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Acceleration and satisfaction of epigenetic drug discovery using profiling technology

Research Project

Project/Area Number 16K15616
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Digestive surgery
Research InstitutionOsaka University

Principal Investigator

KOSEKI Jyun  大阪大学, 医学系研究科, 特任助教(常勤) (20616669)

Co-Investigator(Kenkyū-buntansha) 今野 雅允  大阪大学, 医学系研究科, 寄附講座講師 (80618207)
西田 尚弘  大阪大学, 医学系研究科, 助教 (50588118)
川本 弘一  大阪大学, 医学部附属病院, その他 (30432470)
Co-Investigator(Renkei-kenkyūsha) ISHII Hideshi  大阪大学, 大学院医学系研究科, 特任教授 (10280736)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords癌 / エピゲノム / 創薬 / インシリコスクリーニング
Outline of Final Research Achievements

It was very difficult in the past to screen inhibitors of JARID1B, one of epigenome regulatory factor. We have made it possible using our in silico screening technologies with large-scale computer. In silico screening has been already performed to pick up the candidate compounds from five million drug like compounds. Then, we selected first lead compounds from the picked up candidate compounds with chemical assay. We have investigated the in vitro anti-cancer effects of these lead compounds, and the after, investigated the in vivo anti-cancer effects for the part of them. We succeeded in establishing a pathway to show the synthetic evolution guidelines for lead compounds based on the functional information from these experimental results. According to this procedure, it is possible to design a more efficient drug structure.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (21 results)

All 2018 2017 2016

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 14 results,  Open Access: 12 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Enzymes of the one-carbon folate metabolism as anticancer targets predicted by survival rate analysis2018

    • Author(s)
      Koseki Jun、Konno Masamitsu、Asai Ayumu、Colvin Hugh、Kawamoto Koichi、Nishida Naohiro、Sakai Daisuke、Kudo Toshihiro、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
    • Journal Title

      Sci. Rep.

      Volume: 8 Issue: 1 Pages: 303-303

    • DOI

      10.1038/s41598-017-18456-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Computational trans-omics approach characterised methylomic and transcriptomic involvements and identified novel therapeutic targets for chemoresistance in gastrointestinal cancer stem cells2018

    • Author(s)
      Konno Masamitsu、Matsui Hidetoshi、Koseki Jun、Asai Ayumu、Kano Yoshihiro、Kawamoto Koichi、Nishida Naohiro、Sakai Daisuke、Kudo Toshihiro、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
    • Journal Title

      Sci. Rep.

      Volume: 8 Issue: 1 Pages: 899-899

    • DOI

      10.1038/s41598-018-19284-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA profiles involved in trifluridine resistance2017

    • Author(s)
      Tsunekuni Kenta、Konno Masamitsu、Asai Ayumu、Koseki Jun、Kobunai Takashi、Takechi Teiji、Doki Yuichiro、Mori Masaki、Ishii Hideshi
    • Journal Title

      Oncotarget.

      Volume: 8 Issue: 32 Pages: 53017-53027

    • DOI

      10.18632/oncotarget.18078

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low expression of the GOPC is a poor prognostic marker in colorectal cancer2017

    • Author(s)
      Ohara Nobuyoshi、Haraguchi Naotsugu、Koseki Jun、Nishizawa Yujiro、Kawai Kenji、Takahashi Hidekazu、Nishimura Junichi、Hata Taishi、Mizushima Tsunekazu、Yamamoto Hirofumi、Ishii Hideshi、Doki Yuichiro、Mori Masaki
    • Journal Title

      Oncol. Lett.

      Volume: 14 Issue: 4 Pages: 4483-4490

    • DOI

      10.3892/ol.2017.6817

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The epitranscriptome m6A writer METTL3 promotes chemo- and radioresistance in pancreatic cancer cells2017

    • Author(s)
      Taketo Kosuke、Konno Masamitsu、Asai Ayumu、Koseki Jun、Toratani Masayasu、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi、Ogawa Kazuhiko
    • Journal Title

      Int. J. Oncol.

