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ANALYSIS OF BIOLOGICAL PROGNOSTIC FACTOR TO ESTABLISH TREATMENT FOR PEDIATRIC LIVER TUMOR BY GROUP STUDY

Research Project

Project/Area Number 12470372
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatric surgery
Research InstitutionCHIBA UNIVERSITY

Principal Investigator

OHNUMA Naomi  Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (50125910)

Co-Investigator(Kenkyū-buntansha) HASHIZUME Kohei  Tokyo University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (50180815)
HAYASI Yutaka  Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40125638)
SASAKI Fumiaki  Hokkaido University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (40178661)
NAKAGAWARA Akira  Chiba Cancer Center, Division of Biochemistry, Director, 生化学研究部, 部長 (50117181)
HIYAMA Eiso  Hiroshima University Hospital, Assistant Professor, 医学部・歯学部附属病院, 助教授 (00218744)
Project Period (FY) 2000 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥3,800,000 (Direct Cost: ¥3,800,000)
KeywordsHEPATOBLASTOMA / BETA-CATENIN / cDNA PROJECT / TELOMERASE / MDR1 / P-gp / MRP / cMOAT / Real time PCR / 肝悪性腫瘍 / 薬剤耐性 / CMOAT / cDNA / hTERT / P-glycoprotein / APC / サイクリンD1
Research Abstract

We analyzed beta-catenin abnormality in 68 childhood hepatoblastomas. The high frequency of the beta-catenin abnormality (44/68=65%) indicates an important role in the pathogenesis of hepatoblastoma. The beta-catenin abnormalities do not correlated with patient's outcome. These data suggest that disregulation of the Wnt/beta-catenin pathway is an obligatory step in hepatoblastoma pathogenesis. To identify novel hepatoblastoma (HBL)-related genes as biological markers, we have performed a cDNA project of HBL. Expression profile from HBL was very similar to that from a normal liver, and most genes were related to metabolism in liver. Seven novel genes and 33 novel genes were identified to be expressed at high levels in HBLs and normal livers, respectively. On the other hand, 4 known genes and 43 known genes were identified to be expressed at high levels in HBLs and normal livers, respectively. We examined the levels of hTERT mRNA expression and telomerase activity in 48 hepatoblastoma mRNA samples and 28 frozen tumor samples, respectively. The outcomes of the patients with high hTERT expression or high telomerase activity were significantly worse when compared to other patients (p<0.01). These results indicate that high levels of hTERT mRNA expression as well as telomerase activity may be an independent prognosis-predicting factors in the patients with hepatoblastoma.

Report

(5 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Matsunaga T, et al.: "Analysis of treatment outcome for children with recurrent or metastatic hepatoblastoma"Pediatric Surgery International. 19. 142-146 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sasaki F et al.: "Outcome of Hepatoblastoma Treated with The JPLT-1 (Japanese Study Group For Pediatric Liver Tumor) Protocol-1"Journal of Pediatric Surgery. 37. 851-856 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hajime Takayasu et al.: "Frequent deletions and mutations of the beta-catenin gene are associated with overexpression of cycline D1 and fibronectin and poorly-differentiated histology in childhood hepatoblastoma"Clinical Cancer Research. 7. 901-908 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 松永正訓 他: "再発肝芽腫に対する治療戦略-日本小児肝癌スタディグループ(JPLT)からの報告-"小児外科. 35,5. 628-632 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 大沼直躬 他: "小児肝癌に対する新しい治療"小児外科. 33,11. 1247-1251 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tadashi Matsunaga, Fumiaki Sasaki, Mutsuro Ohira, Kohei Hashizume, Akira Hayashi, Yutaka Hayashi, Hideo Mugishima, Naomi Ohnuma: "Analysis of Treatment Outcome for Children with Recurrent or Metastatic Hepatoblastoma -Report From Japanese Study Group for Pediatric Liver Tumor-"Pediatr Surg Int. 19. 142-146 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sasaki F, Matsunaga T, Iwafuchi M, Hayashi Y, Ohkawa H, Ohira M, OKamatsu T, Sugito T, Tsuchida Y, Toyosaka A, Nagahara N, Nishihira H, Hata Y, Uchino J, Misugi K, Ohnuma N: "Outcome of Hepatoblastoma Treated with The JPLT-1 (Japanese Study Group For Pediatric Liver Tumor) Protocol-1 : A Report from The Japanese Study Group for Pediatric Liver Tumor."J Pediatr Surg. 37. 851-856 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hajime Takayasu, Hiroshi Horie, Eiso Hiyama, Tadashi Matsunaga, Yutaka Hayashi, Yoshio Watanabe, Sachiyo Suita, Michio Kaneko, Fumiaki Sasaki, Kohei Hashizume, Toshinori Ozaki, Keiji Furuuchi, Mitsuhiro Tada, Naomi Ohnuma, Akira Nakagawara: "Frequent deletions and mutations of the beta-catenin gene are associated with overexpression of cycline D1 and fibronectin and poorly-differentiated histology in childhood hepatoblastoma"Clinical Cancer Research. 7. 901-908 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tadashi Matsunaga, Fumiaki Sasaki, Mutsuro Ohira, Kohei Hashizume, Akira Hayashi, Yutaka Hayashi, Hideo Mugishima, Naomi Ohnuma: "Treatment strategy for children with recurrent hepatoblastoma -Report from Japanese Study Group for Pediatric Liver Tumor-"Shonigeka. 35. 628-632 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Naomi Ohnuma, Tadashi Matsunaga, Fumiaki Sasaki, Mutsuro Ohira, Kohei Hashizume, Akira Hayashi, Yutaka Hayashi, Takaharu Matsuyama, Hideo Mugishima: "New therapeutic approach for hepatoblastoma in children"Shonigeka. 33. 1247-1251 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsunaga T, et al.: "Analysis of treatment outcome for children with recurrent or metastatic hepatoblastoma"Pediatric Surgery International. 19. 142-146 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sasaki F et al.: "Outcome of hepatoblastoma treated with the JPLT Protocol-1 : A report from the Japanese Study Group for Pediatric Liver Tumor"Journal of Pediatric Surgery. Vol.37. 851-856 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hajime Takayasu: "Frequent Deletions and Mutations of the s-Catenin Gene Are Associated with Overexpression of Cyclin D1 and Fibronectin and Poorly Differentiated Histology in Childhood Hepatoblastoma"Clinical Cancer Research. Vol.7. 901-908 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fumiaki Sasaki: "Outcome of hepatoblastoma treated with JPLT protocol-1:A report from the Japanese Study Group for Pediatric Liver Tumor"Journal of Pediatric Surgery. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Hajime Takayasu: "Frequent deletions and mutations of the β-catenin gene are associated with over expression of cydinD1 and fibronectin and poorly differentiated histology in childhood hepatoblastoma"Clinical Cancer Research. in press.

    • Related Report
      2000 Annual Research Report
  • [Publications] 大沼直躬: "日本小児肝癌グループスタディ"小児外科. 32・8. 798-805 (2000)

    • Related Report
      2000 Annual Research Report

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

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