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Development of New diagnostic methods and treatments against EB virus as a target in nasal NK/T cell lymphoma

Research Project

Project/Area Number 17390455
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionAsahikawa Medical College

Principal Investigator

HARABUCHI Yasuaki  Asahikawa Medical College, Otolaryngology, Professo (80208686)

Co-Investigator(Kenkyū-buntansha) OGINO Takeshi  Asahikawa Medical College, Otolaryngology, assistant professor (00312455)
BANDOH Nobuyuki  Asahikawa Medical College, Otolaryngology, assistant professor (60312469)
KOBAYASHI Hiroya  Asahikawa Medical College, Pathology, assistant professor (90280867)
TAKAHARA Miki  Asahikawa Medical College, Otolaryngology, assistant professor (50322904)
岸部 幹  旭川医科大学, 大学病院, 医員 (80447101)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥10,770,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2007: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2006: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥4,000,000 (Direct Cost: ¥4,000,000)
Keywordsnasal NK / T cell lymphoma / IL-9 / LMP1 / LMP2 / IP-10 / EBV DNA / intra-arterial chemotherapy / promiscuous epitope / ケモカイン / CXCR3 / EBウイルス / EBV DNA量 / NKレセプター / 動注化学療法
Research Abstract

(1) Virological analysis
We analyzed nasal NK/T cell lymphoma cell line to investigate the role of cytokines by cDNA microarray. IL-9 was expressed in EB virus positive nasal NK/T cell lymphoma cell line but not negative cell lines. In addition, it seems that IL-9 has contributed for the cell proliferation by autocrine mechanism in the cell line. s.
We analyzed gene mutation of LMP1 and LMP2A in nasal NK/T cell lymphoma tissues. Deletion of LMP1 and mutations of LMP2A were discovered in the tissues
We analyzed chemokines in nasal NK/T cell lymphoma cell line by the antibody array. IP-10 was expressed in nasal NK/T cell lymphoma cell line. In addition, it seems that IP-10 has contributed for the cell migration by autocrine mechanism.
(2) Development of new diagnostic methods
We developed a real time PCR method to measure EBV DNA load in sera of nasal NK/T cell lymphoma patients. Serum EBV DNA load was useful for diagnosis of this disease and to predict patient's prognosis and recurrence.
(3) Development of new treatment methods
Intra-arterial chemotherapy and radiotherapy we developed was useful and safety to treat nasal NK/T cell lymphoma.
Helper T lymphocytes were developed using LMP1 peptides. The T cells recognize a peptide (LMP1 159-175) with promiscuous epitopes of LMP1 and restricted HLA-DR9, DR53 and DR15. In addition, the T cells killed lymphoma cells.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (34 results)

All 2008 2007 2006 2005

All Journal Article (26 results) (of which Peer Reviewed: 11 results) Presentation (7 results) Book (1 results)

  • [Journal Article] Induction of EBV-latent membrane protein l-specific MHC class II-restricted T-cell responses against natural killer lymphoma cells.2008

    • Author(s)
      Kobayashi H
    • Journal Title

      Cancer Research 68

      Pages: 901-908

    • 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] Induction of EBV-latent membrane protein 1-specific MHC class II-restricted T-cell responses against natural killer lymphoma cells.2008

    • Author(s)
      Kobayashi H, Nagato T, Takahara M, Sato K, Kimura S, Aoki N, Azumi M, Tateno M, Harabuchi Y, Celis E
    • Journal Title

      Cancer Res 68

      Pages: 901-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Sequence variations of Epstein-Barr virus LMP1 gene in nasal NK/T-cell lymphoma.2007

    • Author(s)
      Nagamine M, et. al.
    • Journal Title

      Virus Genes 34

      Pages: 47-54

    • 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] Clinical usefulness of serum EBV DNA levels of BamHI W and LMP1 for Nasal NK/T-cell lymphoma.2007

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

      Journal of Medical Virology 79

      Pages: 562-572

    • 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] Selected amino acid change encoding Epstein-Barr virus-specific T cell epitope of the LMP2A gene in Japanese nasal NK/T cell2007

    • Author(s)
      Nagamine M, et. al.
    • Journal Title

      Intervirology 50

      Pages: 319-322

    • 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] Sequence variations of Epstein-Barr virus LMP 1 gene in nasal NK/T-cell lymphoma.2007

