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Inflammation-Associated Lipid Mediators in Cholestatic Hepatobiliary Diseases and Effect of PAF-AH

Research Project

Project/Area Number 12670456
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionTHE UNIVERSITY OF TSUKUBA

Principal Investigator

SHODA Junichi  Institute of Clinical Medicine, University of Tsukuba, Assistant Professor, 臨床医学系, 講師 (90241827)

Co-Investigator(Kenkyū-buntansha) SUZUKI Hiroshi  Graduate School of Pharmaceuticak Sciences, University of Tokyo, 薬学部, 助教授 (80206523)
KAWAMOTO Toru  Institute of Clinical Medicine, University of Tsukuba, Assistant Professor, 臨床医学系, 講師 (30282354)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
Keywordsbilirubin / obstractive cholestasis / primary hepatolithiasis / hepatobiliary malignancy / biliary secretory mechanism / canalicular membrane transporter / bile acid / oxidative stress / 経皮経肝胆道ドレナージ / 輸送蛋白 / 胆汁うっ滞 / 脂質メディエーター / 炎症病態 / ホスホリパーゼAz / 血小板活性化因子 / PAF-AH / 肝輸送蛋白
Research Abstract

The transport of biliary constituents across the canalicular membrane is the rate-limiting step in bile formation. Since long-standing biliary obstruction and complication of cholangitis associated with biliary infection have a large influence upon the hepatic secretory function through inflammation-related oxidative stress on the liver, interest should be focused on the expression levels of canalicular membrane transporter proteins in the cholestatic liver of patients with hepatobiliary diseases. We determined the molecular and immunohistochemical expression of canalicular transporter proteins, for bilirubin conjugate and bile acid,in the liver of patients with hepatolithiasis and in those of the patients with obstructive cholestasis who had undergone preoperative biliary drainage. Furthermore, their expression levels were correlated with the impairment of biliary secretion.
This study concludes that in the liver of hepatobiliary diseases, the altered expression of the canalicular transporters may be associated with the impairment of bile formation and secretion, propably through inflammation-related oxidative stress on the liver.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Shoda, J., et al.: "Etiological significance of metabolic defects of cholesterol, phospholipid, and bile acid in the liver of patients with intrahepatic calculi"Hepatology. 33. 1194-1205 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shoda, J., et al.: "The expression level of the plasma membrane transporters, multidrug resistance-associated protein (MRP) 2, MRP 3 and bile salt export pump, in the cholestatic"Am J Gastroenterol. 96. 3368-3378 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawamoto, T., Shoda, J., et al.: "Expression of cyclooxygenase-2 in the subserosal layer correlates with postsurgical prognosis of pathological tumor stage 2 carcinoma of the gallbladder"Int J Cancer. 98. 427-434 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Asano, T., Shoda, J., et al.: "Expression of cyclooxygenase-2 in carcinoma of the gallbladder-crucial role of arachidonate metabolism in tumor growth and progression"Clin Cancer Res. 8. 1157-1167 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shoda, J., et al.: "The molecular basis of gallstone pathogenesis and its potential therapy. Hepatolithiasis-Epidemiology and pathogenesis update"Frontiers in Bioscience. 8. 398-409 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shoda, J., et al.: "Involvement of prostaglandin E_2, and its specific receptor subtype EP_4 in chronic proliferative cholangitis in the bile ducts of patients with hepatolithiasis"Clin Gastroenterol & Hepatol. (In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shoda, J., Oda, K., Suzuki, H., Sugiyama, Y., Ito., K, Cohen, D.E., Feng, L., Kamiya, Nimura, Y., Miyazaki, H., Kano, M., Matsuzaki, Y., Tanaka, N.: "Metabolic defects of cholesterol, phospholipid, and bile acid in the liver of patients with intrahepatic calculi, and etiological significance"Hepatology. 33. 1194-1205 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shoda, J., Kano,M., Oda, K., Kamiya, J., Nimura, Y., Suzuki H., Sugiyama, Y., Miyazaki, H., Todoroki, T., Stengelin, S., Kramer, W., Matsuzaki, Y., Tanaka, N.: "The expression level of the plasma membrane transporters, multidrug resistance-associated protein (MRP) 2, MRP 3 and bile salt export pump, in the cholestatic liver of patients undergoing biliary drainage."Am J Gastroenterol. 