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Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients : Possible involvement of c-myc suppression by IFN-γ in situ

Research Project

Project/Area Number 18591454
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NISHIMORI Takanori  Chiba University, HOSPITAL, FRONTIER SURGERY, ASSISTANT PROFESSOR (30401003)

Co-Investigator(Kenkyū-buntansha) MATSUSHITA Kazuyuki  CHIBA UNIVERSITY, HOSPITAL, EMERGENCY AND CRITICAL CARE MEDICINE, ASSISTANT PROFESSOR (90344994)
TOMONAGA Takeshi  CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICIE, MOLECULAR DIAGNOSIS, ASSOCIATE PROFESSOR (80227644)
NOMURA Fumio  CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICIE, MOLECULAR DIAGNOSIS, PROFESSOR (80164739)
SHIMADA Hideaki  CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICIE, FRONTIER SURGERY, ASSOCIATE PROFESSOR (20292691)
SUNAGA Masahiko  CHIBA UNIVERSITY, HOSPITAL, MOLECULAR DIAGNOSIS, ASSISTANT PROFESSOR (10361437)
落合 武徳  千葉大学, 大学院医学研究院, 教授 (80114255)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsHuman Leukocyte Antigen / HLA-DR antigen / cytokine / c-myc gene / helper T-cell
Research Abstract

Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients, although the precise mechanism is controversial. From an immunologic point of view, HLA-DR antigen, induced by IFN-γ, is required for tumor-associated antigen recognition by CD4+ T cells. For instance, as reported previously, the expression of HLA-DR antigen in normal colorectal epithelium immediately adjacent to cancer coincided significantly with the existence of IFN-γ mRNA in the tissue. From another aspect, IFN-γ has been revealed to suppress c-myc expression in vivo through stat1-dependent mechanism, which is important for cell growth, cell cycle, and chromosome instability. In this study, strong HLA-DR-positive expression on cancer cells, as expectedly, was significantly related to better prognosis of colorectal cancer patients. High IFN-γ mRNA expression in situ indicated significantly less activation of c-myc mRNA expression. Further, HLA-DR antigen expression in cancer cells, as well as Dukes stages, was an independent factor for better long-term survival by multivariate analysis. Taken together, IFN-γ, which induces HLA-DR antigens on the cell surface, also suppresses c-myc expression in situ, and is a possible non-immunologic mechanism involved in the better long-term survival of colorectal cancer patients.

Report

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

Research Products

(28 results)

All 2008 2007 Other

All Journal Article (16 results) (of which Peer Reviewed: 10 results) Presentation (6 results) Book (2 results) Remarks (4 results)

  • [Journal Article] Recent advances in esophageal cancer gene therapy.2008

    • Author(s)
      Shimada H, et. al (other 2 authors)
    • Journal Title

      Ann Thorac Cardiovasc Surg. 14(1)

      Pages: 3-8

    • NAID

      10024306785

    • 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] Recent adcances in esophageal cancer gene therapy2008

    • Author(s)
      Shimada H, et. al. (other 2 authors)
    • Journal Title

      Ann Thorac Cardiovasc Surg 14(1)

      Pages: 3-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Gene expression profiling induced by histone deacetylase Inhibitor, FK228, in human esophageal squamous cancer cells2008

    • Author(s)
      Hashino I, Nishimori T, et. al. (other 7 authors)
    • Journal Title

      Oncol Rep 18(3)

      Pages: 585-592

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Identification of novel immunohistochemical markers for primary hepatocellular carcinoma; clathrin heacy chain and formiminotransferase cyclodeaminase2008

    • Author(s)
      Seimiya M, et. al. (other 14 authors)
    • Journal Title

      Hepatology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Identificaton of novel immunohistochemical markers for primary hepatocellular carcinoma;clathrin heavy chain and formiminotransferase cyclodeaminase2008

    • Author(s)
      Masanori S, Tomonaga T, Matsushita K, Sunaga M, Ohrishi M, Kodera Y, Meda T, Takanpo S, Togawa A, Yoshitomi H, Otuka M, Yamamoto M, Nakano M, Miyazaki M, Nomura F
    • Journal Title

      Hepatology

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recent advances in esophageal cancer gene therapy2008

    • Author(s)
      Shimada H, Matsushita K, Tagawa M
    • Journal Title

      Ann Thorac Cardiovasc Surg 14(1)

      Pages: 3-8

    • NAID

      10024306785

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression profiling induced by histone deacetylase inhibitor, FK228, in human esophageal squamous cancer cells.2007

    • Author(s)
      Hanari N, Nishimori T, et. al (other 7 authors)
    • Journal Title

      Anticancer Res 27(4B)

      Pages: 2305-2310

    • 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] Tumor suppressor Prdx1 is a prognostic factor in esophageal squamous cell carcinoma patients.2007

    • Author(s)
      Hoshino I, Nishimori T, et. al (other 7 authors)
    • Journal Title

      Oncol Rep. 18(4)

      Pages: 867-71

    • 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] Gene expression profiling induced by histone deacetylase inhibitor, FK228, in human esophageal squamous cancer cells.2007

    • Author(s)
      Hoshino I, Nishimori T, et. al (other 8 authors)
    • Journal Title

      Oncol Rep. 18(3)

      Pages: 585-92

    • 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] Gene expression profiling induced by histone deacetylase Inhibitor, FK228, in human esophageal squamous cancer cells2007

