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Elucidation of molecular mechanism of lipid mediator involved in metastatic ability of biliary tract cancer / pancreatic cancer and clinical application

Research Project

Project/Area Number 15H04927
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
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, 講師 (30743918)
松田 康伸  新潟大学, 医歯学系, 准教授 (40334669)
小林 隆  新潟大学, 医歯学総合病院, 講師 (40464010)
五十嵐 道弘  新潟大学, 医歯学系, 教授 (50193173)
坂田 純  新潟大学, 医歯学系, 講師 (70447605)
味岡 洋一  新潟大学, 医歯学系, 教授 (80222610)
小杉 伸一  新潟大学, 医歯学総合病院, 特任教授 (90401736)
Co-Investigator(Renkei-kenkyūsha) Komatsu Masaaki  新潟大学, 医歯学系, 教授 (90356254)
Research Collaborator Sarah Spiegel  バージニア州立大学, 教授
Hylemon Phillip B.  バージニア州立大学, 教授
Takabe Kazuaki  Roswell Park Cancer Institution, 教授
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2015: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords脂質メディエーター / 胆道外科学 / 膵臓外科学 / ダブルノックアウトマウス / リンパ管新生 / 細胞外基質 / リンパ管浸潤 / CRISPR/Cas9 / B/6系マウス / 細胞増殖能 / 胆道癌 / 膵癌 / 転移能
Outline of Final Research Achievements

We have developed a method to measure sphingosine-1-phosphate levels in the interstitial fluid that bathes cancer cells in the tumor microenvironment, and reported that high levels of sphingosine-1-phosphate exist in the tumor interstitial fluid. Importantly, sphingosine-1-phosphate can be secreted from cancer cells and non-cancer components such as immune cells and vascular/lymphatic endothelial cells in the tumor microenvironment. We elucidate the roles of sphingosine-1-phosphate in the interaction between cancer and non-cancer cells in tumor microenvironment, and discuss future possibilities for targeted therapies against sphingosine-1-phosphate signaling for cancer patients.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (26 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 8 results,  Open Access: 8 results,  Acknowledgement Compliant: 6 results) Presentation (14 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results)

  • [Int'l Joint Research] Roswell Park Cancer Institute/The State University of New York(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Roswell Park Cancer Institute/University at Buffalo Jacobs School/Virginia Commonwealth University(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Virginia Commonwealth University(米国)

    • Related Report
      2015 Annual Research Report
  • [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
      2017 Annual Research Report
  • [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
      2017 Annual Research Report 2016 Annual Research 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 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Annual Research 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 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Resolvins and omega three polyunsaturated fatty acids: Clinical implications in inflammatory diseases and cancer.2016

    • Author(s)
      Moro K, Nagahashi M, Ramanathan R, Takabe K, Wakai T.
    • Journal Title

      World J Clin Cases.

      Volume: 4 Issue: 7 Pages: 155-64

    • DOI

      10.12998/wjcc.v4.i7.155

    • Related Report
      2016 Annual Research 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 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Interstitial Fluid Sphingosine-1-Phosphate in Murine Mammary Gland and Cancer and Human Breast Tissue and Cancer Determined by Novel Methods.2016

    • Author(s)
      Nagahashi M, Yamada A, Miyazaki H, Allegood JC, Tsuchida J, Aoyagi T, Huang WC, Terracina KP, Adams BJ, Rashid OM, Milstien S, Wakai T, Spiegel S, Takabe K.
    • Journal Title

      J Mammary Gland Biol Neoplasia

      Volume: 21 Issue: 1-2 Pages: 9-17

    • DOI

      10.1007/s10911-016-9354-7

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Comparison of Number Versus Ratio of Positive Lymph Nodes in the Assessment of Lymph Node Status in Extrahepatic Cholangiocarcinoma2016

    • Author(s)
      Sakata J, Wakai T, Matsuda Y, Ohashi T, Hirose Y, Ichikawa H, Kobayashi T, Minagawa M, Kosugi S, Koyama Y, Akazawa K, Ajioka Y
    • Journal Title

      Ann Surg Oncol

      Volume: 23 Issue: 1 Pages: 225-234

    • DOI

      10.1245/s10434-015-4609-x

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Sphingosine-1-phosphate produced by sphingosine kinase type 1 and type 2 works differently in pancreatic cancer2018

    • Author(s)
      M. Nakajima, K. Yuza, J. Tsuchida, Y. Hirose, K. Miura, H. Ichikawa, Y. Shimada, T. Kobayashi, J. Sakata, H. Kameyama, M. Abe, K. Sakimura, T. Wakai, M. Nagahashi
    • Organizer
      The 13th Annual Academic Surgical Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] High levels of sphingolipids in human pancreatic cancer2018

    • Author(s)
      K. Yuza, M. Nagahashi, Y. Hirose, M. Nakajima, K. Miura, H. Ichikawa, Y. Shimada, J. Sakata, H. Kameyama, T. Kobayashi, K. Takabe, T. Wakai
    • Organizer
      The 13th Annual Academic Surgical Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 膵がんにおけるCRISPR/Cas9を用いたスフィンゴシン-1-リン酸産生酵素の機能解析2017

