Molecular basis for thefunctions of thymidine phosphorylase and preclinical study of an inhibitor of thymidine phosphorylase , TPI
| 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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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Macrophage stimulating protein promotes liver metastases of small cell lung cancer cells by affecting the organ microenvironme2013
Author(s)
Sato S, Hanibuchi M, Kuramoto T, Yamamori N, Goto H, Ogawa H, Mitsuhashi A, Van TT, Kakiuchi S, Akiyama SI, Nishioka Y, Sone S
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Journal Title
Clin Exp Metastasis
Volume: 30
Issue: 3
Pages: 333-344
DOI
Related Report
Peer Reviewed
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[Journal Article] Dll4-Fc, an inhibitor of Dll4-Notch signaling, suppresses liver metastasis of small cell lung cancer cells through the downregulation of the NF-kappa-B activity.2012
Author(s)
Kuramoto T, Goto H, Mitsuhashi A, Tabata S, Ogawa H, Uehara H, Sijo A, Kakiuchi S, Maekawa, Yasutomo K, Hanibuchi M, Akiyama SI, Sone S, Nishioka Y
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Journal Title
Mol Cancer Ther
Volume: 11
Issue: 12
Pages: 2578-2587
DOI
Related Report
Peer Reviewed
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[Journal Article] Akiyama S, Thymidine phosphorylase enhances reactive oxygen species generation and interleukin-8 expression in human cancer cells2012
Author(s)
Tabata S, Ikeda R, Yamamoto M, Furukawa T, Kuramoto T, Takeda Y, Yamada K, Haraguchi M, Nishioka Y, Sone S
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Journal Title
Oncol Rep
Volume: 28
Pages: 895-902
DOI
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Peer Reviewed
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[Journal Article] a multiple tyrosine kinase inhibitor, inhibits progression of human malignant pleural mesothelioma in an orthotopic model2012
Author(s)
Van TT, Hanibuchi M, Goto H, Kuramoto T, Yukishige S, Kakiuchi S, Sato S, Sakaguchi S, Dat LT, Nishioka Y, Akiyama SI, Sone S, SU666
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Journal Title
Respirology
Volume: 17
Issue: 6
Pages: 984-990
DOI
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Peer Reviewed
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[Journal Article] A Novel targeting therapy of malignant mesothelioma using anti- podoplanin antibody
Author(s)
Abe S, Morita Y, Kaneko MK, Hanibuchi M, Tsujimoto Y, Goto H, Kakiuchi S, Aono Y, Huang J, Sato S, Kishuku M, Taniguchi Y, Azuma M, Kawazoe K, Sekido Y, Yano S, Akiyama S, Sone S, Minakuchi K, Kato Y, Nishioka Y
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