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Development of molecular targeting therapy for head and neck cancer by targeting membrane type MMP and EBV antigen

Research Project

Project/Area Number 15390514
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionKanazawa University

Principal Investigator

YOSHIZAKI Tomokazu  Kanazawa University, Hospital, Assistant professor, 医学部附属病院, 講師 (70262582)

Co-Investigator(Kenkyū-buntansha) MURONO Shigeyuki  Kanazawa University, Graduate School of Medicine, Instructor, 大学院・医学系研究科, 助手 (20345622)
FURUKAWA Mitsuru  Kanazawa University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40092803)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥10,900,000 (Direct Cost: ¥10,900,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2003: ¥7,100,000 (Direct Cost: ¥7,100,000)
KeywordsEB virus / MT1MMP / antibody / LMP1 / MMP inhibitor / MMP / 頭頸部がん / 分子標的 / 上咽頭がん
Research Abstract

1)Cytotoxic and cytostatic effect of Anti-MT1-MMP antibody 114F1 labeled with 131I was evaluated between HEK293 cell and MT1-MMP stable transfected-HEK293. Colony, formation assay showed there was no difference between these two cells, indicating that anti-MT1MMP with 131I did not have cytostatic effect. However, additional BB94, an inhibitor of MMP, enhanced the expression of cell surface MT1-MMP, and binding affinity of antibody to cell was enhanced 10 to 20% when 100ug of antibody was administrated.
2)Affinity to MT1MMP was reevaluated among,114F,113-5B7 and AB815 using flow cytometry. It showed that AB815 had 5 to 10 fold binding affinity compared with either 114F or 113-5B7. These, results suggests that molecular targeting therapy against MT1-MMP would be improved by the use of higher affinity antibodies and MMP inhibitors.
3)Epstein-Barr virus primary oncogene LMP1 locates on cell membrane. Establishment of antibody to LMP1 was first designed. However, ectodomain of LMP1 was revealed to have 6to 7 amino acids, which is insufficient to raise antibody.
4)Then, the strategy was switched to look for the cell surface molecule induced by LMP1. Mucin1 was found to a specific molecule induced by LMP1 and effect, of antibody against-mucin1 should be examined in the successional experiment.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (34 results)

All 2006 2005 2004 2003

All Journal Article (32 results) Book (2 results)

  • [Journal Article] 黄河の米2006

    • Author(s)
      中村 慎一
    • Journal Title

      藤本強先生古稀記念論文集(同成社) (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 中国考古学の現在2006

    • Author(s)
      中村 慎一
    • Journal Title

      現代の考古学 第1巻 考古学への招待(朝倉書店) (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Endoscopic nasophaiyngectomy for patients with recurrent nasopharyngeal carcinoma at the primary site.2005

    • Author(s)
      Yoshizaki T, et al.
    • Journal Title

      Laryngoscope. 115

      Pages: 1517-1519

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Endoscopic nasophaiyngectomy for patients with recurrent nasophaiyngeal carcinoma at the primary site.2005

    • Author(s)
      Yoshizaki T, et al.
    • Journal Title

      Laryngoscope. 115

      Pages: 1517-1519

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Le riz, le jade et la ville : Evolution des societes neolithiques du Yangzi.2005

    • Author(s)
      Shinichi Nakamura(中村慎一)
    • Journal Title

      Annales : economies, societes, civilisations. 60-5

      Pages: 1009-1034

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 韓国農村の内側2005

    • Author(s)
      金 〓哲
    • Journal Title

      歴史と地理 588

      Pages: 61-69

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Endoscppic nasopharyngectomy for patients with recurrent nasopharyngeal carcinoma at the primary site.2005

    • Author(s)
      Yoshizaki T, et al.
    • Journal Title

      Laryngoscope. 115

      Pages: 1517-1519

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Epstein-Barr virus latent membrane protein 1 induces the matrix metalloproteiniase-1 promoter via ah Ets binding site formed by a single nucleotide polymorphism : Enhanced susceptibility to nasopharyngeal carcinoma.2005

    • Author(s)
      Kondo S, et al.
    • Journal Title

      Int J Cancer. 115

      Pages: 368-376

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression of Interleukin-8 Receptor A Predicts Poor Outcome in Patients With Nasopharyngeal Carcinoma.2005

    • Author(s)
      Horikawa T, et al.
    • Journal Title

      Laryngoscope. 115

      Pages: 62-67

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Ribonucleotide reductase inhibitors enhance cidofovir-induced apoptosis in EBV-positive nasopharyngeal carcinoma xenografts.2005

    • Author(s)
      Wakisaka N, et al.
    • Journal Title

      Int J Cancer. 116

      Pages: 640-645

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Endoscopic nasopharyngectomy for patients with recurrent nasopharyngeal carcinoma at the primary site.2005

    • Author(s)
      Yoshizaki T, et al.
    • Journal Title

      Laryngoscope. 115

      Pages: 1517-1519

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Epstein-Barr virus latent membrane protein 1 induces the matrix metalloproteinase-1 promoter via an Ets binding site formed by a single nucleotide polymorphism : Enhanced susceptibility to nasopharyngeal carcinoma.2005

