| Project/Area Number |
18K07672
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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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| Review Section |
Basic Section 52040:Radiological sciences-related
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| Research Institution | Nagoya University |
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Principal Investigator |
Furukawa Takako 名古屋大学, 医学系研究科(保健), 教授 (00221557)
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| Co-Investigator(Kenkyū-buntansha) |
清野 泰 福井大学, 高エネルギー医学研究センター, 教授 (50305603)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 放射性薬品 / 腫瘍イメージング / 低酸素 / がん幹細胞 / CuATSM / CtBP / がん幹細胞性 / Cu-ATSM / NADH / エピジェネティック / 低酸素腫瘍 / がん / 低酸素耐性 / 低酸素イメージング |
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| Outline of Final Research Achievements |
High Cu-64-ATSM accumulation in tumor was shown to predict poor prognosis. Cancer stem cell-like cells were reported to be more abundant in the area of high Cu-ATSM accumulation. Increased cellular accumulation of Cu-ATSM has also been reported to associate with increased NADH/NAD+ ratio, which was shown to increase the C-terminal binding protein (CtBP) activity involved in the acquisition of cancer cell stemness. In this study, we focused on CtBP, and pursued the possible mechanism of treatment resistance which can relate to the accumulation of Cu-ATSM.
In MCF7 cells conditioned to 5% O2, both CtBP and CD133, a stem cell marker, expression and Cu-ATSM accumulation significantly increased, which suggest that Cu-ATSM may capture the changes in cancer cell characteristics mediated by CtBP dependent on high cellular NADH/NAD+ ratio. High levels of intratumoral Cu-ATSM accumulation was observed where CtBP expression tends to be high, which supported the in vitro results.
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| Academic Significance and Societal Importance of the Research Achievements |
放射性の銅で標識されたCu-ATSMは低酸素細胞の過還元状態を反映して集積し、低酸素PETイメージング剤の一つとして利用されているが、その集積と腫瘍の予後不良を結ぶメカニズムは明確には示されていない。今回Cu-ATSMの集積に関わる、HIF-1活性化以外の新たな治療抵抗性獲得の機序として、CtBPを介するがん幹細胞性の獲得の可能性が示され、Cu-ATSMの細胞集積に反映されるがんの特性を探る一助となった。今後Cu-ATSMを用いる診断・治療を推進する上で有用な情報となると考えられる。
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