    • Author(s)
      中島 真人,永橋 昌幸,三浦 要平,安藤 拓也,油座 築,土田 純子,田島 陽介,坂田 純,小林 隆,亀山 仁史,阿部 学,崎村 建司,若井 俊文
    • Organizer
      第117回日本外科学会定期学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 膵癌細胞におけるスフィンゴシン-1-リン酸産生酵素の働きとその代謝動態制御の解析2017

    • Author(s)
      中島 真人,永橋 昌幸,三浦 要平,安藤 拓也,油座 築,土田 純子,田島 陽介,坂田 純,小林 隆,亀山 仁史,阿部 学,﨑村 建司,曽我 朋義,若井 俊文
    • Organizer
      日本外科代謝栄養学会第54回学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Function Analysis of Sphingosine-1-Phosphate Produced by Sphingosine Kinases in Pancreatic Cancer Progression.2017

    • Author(s)
      Masato Nakajima,Masayuki Nagahashi,Junko Tsuchida,Hiroshi Ichikawa,Yoshifumi Shimada,Toshifumi Wakai
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 肥満を伴う乳癌患者における血清スフィンゴシン-1-リン酸の定量2016

    • Author(s)
      土田 純子, 永橋 昌幸, 遠藤 麻巳子, 大溪 彩香, 庭野 稔之, 辰田 久美子, 利川 千絵, 長谷川 美樹, 五十嵐 麻由子, 中島 真人, 小山 諭, 高部 和明, 若井 俊文
    • Organizer
      第78回 日本臨床外科学会総会
    • Place of Presentation
      グランドプリンスホテル新高輪(東京都港区)
    • Year and Date
      2016-11-24
    • Related Report
      2016 Annual Research 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 Annual Research Report
  • [Presentation] 検診発見および自己発見乳癌の臨床病理学的特徴と長期成績2016

    • Author(s)
      土田 純子, 永橋 昌幸, 諸 和樹, 庭野 稔之, 辰田 久美子, 利川 千絵, 長谷川 美樹, 萬羽 尚子, 五十嵐 麻由子, 小山 諭, 市川 寛, 中島 真人, 島田 能史, 坂田 純, 小林 隆, 亀山 仁史, 若井 俊文
    • Organizer
      第116回 日本外科学会定期学術集会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市北区)
    • Year and Date
      2016-04-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] 肝胆膵「肝胆膵外科診療の最前線」2015

    • Author(s)
      若井俊文
    • Organizer
      第53回日本癌治療学会学術集会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2015-10-30
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 胆汁酸はスフィンゴシン-1-リン酸シグナル伝達系を介して 肝臓における脂質代謝を調節している2015

    • Author(s)
      永橋 昌幸,廣瀬 雄己,須藤 翔,大橋 拓,滝沢 一泰,高野 可赴,坂田 純,小林 隆,若井 俊文
    • Organizer
      第51日本胆道学会学術集会
    • Place of Presentation
      ホテル東日本宇都宮(栃木県宇都宮市)
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] IMPACT OF SURGICAL RESECTION AND CHEMOTHERAPY ON LONG-TERM OUTCOMES IN PATIENTS WITH LOCALLY ADVANCED GALLBLADDER CARCINOMA2015

    • Author(s)
      T. Wakai, J. Sakata, Y. Hirose, N. Sudo, T. Katada, K. Takizawa, M. Nagahashi, T. Kobayashi
    • Organizer
      46th World Congress of Surgery
    • Place of Presentation
      Bangkok, Thailand
    • Year and Date
      2015-08-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] LONG-TERM OUTCOMES OF SURGICAL RESECTION FOR EARLY GALLBLADDER CARCINOMA2015

    • Author(s)
      T. Wakai, J. Sakata, Y. Hirose, N. Sudo, T. Katada, K. Takizawa, M. Nagahashi, T. Kobayashi
    • Organizer
      46th World Congress of Surgery
    • Place of Presentation
      Bangkok, Thailand
    • Year and Date
      2015-08-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SymposiumⅢ Laparoscopic cholecystectomy with LN dissection2015

    • Author(s)
      Toshifumi Wakai
    • Organizer
      The 36th Annual Meeting of the Korean Society of Endoscopic & Laparoscopic Surgeons, 2015 International Symposium
    • Place of Presentation
      Jeju, Korea
    • Year and Date
      2015-05-29
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 肥満はスフィンゴシン-1-リン酸を癌微小環境において増加させる2015

    • Author(s)
      永橋 昌幸,諸 和樹,土田 純子,辰田 久美子,利川 千絵,長谷川 美樹,萬羽 尚子,五十嵐 真由子,坂田 純,小林 隆,亀山 仁史,皆川 昌広,小杉 伸一,小山 諭,高部 和明,若井 俊文
    • Organizer
      第115回日本外科学会定期学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-04-16
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2022-10-07  

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