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Elucidation of a novel cell signaling mechanism by lipid mediators and bile acids in biliary diseases

Research Project

Project/Area Number 16K15610
Research Category

Grant-in-Aid for Challenging Exploratory Research

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

Principal Investigator

WAKAI TOSHIFUMI  新潟大学, 医歯学系, 教授 (50372470)

Co-Investigator(Kenkyū-buntansha) 永橋 昌幸  新潟大学, 医歯学総合病院, 研究准教授 (30743918)
小林 隆  新潟大学, 医歯学総合病院, 講師 (40464010)
坂田 純  新潟大学, 医歯学系, 講師 (70447605)
Research Collaborator Kameyama Hitoshi  
Katada Tomohiro  
Hirose Yuki  
Ando Takuya  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords脂質メディエーター / スフィンゴシン-1-リン酸 / 胆汁酸 / 胆道疾患 / 細胞情報伝達機構 / 胆道癌 / リンパ行性進展転移 / リンパ行性転移 / リピドミクス解析 / セラミド
Outline of Final Research Achievements

It has been revealed that bile acids work not only as detergent in the biliary tract and intestine, but also as signaling molecules that cause a variety of biological effects. We have previously reported that bile acids act directly on specific receptors of the lipid mediator, sphingosine-1-phosphate (S1P), to activate intracellular signal transduction. In this study, we investigated bile acids and S1P signaling in biliary diseases (cholecystitis, gallbladder cancer, cholangiocarcinoma, etc.). In this study, we measured S1P levels in bile and tissue in patients with each biliary disease, and revealed that S1P levels were significantly elevated in biliary tract cancer tissue compared with normal tissue. Furthermore, we revealed that S1P plays an important role in the lymphatic metastasis of biliary tract cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究は、胆道疾患において胆汁及び組織中のS1P濃度を質量分析装置で測定した初めての研究であり、学術的に意義がある。また、ヒトの胆道癌組織を用いた解析により、生体内の胆道癌組織においてもこれまでの基礎実験と同様、S1Pが癌のリンパ行性転移に寄与していることを明らかにしたことは臨床的に意義がある。今後、胆道癌のリンパ行性転移におけるS1Pの役割を明らかにすることで、胆道癌のリンパ行性進展転移を制御する新たな治療法開発へつながる可能性が期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (23 results)

All 2018 2017 2016 Other

All Int'l Joint Research (4 results) Journal Article (11 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 11 results,  Open Access: 10 results,  Acknowledgement Compliant: 6 results) Presentation (8 results) (of which Int'l Joint Research: 5 results)

  • [Int'l Joint Research] Roswell Park Comprehensive Cancer Center/Virginia Commonwealth University(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Roswell Park Cancer Institute(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Virginia Commonwealth University(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research]

    • Related Report
      2017 Research-status Report
  • [Journal Article] Generation of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasis2018

    • Author(s)
      Hirose Y, Nagahashi M, Katsuta E, Yuza K, Miura K, Sakata J, Kobayashi T, Ichikawa H, Shimada Y, Kameyama H, McDonald KA, Takabe K, Wakai T
    • Journal Title

      Sci Rep

      Volume: 8 Issue: 1 Pages: 10814-10814

    • DOI

      10.1038/s41598-018-29144-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Relevance of Dissection of the Posterior Superior Pancreaticoduodenal Lymph Nodes in Gallbladder Carcinoma.2017

    • Author(s)
      Sakata J,Kobayashi T,Tajima Y,Ohashi T,Hirose Y,Takano K,Takizawa K,Miura K,Wakai T
    • Journal Title

      Ann Surg Oncol.

      Volume: 24 Issue: 9 Pages: 2474-2481

    • DOI

      10.1245/s10434-017-5939-7

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The role of sphingosine 1-phosphate receptor 2 in bile-acid-induced cholangiocyte proliferation and cholestasis-induced liver injury in mice2017

    • Author(s)
      Wang Y, Aoki H, Yang J, Peng K, Liu R, Li X, Qiang X, Sun L, Gurley EC, Lai G, Zhang L, Liang G, Nagahashi M, Takabe K, Pandak WM, Hylemon PB, Zhou H.
    • Journal Title

      Hepatology

      Volume: 印刷中 Issue: 6 Pages: 2005-2018

    • DOI

      10.1002/hep.29076

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bile acids as global regulators of hepatic nutrient metabolism.2017

    • Author(s)
      Hylemon PB, Takabe K, Dozmorov M, Nagahashi M, Zhou H
    • Journal Title

      Liver Res.

      Volume: 1 Issue: 1 Pages: 10-16

    • DOI

      10.1016/j.livres.2017.03.002

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The role of sphingosine-1-phosphate in the tumor microenvironment and its clinical implications2017

    • Author(s)
      Nakajima M, Nagahashi M, Rashid OM, Takabe K, Wakai T
    • Journal Title

      Tumour Biol.

      Volume: 39 Issue: 4 Pages: 101042-101042

    • DOI

      10.1177/1010428317699133

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Prognostic heterogeneity of the seventh edition of UICC Stage III gallbladder carcinoma: Which patients benefit from surgical resection?2017

    • Author(s)
      Sakata J, Kobayashi T, Ohashi T, Hirose Y, Takano K, Takizawa K, Miura K, Ishikawa H, Toge K, Yuza K, Soma D, Ando T, Wakai T
    • Journal Title

      Eur J Surg Oncol.

