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Development of high sensitive screening method by fecal DNA test targeting colorectal cancer; pancreatic and binary tract cancers

Research Project

Project/Area Number 17591403
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MATSUBARA Nagahide  Okayama University, Medical and Dental Hospital, Assistant Professor, 医学部・歯学部附属病院, 助手 (70314672)

Co-Investigator(Kenkyū-buntansha) HAYATSU Hikoya  Shujitsu University, School of Pharmacy, Professor, 薬学部, 教授 (10012593)
SHIMIZU Kenji  Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院医歯薬学総合研究科, 教授 (10037286)
KAMBARA Takeshi  Okayama University, Medical School, Visiting Scientist, 医学部, 客員研究員 (60379724)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsgastroenterological cancer / carcinogenesis / genetic alteration / epigenetic alteration / colorectal cancer / gastric cancer / esophageal cancer / mi crosatel1ite instability / 遺伝子 / 癌 / 診断 / 臨床
Research Abstract

We have been studied molecular mechanisms of gastrointestinal carcinogenesis and cancer progression. Recently not only genetic, including mutations and deletions, but also epigenetic alterations are involved in many types of carcinogenesis. The most typical epigenetic alteration is the promoter hypermethylation, which causes the silencing of the gene. DNA methylation occurs preferentially within dense clusters of CpG sites know as CpG islands. Therefore reference is made to a CpG island methylator phenotype (CIMP). we classified colorectal cancer by mutational status of KRAS and BRAF, and showed close correlation to the methylation status of the multiple promoter methylation in colorectal cancer (Journal of Clinical Oncology). More recently, we investigated the overall relationship between activation of RAS-RAF signaling pathway and global hypermethylation in a large panel of methylation markers that included both CIMP-related and unrelated loci. Interestingly, we found that aberrant DNA methylation is only a disease of older individuals with MSI-H but in associated with all subsets of colorectal cancers. Herein, we found that epigenetic markers can be used for the screening of colorectal cancer if we chose the correct methylation marker. We also developed a novel method to detect cancer-derived methylation in the exfoliated DNA from cancer in feces and applied several patents. We have also focused on the cancer with poor prognosis mainly due to the difficulty in screening and early diagnosis, such as pancreatic and hepato-biliary tract cancers.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (17 results)

All 2007 2006 2005

All Journal Article (12 results) Patent(Industrial Property Rights) (5 results)

  • [Journal Article] Oesophageal squamous cell cancer may develop within a background of accumulating DNA methylation in normal and dysplastic mucosa2007

    • Author(s)
      Tatsuhiko Isii et al.
    • Journal Title

      GUT 56

      Pages: 13-19

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] No duplicate KRAS mutation is identified on the same allele of gastric or colorectal cancer cells with multiple KRAS mutations.2007

    • Author(s)
      Kimura K. et al.
    • Journal Title

      J. Int. Med. Res. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] No duplicate KRAS mutation is identified on the same allele of gastric or colorectal cancer cells with multiple KRAS mutations.2007

    • Author(s)
      Kimura K., Nagasaka T., Sasamoto H., Notohara K., Takeda M., Komnami K., Ishii T., Tanaka N., Matsubara.N.
    • Journal Title

      J. Int. Med. Res. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Oesophageal squamous cell cancer may develop within a background of accumulating DNA methylation in normal and dysplastic mucosa.2007

    • Author(s)
      Ishii T., Murakami J., Notohara K., Cullings H.M., Sasamoto H., Kambara T., Shirakawa Y., Naomoto Y., Ouchida M., Shimizu K., Tanaka N., Jass J.R., Matsubara.N.
    • Journal Title

      Gut 56

      Pages: 13-19

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Oesophageal squamous cell cancer may develop within a background of accumulating DNA methylation in normal and dysplastic mucosa.2007

