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Clonal diversity and its imphcution in multistage development of hepatocellnlar caronoma

Research Project

Project/Area Number 18590729
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKyoto University

Principal Investigator

FUKUDA Yoshihiro  Kyoto University, Graduate School of Mechicine, Professor (50127130)

Co-Investigator(Kenkyū-buntansha) UEDA Mikiko  Kyoto University, Graduate School of Medicine, Lecturer (20322159)
NISHIMURA Takafumi  Kyoto University, Graduate School of Medicine, Assistant Professor (40378732)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,760,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordshepatocellular carcinoma / living donor liver transplantation / 移植・再生医療 / 遺伝子 / 癌 / 外科 / 病理学
Research Abstract

Genomic diversity and its implication in multistage development were explored by analyzing chrmosomal alterations found in multiple liver nodule obtained from patients with hepatocellular carcinoma who had and one living donor orthotopic liver transplantation.
Tumor and non tumor tissue were obtained at the time of surgery, from patients who had provided written informed consent DNA was extracted by using conventional proteinase K/phenol-chloroform method Four-hundred pane of PCR primers that distribute almost equally throughout 22 autosome and X chromosome wee used to amplify microsatellite loci. Allelic imbalances were determined on the bass of the area under the curve of PCR product that derived from the tumor and the non-tumor sample Single nucleotide polymorphism (SNP) array were used to discriminate chromosomal and losses.
Seventy-two patients with hepatocellular carcinoma had received living-donor liver transplantation in between April 2004 and August and August 2007. A total of 20 nodules were obtained from eight of these patients. Recurrent chromosome alterations, such as -1p, +1q, +5, +7, -8p, +8q, -16q, -17p, were detected. Chromosomal relationship analysis revealed that seven patients out of eight had metastatic nodule, while only one patient had tumors of multicentric origin.
Furthermore, chromosome analysis of 30 nodules m a patient detected both genetically stable tumors that was hind to have common chromosome alterations such as -1p, +1q, -6q, -16q, +22q, and unstable tumors that had multiple alterations throughout almost all chromosome.
Although chromosomal alterations detected m hepatocellular carcinoma m patients with end-stage liver disease were generally stable, chromosomal instability might occur by an unknown but possibly different mechanism.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (31 results)

All 2008 2007 2006

All Journal Article (27 results) (of which Peer Reviewed: 16 results) Presentation (4 results)

  • [Journal Article] Superiority of serum type-I arginase and ornithine carbamyltransferase in the detection of toxicant-induced acute hepatic injury in rats.2008

    • Author(s)
      Murayama H, Ikemoto M, Fukuda Y, Nagata A.
    • Journal Title

      Clinica Chimica Acta

    • NAID

      130007003630

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Aberrant methylation of multiple tumor suppressor genes in aging liver, chronic hepatitis, and hepatocellular carcinoma.2008

    • Author(s)
      Nishida N, Nagasaka T, Nishimura T, Ikai I, Boland CR, Goel A.
    • Journal Title

      Hepatology 47

      Pages: 908-18

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Superiority of serum type-I arginase and ornithine carbamyltransferase in the detection of toxicant-induced acute hepatic injury in rats2008

    • Author(s)
      Murayama, H, Ikemoto, M, Fukuda, Y, Nagata, A
    • Journal Title

      Clinica Chimica Acta (Epub)

    • NAID

      130007003630

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Aberrant methylation of multiple tumor suppressor genes in aging liver, chronic hepatitis and hepatocellular carcinoma2008

    • Author(s)
      Nishida, N, Nagasaka, T, Nishimura, T, Ikai, I, Boland, CR, Goel, A
    • Journal Title

      Hepatology 47

      Pages: 908-18

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Superiority of serum type-I arginase and ornithine carbamyltransferase in the detection of toxicant-induced acute hepatic injury in rats.2008

    • Author(s)
      Murayama H, Ikemoto M, Fukuda Y, Nagata A.
    • Journal Title

      Clinica Chimica Acta (Epub)

    • NAID

      130007003630

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum level of ornithine carbamoyltransferase is influenced by the state of Kupffer cells2007

    • Author(s)
      Murayama H, Ikemoto M, Fukuda Y, Tsunekawa S, Nagata A.
    • Journal Title

      Clinica Chimica Acta 380

      Pages: 170-4

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Ratio of serum ornithine carbamoyltransferase to alanine aminotransfer ase as a potent indicator for hepatocellular carcinoma2007