    • Author(s)
      Kondo S, et al.
    • Journal Title

      Int J Cancer. 115

      Pages: 368-376

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 超選択的動注化学療法-上咽頭癌-2005

    • Author(s)
      吉崎智一
    • Journal Title

      JOHNS 21

      Pages: 83-86

    • Related Report
      2005 Annual Research Report
  • [Journal Article] MRI症例ファイル-上咽頭癌-2005

    • Author(s)
      吉崎智一
    • Journal Title

      JOHNS 21

      Pages: 419-422

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Epstein-Barr Virus (EBV) Latent Membrane Protein 1 Induces Interleukin-8 through the Nuclear Factor-kappaB Signaling Pathway.2004

    • Author(s)
      Ren Q, et al.
    • Journal Title

      Laryngoscope. 114

      Pages: 855-859

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of angiogenic factors by Epstein-Barr virus gene products in nasopharyngeal carcinoma.2004

    • Author(s)
      Yoshizaki T, et al.
    • Journal Title

      Recent Research Development in Cancer 6

      Pages: 311-316

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Metastasizing mixed tumour of the parotid gland presenting as multiple lung metastases.2004

    • Author(s)
      Yoshizaki T et al.
    • Journal Title

      J Laryngol Otol. 118

      Pages: 724-726

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Epstein-Barr Virus (EBV) Latent Membrane Protein 1 Induces Interleukin-8 through the Nuclear Factor-kappaB Signaling Pathway.2004

    • Author(s)
      Ren Q, et al.
    • Journal Title

      Latyngoscope. 114

      Pages: 855-859

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 良渚文化石器の分類2004

    • Author(s)
      中村 慎一
    • Journal Title

      金沢大学考古学紀要 27

      Pages: 131-137

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of angiogenic factors by Epstein-Barr virus gene ; products in nasopharyngeal carcinoma.2004

    • Author(s)
      Yoshizaki T, et al.
    • Journal Title

      Recent Research Development in Cancer 6

      Pages: 311-316

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Epstein-Barr Virus (EBV) Latent Membrane Protein 1 Induces Interleukin-8 through the Nuclear Factor-kappaB Signaling Pathway。2004

    • Author(s)
      Ren Q, et al.
    • Journal Title

      Laryngoscope. 114

      Pages: 855-859

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of angiogenic factors by Epstein-Barr virus gene products in nasopharyngeal carcinoma2004

    • Author(s)
      Yoshizaki T.Murono S, Wakisaka N, Pagano JS, Furukawa M
    • Journal Title

      Recent Research Development in Cancer 6

      Pages: 311-316

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 臓器特異的なレジメン-上咽頭癌-2004

    • Author(s)
      吉崎智一
    • Journal Title

      耳鼻咽喉科・頭頸部外科 76

      Pages: 967-971

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 上咽頭癌の超選択的動注療法2004

    • Author(s)
      吉崎智一
    • Journal Title

      JOHNS 20

      Pages: 1730-1731

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 耳鼻咽喉科・頭頸部領域の悪性リンパ腫2004

    • Author(s)
      吉崎智一
    • Journal Title

      ENTONI 41

      Pages: 19-23

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Metastasizing mixed tumour of the parotid gland presenting as multiple lung metastases.2004

    • Author(s)
      Yoshizaki T, Kinsen H, Minato H, Kita T, Furukawa M.
    • Journal Title

      J Laryngol Otol. 118

      Pages: 724-726

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Epstein-Barr Virus(EBV) Latent Membrane Protein 1 Induces Interleukin-8 through the Nuclear Factor-kappaB Signaling Pathway2004

    • Author(s)
      Ren Q, Sato H, Murono S, Furukawa M, Yoshizaki T.
    • Journal Title

      Laryngoscope. 114

      Pages: 855-859

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Modulation of cell growth and matrix metalloproteinase-2 activation of oral squamous cell carcinoma as a function of culture condition with type I collagen.2003

    • Author(s)
      Kinsenn H, Sato H, Furukawa M, Yoshizaki T
    • Journal Title

      Acta Otolatyngol. 123

      Pages: 987-993

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cleavage of syndecan-1 by membrane type matrix metalloproteinase-1 stimulates cell migration.2003

    • Author(s)
      Endo K, et al.
    • Journal Title

      J Biol Chem. 278

      Pages: 40764-40770

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression of intercellular adhesion molecule (ICAM)-1 in adenoid cystic carcinoma of the head and neck.2003

    • Author(s)
      Shirai A, et al.
    • Journal Title

      Laryngoscope. 113

      Pages: 1955-1960

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Modulation of cell growth and matrix metalloproteinase-2 activation of oral squamous cell carcinoma as a function of culture condition with type I collagen.2003

    • Author(s)
      Kinsenn H, et al.
    • Journal Title

      Acta Otolaryngol. 123

      Pages: 987-993

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cleavage of syndecan-1 by membrane type matrix metalloproteinase-1 stimulates cell migration.2003

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

      J Biol Chem. 278

      Pages: 40764-40770

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Chapter 12,Epstein-Barr virus, invasion and metastasis "Epstein-Barr virus".2005

    • Author(s)
      Yoshizaki T., et al.
    • Publisher
      Caister Academic Press, London, UK
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Chapter 12, Epstein-Barr virus, invasion and metastasis, "Epstein-Barr virus".2005

    • Author(s)
      Yoshizaki T., et al.
    • Publisher
      Caister Academic Press, London, UK
    • Related Report
      2005 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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