      Volume: 52 Pages: 621-629

    • DOI

      10.3892/ijo.2017.4219

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hypoxia stimulates the cytoplasmic localization of oncogenic long noncoding RNA LINC00152 in colorectal cancer2017

    • Author(s)
      Nishizawa Yujiro、Konno Masamitsu、Asai Ayumu、Koseki Jun、Kawamoto Koichi、Miyoshi Norikatsu、Takahashi Hidekazu、Nishida Naohiro、Haraguchi Naotsugu、Sakai Daisuke、Kudo Toshihiro、Hata Taishi、Matsuda Chu、Mizushima Tsunekazu、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
    • Journal Title

      Int. J. Oncol.

      Volume: 52 Pages: 453-460

    • DOI

      10.3892/ijo.2017.4218

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oncogene c-Myc promotes epitranscriptome m6A reader YTHDF1 expression in colorectal cancer2017

    • Author(s)
      Nishizawa Yujiro、Konno Masamitsu、Asai Ayumu、Koseki Jun、Kawamoto Koichi、Miyoshi Norikatsu、Takahashi Hidekazu、Nishida Naohiro、Haraguchi Naotsugu、Sakai Daisuke、Kudo Toshihiro、Hata Taishi、Matsuda Chu、Mizushima Tsunekazu、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
    • Journal Title

      Oncotarget.

      Volume: 9 Issue: 7 Pages: 7476-7486

    • DOI

      10.18632/oncotarget.23554

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial pyruvate carrier modulates the epithelial-mesenchymal transition in cholangiocarcinoma2017

    • Author(s)
      Ohashi Tomofumi、Eguchi Hidetoshi、Kawamoto Koichi、Konno Masamitsu、Asai Ayumu、Colvin Hugh、Ueda Yuji、Takaoka Hirofumi、Iwagami Yoshifumi、Yamada Daisaku、Asaoka Tadafumi、Noda Takehiro、Wada Hiroshi、Gotoh Kunihito、Kobayashi Shogo、Koseki Jun、Satoh Taroh、Ogawa Kazuhiko、Doki Yuichiro、Mori Masaki、Ishii Hideshi
    • Journal Title

      Oncol. Rep.

      Volume: 39 Pages: 1276-1282

    • DOI

      10.3892/or.2017.6172

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical significance of histone demethylase NO66 in invasive colorectal cancer.2017

    • Author(s)
      Nishizawa, Y., Nishida, N., Konno, M., Kawamoto, K., Asai, A., Koseki, J., Takahashi, H., Haraguchi, N., Nishimura, J., Hata, T., Matsuda, C., Mizushima, T., Satoh, T., Doki, Y., Mori, M., Ishii, H.
    • Journal Title

      Ann. Surg. Oncol.

      Volume: 24 Issue: 3 Pages: 841-849

    • DOI

      10.1245/s10434-016-5395-9

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The importance of mitochondrial folate enzymes in human colorectal cancer.2017

    • Author(s)
      Miyo, M., Konno, M., Colvin, S. H., Nishida, N., Koseki, J., Kawamoto, K., Tsunekuni, K., Nishimura, J., Hata, T., Takemasa, I., Mizushima, T., Doki, Y., Mori, M., Ishii, H.
    • Journal Title

      Oncol. Rep.

      Volume: 37 Issue: 1 Pages: 417-425

    • DOI

      10.3892/or.2016.5264

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High expression of ADAMTS5 is a potent marker for lymphatic invasion and lymph node metastasis in colorectal cancer.2017

    • Author(s)
      Haraguchi, N., Ohara, N., Koseki, J., Takahashi, H., Nishimura, J., Hata, T., Mizushima, T., Yamamoto, H., Ishii, H., Doki, Y., Mori, M.
    • Journal Title

      Mol. Clinic. Oncol.