    • Author(s)
      Hanari N, Nishimori T, et. al. (other 7 authors)
    • Journal Title

      Antidancer Res 27(4B)

      Pages: 2305-2310

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Tumor suppressor Prdx1 is a prognostic factor in Esoghageal squamous cell carcinoma patients2007

    • Author(s)
      Hashino I, Nishimori T, et. al. (other 5 authors)
    • Journal Title

      Oncol Rep 18(4)

      Pages: 867-871

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] An essential role of alternative splicing of c-myc suppressor FIR for cancer gene therapy2007

    • Author(s)
      Matsushita K, et. al. (other 5 authors)
    • Journal Title

      Gene therapy

      Pages: 10-21

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Combinatory gene therapy with electrotransfer of midkine promoter-HSV-TK and interleukin-212007

    • Author(s)
      Hanari N., Matsubara, H, Hoshino, L, Akutsu, Y., Nishimori, T., Murakami, K., Sakata, H., Miyazawa, Y., Ochiai, T
    • Journal Title

      Anticancer Res 27(4B)

      Pages: 2305-2310

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor suppressor Prdxl is a prognostic factor in esophageal squamous cell carcinoma patients2007

    • Author(s)
      Hishino I, Matsubara H, Akutsu Y, Nishimori T, Yoneyama Y, Murakami K, Sakata H, Matsushita K, Ochiai T.
    • Journal Title

      Oncol Rep 18(4)

      Pages: 867-71

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression profiling induced by histone deacetylase inhibitor,FK228,in human esophageal squamous cancer cells2007

    • Author(s)
      Hoshino I, Matsubara H, Akutsu Y, Nishimori T, Yoneyama Y, Murakami K, Komatsu A, Sakata H, Matsushita K, Ochiai T
    • Journal Title

      Oncol Rep 18(3)

      Pages: 585-92

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identificaton of novel immunohistochemical markers for primary hepatocellular carcinoma; clathrin heavy chain and formiminotransferase cyclodeaminase.

    • Author(s)
      Masanori S, et. al (other 14 authors)
    • Journal Title

      Hepatology. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Presentation] がんの早期診断に役立つ遺伝子腫瘍マーカーの開発.2008

    • Author(s)
      松下 一之
    • Organizer
      千葉大学新技術説明会
    • Place of Presentation
      東京
    • Year and Date
      2008-03-07
    • Related Report
      2007 Annual Research Report
  • [Presentation] 遺伝子発現調節(転写・スプライシンク)を分子標的とした癌診断法・治療法の開発2008

    • Author(s)
      松下 一之
    • Organizer
      第1回ちばBasic&Cinical Research Chnference
    • Place of Presentation
      千葉
    • Year and Date
      2008-01-09
    • Related Report
      2007 Annual Research Report
  • [Presentation] c-myc遺伝子の発現制御因子を利用した癌治療・診断法の開発2007

    • Author(s)
      松下 一之
    • Organizer
      平成19年度千葉大学先端応用外科例会
    • Place of Presentation
      千葉
    • Year and Date
      2007-12-15
    • Related Report
      2007 Annual Research Report
  • [Presentation] e-myc,遺伝子転写抑制因子FIR癌遺伝子治療の開発.2007

    • Author(s)
      松下 一之, 朝長 毅, 島田 英昭, 梶原 寿子, 間宮 後太, 松原 久裕, 山田 滋, 加野 将之, 野村 文夫
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-03
    • Related Report
      2007 Annual Research Report
  • [Presentation] c-myc遺伝子転写抑制因子FIR遣伝子と重粒子線を用いた消化管癌治療法の開発2007

    • Author(s)
      松下 一之, 落合 武徳, 島田 英昭, 朝長 毅, 松原 久裕, 加野 将之, 山田 滋
    • Organizer
      第62回日本消化器外科学会定期学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-07-18
    • Related Report
      2007 Annual Research Report
  • [Presentation] e-myc遺伝子抑制因子FIRのSplicing variantと癌化への関与.2007

    • Author(s)
      松下 一之
    • Organizer
      千葉県がんセンター研究局第626回集談会
    • Place of Presentation
      千葉
    • Year and Date
      2007-01-10
    • Related Report
      2007 Annual Research Report
  • [Book] Gene therapy An essential role of alternative splicing of c-myc suppressor FIR for cancer genetherapy.2007

    • Author(s)
      Matsushita K, et. al. (other 5 authors)
    • Publisher
      Medical View, Co., Ltd.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Gene therapy An essential role of alternative splicing of cmyc suppressor FIR for cancer gene therapy2007

    • Author(s)
      Matsushita K, Ochiai T, Shimada H, Tomonaga T, Matsubara H, Nomura F.
    • Publisher
      Medical View, Co., Ltd.
    • Related Report
      2007 Annual Research Report
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.academic-surgery.jp/

    • Related Report
      2007 Final Research Report Summary
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.m.chiba-u.ac.jp/class/moldiag/

    • Related Report
      2007 Final Research Report Summary
  • [Remarks] 千葉大学大学院医学研究院先端応用外科学

    • URL

      http://www.academic-surgery.jp/

    • Related Report
      2007 Annual Research Report
  • [Remarks] 千葉大学大学院医学研究院分子病態解析学

    • URL

      http://www.m.chiba-u.ac.jp/class/moldiag/

    • Related Report
      2007 Annual Research Report

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Published: 2006-03-31   Modified: 2016-04-21  

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