The Involvement of PLDR inhibition and unreparable DNA double-strand breaks as a basis for radiotherapy
Project/Area Number |
16K19855
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Radiation science
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Research Institution | Hamamatsu University School of Medicine (2019) Yokohama City University (2018) Juntendo University (2016-2017) |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | DNA修復 / 潜在的致死損傷回復 / クロマチンリモデリング / DNA損傷・修復 / 放射線治療 / PLDR阻害 / 放射線治療生物学 / クロマチン構造変化 / DNA二重鎖切断 |
Outline of Final Research Achievements |
Using the measurement of unrepairable DNA double strand breaks(DNA-DSBs) as a indicator, we examined how inhibition of potentially lethal damage recovery(PLDR) affects the production of unrepairable DNA-DSBs by radiation. The inhibition of PLDR increased the number of unrepairable DNA-DSB. But there was no significant difference in the number of DSBs immediately after irradiation. We next tested whether histone demethylation inhibitors enhance the antitumor effects of radiation and anticancer agents in human prostate cancer and oral cancer cell lines. In both cell lines, the treatment with a histone demethylation inhibitor inhibited cell growth in a dose dependent manner. Furthermore, it was suggested that JIB-04 enhances the antitumor effect of radiation and is associated with DNA repair in prostate cancer.
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Academic Significance and Societal Importance of the Research Achievements |
本研究は長年期待されていたPLDR阻害メカニズム解明に対して、最新の分子生物学を用いて挑む野心的な試みであり、放射線や抗がん剤によるがん治療に対する新しい考え方の基盤となる。それと同時に最近のホットトピックである、クロマチン構造の変化とDSB修復の関連性のより深い理解にも貢献できる。特に修復不能なDSBとの関係を検証するのは世界初の試みである。
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Report
(5 results)
Research Products
(18 results)
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[Journal Article] Inhibition of FAO in AML co-cultured with BM adipocytes: mechanisms of survival and chemosensitization to cytarabine.2018
Author(s)
Tabe Y, Saitoh K, Yang H, Sekihara K, Yamatani K, Ruvolo V, Taka H, Kaga N, Kikkawa M, Arai H, Miida T, Andreeff M, Spagnuolo PA, Konopleva M.
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Journal Title
Sci Rep
Volume: 8
Issue: 1
Pages: 16837-16837
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Targeting mantle cell lymphoma metabolism and survival through simultaneous blockade of mTOR and nuclear transporter exportin-1.2017
Author(s)
Sekihara K, Saitoh K, Han L, Ciurea S, Yamamoto S, Kikkawa M, Kazuno S, Taka H, Kaga N, Arai H, Miida T, Andreeff M, Konopleva M, Tabe Y.
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Journal Title
Oncotarget
Volume: in press
Issue: 21
Pages: 34552-34564
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Bone Marrow Adipocytes Facilitate Fatty Acid Oxidation Activating AMPK and a Transcriptional Network Supporting Survival of Acute Monocytic Leukemia Cells.2017
Author(s)
Tabe Y, Yamamoto S, Saitoh K, Sekihara K, Monma N, Ikeo K, Mogushi K, Shikami M, Ruvolo V, Ishizawa J, Hail N Jr, Kazuno S, Igarashi M, Matsushita H, Yamanaka Y, Arai H, Nagaoka I, Miida T, Hayashizaki Y, Konopleva M, Andreeff M.
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Journal Title
Cancer Res.
Volume: 77
Issue: 6
Pages: 1453-1464
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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