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Molecular mechanism of hypoxia-induced genome instability in human colorectal cancer

Research Project

Project/Area Number 21591736
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

HEMMI Hiromichi  東邦大学, 医学部, 准教授 (90165514)

Co-Investigator(Kenkyū-buntansha) SHIBUYA Kazutoshi  東邦大学, 医学部, 教授 (20196447)
ARITA Michitsune  東邦大学, 医学部, 助教 (80307719)
KOIKE Junichi  東邦大学, 医学部, 講師 (30339155)
Co-Investigator(Renkei-kenkyūsha) KANAZAWA Shinsaku  東邦大学, 医学部, 助教 (00408767)
Research Collaborator LI Jie  東邦大学, 医学部, 大学院生
YAMADA Kanae  東邦大学, 医学部, 研究生
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords遺伝子 / 大腸がん / ゲノム不安定性 / EMAST / 発現制御 / 低酸素 / DNA修復 / GLUT1
Research Abstract

Frequency of EMAST, a phenotype of genetic instability, in Japan was approximately 60%, which is similar to USA. Down-regulation of hMSH3 by hypoxia was studied in human cell lines derived from different origins including colon. Three patterns : rapid, moderate, and none responses were observed. Moderate type was observed in cells having mutant p53.Histochemical staining of clinical samples supports that down-regulation of hMSH3 is induced by hypoxia. Transient hypoxia is not enough for generation of EMAST tumor. Repeated states of hypoxia-reoxyganation may require for induction of EMAST.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (24 results)

All 2012 2011 2010 2009

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (14 results)

  • [Journal Article] MicroRNA-200c modulates epithelial-to-mesenchymal transition(EMT) in human colorectal cancer metastasis2012

    • Author(s)
      Hur K, Toiyama Y, Takahashi M, Koike J, Hemmi H, Balaguer F, Nagasaka T, Koi M, Boland CR, Goel A
    • Journal Title

      GUT

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Downregulation of MutS homolog 3 by hypoxia in human colorectal cancer2012

    • Author(s)
      Li J, Koike J, Kugoh H, Arita M, Ohhira T, Kikuchi Y. Funahashi K, Takamatsu K, Boland CR, Koi M, Hemmi H
    • Journal Title

      Biochim Biophys Acta

      Volume: 1823(4) Pages: 889-99

    • URL

      http://dx.doi.org/10.1016/j.bbamcr.2012.01.017

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Down-regulation of MutS homolog 3 by hypoxia in human colorectal cancer2012

    • Author(s)
      Li J, Koike J, Kugoh H, Arita M, Ohhira T, Kikuchi Y, Funahashi K, Takamatsu K, Boland CR, Koi M, Hemmi H
    • Journal Title

      Biochim Biophys Acta -Molecular Cell Research

      Volume: 1823(4) Issue: 4 Pages: 889-899

    • DOI

      10.1016/j.bbamcr.2012.01.017

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effluent markers related to epithelial mesenchymal transition with adjusted values for effluent cancer antigen 125 in peritoneal dialysis patients2011

    • Author(s)
      Mizuiri S, Hemmi H, et al
    • Journal Title

      Int J Nephrol

      Volume: 2011 Pages: 2610401-5

    • DOI

      10.4061/2011/261040

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Factors regulating angiotensin-converting enzyme 2 expression in a human proximal tubular cell line HK-2.2011

    • Author(s)
      Aoki T, Hemmi H, Arita M, et al
    • Journal Title

      J Med Soc Toho

      Volume: 58(1) Pages: 19-26

    • NAID

      40017650365

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effluent markers related to epithelial mesenchymal transition with adjusted values for effluent cancer antigen 125 in peritoneal dialysis patients.2011

    • Author(s)
      Mizuiri S, Hemmi H, Arita M, et al
    • Journal Title

      Int J Nephrol

      Volume: (in Press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Microsatellite instability at tetranucleotide repeats in sporadic colorectal cancer in Japan2010

    • Author(s)
      Yamada K, Kanazawa S, Koike J, Sugiyama H, Xu C, Funahashi K, Boland CR, Koi M, Hemmi H
    • Journal Title

      Oncol Rep

      Volume: 23(2) Pages: 551-61

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Microsatellite instability at tetranucleotide repeats in sporadic colorectal cancer in Japan2010

    • Author(s)
      Yamada K, Kanazawa S, Koike J, Boland CR, Koi M, Hemmi H, 他3名
    • Journal Title

      Oncol Rep 23

      Pages: 551-561

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 14-3-3σ-dependent resistance to cisplatin2009

    • Author(s)
      Han Z, Dimas K, Tian X, Wang Y, Hemmi H, Yamada K, Kato N, Pantazis P, Ramanujam RJ, Anant S, Wyche JH, Houchen CW
    • Journal Title

