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2012 Fiscal Year Final Research Report

Studies on Helicobacter species on gastric MALT lymphoma and effect of molecular target drugs

Research Project

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Project/Area Number 22590690
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKitasato University

Principal Investigator

NAKAMURA Masahiko  北里大学, 薬学部臨床薬学研究・教育センター病態解析学, 准教授 (30155858)

Co-Investigator(Kenkyū-buntansha) MATSUI Hidenori  北里大学, 感染制御科学府, 講師 (30219373)
TAKAHASHI Tetsufumi  北里大学, 薬学部, 助教 (40449004)
Project Period (FY) 2010 – 2012
Keywords上部消化管学(食道、胃、十二指腸)
Research Abstract

By the investigation of the specimens obtained from the upper gastrointestinal endoscopy of the patients suffering from chronic gastritis, gastric ulcer, gastric polyp, gastric cancer and gastric MALT lymphoma, 7 MALT lymphoma cases out of 18 (38%) were found to be positive to Helicobacter heilmannii, while only 2% were positive in other gastric diseases. By the cluster analysis using GENENTYC-MAC UPGMA, these cases were found to be infected by Helicobacter heilmannii and suis. Among other gastric diseases, nodular gastritis patents were found to be highly positive to H. heilmannii, suggesting the possible interaction with the gastric cancer. In H. heilmannii positive cases, more than half cases were found to show the positivity to H. pylori as well.By the in vivo study using the infection model using C57BL/6 mice, VEGF-related immunoreactities were recognized in the MALT lymphoma, suggesting the VEGF-mediated angiogenesis was closely related to the expansion of the tumor. The administration of Flt-4 and Flt-1 antibody suppressed the tumor, supporting this hypothesis. c-Met immunoreactivity was found in the lymphocytes composing the MALT lymphoma, and HGF immunoreactivity was recognized mostly in the endothelial cells and macrophages. HGFA was localized on mesenchymal cells other than the lymphocytes. The administration of antibodies against c-Met to the infected mice induced the significant suppression of hepatic and pulmonary lesions as well as the gastric MALT lymphoma.In conclusion, HGF and c-Met pathway were suggested to contribute to the lymphomagenesis in the liver and lung after Helicobacter heilmannii infection.

  • Research Products

    (20 results)

All 2013 2012 2011 2010

All Journal Article (7 results) (of which Peer Reviewed: 4 results) Presentation (12 results) Book (1 results)

  • [Journal Article] Helicobacter heilmannii感染MALTリンパ腫における幹細胞の意義: CD44, CD133免疫活性との関連および除菌の効果2013

    • Author(s)
      中村正彦、高橋哲史、松井英則、高橋信一、土本寛二
    • Journal Title

      Ulcer Research

      Volume: 40巻 Pages: 9 -11

    • Peer Reviewed
  • [Journal Article] 胃、肝 MALT リンパ腫形成および進展における幹細胞の関与2012

    • Author(s)
      中村正彦、 高橋哲史、横山展子、松田 唯、松井英則、土本寛二
    • Journal Title

      Prog Med

      Volume: 32巻 Pages: 553-555

  • [Journal Article] 胃、肝、肺MALTリンパ腫形成におけるc-Met, Hepatocyte Growth Factorの関与:c-Met抗体による腫瘍縮小効果2012

    • Author(s)
      横山展子、 中村正彦、松田唯、馬庭優子、伊香萌菜、松井英則、高橋哲史、高橋信一、土本寛二
    • Journal Title

      Prog Med

      Volume: 33巻 Pages: 397-400

  • [Journal Article] 胃粘膜微小循環系-潰瘍2011

    • Author(s)
      中村正彦、土本寛二
    • Journal Title

      リンパ腫形成時の変化、脈管学

      Volume: 51巻 Pages: 139-144

    • Peer Reviewed
  • [Journal Article] Helicobacter heilmannii感染に対する宿主応答因子の網羅的解析2011

    • Author(s)
      品川桂子、小松陽子、高橋哲史、中村正彦
    • Journal Title

      Prog Med

      Volume: 31巻 Pages: 814-816

  • [Journal Article] Suppression of lymphangiogenesis induced by Flt-4 antibody in gastric low-grade mucosa-associated lymphoid tissue lymphoma by Helicobacter heilmannii infection2010

    • Author(s)
      Nakamura, M., Matsui, H., Takahashi, T., Ogawa, S., Tamura, R., Murayama, S.Y., Takahashi, T. and Tsuchimoto, K
    • Journal Title

      J. Gastroenterol. Hepatol

      Volume: 25巻 Pages: S1-S6

    • Peer Reviewed
  • [Journal Article] Helicobacter heilmannii can induce gastric lymphoid follicles in mice via a Peyer's patch-independent pathway2010

    • Author(s)
      Nobutani, K., Yoshida, M., Nishiumi, S., Nishitani, Y., Takagawa, T,, Tanaka, H., Yamamoto, K., Miura, T., Bensuleiman, Y., Ota, H., Takahashi, S., Matsui, H., Nakamura, M.and Azuma, T
    • Journal Title

