| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
Esophageal carcinoma remains intractable despite therapeutic multi-modality when it develops into an advanced case or became chemotherapy-resistant. A next-generation sequencing technique revealed that a majority of the patients in East Asia had aberration of p53 gene and the down-stream pathways, which consequently indicated that the p53 pathways was the major therapeutic target. We then investigated a novel therapeutic approach to augment the p53 pathways with gene medicine and a molecular targeted agent. Recombinant replicative adenoviruses (Ad) induced up-regulated p53 expression and produced cytotoxic effects on esophageal carcinoma cells. Transduction of the cells with the wild-type p53 gene increased the cytotoxicity but the replicative Ad numbers decreased. In contrast, molecular targeted agents which stabilize the wild-type p53 in the terms of ubiquitination or functionally convert mutated p53 into the wild-type were not effectively cytotoxic to esophageal carcinoma.
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