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Identification of new prognostic markers for esophageal cancer using molecular biologic techniques, and their clinical application for diagnosis and treatment.

Research Project

Project/Area Number 09470264
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionThe University of Tokyo

Principal Investigator

MAFUNE Ken-ichi  Department of Surgery, Faculty of Medicine, the University of Tokyo, Lecturer, 医学部・附属病院, 講師 (40192348)

Co-Investigator(Kenkyū-buntansha) TAKUBO Kaiyo  Department of Clinical Pathology, Tokyo Metropolitan Institute of Gerontology, Head (Researcher), 臨床病理部門, 室長(研究員) (00154956)
MORI Masaki  Department of Surgical Oncology, Medical Institute of Bioreguration, Kushu University, Professor, 生体防御医学研究所, 教授 (70190999)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1997: ¥7,300,000 (Direct Cost: ¥7,300,000)
Keywordsesophageal cancer / prognostic factor / ornithine decarboxylase / integrin α6 / pynrimidine nucleoside phosphorylase / MAGE gene family / Grb7 / オルニチン脱炭酸酵素 / L-myc遺伝子多型 / p53遺伝子多型 / DMBT1 / テロメラーゼ活性
Research Abstract

Esophageal cancer usually behaves aggressively and carries a poor prognosis against intensive multimodality treatment Therefore, it is very important to identify novel prognostic markers for esophageal cancer. In this project, more than 20 cancer-related genes were selected using molecular biological techniques, such as differential screening, subtraction library, and differential display. Genetic changes, such as mutations, polymorphisms, and mRNA over expression, of these genes were examined in surgical specimens of esophageal cancer, and correlated with clinicopathologic factors. In this term of the project, we have published papers concerning telomerase activity, MAGE genes, omithine decarboxylase (ODC), integrin α6, Grb7, pyramiding nucleoside phosphorylase (PyNPase), and L-myc polymorphism. In addition, we have presented papers concerning insulin-like growth factor 2, p53, Rb, bcl-2, manganese super oxide dismutase, matrix metallopreteinase-7, point mutations and polymorphism of p53, and microsatellite instability in esophageal cancer at national aid international meetings. Of those genetic changes in esophageal cancer, mRNA expressions of ODC, integrin α6, Grb7, and PyNPase are candidates for prognostic factors. Among these candidates including other genes reported as prognostic factors (such as c-myc, EGF-receptor. hst-1/int-2, cycline D. and elongation factor-γ), Prognostic factors for esophageal cancer should be carefully selected. As clinical applications. ODC mRNA expression was also examined in endoscopic, biopsied specimens, and could be correlated with clinicopathologic factors. Furthermore. MAGE genes are now trying to apply immunotherapy.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] K. Takubo, et al.: "Telomerase activity in esophageal carcinoma."Journal of Surgical Oncology. 66. 88-92 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] F. Tanaka, et al.: "High frequency of the expression of the MAGE gene family in human esophageal carcinoma."Internationa Journal of Oncology. 10. 1113-1117 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 森正樹,他: "Matrix meralloproteinase7,integrin α6と 消化器癌の湿潤・転移"消化器癌の発生と進展. 9. 19-20 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Tanaka, et al.: "A novel variant of human Grb7 is associated with invasive esophage carcinoma."Journal of Clinical Investigation. 102. 821-827 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 仲村賢一,他: "腫瘍マーカーとしてのテメロレース活性-食道癌を例として"腫瘍マーカー研究会誌. 13. 547-551 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 田久保海誉,他: "噴門部の病理"日本外科学会雑誌. 99. 547-551 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M. Mori, et al.: "Lack of DMBTI expression in oesophageal, gastric and colon cancers"British Journal of Cancer. 79. 211-213 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Takubo, et al.: "Primary undifferentiated small cell carcinoma of the esophagus."Human Pathology. 30. 216-221 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Takubo, et al.: "Telomere shortening with with aging in the esophageal mucosa."Age. 22. 95-99 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M. Yamagata, et al.: "Expression of pyrimidine nucleoside phospherylase mRNA plays an impertant role in prognosis of patients with cesophageal cancer."British Journal of Cancer. 79. 565-569 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 仲村賢一,他: "消化管(食道,胃,大腸)の癌部と非癌部のテロメア長"腫瘍マーカー研究会誌. 14. 33-35 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Mafune, et al.: "Increased expression of ornithine decarboxylase messenger RNA in human esophageal caranoma."Clinical Cancer Research. 5. 4073-4078 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Shibuta, et al.: "L-myc restriction fragment length polymorphism in Japanese patients with esophageal cancer."Japanese Journal of Cancer Research. 91. 199-203 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Tanaka, et al.: "a6 integrin exprission in esophageal carcinoma."International Journal of Oncology. 16. 725-729 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M. Mori, et al.: "Altered expression of Fhit in carcinoma and precarcinomatous lesions of the esophagus."Cancer Research. 60. 1177-1182 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kaiyo Takubo: "Pathology of the Esophagus"Educa, Tokyo. 325 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takubo K, Nakamura K, Izumiyama N, Mafune K, Tanaka Y, Miyashita M, Sasajima K, Kato M, Oshimura M.: "Telomerase activity in esophageal carcinoma"J Surg Oncol. 66. 88-92 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka F, Mori M, Li J, Fujie T, Mimori K, Haraguchi M, Tanaka Y, Mafune K, Akiyoshi T.: "High frequency of the expression of the MAGE gene family in human esophageal carcinoma."Int J Oncol. 