| Project/Area Number |
22501048
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Clinical oncology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
AKIYAMA Shin-ichi 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 客員教授 (60117413)
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| Co-Investigator(Kenkyū-buntansha) |
SONE Saburo 徳島大学, 大学院・ヘスルバイオサイエンス研究部, 客員教授 (40145024)
NISHIOKA Yasuhiko 徳島大学, 大学院・ヘスルバイオサイエンス研究部, 教授 (70274199)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 分子標的治療 / thymidine phosphorylase / 解糖経路 / ペントースリン酸経路 / IL-8 / TP / NADPH / NFkB / NADPH oxidase / ROS / pentose phosphate pathway / チミジンホスホリラーゼ / 解糖系 |
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| Research Abstract |
Thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor (PD-ECGF). Although many reports indicate that TP has angiogenic activity and plays pivotal role in tumor progression, the mechanism of the TP functions is not fully understood. We therefore investigatedthe molecular basis for the TP functions. TP augmented the production of ROS by increasing the intracellular level of NADPH, a substrate for NADPH oxidase. The ROS induced by TP activated NF・B, which subsequently enhanced the promoter activity and expression of IL-8. Furthermore, we demonstrated for the first time that thymidine-derived metabolites entered the glycolytic pathway and the pentose phosphate pathway. Production of ATP and NADPH was consequently augmented in TP-expressing cells. These findings suggest that catabolism of thymidine plays an important role in the survival and growthof cancer cells in a microenvironment where nutrients are insufficient.
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