Combined inhibition of stem cell markers and histone modification enzymes in non-small cell lung cancer
Project/Area Number |
26461175
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
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Research Institution | Hokkaido University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
JINUSHI Masahisa 慶應義塾大学, 医学部, 特任准教授 (40318085)
AKITA Hirotoshi 北海道大学, 医学研究科, 教授 (70222528)
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | 肺癌 / ヒストン修飾 / 癌幹細胞 / EZH2 / DZNep / HDAC / SAHA / side population / ヒストン修飾酵素 / 非小細胞肺癌 / 幹細胞 / EGFR |
Outline of Final Research Achievements |
EGFR-tyrosine kinase inhibitor (TKI) resistant non-small lung cancer (NSCLC) cell H1975 had 1% side population fraction, which showed increased tumorigenicity, elevated expression of stem cell markers and histone H3K27 trimethyl transferase EZH2, suggesting that EZH2 may play a role in maintenance of cancer stem cells. The combined treatment with inhibitors of the EZH2 and the histone deacetylases HDACs showed synergistic growth suppressive effects, suppression of EGFR signaling, and decrease in the in vivo tumor growth of H1975 cells, suggesting that the combined pharmacological targeting of the histone modification enzymes may provide more effective epigenetic therapeutics for NSCLCs including those with EGFR-TKI-resistant mutations.
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] A phase II study of bevacizumab with carboplatin-pemetrexed in non-squamous non-small cell lung carcinoma patients with malignant pleural effusions: North East Japan Study Group Trial NEJ013A.2016
Author(s)
Usui K, Sugawara S, Nishitsuji M, Fujita Y, Inoue A, Mouri A, Watanabe H, Sakai H, Kinoshita I, Ohhara Y, Maemondo M, Kagamu H, Hagiwara K, Kobayashi K
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Journal Title
Lung Cancer
Volume: 99
Pages: 131-136
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] The coordinated actions of TIM-3 on cancer and myeloid cells in the regulation of tumorigenicity and clinical prognosis in clear cell renal cell carcinomas2015
Author(s)
Komohara Y, Morita T, Annan DA, Horlad H, Ohnishi K, Yamada S, Nakayama T, Kitada S, Suzu S, Kinoshita I, Dosaka-Akita H, Akashi K, Takeya M, Jinushi M
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Journal Title
Cancer Immunol Res
Volume: -
Related Report
Peer Reviewed
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[Journal Article] Randomized phase II study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non-small cell lung cancer with sensitive EGFR mutations: NEJ005/TCOG0902.2015
Author(s)
Sugawara S, Oizumi S, Minato K, Harada T, Inoue A, Fujita Y, Maemondo M, Yoshizawa H, Ito K, Gemma A, Nishitsuji M, Harada M, Isobe H, Kinoshita I, Morita S, Kobayashi K, Hagiwara K, Kurihara M, Nukiwa T; North East Japan Study Group and Tokyo Cooperative Oncology Group
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Journal Title
Ann Oncol.
Volume: 26(5)
Issue: 5
Pages: 888-94
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Expression of Fucosyltransferase 8 Is Associated with an Unfavorable Clinical Outcome in Non-Small Cell Lung Cancers2015
Author(s)
Honma R, Kinoshita I, Miyoshi E, Tomaru U, Matsuno Y, Shimizu Y, Takeuchi S, Kobayashi Y, Kaga K, Taniguchi N, Dosaka-Akita H
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Journal Title
Related Report
Peer Reviewed
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