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Mechanism of therapy-resistant GVHD and its treatment strategy

Research Project

Project/Area Number 20591246
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionTokyo Medical and Dental University

Principal Investigator

NAGASAWA Masayuki  Tokyo Medical and Dental University, 大学院・医歯学総合研究科, 寄附講座教員 (90262196)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsGVHD / Jun kinase / MEKK2 / 活性化T細胞 / JurkatT細胞 / カルシニューリン阻害剤 / IL-2 / Jnk / AP-1 / シクロスホリン / Jurkat細胞 / NFkB / band3 / カルシニューリン阻害 / フェリチン / 免疫沈降 / 抗原提示細胞
Research Abstract

Jun kinase (Jnk) is an important kinase that is involved in T cell activation, proliferation and IL-2 production. We have found that Jnk activation by anti-CD3 plus anti-CD28 stimulation is enhanced in activated T cells compared to resting T cells. Although MEKK2 is important in Jnk activation, phosphorylated MKK4 in activated T cells, which is not found in resting T cells seems to be involved in enhanced Jnk activation. Jnk activation in activated T cells is not inhibited enough by calcineurin inhibitor, and this may explain some part of therapy-resistant GVHD.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (39 results)

All 2011 2010 2009 2008 Other

All Journal Article (19 results) (of which Peer Reviewed: 10 results) Presentation (15 results) Book (3 results) Remarks (2 results)

  • [Journal Article] Autoimmune Lymphoproliferative Syndrome Like Disease With Somatic KRAS Mutation2011

    • Author(s)
      Takagi M, Shinoda K, Piao J, Mitsuiki N, Takagi M, Matsuda K, Muramatsu H, Doisaki S, Masayuki Nagasawa, Morio T, Kasahara Y, Koike K, Kojima S, Takao A, Mizutani S.
    • Journal Title

      Blood 117(10)

      Pages: 2887-2890

    • Related Report
      2010 Final Research Report
  • [Journal Article] Minegishi Defective IL-10 signaling in hyper-IgE syndrome results in impaired generation of tolerogenic dendritic cells and induced regulatory T cells.2011

    • Author(s)
      Masako Saito, Masayuki Nagasawa, Hidetoshi Takada, Toshiro Hara, Shigeru Tsuchiya, Kazunaga Agematsu, Masafumi Yamada, Nobuaki Kawamura, Tadashi Ariga, Ikuya Tsuge, Shigeaki Nonoyama, Hajime Karasuyama, Yoshiyuki
    • Journal Title

      Journal of Experimental Medicine. 208(2)

      Pages: 235-249

    • Related Report
      2010 Final Research Report
  • [Journal Article] Defective IL-10 signaling in hyper-IgE syndrome results in impaired generation of tolerogenic dendritic cells and induced regulatory T cells.2011

    • Author(s)
      Masako Saito , Masayuki Nagasawa , Hidetoshi Takada , et al.
    • Journal Title

      Journal of Experimental Medicine.

      Volume: 208 Pages: 235-249

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum granulysin as a possible biomarker of natural killer cell neoplasm.2010

    • Author(s)
      Masayuki Nagasawa, Ogawa K, Nagata K, Shimizu N.
    • Journal Title

      British Journal of Haematology 148

      Pages: 812-814

    • Related Report
      2010 Final Research Report
  • [Journal Article] Pharmacokinetic monitoring is still required for intravenous busulfan in SCT for small children2010

    • Author(s)
      Masayuki Nagasawa, Noriko Mitsuiki, Toshiaki Ono, Masatoshi Takagi, Hiromi Oda, Masato Yasuhara, Shuki Mizutani
    • Journal Title

      International Journal of Hematology 91

      Pages: 728-730

    • NAID

      10026402408

    • Related Report
      2010 Final Research Report
  • [Journal Article] 細胞傷害性蛋白グラニュライシンの機能とその測定の臨床的意義について2010

    • Author(s)
      長澤正之
    • Journal Title

      日本小児血液学会雑誌 24

      Pages: 195-203

    • NAID

      10026624560

    • Related Report
      2010 Final Research Report
  • [Journal Article] Pharmacokinetic monitoring is still required for intravenous busulfan in SCT for small children2010

    • Author(s)
      Masayuki Nagasawa, Noriko Mitsuiki, Toshiaki Ono, et al.
    • Journal Title

      International Journal of Hematology

      Volume: 91 Pages: 728-730

    • NAID

      10026402408

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum granulysin as a possible biomarker of natural killer cell neoplasm.2010

    • Author(s)
      Masayuki Nagasawa, Ogawa K, Nagata K, Shimizu N.
    • Journal Title

      British Journal of Haematology

      Volume: 148 Pages: 812-814

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Syndrome Like Disease With Somatic KRAS Mutation2010