    • Author(s)
      Murayama H, Fukuda Y, Tsunekawa S, Ikemoto M, Nagata A.
    • Journal Title

      Clinical Biochemistry 40

      Pages: 1077-80

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The technical pitfalls of duct-to-duct biliary reconstruction in pediatric living-donor left-lobe liver transplantation: The impact of stent placement.2007

    • Author(s)
      Sakamoto S, Egawa H, Ogawa K, Ogura Y, Oike F, Ueda M, Yazumi S, Shibata T, Takada Y, Uemoto S.
    • Journal Title

      Pediatric transplantation

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Expansion of selection criteria for patients with hepatocellular carcinoma in living donor liver transplantation.2007

    • Author(s)
      Ito T, Takada Y, Ueda M, Haga H, Maetani Y, Oike F, Ogawa K, Sakamoto S, Ogura Y, Egawa H, Tanaka K, Uemoto S.
    • Journal Title

      Liver Transplantation 13

      Pages: 1637-44

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Living donor liver transplantation for patients with HCC exceeding the Milan criteria: a proposal of expanded criteria.2007

    • Author(s)
      Takada Y, Ito T, Ueda M, Saka moto S, Haga H, Maetani Y, Ogawa K, Ogura Y, Oike F, Egawa H, Uemoto S.
    • Journal Title

      Digestive Disease 25

      Pages: 299-302

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Living donor liver transplantation with reduced monosegments for neonates and small infants.2007

    • Author(s)
      Ogawa K, Kasahara M, Sakamoto S, Ito T, Taira K, Oike F, Ueda M, Egawa H, Takada Y, Uemoto S.
    • Journal Title

      Transplantation 83

      Pages: 1337-40

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Prevalence and incidence of anemia in Japanese cancer patients receiving outpatient chemotherapy.2007

    • Author(s)
      Kitano T, Tada H, Nishimura T, Teramukai S, Kanai M, Nishimura T, Misawa A, Yoshikawa K, Yasuda H, Ishiguro H, Matsumoto S, Yanagihara K, Fukushima M.
    • Journal Title

      International Journal of Hematology 87

      Pages: 37-41

    • NAID

      10018515509

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Extensive methylation is associated with beta-catenin mutations in hepatocellular carcinoma: evidence for two distinct pathways of human hepa tocarcinogenesis.2007

    • Author(s)
      Nishida N, Nishimura T, Nagasaka T, Ikai I, Goel A, Boland CR
    • Journal Title

      Cancer Res 67

      Pages: 4586-94

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Serum level of ornithine carbamoyltransferase is influenced by the state of Kupffer cells2007

    • Author(s)
      Murayama, H, Ikemoto, M, Fukuda, Y, Tsunekawa, S, Nagata, A
    • Journal Title

      Clinica Chimica Acta 380

      Pages: 170-4

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Ratio of serum ornithine carbamoyltransferase to alanme aminotransferase as a potent indicator for hepatocellular carcinoma2007

    • Author(s)
      Murayama, H, Fukuda, Y, Tsunekawa, S, Ikemoto, M, Nagata, A
    • Journal Title

      Clinical Biochemistry 40

      Pages: 1077-80

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The technical pitfalls of duct-to-duct bihary reconstruction m pediatric living-donor left-lobe liver transplantation : The impact of stent placement2007

    • Author(s)
      Sakamoto, S, Egaiva, H, Ogawa, K, Ogura, Y, Oike, F, Ueda, M, Yazumi, S, Shibata, T, Takada, Y, Uemoto, S
    • Journal Title

      Pediatric transplantation (Epub)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Expansion of selection criteria for patients with hepatocellular carcinoma in living donor liver transplantation2007

    • Author(s)
      Ito, T, Takada, Y, Ueda, M, Haga, H, Maetani, Y, Oike, F, Ogawa, K, Sakamoto, S, Ogura, Y, Egavva, H, Tanaka, K, Uemoto, S
    • Journal Title

      Liver Transplantation 13

      Pages: 1637-44

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Living donor liver transplantation for patients with HCC exceeding the Milan criteria : a proposal of expanded criteria2007

    • Author(s)
      Takada, Y, Ito, T, Ueda, M, Sakamoto, S, Haga, H, Maetani, Y, Ogawa, K Ogura, Y, Oike, F, Egawa, H, Uemoto, S
    • Journal Title

      Digestive Disease 25

      Pages: 299-302

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Living donor liver transplantation with reduced monosegments for neonates and small infante2007