10. 113-1117 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mori- M, Haraguchi M, Tanaka S, Mimori K, Shiraishi T, Mafune K, Tanaka Y, Ueo H, Sugimachi K, Akiyoshi T.: "Significance of Matrix metalloproteinase 7 and Integrin α6 in gastrointestinal tumor cell Invasion and metastasis."Journal of Japanese Society for Gastroenterological Carcinogenesis. 9. 19-20 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka S, Mori M, Akiyoshi T, Tanaka Y, Mafune K, Wands JR, Sugimachi K.: "A novel variant of human Grb7 is associated with invasive esophageal carcinoma."J Clin Invest. 102. 821-827 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura K, Takubo K, Tanaka Y, Mafune K, Sasajima K, Miyashita M, Esaki Y, Kato M, Oshimura M.: "Telomerase activity as a tumor maker : for esophageal carcinoma."Journal of Tumor Marker Society. 13. 117-119 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takubo K, Mafune K, Tanaka Y, Sasajima K.: "Pathology of cardia"J Jpn Surg Soc. 99. 547-551 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mori M, Shiraishi T, Tanaka S, Yamagata Mm, Mafune K, Tanaka Y, Ueo H, GF Barnard, Sugimachi K.: "Lack of DMBT1 expression in oesophageal, gastric and colon cancers."Br J Cancer. 79. 211-213 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takubo K, Sawabe M, Arai T, Esaki Y, Miyashita M, Mafune K, Tanaka Y, Sasajima K.: "Primary undifferentiated small cell carcinoma of the esophagus."Hum Pathol. 30. 216-221 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takubo K, Nakamura K, Izumiyama N, Sawabe M, Arai, T, Esaki Y, Tanaka Y, Mafune K, Fujiwara M, Kammori M, Sasajima K.: "Telomere shortening with aging in the esophageal mucosa."Age. 22. 95-99 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamagata M, Mori M, Mimori K, Mafune K, Tanaka Y, Ueo H, Akiyoshi T.: "Expression of pyrimidine nucleoside phosporylase mRNA plays an important role in the prognosis of patients with oesophageal cancer."Br J Cancer. 79. 565-569 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nkamura K, Furugori E, Takubo K, Izumiyama N, Arai T, Esaki Y, Fujiwara M, Okayasu I, Osimura M.: "Telomere shortening in gastrointestinal (esophageal, gastric and colon) cancers."Journal of Tumor Marker Society. 14. 33-35 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mafune K, Tanaka Y, Minori K, Mori M, Takubo K, Makuuchi M.: "Increased expression of ornithine decarbxylase messenger RNA in human esophageal carcinoma."Clin Cancer Res. 5. 4073-4078 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sihbuta K, Sato K, Matsuyama A, Ueo H, Tanaka Y, Mafune K, Barnard GF, Mori M.: "L-myc restriction fragment length polymorphism in Japanese patients with esophageal cancer."Jpn J Cancer Res. 91. 199-203 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka Y, Mimori K, Shiraishi T< Ohkura Y, Takubo K, Mafune K, Barnard G, Mori M.: "α6 integrin expression in esophageal carcinoma."Int J Oncol. 16. 1177-1182 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mori M, Mimori K, Shiraishi T, Alder H, Inoue H, Tanaka Y, Sugimachi K, Huebner K, Croce C.: "Altered expression of Fhit in carcinoma and precarcinomatous lesions of the esophagus."Cancer Res. 60. 1177-1182 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kaiyo Takubo: "Pathology of the Esophagus"Educa, Tokyo. 325 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takubo, K., et al.: "Primary undifferentiated small cell carcinoma of the esophagus"Human Pathology. 30. 216-221 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mafune, K., et al.: "Increased expression of ornithine decarboxylase messenger RNA in human esophageal carcinoma"Clinical Cancer Research. 5. 4073-4078 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shibuta, K., et al.: "L-myc restriction fragment length polymorphism in Japanese patients with esophageal cancer"Japanese Journal of Cancer Research. 91・2. 199-203 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tanaka, Y., et al.: "α6 integrin expression in esophageal carcinoma"Intenational Journal of Oncology. 16(in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takubo, K., et al.: "Telomere shortening with aging in the esophageal mucosa"Age. 23(in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Tabaka, S., et al.: "A dominant negative mutation of transforming growth factor-beta receptor type II in microsatellite stable oesophageal carcinoma"British Journal of Cancer. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Kaiyo Takubo: "Pathology of the Esophagus"Educa, Tokyo (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shinji Tanaka,et al.: "a novel variant of human Grb7 is associated with invasive esophageal carcinoma" Journal of Clinical Investigation. 102・4. 821-827 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Mori,et al.: "Lack of DMBT1 expression in oesophageal,gastric and colon cancers" British Journal of Cancer. 79・2. 211-213 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Yamagata,et al.: "Expression of pyrimidine nucleoside phosphorylase mRNA plays an improtant role in the prognosis of patients with oesophageal cancer" British Journal of Cancer. 79・3/4. 565-569 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kaiyo Takubo, et al.: "Telomerase activity in esophageal carcinoma." Journal of Surgical Oncology. 66・1. 88-92 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fumiaki Tanaka, et al.: "High frequency of the expression of the MAGE gene family in human escphageal carcinoma." International Journal of Oncology. 10. 1113-1117 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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