      Anticancer Res

      Volume: 29(6) Pages: 2009-2014

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] FOLFOX therapy for advanced metastatic rectal cancer with Gibert syndrome2009

    • Author(s)
      Koike J, Funahashi K, Saito N, Shirasaka K, Hemmi H, Kaneko S, Teramoto T
    • Journal Title

      J Toho Med Soc

      Volume: 56(1) Pages: 27-32

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Presentation] 低酸素によるhMLH1発現抑制におけるSYF2およびhnRPH1の役割2011

    • Author(s)
      有田通恒, 逸見仁道, 他
    • Organizer
      第70回日本癌学会学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2011-10-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] Identification of gene loci with microsatellite repeats frequently altered in liver metastasis exhibiting moderate levels of microsatellite instability from primary CRC2011

    • Author(s)
      Garcia M, Choi C, Kim H, Koike J, Hemmi H, Li J, Nagasaka T, Boland CR, Koi M
    • Organizer
      Digestive Disease Week 2011
    • Place of Presentation
      Chicago, IL.
    • Year and Date
      2011-05-17
    • Related Report
      2011 Final Research Report
  • [Presentation] MicroRNA-200c/141 cluster as a control switch between epithelial-to-mesenchymal transition(EMT) and mesenchymal-to-epithelial transition(MET) in human colorectal cancer metastasis2011

    • Author(s)
      Goel A, Hemmi H, Koi M, Boland CR, et al
    • Organizer
      Digestive Disease Week 2011
    • Place of Presentation
      Chicago, IL
    • Year and Date
      2011-05-17
    • Related Report
      2011 Final Research Report
  • [Presentation] 低酸素によるhMLH1発現抑制時の転写因子CXXC5, SYF2およびhnRPH1の関与2011

    • Author(s)
      有田通恒, 李傑, 菅野新一郎, 菊池由宣, 安井明, 近藤元就, 逸見仁道
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Final Research Report
  • [Presentation] N-myc非増幅神経芽腫細胞におけるN-mycの役割2011

    • Author(s)
      李傑, 有田通恒, 柴田祐充子, 岩崎維和夫, 黒岩実, 近藤元就, 逸見仁道
    • Organizer
      第53回日本小児血液・がん学会学術集会
    • Place of Presentation
      前橋
    • Related Report
      2011 Final Research Report
  • [Presentation] 低酸素によるhMLH1発現抑制におけるSYF2およびhnRPH1の役割2011

    • Author(s)
      有田通恒, 李傑, 安井明, 近藤元就, 逸見仁道
    • Organizer
      The 70th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Nagoya
    • Related Report
      2011 Final Research Report
  • [Presentation] Regulation of MMR genes and stem cell markers in hypoxia in colorectal cancer cells.(English Workshop)2010

    • Author(s)
      Li J, Arita M, Koike J, Hemmi H.
    • Organizer
      The 69th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] 大腸がん由来細胞株におけるhMSH3転写制御機構2010

    • Author(s)
      李傑, 有田通恒, 児井稔, 逸見仁道
    • Organizer
      第33回日本分子生物学会・第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2011 Final Research Report
  • [Presentation] CXXC5とSYF/p29によるhM転写制御, a zinc finger protein2010

    • Author(s)
      有田通恒, 李傑, 菅野新一郎, 安井明, 逸見仁道
    • Organizer
      第33回日本分子生物学会・第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2011 Final Research Report
  • [Presentation] Regulation of MMR genes and stem cell markers in hypoxia in colorectal cancer cells2010

    • Author(s)
      Li J, Arita M, Koike J, Hemmi H
    • Organizer
      The 69th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Osaka
    • Related Report
      2011 Final Research Report
  • [Presentation] A novel transcriptional regulator, CXXC5 zinc finger protein, for a DNA mismatch repair gene, hMLH12010

    • Author(s)
      Arita M, Li J, Yasui A, Hemmi H
    • Organizer
      The 69th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Osaka
    • Related Report
      2011 Final Research Report
  • [Presentation] A study in regulatory mechanism of the MSH3 gene expression2009

    • Author(s)
      Li J, Min Z, Arita M, Koi M, Hemmi H
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2009-12-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] Transcriptional regulation of the hMLH1 gene by CXXC5, a zinc finger protein2009

    • Author(s)
      有田通恒, 李傑, 菅野新一郎, 安井明, 逸見仁道
    • Organizer
      The 32nd Annual Meeting of the Molecular Biology Society of Japan
    • Place of Presentation
      Yokohama
    • Related Report
      2011 Final Research Report
  • [Presentation] A study in regulatory mechanism of the MSH3 gene expression2009

    • Author(s)
      Li J, Min Z, Arita M, Koi M, Hemmi H
    • Organizer
      The 32nd Annual Meeting of the Molecular Biology Society of Japan
    • Place of Presentation
      Yokohama
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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