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Diagnostic and therapeutic strategies targeting microRNAs and epigenome alterations in biliary tract and pancreatic cancer stem cells

Research Project

Project/Area Number 26290049
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Tumor diagnostics
Research InstitutionKeio University

Principal Investigator

Saito Yoshimasa  慶應義塾大学, 薬学部, 准教授 (90360114)

Co-Investigator(Renkei-kenkyūsha) SATO Toshiro  慶應義塾大学, 医学部, 准教授 (70365245)
KANAI Yae  慶應義塾大学, 医学部, 教授 (00260315)
OOE Tomoyuki  慶應義塾大学, 薬学部, 准教授 (30624283)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords胆道がん / 膵臓がん / がん幹細胞 / オルガノイド培養 / マイクロRNA / エピゲノム / 個別化治療 / 胆道・膵臓がん / 癌 / 幹細胞
Outline of Final Research Achievements

Cancer stem cells are resistant to conventional chemotherapies and responsible for cancer initiation, invasive growth, and metastasis formation. The aim of this study is to develop a novel therapeutic strategy targeting biliary tract and pancreatic cancer stem cells. The newly developed 3D culture system called “organoid culture” allows long-term expansion of LGR5 positive stem cells into budding cyst-like structures (organoids) with properties resembling those of the original tissues. To reach our goal, we established organoids derived from biliary tract cancers and pancreatic cancers. We analyzed gene mutation and gene expression and performed drug screening test using these cancer organoids. Here we demonstrated that low molecular compounds and tumor suppressor microRNAs including miR-34a are safe and effective therapeutic drug candidates against biliary tract and pancreatic cancers.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (19 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 8 results,  Acknowledgement Compliant: 5 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] 南カリフォルニア大学ノリスがんセンター(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Cluster microRNAs miR-194 and miR-215 suppress the tumorigenicity of intestinal tumor organoids.2017

    • Author(s)
      Nakaoka T, Saito Y, Shimamoto Y, Muramatsu T, Kimura M, Kanai Y, Saito H.
    • Journal Title

      Cancer Sci,

      Volume: 108 Issue: 4 Pages: 678-684

    • DOI

      10.1111/cas.13165

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A New Molecular Mechanism Underlying the Antitumor Effect of DNA Methylation Inhibitors via an Antiviral Immune Response.2017

    • Author(s)
      Saito Y, Nakaoka T, Saito H
    • Journal Title

      Advances in Protein Chemistry and Structural Biology

      Volume: 106 Pages: 227-242

    • DOI

      10.1016/bs.apcsb.2016.08.005

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] microRNA-mediated resistance to hypoglycemia in the HepG2 human hepatoma cell line.2016

    • Author(s)
      Ueki S, Murakami Y, Yamada S, Kimura M, Saito Y, Saito H
    • Journal Title

      BMC Cancer

      Volume: 16 Issue: 1 Pages: 732-732

    • DOI

      10.1186/s12885-016-2762-7

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Inhibition of DNA Methylation Suppresses Intestinal Tumor Organoids by Inducing an Anti-Viral Response.2016

    • Author(s)
      Saito Y, Nakaoka T, Sakai K, Muramatsu T, Toshimitsu K, Kimura M, Kanai T, Sato T, Saito H
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 25311-25311

    • DOI

      10.1038/srep25311

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Inhibition of DNA Methylation Suppresses Intestinal Tumor Organoids by Inducing an Anti-Viral Response2016

    • Author(s)
      Yoshimasa Saito, Toshiaki Nakaoka, Kasumi Sakai, Toshihide Muramatsu, Kohta Toshimitsu, Masaki Kimura, Takanori Kanai, Toshiro Sato, Hidetsugu Saito
    • Journal Title

      Scientific Reports

      Volume: 印刷中

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] First-line eradication for Helicobacter pylori-positive gastritis by esomeprazole-based triple therapy is influenced by CYP2C19 genotype.2015

    • Author(s)
      Saito Y, Serizawa H, Kato Y, Nakano M, Nakamura M, Saito H, Suzuki H, Kanai T.
    • Journal Title

      World J. Gastroenterol.

