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Biliary carcinogenesis based upon degradated phospholipids

Research Project

Project/Area Number 24500977
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Eating habits, studies on eating habits
Research InstitutionHiroshima University

Principal Investigator

TAZUMA Susumu  広島大学, 大学病院, 教授 (80201614)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsBile / Bile duct / phospholipids / lysolecithin / apoposis / SASP / hepatolithiasis / 胆管 / リゾリン脂質 / 膵胆管合流異常 / 胆管癌 / アポトーシス / 炎症性サイトカイン / 細胞老化 / 劣化脂質 / リゾレシチン / Gタンパク共役型受容体 / 胆管上皮 / SASP
Outline of Final Research Achievements

In biliary diseases, biliary lysophosphatidylcholine (LPC) level is increased, LPC exhibited cytotoxicity with significant induction of apoptosis. Here, the influence of LPC on cholangiocytes was focussed in the light of cellular senescence and its contribution to carcinogenesis. Treatment of human cholangiosytes with LPC demonstrated cytotoxicity with significant ROS generation. In keeping with this change, LPC provoked oxidative DNA injury while the gene expressions of DNA repair enzyme remained unchanged. Microarray analysis identified differentially regulated genes in response to LPC, which included the components of senescence-associated secretory phenotype (SASP). Based upon these data, cholangiocyte senescence and SASP caused by LPC via induction of oxidative stress are an important pathogenic mechanism in the development of biliary tract cancer.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (25 results)

All 2015 2014 2013 2012

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 5 results,  Acknowledgement Compliant: 5 results) Presentation (3 results) (of which Invited: 1 results) Book (7 results)

  • [Journal Article] Cholangiocyte senescence caused by lysophosphatidylcholine as a potential implication in carcinogenesis.2015

    • Author(s)
      Shimizu R, Kanno K, Sugiyama A, Ohata H, Araki A, Kishikawa N, Kimura Y, Yamamoto H, Kodama M, Kihira K, Tazuma S.
    • Journal Title

      J Hepatobiliary Pancreat Sci.

      Volume: 22 Issue: 9 Pages: 675-682

    • DOI

      10.1002/jhbp.256

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Classification of biliary tract cancers established by Japanese Society of Hepato-Biliary-Pancreatic Surgery: class FormattedString { value: 3<sup>rd</sup> english edition }2015

    • Author(s)
      Miyazaki M, Ohtsuka M, Miyakawa S, Nagino M, Yamamoto M, Kokudo N, Sano K, Endo I, Unno M, Chijiiwa K, Horiguchi A, Kinoshita H, Oka M, Kubota K, Sugiyama M, Uemoto S, Shimada M, Suzuki Y, Inui K, Tazuma S, Furuse J, Yanagisawa A, Nakanuma Y, Kijima H, Takada T.
    • Journal Title

      J Hepatobiliary Pancreat Sci.

      Volume: 22 Issue: 3 Pages: 181

    • DOI

      10.1002/jhbp.211

    • URL

      https://localhost/en/publications/c1c0f571-2393-4f43-8e12-c2b601bf8d24

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Report on the 2013 national cholelithiasis survey in Japan.2015

    • Author(s)
      Tazuma S, Kanno K, Kubota K, Tsuyuguchi T, Kamisawa T, Isayama H, Nakagohri T, Inui K; Academic Committee of the Japan Biliary Association.
    • Journal Title

      J Hepatobiliary Pancreat Sci.

      Volume: 22 Issue: 5 Pages: 392-395

    • DOI

      10.1002/jhbp.206

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The mechanism of increased biliary lipid secretion in mice with genetic inactivation of bile salt export pump.2015

    • Author(s)
      Gooijert KE, Havinga R, Wolters H, Wang R, Ling V, Tazuma S, Verkade HJ.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol.

      Volume: 308 Issue: 5 Pages: G450-G457

    • DOI

      10.1152/ajpgi.00391.2014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Clinical profiles of patients with primary sclerosing cholangitis in the elderly.2015

    • Author(s)
      Tanaka A, Tazuma S, Okazaki K, Tsubouchi H, Inui K, Takikawa H.
    • Journal Title

      J Hepatobiliary Pancreat Sci.