96. 3368-3378 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shoda, J., et al.: "Etiological significance of metabolic defects of cholesterol, phospholipid, and bile acid in the liver of patients with intrahepatic calculi"Hepatology. 33. 1194-1205 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shoda, J., et al.: "The expression level of the plasma membrane transporters, multidrug resistance-associated protein (MRP) 2, MRP 3 and bile salt export pump, in the cholestatic"Am J Gastroenterol. 96. 3368-3378 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawamoto, T., Shoda, J., et al.: "Expression of cyclooxygenase-2 in the subserosal layer correlates with postsurgical prognosis of pathological tumor stage 2 carcinoma of the gallbladder"Int J Cancer. 98. 427-434 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Asano, T., Shoda, J., et al.: "Expression of cyclooxygenase-2 in carcinoma of the gallbladder-crucial role of arachidonate metabolism in tumor growth and progression"Clin Cancer Res. 8. 1157-1167 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shoda, J., et al.: "The molecular basis of gallstone pathogenesis and its potential therapy Hepatolithiasis-Epidemiology and pathogenesis update"Frontiers in Bioscience. 8. 398-409 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shoda, J., et al.: "Involvement of prostaglandin E_2 and its specific receptor subtype EP_4 in chron proliferative cholangitis in the bile ducts of patients with hepatolithiasis"Clin Gastroenterol & Hepatol. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawamoto, T., Shoda, J., et al.: "Expression of MUC1 mucins in the subserosal layer correlates with post-surgical prognosis of pT_2 carcinoma of the gallbladder"Clinical Cancer Research. 7. 1333-1342 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shoda, J., et al.: "Etiological significance of metabolic defects of cholesterol, phospholipid, and bile acid in the liver of patients with intrahepatic calculi."Hepatology. 33. 1194-1205 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shoda, J., et al.: "The expression level of the plasma membrane transporters, multidrug resistance-associated protein (MRP)2, MRP3 and bile salt export pump, in the cholestatic liver of patients undergoing biliary drainage"American Journal of Gastroenterology. 96. 3368-3378 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawamoto, T., Shoda, J. et al.: "Expression of cyclooxygenase-2 in the subserosal layer correlates with postsurgical prognosis of pathological tumor stage 2 carcinoma of the gallbladder"International Journal of Cancer. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Asano, T., Shoda, J., et al.: "Expression of cyclooxygenase-2 in carcinoma of the gallbladder-crucial role of arachidonate metabolism in tumor growth and progression"Clincal Cancer Research. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kano, M., Shoda, J., et al.: "Increased expression of gallbladder cholecystokinin-A receptor in prairie dog fed a high-cholesterol diet and its dissociation with decreased contractility in response to cholecystokinin"Journal of Laboratory and Clincal Medicine. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Itoh, S. et al.: "Suppression of hepatic lesions in a murine graft-versus-host reaction by antibodies against adhesion molecules"Journal of Hepatology. 32. 587-595 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Todoroki,T. et al.: "Treatment strategy for patients with middle and lower third bile duct cancer"British Jornal of Cancer . (In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawamoto,T. et al.: "Expression of MUCI mucins in the subserosal layer correlates with post-surgical prognosis of pT_2 carcinoma of the gallbladder"Clinical Cancer Research. (In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shoda,J. et al.: "Metabolic defects of cholesterol, phospholipid, and bile acid in the liver of patients with intrahepatic calculi, and etiological significance"Hepatology. (In press). (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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