      Volume: 21 Issue: 48 Pages: 13548-54

    • DOI

      10.3748/wjg.v21.i48.13548

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] microRNA-34a as a therapeutic agent against human cancer.2015

    • Author(s)
      Saito Y, Nakaoka T, Saito H.
    • Journal Title

      J Clin Med

      Volume: 4 Issue: 11 Pages: 1951-1959

    • DOI

      10.3390/jcm4111951

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Silencing of microRNA-122 is an early event during hepatocarcinogenesis from non-alcoholic steatohepatitis.2014

    • Author(s)
      Takaki Y, Saito Y, Takasugi A, Toshimitsu K, Yamada S, Muramatsu T, Kimura M, Sugiyama K, Suzuki H, Arai E, Ojima H, Kanai Y, Saito H.
    • Journal Title

      Cancer Sci.

      Volume: 105 Issue: 10 Pages: 1254-1260

    • DOI

      10.1111/cas.12498

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Intrahepatic cholangiocarcinoma cells can be converted into functional hepatocytes by inhibition of Wnt signaling pathway.2017

    • Author(s)
      Saito Y, Nakaoka T, Muramatsu T, Kimura M, Saito H
    • Organizer
      American Association for Cancer Research (AACR) Annual Meeting 2017
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2017-04-05
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibition of DNA Methylation Suppresses Intestinal Tumor Organoids by Inducing an Anti-Viral Response.2016

    • Author(s)
      Saito Y, Sakai K, Muramatsu T, Nakaoka T, Kimura M, Saito H
    • Organizer
      American Association for Cancer Research (AACR) Annual Meeting 2016
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2016-04-19
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibition of DNA Methylation Suppresses Intestinal Tumor Organoids by Inducing an Anti-Viral Response2016

    • Author(s)
      Yoshimasa Saito, Kasumi Sakai, Kohta Toshimitsu, Toshihide Muramatsu, Toshiaki Nakaoka, Masaki Kimura, Hidetsugu Saito
    • Organizer
      Annual Meeting of American Association for Cancer Research (AACR)
    • Place of Presentation
      ニューオーリンズ(アメリカ合衆国)
    • Year and Date
      2016-04-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] オルガノイド培養技術を用いたがんエピゲノム研究の進展開2016

    • Author(s)
      齋藤 義正, 中岡 哉彰, 村松 俊英, 木村 真規, 齋藤 英胤
    • Organizer
      第53回日本臨床分子医学会学術集会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2016-04-16
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 腸管腫瘍オルガノイドにおける miR-194 および miR-215 を含むマイクロRNAクラスターの役割2015

    • Author(s)
      中岡 哉, 齋藤 義正, 島本 百合子, 村松 俊英, 木村 真規, 齋藤 英胤.
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Suppression of Intestinal Tumor-Initiating Cells by Inhibition of DNA Methylation2014

    • Author(s)
      Saito Y, Sakai K, Toshimitsu K, Muramatsu T, Kimura M, Sato T, Kanai T, Saito H
    • Organizer
      United European Gastroenterology Week 2014
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      2014-10-20 – 2014-10-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] Silencing of microRNA-122 is an early event during hepatocarcinogenesis from nonalcoholic steatohepatitis2014

    • Author(s)
      Saito Y, Takaki Y, Toshimitsu K, Takasugi A, Yamada S, Muramatsu T, Kimura M, Sugiyama K, Kanai T, Saito H.
    • Organizer
      United European Gastroenterology Week 2014
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      2014-10-20 – 2014-10-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] DNAメチル化阻害による腸管腫瘍幹細胞の増殖抑制2014

    • Author(s)
      利光孝太、齋藤義正、齋藤英胤
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] がん幹細胞集団の調製方法、異種移植片の調製方法、スクリーニング方法、miR-34aの発現量を低下させる方法及びがん幹細胞増殖抑制剤2015

    • Inventor(s)
      齋藤 義正 他4名
    • Industrial Property Rights Holder
      齋藤 義正 他4名
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-142164
    • Filing Date
      2015-07-16
    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] がん幹細胞集団の調製方法2014

    • Inventor(s)
      齋藤義正、齋藤英胤、佐藤俊朗、尾島英知、金井弥栄、村松俊英
    • Industrial Property Rights Holder
      慶應義塾
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-146144
    • Filing Date
      2014-07-16
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2022-01-27  

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