    • Author(s)
      Nagamine M, Takahara M, Kishibe K, Nagato T, Ishii H, Bandoh N, Ogino T, Harabuchi Y
    • Journal Title

      Virus Genes 34

      Pages: 47-54

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Clinical usefulness of serum EBV DNA levels of BamHI W and LMPl for Nasal NK/T-cell lymphoma.2007

    • Author(s)
      Ishii H, Ogino T, Berger C, Kochli-Schmitz N, Nagato T, Takahara M, Nadal D, Harabuchi Y
    • Journal Title

      J Med Virol 79

      Pages: 562-572

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Selected amino acid change encoding Epstein-Barr virus-specific T cell epitope of the LMP2A gene in Japanese nasal NK/T cell lymphoma patients.2007

    • Author(s)
      Nagamine M, Kishibe K, Takahara M, Nagato T, Ishii H, Bandoh N, Ogino T, Harabuchi Y
    • Journal Title

      Intervirology 50

      Pages: 319-322

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Sequence variations of Epstein-Barr virus LMPI gene in nasal NK/T-cell lymphoma.2007

    • Author(s)
      Nagamine M, et. al.
    • Journal Title

      Virus Genes 34

      Pages: 47-54

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical usefulness of serum EBV DNA levels of BamHI W and LMP1 for Nasal NK/T-cell lymphoma.2007

    • Author(s)
      Ishii H
    • Journal Title

      Journal of Medical Virology 79

      Pages: 562-572

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of EBV-latent membrane protein 1-specific MHC class II-restricted T-cell responses against natural killer lymphoma cells.2007

    • Author(s)
      Kobayashi H
    • Journal Title

      Cancer Research 68

      Pages: 901-908

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sequence variations of Epstein-Barr virus LMP1 gene in nasal NK/T-cell lymphoma.2007

    • Author(s)
      Nagamine M
    • Journal Title

      Virus Genes 34

      Pages: 47-54

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Clinical usefulness of serum EBV DNA levels of BamHI W and LMP1 for Nasal NK/T-cell lymphoma.2007

    • Author(s)
      Ishii H
    • Journal Title

      J Med Virol 79

      Pages: 562-572

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Clinical usefulness of serum EBV DNA levels of BamHI W and LMP1 for Nasal NK/T-cell lymphoma. Concomitant increase of LMP1 and CD25(IL-2-receptoralpha) expression induced by IL-10 in the EBV-positive NK lines SNK6 and KAI3.2006

    • Author(s)
      Takahara M, et. al.
    • Journal Title

      Int J Cnacer 119

      Pages: 2775-2783

    • 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] Life-style and environmental factors in the development of nasal NK/T-celllymphoma: a case-control study in East Asia.2006

    • Author(s)
      Xu JX, et. al.
    • Journal Title

      Int J Cancer 15

      Pages: 406-410

    • 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] Concomitant increase of LMP1 and CD25 (IL-2-receptor alpha) expression induced by IL-10 in the EBV-positive NK lines SNK6 and KAI3.2006

    • Author(s)
      Takahara M, Kis LL, Nagy N, Liu A, Harabuchi Y, Klein G, Klein E
    • Journal Title

      Int J Cnacer 119

      Pages: 2775-2783

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Life-style and environmental factors in the development of nasal NK/T-cell lymphoma: a case-control study in East Asia.2006

    • Author(s)
      Xu JX, Hoshida Y, Yang WI, Inohara H, Kubo T, Kim GE, Yoon JH, Kojya S, Bandoh N, Harabuchi Y, Tsutsumi K, Koizuka I, Jia XS, Kirihata M, Tsukuma H, Aozasa K
    • Journal Title

      Int J Cancer 15

      Pages: 406-10

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Concomitant increase of LMP1 and CD25 (IL-2-receptor alpha) expression induced by IL-10 in the EBV-positive NK lines SNK6 and KAI32006

    • Author(s)
      Takahara M
    • Journal Title

      Int J Cancer 119

      Pages: 2775-2783

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 鼻性NK/T細胞リンパ腫 症例で学ぶ鼻科診療の実際2006

