| Project/Area Number |
19390253
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Nagasaki University |
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Principal Investigator |
YAMASHITA Shunichi Nagasaki University, 大学院・医歯薬学総合研究科, 教授 (30200679)
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| Co-Investigator(Kenkyū-buntansha) |
OHTSURU Akira 長崎大学, 大学病院, 准教授 (00233198)
MITSUTAKE Norisato 長崎大学, 大学院・医歯薬学総合研究科, 助教 (50404215)
SAENKO Vladimir 長崎大学, 大学院・医歯薬学総合研究科, 助教 (30343346)
難波 裕幸 長崎大学, 大学院・医歯薬学総合研究科, 准教授 (80237635)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2009: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2008: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2007: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | 内分泌学 / 甲状腺がん / 遺伝子多型解析 / 細胞機能解析 / 放射線影響 / 分子標的治療 / 病態生理 / 放射線治療 / 遺伝子多型 / 細胞内情報伝達系 / DNA損傷修復 / 4.PMLボディー等の核内構造の形成機構の解析 / がん基礎研究 |
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| Research Abstract |
In order to clarify the involvement of abnormalities of intracellular signaling pathway and genomic instability of thyroid carcinogenesis, we performed molecular analysis of related genes on thyroid cancers using operated thyroid tissues and cell culture systems. There were no specific abnormal genetic alterations on ARAF, RAPA1 and GNAQ on operated thyroid cancer tissues and cancer cell lines besides BRAF and RET?PTCs. The cell transformation assay suggested the involvement of ARAF abnormality in vitro, however, no ARAF mutation was proved in vivo. The data obtained suggested the relationship between DNA damage response and cell cycle regulation on thyroid cell transformation by irradiation. The molecular epidemiological study using Chernobyl samples suggested the involvement of FOXOE1 (TTF2) SNPs on genetic susceptibility on radiation-induced thyroid carcinogenesis although further confirmation is needed. Moreover, there were some disease-related SNPs of DNA damage response genes on thyroid carcinogenesis.
In contrast clinical application of molecular targeting therapy has been hampered because of various barriers on clinical trial. The effectiveness of targeting restoration of p53 function has been proved but other molecules targeted are not yet applied yet. So we have tried the combination therapy of Gleevec and external radiation for the patients with advanced and anaplastic cancers with some partial response.
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