    • Author(s)
      Takagi M, Shinoda K, Nagasawa M, et al.
    • Journal Title

      Blood

      Volume: 117 Pages: 2887-2890

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 細胞傷害性蛋白グラニュライシンの機能とその測定の臨床的意義について2010

    • Author(s)
      長澤正之
    • Journal Title

      日本小児血液学会雑誌

      Volume: 24 Pages: 195-203

    • NAID

      10026624560

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum granulysin as a possible biomarker of natural killer cell neoplasm.2010

    • Author(s)
      Masayuki Nagasawa, et al
    • Journal Title

      British Journal of Haematology 148

      Pages: 812-814

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome.2009

    • Author(s)
      Minegishi Y, Saito M, Masayuki Nagasawa, Takada H, Hara T, Tsuchiya S, Agematsu K, Yamada M, Kawamura N, Ariga T, Tsuge I, Karasuyama H.
    • Journal Title

      Journal of Experimental Medicine. 206(6)

      Pages: 1291-1301

    • Related Report
      2010 Final Research Report
  • [Journal Article] Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome.2009

    • Author(s)
      Minegishi Y, Saito M, Nagasawa M, et al.
    • Journal Title

      Journal of Experimental Medicine 206

      Pages: 1291-1301

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Soluble TWEAK is markedly elevated in hemophagocytic lymphohistiositosis2008

    • Author(s)
      Masayuki Nagasawa, Zhu Yi, Shinsaku Imashuku, Shigeaki Nonoyama, Kazuyuki Ogawa, Ko Okumura, Shuki Mizutani
    • Journal Title

      American Journal of Hematology 83

      Pages: 222-225

    • Related Report
      2010 Final Research Report
  • [Journal Article] Allogeneic hematopoietic stem cell transplantation for Epstein-Barr virus-associated T/ natural killer-cell lymphoproliferative disease in Japan2008

    • Author(s)
      Emiko Sato, Shoichi Oga, Hiroshi Kuroda, Fumiaki Yoshiba, Miki Nishimura, Masayuki Nagasawa, Masami Inoue, Keisei Kawa.
    • Journal Title

      American Journal of Hematology 83

      Pages: 721-727

    • Related Report
      2010 Final Research Report
  • [Journal Article] Caffeine yields aneuploidy through asymmetrical cell division caused by misalignment of chromosomes.2008

    • Author(s)
      Yoko Katsuki,Shinichiro Nakada, Tetsuji Yokoyama, Issei Imoto, Johji Inazawa, Masayuki Nagasawa, Shuki Mizutani.
    • Journal Title

      Cancer Science 99

      Pages: 1539-1545

    • NAID

      10024009549

    • Related Report
      2010 Final Research Report
  • [Journal Article] Soluble TWEAK is markedly elevated in hemophagocytic lymphohistiositosis2008

    • Author(s)
      Masayuki Nagasawa, et al
    • Journal Title

      American Journal of Hematology 83

      Pages: 222-225

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Allogeneic hematopoietic stem cell transplantation for Epstein-Barr virus-associated T/ natural killer-cell lymphoproliferative disease in Japan2008

    • Author(s)
      Sato E, Masayuki Nagasawa, et al
    • Journal Title

      American Journal of Hematology 83

      Pages: 721-727

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Caffeine yields aneuploidy through asymmetrical cell division causedby misalignment of chromosomes.2008

    • Author(s)
      Katsuki Y, Nakada s, MasayukiNagasawa, et al
    • Journal Title

      Cancer Science 99

      Pages: 1539-1545

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 造血幹細胞移植における凝固異常とその予後の解析-その対策に向けての提案-2011

    • Author(s)
      長澤正之、大川哲平、遠藤明史、満生紀子、青木由貴、小野敏明、磯田健志、富澤大輔、高木正稔、梶原道子*、森尾友宏、水谷修紀
    • Organizer
      第33回日本造血幹細胞移植学会
    • Place of Presentation
      愛媛:松山
    • Year and Date
      2011-03-10
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 誘電分光法による造血幹細胞移植患者赤血球の細胞誘電測定2011

    • Author(s)
      長澤正之、早川智広,林義人,大森真二
    • Organizer
      第33回日本造血幹細胞移植学会
    • Place of Presentation
      愛媛:松山
    • Year and Date
      2011-03-09
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 造血幹細胞移植における新規「DIC・微小血管障害の臨床スコア」作成とその有効性・有用性の後方視的検討2010

    • Author(s)
      長澤正之、大川哲平、遠藤明史、満生紀子、青木由貴、小野敏明、磯田健志、富澤大輔、高木正稔、梶原道子、森尾友宏、水谷修紀
    • Organizer
      第52回日本小児血液学会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-12-18
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 血清granulysin測定の臨床的意義について2010

    • Author(s)
      長澤正之、永田欽也、小川一行
    • Organizer
      第113回日本小児科学会学術集会
    • Place of Presentation
      盛岡
    • Year and Date
      2010-04-23
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 当科における同種造血幹細胞移植(1995-2007年)でのGVHD移植関連合併症の検討2010

