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THE MECHANISM OF LIVER FAILURE AFTER EXCESSIVE HEPATECTOMY INVESTIGATED USING CDAN MICROARRAY

Research Project

Project/Area Number 13671322
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionYokohama City University

Principal Investigator

TOGO Shinji  YOKOHAMA CITY UNIV., SCHOOL OF MEDCINE, ASSOCIATE PROF., 大学院・医学研究科, 助教授 (10244477)

Co-Investigator(Kenkyū-buntansha) HAYASHIZAKI Yoshihide  RIKEN GENOME SCIENCE, INSTITUTE PROJECT LEADER, ゲノム科学総合研究センター, プロジェクトディレクター (70192705)
ISHIKAWA Takashi  YOKOHAMA CITY UNIV., SCHOOL OF MEDCINE, ASSIST PROF., センター病院・総合外科, 講師 (80275049)
岡崎 康司  横浜市立大学, 医学部, 助教授 (80280733)
窪田 徹  横浜市立大学, 医学部, 助手 (10315773)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2003: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsapoptosis / postoperative liver failure / cDNA Microarray / Liver regeneration / hepatectomy / cDNA microarra
Research Abstract

Massive hepatectomy often induced lethal hepatic failure. The mechanism has been described using two theories : indirect injury caused by microcircular disturbance induces necrosis to hepatocytes, and direct injury caused by cytotoxic disturbance induces apoptosis to hepatocyte.
Exp.1
Excessive hepatectomy often causes fatal liver failure. We have reported that this is mainly mediated by apoptosis, characterized pathologically by TUNEL assay positive hepatocytes and a ladder pattern in DNA fragmentation assays. To investigate the mechanism, we used a cDNA microarray analysis to compare clearly differentiated rat partial hepatectomy (PHx) models (90%PHx, and 95%PHx). All 90%PHx rats survived, but the 95%PHx animals died of hepatic failure within 96 hours. The remnant liver was obtained at 4 time points (1,3,12, and 24 hrs after PHx). After RNA extraction, two samples were labeled with different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse cDNA arra … More ys. Scanning for fluorescent dye signals was performed, and many caspases were upregulated at 1 hr after PHx in the 95%PHx group. On the other hand, genes of Bcl-2, heat shock proteins and gluthatione-S-transferase were downregulated. We concluded that fatal hepatic after excessive hepatectomy was characterized by increased apoptosis and diminished liver regeneration.
Exp.2
Background/Aim : The liver has the capacity to regenerate after partial hepatectomy. In order to clarify the mechanism of liver regeneration, we observed the initial stage, especially the mechanism of gene expression during progress from G0 to S phase (0〜24 hrs), and attempted to identify the new gene controlling progress to the S phase.
Methods : We applied large-scale gene expression analysis with complementary DNA (cDNA) microarrays in mouse hepatectomy models to clarify the mechanism of liver regeneration after partial hepatectomy.
Results : As a result, 23 new immediate-early gene candidates such as IRAK-1 (interleukin-1 receptor associated kinase-1) and karyopherin alpha 1, which are involved in transportation within the nucleus, were discovered. Candidates for new genes concerned with the progress to the S phase were discovered : ID2 (inhibitor of DNA binding 2) and ID3 (inhibitor of DNA binding 3), both new liver regeneration factors that promoted progress to the S phase, and Gadd45 gamma (growth arrest and DNA-damage-inducible protein) as a factor inhibiting that process.
Conclusions : The above result not only suggests the importance of NF-κB in the initial stage of liver regeneration but also points to the orderly maintenance of the proliferation of the cells in liver regeneration. Less

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Togo S et al.: "Mechanism of liver regeneration after partial hepatectomy using mouse cDNA microarray"J Hepatology. 40(3). 464-471 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 渡会伸治 他: "術後肝障害の発生機序"肝胆膵. 48. 197-205 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimizu D, Togo S et al.: "Current progress in the prediction of chemosensitivity for breast cancer"Breast Cancer. 11(1). 42-48 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujii Y, Togo S et al.: "Risk factor of posthepatectomy liver failure after portal vein embolization"J Hepatobiliary Pancreat Surg. 10. 226-232 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujii Y, Togo S et al.: "Effect of portal vein embolization before major hepatectomy"Hepato-Gastroenterology. 50. 438-442 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tomoyuki Morita et al.: "Mechanism of postoperative liver failure after excessive hepatectomy investigated using cDNA micoarray."J Hep Bil Pancr Surg.. 9. 352-359 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takeda K et al.: "Clinicohistological features of liver failure after excessive hepatectomy."Hepato-Gastroenterology. 49. 354-358 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujii Y et al.: "Risk factors of posthepatectomy liver failure after portal vein embolization."J Hep Bil Pancr Surg.. 10. 226-232 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Togo S et al.: "Mechanism of liver regeneration after partial hepatectomy using mouse cDNA microarray"J Hepatology. 40. 464-471 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Togo S: "Mechanism of liver regeneration after partial hepatectomy using mouse cDNA microarray"J hepatology. 40(3). 464-471 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 渡会伸治: "術後肝障害の発生機序"肝胆膵. 48. 197-205 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimizu D: "Current progress in the prediction of chemosensitivity for breast cancer"Breast Cancer. 11(1). 42-48 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujii Y: "Risk factor of posthepatectomy liver failure after portal vein embolization"Hepatobiliary Pancreat Surg. 10. 226-232 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujii Y: "Effect of portal vein embolization before major hepatectomy"Hepato-Gastroenterology. 50. 438-442 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishizuka I, Togo S et al.: "Analysis of Gene Expression Involved in Brain Metastasis from Brest Cancer Using cDNA Microarray"Brest Cancer. 9(1). 26-32 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 石川孝, 渡会伸治, 他: "マウスcDNAマイクロアレイを用いた癌関連遺伝子の発現解析"ゲノム医学. 2(1). 19-27 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takeda K, Togo S, et al.: "Clinicohistological features of liver failure after excessive hepatectomy"Hepato-Gastoenterology. 49. 354-358 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagano Y, Togo S et al.: "Improved functional reserve of hypertrophied contra lateral liver after Portal vein ligation in rats"J.Hepatology. 37(7). 72-77 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ichikawa Y, Togo S et al.: "Identification of genes regulating colorectal carcinogenesis by using the algorithm for diagnosing malignant state method"Biochemical and Biophysical Research Communications. 296. 497-506 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Morita T, Togo S et al.: "Mechanism of postoperative liver failure after excessive hepatectomy investigated using a cDNA microarray"J Hepatobiliary Pancreat Surg. 9. 352-359 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kamimukai N, Toga S et al.: "Expression of Bcl-2 family reduces apoptotic hepatocytes after excessive hepatectomy"Eur Surg Res. 33. 8-15 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tanaka K, Toga S et al.: "Is hepatic resection for multiple liver metastases from colorectal carcinoma acceptable treatment ?"Hepato-Gastroenterology. 48. 803-807 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Komatsu S, Toga S et al.: "Monocyte CD 1 4 changes and endotoxemia after major hepatectomy"Hepato-Gastroenterology. 48. 1716-1720 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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