2006 Fiscal Year Final Research Report Summary
Identification of biomarkers to predict anticancer drug sensitivities by means of transgene experiments
| Project/Area Number |
17591136
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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 |
Pediatrics
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| Research Institution | National Kyushu Cancer Center Institute for Clinical Research |
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Principal Investigator |
OKAMURA Jun National Kyushu Cancer Center Institute for Clinical Research, Institute for Clinical Research, Director, 部長 (40360854)
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| Co-Investigator(Kenkyū-buntansha) |
ODA Shinya National Kyushu Cancer Center Institute for Clinical Research, Institute for Clinical Research, Laboratory head, 臨床研究部, 研究室長 (40333372)
TAKIGUCHI Soichi National Kyushu Cancer Center Institute for Clinical Research, Institute for Clinical Research, Staff scientist, 臨床研究部, 研究員 (00280793)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Cancer / Antineoplastic agents / Chemosensitivity / DNA metabolism |
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| Research Abstract |
All of the classical antineplastic agents, with the exception of vinca alkaloids and taxanes, work on DNA metabolism in cells and can therefore be categorised as 'DNA metabolism inhibitor'. Cellular sensitivity against these drugs largely depends on various activities in DNA metabolism. Thymidylate synthase (TS), which regulate the limiting step of thymidylate synthesis, has long received attention as a determinant of cellular sensitivity against the most widely used anticancer agent, 5-fluorouracil (5-FU). However, this possibility has thus far been studied by retrospective, i.e. inductive, approaches, with few exceptions, and has not been concluded yet. In order to approach this problem a priori, a TS-expression plasmid vector has been introduced into a human colorectal cancer cell line, DLD-1. In this system, the expression of the TS transgene is under the control of tetracycline-dependent promoter and inducible by depletion of the antibiotics in the culture media. Ten TS-expressing transformants were isolated and established as a cellline. In one, the dynamic range of TS expression was over ten-fold. Using this transformant cell line, the 5-FU sensitivity at diverse levels of TS expression are now being approached from various angles.
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