    • Author(s)
      原渕保明
    • Journal Title

      鼻アレルギーフロンティア 6

      Pages: 41-46

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 鼻性NK/T細胞リンパ腫のEBウイルス学的、分子腫瘍学的解析2006

    • Author(s)
      原渕保明
    • Journal Title

      耳鼻免疫アレルギー 24

      Pages: 1-9

    • NAID

      10018168471

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Interleukin-9 in Nasal Natural Killer/T-cell Lymphoma Cell Lines and patients.2005

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

      Clinical Cancer Research 11

      Pages: 8250-8257

    • 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] p53, K-ras, c-kit and beta-catenin gene mutations in sinonasal NK/T-cell lymphoma in Korea and Japan.2005

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

      Oncol Rep 13

      Pages: 265-271

    • 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] Expression of Interleukin-9 in Nasal Natural Killer/T-cell Lymphoma Cell Lines and Patients.2005

    • Author(s)
      Nagato T, Kobayashi H, Kishibe K, Takahara M, Ogino T, Ishii H, Oikawa K, Aoki N, Sato K, Kimura S, Simizu N, Tateno M, Harabuchi Y.
    • Journal Title

      Clin Cancer Res 11

      Pages: 8250-8257

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] p53, K-ras, c-kit and beta-catenin gene mutations in sinonasal NK/T-cell lymphoma in Korea and Japan.2005

    • Author(s)
      Hongyo T, Hoshida Y, Nakatsuka S, Syaifudin M, Kojya S, Yang WI, Min YH, Chan H, Kim CH, Harabuchi Y, Himi T, Inuyama M, Aozasa K, Nomura T
    • Journal Title

      Oncol Rep 13

      Pages: 265-71

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Expression of interleukin-9 in nasal natural killer/T-cell lymphoma cell lines and patients.2005

    • Author(s)
      Toshihiro Nagato
    • Journal Title

      Clinical Cancer Research 11

      Pages: 8250-8257

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 特集・ステロイド薬の正しい使い方 悪性リンパ腫-耳鼻科医の立場から-2005

    • Author(s)
      原渕保明
    • Journal Title

      ENTONI 48

      Pages: 90-95

    • Related Report
      2005 Annual Research Report
  • [Presentation] 鼻性NK/T細胞リンパ腫におけるIP-10の発現と機能2008

    • Author(s)
      森合重誉
    • Organizer
      第26回日本耳鼻咽喉科免疫アレルギー学会
    • Place of Presentation
      大阪
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression and function of IP-10 in nasal NK/T cell lymphoma cell lines.2008

    • Author(s)
      Shigetaka Moriai, et. Al
    • Organizer
      26^<th> annual meeting of Japan society of Immunology and Allergology in Otolaryngoogy
    • Place of Presentation
      osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 鼻性NK/T細胞リンパ腫細胞株におけるIP-10の発現と機能2008

    • Author(s)
      森合重誉
    • Organizer
      第26回日耳鼻免疫アレルギー学会
    • Place of Presentation
      大阪
    • Related Report
      2007 Annual Research Report
  • [Presentation] 鼻性NK/T細胞リンパ腫細胞株SNK6におけるIL-10によるLMP1を介したCD25の発現上昇2007

    • Author(s)
      高原 幹
    • Organizer
      第66回日本癌学会
    • Place of Presentation
      横浜
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Upregulation of CD25 by IL-10 in nasal NK/T cell lymphoma cell line SNK6.2007

    • Author(s)
      Miki Takahara, et. al
    • Organizer
      66^<th> annual meeting of Japan cancer association
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 鼻性NK/T細胞リンパ腫における放射線同時併用動注化学療法2006

    • Author(s)
      原渕保明
    • Organizer
      第30回日本頭頸部癌学会
    • Place of Presentation
      大阪
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Intra-arterial chemoradiotherapy of neck cancer association nasal NK/T cell lymphoma.2006

    • Author(s)
      Yasuaki Harabuchi, et.al
    • Organizer
      30^<th> annual meeting of Japan head and neck cancer association
    • Place of Presentation
      osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 新しい診断と治療のABC2007

    • Author(s)
      原渕保明
    • Total Pages
      10
    • Publisher
      最新医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary

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

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