adenovirus-mediated p53 gene therapy occurred in vitro in cell lines with different mutations of p53 but was dependent on the overexpression of p53. The apoptotic pathway was identified to be via the mitochondrial pathway and induced by the depletion of mitochondrial membrane potential. Our results showed that adenovirus-mediated p53 gene therapy can induce apoptosis in multiple human cancers irrespective of the p53 status of the tumor. Taken together, these data indicate that adenovirus-mediated p53 gene therapy may be an attractive therapeutic approach to many human cancers.Archive for March, 2011

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Lecture on “Sanatan Darshan and Yoga” at VUW University on June 18th, 2011

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