      Volume: 22 Issue: 3 Pages: 230-236

    • DOI

      10.1002/jhbp.194

    • NAID

      40020403869

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Clinical efficacy of intravenous doripenem in patients with acute biliary tract infection: a multicenter, randomized, controlled trial with imipenem/cilastatin as comparator.2014

    • Author(s)
      Tazuma S, Igarashi Y, Inui K, Ohara H, Tsuyuguchi T, Ryozawa S; The BTI Therapy Research Group
    • Journal Title

      J Gastroenterol

      Volume: Epub ahead of print Issue: 2 Pages: 221-229

    • DOI

      10.1007/s00535-014-0960-0

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nationwide survey for primary sclerosing cholangitis and IgG4-related sclerosing cholangitis in Japan.2014

    • Author(s)
      Tanaka A, Tazuma S, Okazaki K, Tsubouchi H, Inui K, Takikawa H.
    • Journal Title

      J Hepatobiliary Pancreat Sci.

      Volume: 21 Issue: 1 Pages: 43-50

    • DOI

      10.1002/jhbp.50

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nutritional factors (nutritional aspects) in biliary disorders: bile acid and lipid metabolism in gallstone diseases and pancreaticobiliary maljunction.2014

    • Author(s)
      Tazuma S, Kanno K, Sugiyama A, Kishikawa N.
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: Suppl 4: Issue: S4 Pages: 103-107

    • DOI

      10.1111/jgh.12241

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Partial characterization of proapoptotic action of biliary deteriorated lipids on biliary epithelial cells in pancreaticobiliary diseases.2014

    • Author(s)
      Fujita K, Sugiyama A, Otoshi K, Taogoshi T, Kimura Y, Kishikawa N, Kodama M, Kanno K, Kihira K, Tazuma S
    • Journal Title

      J Hepatobiliary Pancreat Sci

      Volume: 21 Issue: 3 Pages: 212-218

    • DOI

      10.1002/jhbp.20

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A case of paraneoplastic syndrome mimicking adult Still's disease caused by rectal cancer.2014

    • Author(s)
      Okamoto M, Kanno K, Egi H, Ohdan H, Tazuma S.
    • Journal Title

      J Am Geriatr Soc.

      Volume: 61 Issue: 7 Pages: 1243-1245

    • DOI

      10.1111/jgs.12335

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diagnostic workup for fever of unknown origin: a multicenter collaborative retrospective study2013

    • Author(s)
      Naito T, Mizooka M, Mitsumoto F, Kanazawa K, Torikai K, Ohno S, Morita H, Ukimura A, Mishima N, Otsuka F, Ohyama Y, Nara N, Murakami K, Mashiba K, Akazawa K, Yamamoto K, Senda S, Yamanouchi M, Tazuma S, Hayashi J
    • Journal Title

      BMJ Open

      Volume: 20 Issue: 12 Pages: e003971-e003971

    • DOI

      10.1136/bmjopen-2013-003971

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Management for pancreatolithiasis: a Japanese multicenter study.2013

    • Author(s)
      Suzuki Y, Sugiyama M, Inui K, Igarashi Y, Ohara H, Tazuma S, Tsuji T, Miyakawa H, Atomi Y.
    • Journal Title

      Pancreas.

