Fundamental research on drug resistance mediated by epigenetic regulation and novel colorectal cancer stem cell targeted therapy
| Project/Area Number |
16K10559
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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 |
Digestive surgery
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| Research Institution | Chiba Cancer Center (Research Institute) |
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Principal Investigator |
SHIMOZATO OSAMU 千葉県がんセンター(研究所), がん予防センター 腫瘍ゲノム研究室, 室長心得 (30344063)
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| Co-Investigator(Kenkyū-buntansha) |
尾崎 俊文 千葉県がんセンター(研究所), がん予防センター 腫瘍ゲノム研究室, 客員研究員 (40260252)
早田 浩明 千葉県がんセンター(研究所), 消化器外科, 主任医長 (90261940)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 大腸がん / 癌幹細胞 / エピゲノム的制御 / JHDM1B / 薬剤耐性 / JHDM1B/KDM2B / エピゲノム制御 |
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| Outline of Final Research Achievements |
Molecular mechanisms underlying drug resistance should be clarified to cure patients with refractory malignant tumors. In the present study, we demonstrated that a lower expression of the H3K4me3-related demethylase JHDM1B is associated with the poor prognosis of colon cancer patients received adjuvant chemotherapy and that JHDM1B repressed several drug resistance-related genes through the H3K4me3 modification. These findings suggest that the expression level of JHDM1B correlates with the sensitivity of colon cancer patients to FOLFOX regimen.
The present study also revealed a relationship between the hydrophobicity and the primary structure of pyrrole-imidazole-polyamide (PIP), which is considered as a gene switch to regulate JHDM1B expression. This study revealed that the primary structure of PIP alters the degree of hydrophobicity of the molecule, which in turn affects the accumulation of the molecule in tumor tissue in vivo.
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| Academic Significance and Societal Importance of the Research Achievements |
切除不能進行性大腸がんでは化学療法が主な選択となるが、薬剤抵抗性の獲得が治療を困難にしている。本研究はJHDM1Bを起点とするエピゲノム的薬剤抵抗性の一端を明らかにした。JHDM1Bのがんにおける機能は不明な点が多く残されており、本研究の学術的意義は大きいと考える。また、この成果は難治性大腸がんの新たな治療戦略を構築する上で重要な知見をもたらすと考え、本研究の社会的意義は大きいと考える。
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Report
(4 results)
Research Products
(11 results)
