Elucidation of a novel cell signaling mechanism by lipid mediators and bile acids in biliary diseases
Project/Area Number |
16K15610
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Digestive surgery
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Research Institution | Niigata University |
Principal Investigator |
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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)
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Research Collaborator |
Kameyama Hitoshi
Katada Tomohiro
Hirose Yuki
Ando Takuya
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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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)
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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.
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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。
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Report
(4 results)
Research Products
(23 results)
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[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
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Journal Title
Sci Rep
Volume: 8
Issue: 1
Pages: 10814-10814
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Hepatology
Volume: 印刷中
Issue: 6
Pages: 2005-2018
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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
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Journal Title
Eur J Surg Oncol.
Volume: 43
Issue: 4
Pages: 780-787
DOI
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
Surg Today
Volume: 印刷中
Issue: 9
Pages: 995-1005
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[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
Int'l Joint Research
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[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
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[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
Int'l Joint Research
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[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
Int'l Joint Research
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