      Volume: 43 Issue: 4 Pages: 780-787

    • DOI

      10.1016/j.ejso.2017.01.001

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 癌と宿主におけるスフィンゴシン-1-リン酸の役割2017

    • Author(s)
      永橋昌幸、若井俊文
    • Journal Title

      BIO Clinica

      Volume: 32 Pages: 397-404

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Sphingosine-1-phosphate in the lymphatic fluid determined by novel methods.2016

    • Author(s)
      Nagahashi M, Yamada A, Aoyagi T, Allegood J, Wakai T, Spiegel S, Takabe K
    • Journal Title

      Heliyon

      Volume: 2 Issue: 12 Pages: e00219-e00219

    • DOI

      10.1016/j.heliyon.2016.e00219

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The roles of bile acids and sphingosine-1-phosphate signaling in the hepatobiliary diseases.2016

    • Author(s)
      Nagahashi M, Yuza K, Hirose Y, Nakajima M, Ramanathan R, Hait NC, Hylemon PB, Zhou H, Takabe K, Wakai T.
    • Journal Title

      J Lipid Res.

      Volume: 57 Issue: 9 Pages: 1636-43

    • DOI

      10.1194/jlr.r069286

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] DNA damage response and sphingolipid signaling in liver diseases2016

    • Author(s)
      Nagahashi M, Matsuda Y, Moro K, Tsuchida J, Soma D, Hirose Y, Kobayashi T, Kosugi SI, Takabe K, Komatsu M, Wakai T
    • Journal Title

      Surg Today

      Volume: 印刷中 Issue: 9 Pages: 995-1005

    • DOI

      10.1007/s00595-015-1270-8

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 脂質メディエーターを介した胆汁酸シグナル伝達系の役割2016

    • Author(s)
      永橋 昌幸, 大橋 拓, 滝沢 一泰, 坂田 純, 小林 隆, 若井 俊文
    • Journal Title

      胆道

      Volume: 30 Pages: 220-227

    • NAID

      130005157398

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Human biliary tract cancer contains high levels of S1P2018

    • Author(s)
      Yuki Hirose, Masayuki Nagahashi, Kizuki Yuza, Kohei Miura, Jun Sakata, Takashi Kobayashi, Hiroshi Ichikawa, Yoshifumi Shimada, Hitoshi Kameyama, Kazuaki Takabe, Toshifumi Wakai
    • Organizer
      The 13th Annual Academic Surgical Congress (Florida, USA)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト胆道癌組織における脂質メディエーターS1Pの発現とその意義2018

    • Author(s)
      廣瀬雄己, 永橋昌幸, 油座築, 安藤拓也, 相馬大輝, 諸和樹, 峠弘治, 石川博補, 堅田朋大, 三浦宏平, 市川寛, 滝沢一泰, 中島真人, 島田能史, 坂田純, 小林隆, 亀山仁史, 若井俊文
    • Organizer
      第118回日本外科学会定期学術集会(東京都)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Human biliary tract cancer contains high levels of S1P2018

    • Author(s)
      Y. Hirose, M. Nagahashi, K. Yuza, K. Miura, J. Sakata, T. Kobayashi, H. Ichikawa, Y. Shimada, H. Kameyama, K. Takabe, T. Wakai
    • Organizer
      The 13th Annual Academic Surgical Congress
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Dysregulation of Sphingolipids in Human Hepatocellular Carcinoma2018

    • Author(s)
      K. Miura, M. Nagahashi, Y. Hirose, T. Kobayashi, J. Sakata, H. Kameyama, Y. Shimada, H. Ichikawa, K. Takabe, T. Wakai
    • Organizer
      The 13th Annual Academic Surgical Congress
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Sphingosine-1-phosphate in the Lymphatic Fluid Determined by Novel Methods2017

    • Author(s)
      Nagahashi M, Yamada A, Aoyagi T, Allegood J, Wakai T, Spiegel S, Takabe K
    • Organizer
      The 12th Annual Academic Surgical Congress
    • Place of Presentation
      Las Vegas, USA
    • Year and Date
      2017-02-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Roles of Sphingosine-1-Phosphate Produced by Sphingosine Kinases in Pancreatic Cancer Progression2017

    • Author(s)
      Nakajima M, Miura Y, Ando T, Yuza K, Tsuchida J, Tajima Y, Abe M, Sakimura K, Wakai T, Nagahashi M
    • Organizer
      The 12th Annual Academic Surgical Congress
    • Place of Presentation
      Las Vegas, USA
    • Year and Date
      2017-02-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Symposia S1:New trends for studying cancer invasion and metastasis The role of sphingosine-1-phosphate in tumor microenvironment and metastasis2017

    • Author(s)
      Nagahashi M, Tsuchida J, Nakajima M, Takabe K, Wakai T
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] スフィンゴシンキナーゼ欠損細胞の開発とその機能解析2016

    • Author(s)
      中島 真人, 永橋 昌幸, 土田 純子, 市川 寛, 島田 能史, 若井 俊文
    • Organizer
      第75回 日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2022-02-21  

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