      FEMS Immunol Med Microbiol

      Volume: 60巻 Pages: 156-164

    • Peer Reviewed
  • [Presentation] Helicobacter heilmannii感染胃粘膜におけるCD86依存的シグナルの活性化2013

    • Author(s)
      伊香萌菜、高橋哲史、松田唯、瀧沢麻子、松井英則、高橋信一、中村正彦、土本寛二
    • Organizer
      日本薬学会第133年会
    • Year and Date
      20130327-30
  • [Presentation] Helicobacter heilmannii感染MALTリンパ腫における幹祭簿と微小循環系:除菌の効果2013

    • Author(s)
      馬庭優子、中村正彦、横山展子、高橋哲史、松井英則、土本寛二
    • Organizer
      日本薬学会第133年会
    • Year and Date
      20130327-30
  • [Presentation] MALT lymphoma stem cell and its niche are related to peculiar microcirculatory network in Helicobacter heilmannii-infected mice stomach2013

    • Author(s)
      Nakamura, M., Matsui, H., Takahashi, T.and Tsuchimoto, K
    • Organizer
      38th Annual Meeting of the Japanese Society for Microcirculation
    • Year and Date
      20130208-09
  • [Presentation] 胃および肝MALTリンパ腫形成および進展における幹細胞マーカーの変化:除菌時の変化2013

    • Author(s)
      中村正彦、松井英則、高橋哲史、高橋信一、土本寛二
    • Organizer
      第9回日本消化管学会総会
    • Place of Presentation
      京王プラザ
    • Year and Date
      20130125-26
  • [Presentation] Helicobacter heilmannii感染惹起胃MALTリンパ腫病態形成時におけるCD86依存的シグナルの活性化2013

    • Author(s)
      高橋哲史、松井英則、瀧沢麻子、伊香萌菜、松田唯、土本寛二、中村正彦
    • Organizer
      第31回Cytoprotection研究会
    • Year and Date
      2013-03-15
  • [Presentation] Helicobacter heilmannii感染MALTリンパ腫における幹細胞の意義:除菌療法との関連2012

    • Author(s)
      中村正彦、高橋哲史、松井英則、土本寛二
    • Organizer
      第44回日本臨床分子形態学会
    • Place of Presentation
      高知
    • Year and Date
      20120928-29
  • [Presentation] MALT Lymphoma Stem Cell in Helicobacter heilmannii-infected Mice Stomach: Effect of Eradication2012

    • Author(s)
      Nakamura, M., Matsui, H., Takahashi, T., Takahashi, S., Hibi, T. and Tsuchimoto, K
    • Organizer
      7th International Symposium on Cell/Tissue Injury and Cytoprotection/Organoprotection -Focus on GT Tract
    • Place of Presentation
      Hawaii, USA
    • Year and Date
      20120909-11
  • [Presentation] Helicobacter heilmannii感染MALTリンパ腫における幹細胞と微小循環系の連関2012

    • Author(s)
      中村正彦、高橋哲史、松井英則、土本寛二
    • Organizer
      第40回日本潰瘍学会
    • Place of Presentation
      京王プラザ
    • Year and Date
      20120712-14
  • [Presentation] c-MET Antibody Administration Reduces Helicobacter heilmannii-induced MALT Lymhoma in Fundus, Liver and Lung2012

    • Author(s)
      Nakamura, M., Takahashi, T., Matsui, H., Takahashi, S. and Tsuchimoto, K
    • Organizer
      14th Meeting of International Conference on Ulcer Week
    • Place of Presentation
      Tokyo
    • Year and Date
      20120712-14
  • [Presentation] Helicobacter heilmanniiによる胃、肝、肺MALTリンパ腫形成および進展におけるc-MET抗体の効果2012

    • Author(s)
      中村正彦、松井英則、高橋哲史、高橋信一、土本寛二
    • Organizer
      第18回日本ヘリコバクター学会学術集会
    • Place of Presentation
      岡山
    • Year and Date
      20120629-30
  • [Presentation] c-MET, HGF and HGFA are closely related to the Liver and Lung Lesion in Helicobacter heilmannii-induced MALT lymphoma2012

    • Author(s)
      Nakamura, M., Matsui, H., Takahashi, T.,Murayama, S.Y., Takahashi, S., Hibi, T. and Tsuchimoto, K
    • Organizer
      DDW 2012
    • Place of Presentation
      San Diego, USA
    • Year and Date
      20120519-22
  • [Presentation] 胃、肝、肺 MALTリンパ腫形成におけるc-MET, Hepatocyte Growth Factorの関与:c-MET抗体による腫瘍縮小効果2012

    • Author(s)
      横山展子、中村正彦、松田唯、高橋哲史、松井英則、土本寛二
    • Organizer
      第31回消化器病態生理勉強会
    • Place of Presentation
      京王プラザホテル
    • Year and Date
      2012-07-28
  • [Book] 日本臨床分子形態学会編、Helicobacter heilmanniiの超微形態および壁細胞への侵入性2011

    • Author(s)
      中村正彦、土本寛二
    • Total Pages
      101
    • Publisher
      学際企画

URL: 

Published: 2014-08-29   Modified: 2017-10-11  

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