    • Author(s)
      Ishii, T., Murakami, J., Notohara, K, Cullings, H.M., Sasamoto, H., Kambara, T., Shirakawa, Y., Naomoto, Y., Ouchida, M., Shimizu, K., Tanaka, N., Jass, J: R., Matsubara, N
    • Journal Title

      Gut 56

      Pages: 13-19

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Heterogeneous microsatellite instability observed within epithelium of ulcerative colitis in oral cancer.2006

    • Author(s)
      Kazuhide, Ozaki et al.
    • Journal Title

      Int. J. Cancer 119

      Pages: 2513-2519

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Heterogeneous microsatellite instability observed within epithelium of ulcerative colitis.2006

    • Author(s)
      Ozaki K., Nagasaka T., Notohara K., Kambara T., Takeda M., Sasamoto H., Jass J.R., Tanaka N., Matsubara.N.
    • Journal Title

      Int. J. Cancer 119 (11)

      Pages: 2513-2519

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Heterogeneous microsatellite instability observed within epithelium of ulcerative colitis.2006

    • Author(s)
      Ozaki, K., Nagasaka, T., Notohara, K., Kambara, T., Takeda, M., Sasamoto, H., Jass, J.R., Tanaka, N., Matsubara, N.
    • Journal Title

      Int. J.Cancer 119

      Pages: 2513-2519

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Role of O^6-methylguanine-DNA methyltransferase and effect of O^6-benzylguanine on the anti-tumor activity of cis-Diaminedichloroplatinum(II) in oral cancer cell lines.2005

    • Author(s)
      Yu Maki et al.
    • Journal Title

      Oral Oncol 41

      Pages: 984-993

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Methylatio profiles of genes utilizing newly developed CpG island methylation microarray on colorectal cancer patients.2005

    • Author(s)
      Naoki Kimura et al.
    • Journal Title

      Nucleic Acids Res 33

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of 06-methylguanine-DNA methyltransferase and effect of O6-benzylguanine on the anti-tumor activity of cis-Diaminedichloroplatinum(II) in oral cancer cell lines.2005

    • Author(s)
      Yu Maki Jun Murakami Jun-ichi Asaumi Hidetsugu Tsujigiwa Hitoshi Nagatsuka Susumu Kokeguchi Kazuhiro Fukui Noriko Kawai Yoshinobu Yanagil Masahiro Kuroda Noriaki Tanaka Nagahide Matsubara Kanji Kishil
    • Journal Title

      Oral Oncol. 41

      Pages: 984-993

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Methylatio profiles of genes utilizing newly developed CpG island methylation microarray on colorectal cancer patients.2005

    • Author(s)
      Naoki Kimura Takeshi Nagasaka Jun Murakami Hiromi Sasamoto Masahiro Murakami Noriaki Tanaka Nagahide Matsubara
    • Journal Title

      Nucleic Acids Res. 33 (5)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 糞便由来遺伝子の簡便増幅法2005

    • Inventor(s)
      松原長秀 etc
    • Industrial Property Rights Holder
      岡山大学
    • Filing Date
      2005-12-09
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 核酸修飾前の検体の前処理方法2005

    • Inventor(s)
      松原長秀 etc
    • Industrial Property Rights Holder
      岡山大学
    • Filing Date
      2005-12-09
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 消化器中の新生物の検出方法2005

    • Inventor(s)
      松原長秀 etc
    • Industrial Property Rights Holder
      岡山大学
    • Filing Date
      2005-12-09
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 核酸増幅反応を行うための生物学的資料の処理方法2005

    • Inventor(s)
      永坂 岳司, 松原 長秀, 田中 紀章
    • Industrial Property Rights Holder
      国立大学法人岡山大学
    • Filing Date
      2005-02-13
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] 遺伝子のメチル化検出方法及びメチル化検出による新生物の検査方法2005

    • Inventor(s)
      永坂 岳司, 松原 長秀, 田中 紀章
    • Industrial Property Rights Holder
      国立大学法人岡山大学
    • Filing Date
      2005-02-13
    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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