    • Author(s)
      Ogawa, K, Kasahara, M, Sakamoto, S, Ito, T, Taira, K Oike, F, Ueda, M, Egawa, H, Takada, Y, Uemoto, S
    • Journal Title

      Transplantation 83

      Pages: 1337-40

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Prevalenceiand incidence of anemia in Japanesecancer patients receiving outpatient chemotherapy2007

    • Author(s)
      Kitano, T, Tada, H, Nishimura, T, Teramukai, S, Kauai, M, Nishimura, T, Misawa, A, Yoshikawa, K, Yasuda, H, Ishiguro, H, Matsumoto, S, Yanagihara, K, Fukushima, M
    • Journal Title

      International Journal of Hematology 87

      Pages: 37-41

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Extensive methylation is associated with beta-catenin mutations in hepatocellular carcinoma, evidence for two2007

    • Author(s)
      Nishida, N, Nishimura, T, Nagasaka, T, Ikai, I, Goel, A, Boland, CR
    • Journal Title

      Cancer Res 67

      Pages: 4586-94

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Ratio of serum ornithine carbamoyltransferase to alanine aminotransferase as a potent indicator for hepatocellular carcinoma2007

    • Author(s)
      Murayama H, Fukuda Y, Tsunekawa S, Ikemoto M, Nagata A.
    • Journal Title

      Clinical Biochemistry 40

      Pages: 1077-80

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The technical pitfalls of duct-to-duct biliary reconstruction in pediatric living-donor left-lobe liver transplantation: The impact of stent placement.2007

    • Author(s)
      Sakamoto S, Egawa H, Ogawa K, Ogura Y, Oike F, Ueda M, Yazumi S, Shibata T, Takada Y, Uemoto S.
    • Journal Title

      Pediatric transplantation (Epub)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Living donor liver transplantation for patients with HCC exceeding the Milan criteria: a proposal of expanded criteria.2007

    • Author(s)
      Takada Y, Ito T, Ueda M, Sakamoto S, Haga H, Maetani Y, Ogawa K, Ogura Y, Oike F, Egawa H, Uemoto S.
    • Journal Title

      Digestive Disease 25

      Pages: 299-302

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence and incidence of anemia in Japanese cancer patients receiving outpatient chemotherapy.2007

    • Author(s)
      Kitano T, Tada H, Nishimura T, Teramukai S, Kanai M, Nishimura T, Misawa A, Yoshikawa K, Yasuda H, Ishiguro H, Matsumoto S, Yanagihara K, Fukushima M.
    • Journal Title

      International Journal of Hematology 86

      Pages: 37-41

    • NAID

      10018515509

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Extensive methylation is associated with beta-catenin mutations in hepatocellular carcinoma: evidence for two distinct pathways of human hepatocarcinogenesis.2007

    • Author(s)
      Nishida N, Nishimura T, Nagasaka T, Ikai I, Goel A, Boland CR.
    • Journal Title

      Cancer Research 67

      Pages: 4586-94

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide semiquantitative microsatellite analysis of human hepatocellular carcinoma : discrete mapping of smallest region of overlap of recurrent chromosomal gains and losses2006

    • Author(s)
      Takafumi Nishimura, et al.
    • Journal Title

      Cancer Genetics and Cytogenetics 167

      Pages: 57-65

    • Related Report
      2006 Annual Research Report
  • [Presentation] ヒト肝細胞癌における染色体不安定性,メチル化不安定性と癌関連遺伝子変異の相関.2007

    • Author(s)
      西田 直生志
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Chromosomal instability, epigenetic instability and mutations of cancerrelated gene in human hepatocellular carcinoma2007

    • Author(s)
      Nishida, N, Nishimura, T, Nagasaka, T, Fukuda, Y Chiba, T
    • Organizer
      Japanese Cancer Association 66th Annual meeting
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Genome alterations in sporadic gastrointestinal cancer: a comprehensive review in the literature.2007

    • Author(s)
      Nishimura T
    • Organizer
      American Association for Cancer Research
    • Place of Presentation
      Los Angeles
    • Year and Date
      2007-04-15
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Genome Alterations m sporadic gastrointestinal cancer : a comprehensive review in the literature2007

    • Author(s)
      Nishimura, T
    • Organizer
      American Association for Cancer Research 98th Annual meeting
    • Place of Presentation
      Los Angeles
    • Year and Date
      2007-04-15
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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