    • Author(s)
      満生紀子、長澤正之, 他
    • Organizer
      第32回日本造血幹細胞移植学会総会
    • Place of Presentation
      浜松(静岡)
    • Year and Date
      2010-02-19
    • Related Report
      2009 Annual Research Report
  • [Presentation] 小児造血幹細胞移植における免疫抑制剤の標準化・適切化に関する研究2009

    • Author(s)
      長澤正之
    • Organizer
      第51回日本小児血液学会
    • Place of Presentation
      東京ベイホテル東急(千葉)
    • Year and Date
      2009-11-29
    • Related Report
      2010 Final Research Report
  • [Presentation] 小児造血幹細胞移植における免疫抑制剤の標準化・適切化に関する研究2009

    • Author(s)
      長澤正之
    • Organizer
      第51回日本小児血液学会
    • Place of Presentation
      舞浜(千葉)
    • Year and Date
      2009-11-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] 当科における移植関連TMAの臨床経験 シンポジウム「移植合併症の問題点」2009

    • Author(s)
      長澤正之
    • Organizer
      第51回日本小児血液学会
    • Place of Presentation
      東京ベイホテル東急(千葉)
    • Year and Date
      2009-11-27
    • Related Report
      2010 Final Research Report
  • [Presentation] 誘電分光法によるカルシニューリン阻害剤投与患者の赤血球解析2009

    • Author(s)
      長澤正之
    • Organizer
      第51回日本小児血液学会
    • Place of Presentation
      東京ベイホテル東急(千葉)
    • Year and Date
      2009-11-27
    • Related Report
      2010 Final Research Report
  • [Presentation] 誘電分光法によるカルシニューリン阻害剤投与患者の赤血球解析2009

    • Author(s)
      長澤正之
    • Organizer
      第51回日本小児血液学会
    • Place of Presentation
      舞浜(千葉)
    • Year and Date
      2009-11-27
    • Related Report
      2009 Annual Research Report
  • [Presentation] 当科における移植関連TMAの臨床経験2009

    • Author(s)
      長澤正之
    • Organizer
      第51回日本小児血液学会
    • Place of Presentation
      舞浜(千葉)
    • Year and Date
      2009-11-27
    • Related Report
      2009 Annual Research Report
  • [Presentation] 当科における同種造血幹細胞移植(1995-2007年)の検討2009

    • Author(s)
      長澤正之
    • Organizer
      第112回日本小児科学会学術集会
    • Place of Presentation
      奈良県文化会館(奈良)
    • Year and Date
      2009-04-19
    • Related Report
      2010 Final Research Report
  • [Presentation] 当科における同種造血幹細胞移植(1995-2007年)の検討2009

    • Author(s)
      長澤正之
    • Organizer
      第112回日本小児科学会学術集会
    • Place of Presentation
      奈良市(奈良)
    • Year and Date
      2009-04-19
    • Related Report
      2009 Annual Research Report
  • [Presentation] 当科における同種造血幹細胞移植(1995-2007年)でのGVHD移植関連合併症の検討2009

    • Author(s)
      小野敏明, 長澤正之, 他
    • Organizer
      第31回日本造血幹細胞移植学会総会
    • Place of Presentation
      札幌(北海道)
    • Year and Date
      2009-02-05
    • Related Report
      2008 Annual Research Report
  • [Presentation] 塞栓子検出用ドプラ装置の静脈への応用2008

    • Author(s)
      中村浩志, 井上芳徳, 工藤敏文, 久米博子, 菅野範英, 岩井武尚, 玉井諭, 五関謹秀
    • Organizer
      日本静脈学会総会
    • Place of Presentation
      箱根(湯本富士屋ホテル)
    • Year and Date
      2008-06-12
    • Related Report
      2008 Annual Research Report
  • [Book] 免疫不全症へのRICの有効性?「2011-2012EBM 小児疾患の治療」(五十嵐隆 編 )2011

    • Author(s)
      長澤正之(分担執筆)
    • Publisher
      中外医学社
    • Related Report
      2010 Final Research Report
  • [Book] 2011-2012EBM 小児疾患の治療2011

    • Author(s)
      五十嵐隆編
    • Total Pages
      711
    • Publisher
      中外医学社
    • Related Report
      2010 Annual Research Report
  • [Book] 小児の脳腫瘍(「今日の診断指針」第6版)2010

    • Author(s)
      長澤正之(分担執筆)
    • Publisher
      医学書院
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ

    • URL

      http://aqua.tmd.ac.jp/ResDB/DispRsch/dsp_resdata.php?id=288&la=ja

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://aqua.tmd.ac.jp/ResDB/DispRsch/dsp_resdata.php?id=288&la=ja

    • Related Report
      2010 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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