      Volume: 6 Issue: 1 Pages: 130-137

    • DOI

      10.3892/mco.2016.1088

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Molecular Orbital Study of the Formation of Intramolecular Hydrogen Bonding of a Ligand Molecule in a Protein Aromatic Hydrophobic Pocket2016

    • Author(s)
      Koseki, J., Gouda, H., Hirono, S.
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 64 Issue: 7 Pages: 1031-1035

    • DOI

      10.1248/cpb.c16-00126

    • NAID

      130005160079

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] MicroRNA miR-374, a potential radiosensitizer for carbon ion beam radiotherapy.2016

    • Author(s)
      Baek, SJ., Sato, K., Nishida, N., Koseki, J., Azuma, R., Kawamoto, K., Konno, M., Hayashi, K., Satoh, T., Doki, Y., Mori, M., Ishii, H., Ogawa, K.
    • Journal Title

      Oncol. Rep.

      Volume: 36 Issue: 5 Pages: 2946-2950

    • DOI

      10.3892/or.2016.5122

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oncometabolite D-2-hydroxyglurate directly induces epithelial-mesenchymal transition and is associated with distant metastasis in colorectal cancer.2016

    • Author(s)
      Colvin, S. H., Nishida, N., Konno, M., Haraguchi, N., Takahashi, H., Nishimura, J., Hata, T., Kawamoto, K. Asai, A., Tsunekuni, K., Koseki, J., Mizushima, T., Satoh, T., Doki, Y., Mori, M., Ishii, H.
    • Journal Title

      Sci. Rep

      Volume: 6 Issue: 1 Pages: 36289-36289

    • DOI

      10.1038/srep36289

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] がん幹細胞におけるオルニチン代謝経路のトランスオミックス解析2017

    • Author(s)
      小関準、今野雅允、浅井歩、松井秀俊、尾崎みゆ希、佐藤太郎、土岐祐一郎、森正樹、石井秀始
    • Organizer
      第5回がんと代謝研究会 in 札幌
    • Related Report
      2017 Annual Research Report
  • [Presentation] トランス-オミックス法を用いたがん幹細胞におけるポリアミン代謝経路の意義の解析2017

    • Author(s)
      小関準、今野雅允、松井秀俊、加納義弘、佐藤太郎、森正樹、土岐祐一郎、石井秀始
    • Organizer
      第26回日本がん転移学会学術集会・総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 新規トランスオミックス法を用いたがん幹細胞における化学療法耐性 の解析2017

    • Author(s)
      小関準、今野雅允、浅井歩、佐藤太郎、土岐祐一郎、森正樹、石井秀始
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Trans-Omics Analysis Shows Novel Functional Change in the Ornithine Metabolic Pathway Between Cancer Stem Cells and Non-Cancer Stem Cells2016

    • Author(s)
      Koseki, J., Matsui, H., Konno, M., Nishida, N., Kawamoto, K., Kano, Y., Asai, A., Doki, Y., Mori, M., Ishii, H.
    • Organizer
      The 26th Hot Spring Harbor International Symposium
    • Place of Presentation
      Kyushu University(福岡)
    • Year and Date
      2016-11-02
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Trans-omics Analysis brings out Novel Functions of the Ornithine Metabolic Pathway in Cancer Stem Cells2016

    • Author(s)
      小関 準, 今野 雅允, 西田 尚弘, 川本 弘一, 土岐 祐一郎, 森 正樹, 石井 秀始
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Thermodynamic and molecular orbital analysis of the effects caused by incorporation of novel anti-tumor agent Trifluridine to DNA2016

    • Author(s)
      Koseki, J., Tsunekuni, K., konno, M., Nishida, N., Kawamoto, K., Doki, Y., Mori, M., Ishii, H.
    • Organizer
      AACR Annual Meeting 2016
    • Place of Presentation
      Ernest N. Morial Convention Center(アメリカ)
    • Year and Date
      2016-04-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] トランスオミックス解析により見い出された癌幹細胞におけるオルニチン代謝経路の新機能2016

    • Author(s)
      小関 準
    • Organizer
      第3回次世代がんインフォマティクス研究会
    • Place of Presentation
      岡山大学(岡山)
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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