| Project/Area Number |
26461953
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
馬場 祥史 熊本大学, 大学院生命科学研究部(医), 講師 (20599708)
志垣 博信 熊本大学, 医学部附属病院, 非常勤診療医師 (30594874)
渡邊 雅之 公益財団法人がん研究会, 有明病院 消化器外科, 部長 (80254639)
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| Research Collaborator |
MURATA Asuka 熊本大学, 医学部附属病院, 非常勤診療医師 (10625768)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | DNA脱メチル化機構 / 5-hmC発現低下 / TET酵素減少 / LINE-1メチル化レベル / 5－hmC / 脱メチル化 / TET酵素 / 食道癌 / 癌化 / 5-hmC |
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| Outline of Final Research Achievements |
The Ten-eleven translocation (TET) enzymes (TET1, TET2, and TET3) are implicated in DNA demethylation, through dioxygenase activity that converts 5′-cytosine methylation (5-methylcytosine [5-mC]) to 5-hydroxymethylcytosine (5-hmC). We evaluated functions of 5-hmC and TET expression in esophageal squamous cell carcinoma (ESCC). ELISA and immunohistochemical testing showed 5-hmC levels were significantly lower in ESCC than in paired normal tissues (P < 0.0001). TET2 expression was significantly lower in ESCCs than paired normal tissues (P < 0.0001), and significantly associated with 5-hmC levels in ESCCs (P = 0.003, r = 0.33). 5-hmC levels were also significantly associated with LINE-1 methylation level (P = 0.0002, r = 0.39). Patients with low 5-hmC levels had shorter overall survival than those with higher levels, although not significantly so (P = 0.084). In conclusion, TET2 reduction and subsequent 5-hmC loss might affect ESCC development and progression.
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