      Volume: 42 Issue: 4 Pages: 584-588

    • DOI

      10.1097/mpa.0b013e31827308c8

    • NAID

      10025227371

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Retrospective cohort study of the incidence and risk of fever in elderly people living at home: a pragmatic aspect of home medical management in Japan.2013

    • Author(s)
      Yokobayashi K, Matsushima M, Fujinuma Y, Tazuma S.
    • Journal Title

      Geriatr Gerontol Int

      Volume: 13 Issue: 4 Pages: 887-893

    • DOI

      10.1111/ggi.12024

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased serum liver X receptor ligand oxysterols in patients with non-alcoholic fatty liver disease.2012

    • Author(s)
      Ikegami T, Hyogo H, Honda A, et al
    • Journal Title

      Journal of Gastroenterology

      Volume: 47 Issue: 11 Pages: 1257-1266

    • DOI

      10.1007/s00535-012-0585-0

    • NAID

      10031126958

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical diagnostic criteria of IgG4-related sclerosing cholangitis 20122012

    • Author(s)
      Ohara H, Okazaki K, Tsubouchi H, Inui K, Kawa S, et al.
    • Journal Title

      J Hepatobiliary Pancreat Sci

      Volume: 19 Issue: 5 Pages: 536

    • DOI

      10.1007/s00534-012-0521-y

    • NAID

      10031039385

    • URL

      https://localhost/en/publications/026a559c-19fa-4ee3-8a1e-4a2831b844b2

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Profibrotic effect of periostin through a positive feedback loop that amplifies and maintains the activation of hepatic stellate cells.2013

    • Author(s)
      Sugiyama A,Kanno K,Nishimichi N,Sumii S,Tazuma S.
    • Organizer
      AGA
    • Place of Presentation
      Orlando(USA)
    • Related Report
      2013 Research-status Report
  • [Presentation] Hypertension enhances hepatic steatosis througt oxidative stress associated with down-regulated expressions of LXR and FXR :Implication to the future strategy for non-alcoholic fatty liver diseases(NAFLD) by nuclear receptor ligands2012

    • Author(s)
      S.Tazuma,T.Ikuta,K.Kanno,M.Nakashima,A.Sugiyama,N.Kishikawa,H.Kodama,M.Okamoto,Y.Kikuchi,S.Kushihta,K.Yokobayashi,M.Mizooka,T.Saeki,K.Arihiro
    • Organizer
      Falk Symposium
    • Place of Presentation
      Austria
    • Related Report
      2012 Research-status Report
  • [Presentation] Topic:Nutritional Factors(Nutritional Aspects)in Biliary Disorders:Bile Acid and Lipid Metabolism in Gallstone diseases and Pancreaticobiliary Maljunction2012

    • Author(s)
      Susumu Tazuma
    • Organizer
      the 3rd APTC
    • Place of Presentation
      Tokyo
    • Related Report
      2012 Research-status Report
    • Invited
  • [Book] 胆と膵2013

    • Author(s)
      田妻進、菅野啓司、岸川暢介、小林知貴、酒見倫子、横林賢一、串畑重行、溝岡雅文、杉山晶子、大屋敏秀
    • Total Pages
      4
    • Publisher
      医学図書出版株式会社
    • Related Report
      2013 Research-status Report
  • [Book] 胆道2013

    • Author(s)
      田中篤、田妻進、岡崎和一、坪内博仁、乾和郎、滝川一
    • Total Pages
      9
    • Publisher
      杏林舎
    • Related Report
      2013 Research-status Report
  • [Book] 臨床・病理胆道癌取扱い規約2013

    • Author(s)
      田妻進
    • Total Pages
      1
    • Publisher
      金原出版株式会社
    • Related Report
      2013 Research-status Report
  • [Book] 胆と膵2013

    • Author(s)
      大屋敏秀、田妻進
    • Total Pages
      3
    • Publisher
      医学図書出版株式会社
    • Related Report
      2013 Research-status Report
  • [Book] 肝臓専門医テキスト2013

    • Author(s)
      田妻進
    • Total Pages
      512
    • Publisher
      株式会社南江堂
    • Related Report
      2012 Research-status Report
  • [Book] 生活習慣病の薬物療法・治療薬を中心とする臨床医学誌2012

    • Author(s)
      田妻進
    • Total Pages
      12
    • Publisher
      医学出版
    • Related Report
      2012 Research-status Report
  • [Book] 日本消化器がん検診学会雑誌2012

    • Author(s)
      田妻進、三宅弘明
    • Total Pages
      5
    • Publisher
      社団法人日本消化器がん検診学会
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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