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Relation of Helicobacter heilmannii infection to gastric MALT lymphoma formation in human and mouse

Research Project

Project/Area Number 18590698
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  Kitasato University, Department of Pharmaceutical Sciences, Associate Professor (30155858)

Co-Investigator(Kenkyū-buntansha) SERIZAWA Hiroshi  Kitasato Institute Hospital, Kitasato Institute, Researcher (60187870)
MATSUI Hidenori  Kitasato University, Kitasato Institute for Life Sciences, Assistant Professor (30219373)
MATSUMOTO Tsukasa  Kitasato University, Kitasato Institute for Life Sciences, Assistant Professor (00173906)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,620,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsGastric MALT Lymohoma / Helicobacter heilmannii / VEGF / Flt-1 / Flk-1 / Helicobacter pylori / Helicobacter suis / MALTリンパ腫 / RCR法 / in situ hybridization法 / C57BL / 6マウス / apoptosis / B cell lymphoma
Research Abstract

1. Mouse Model
the MALT lymphoma tissue was shown to have rich microvascular network consisting of the immature capillaries and venules, revealed by electron microscopy. By the immunohistochemical analysis, very much enhanced VEGF-A immunoreactivity was observed in the whole MALT lymphoma tissue, while VEGF-C immunoreactivity was observed only in the marginal area of the lymphoma. Both Flt-1 and Flk-1 were expressed in the lymphoma tissues. Flk-1 were mainly expressed in the immature endothelial cells, while Flt-1 were observed in the accumulated lymphocytes. The treatment with VEGF receptor monoclonal antibody significantly decreased the size of the protrusive lesion. In conclusion, VEGF-mediated mechanism was shown to play an important role in the expansion of the MALT lymphoma tissue induced by Hh infection in C57BL/6 mice.
2. Human Cases
out of 12 MALT lymphoma cases 4 cases were positive to Hp, 5 positive to HHLO and among them 4 cases were doubly positive to HHLO and Hp. By Fisher's exact test, HHLO infection as well as Hp and HHLO co-nfection was significantly related to the MALT lymphoma. By the analysis of urease gene, 4 cases were found to belong to Hs 'infection among 9 HHLO positive patients, while other cases were not identified to either Hh, Hs or Hf. By the in situ hybridization method, the Hh was recognized near the surface epithelial cells and fundic glandular cells including parietal cells, which coincided well with our previous infection study using C57BL/6 mice. On the other hand, 129 cases were positive to Hp and only 4 cases were positive to HHLO out of 221 non-MALT lymphoma cases. In conclusion, HHLO and Hp coinfection has shown to be closely related to MALT lymphoma in Japanese cases.

Report

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

    (16 results)

All 2008 2007 2006

All Journal Article (12 results) (of which Peer Reviewed: 6 results) Presentation (3 results) Book (1 results)

  • [Journal Article] Increased apoptosis and angiogenesis in gastric low-grade mucosa-associated lymphoid tissue-type lymphoma by Hell cobacter heilmannii infection in C57/BL6 mice2007

    • Author(s)
      Nishikawa, K.
    • Journal Title

      FEMS Immunol.Med.Microbiol 50

      Pages: 268-272

    • 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] Candidatus Helicobacter heilmannii from Cynomolgus monkey brought about gastric low grade MALT lymphoma in C 57BL/6 mice2007

    • Author(s)
      Nakamura, M.
    • Journal Title

      Infect.Immun 75

      Pages: 1214-1222

    • NAID

      10018262517

    • 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] Interaction of VEGF to gastric low grade MALT lymphoma by Helicobacter heilmannii infection in C57BL/6 mice2007

    • Author(s)
      Nakamura, M.
    • Journal Title

      Inflammopharmacology 15

      Pages: 115-118

    • 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] Increased apoptosis and angiogenesis in gastric low-grade mucosa-associated lymphoid tissue-type lymphoma. by Helicobacter heilmannii infection in C57/BL6 mice2007

    • Author(s)
      Nishikawa, K., Nakamura, M., Takahashi, S., Murayama, S. Y., Matsumoto, T., Yamada, H., Tsuchimoto, K
    • Journal Title

      FEMS Immunol. Med. Microbiol 50

      Pages: 268-272

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Candidatus Helicobacter heilmannii from Cynomolgus monkey brought about gastric low grade MALT lymphoma in C57BL/6 mice2007

    • Author(s)
      Nakamura, M., Murayama, S. Y., Serizawa, H., Sekiya, Y., Eguchi, M., Takahashi, S., Nishikawa, K., Takahashi, T., Matsumoto, T., Yamada, H., Hibi, T., Tsuchimoto, K., Matsui, H
    • Journal Title

      Infect. Immun 75(3)

      Pages: 1214-1222

    • NAID

      10018262517

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Interaction of VEGF to gastric low grade MALT lymphoma by Helicobacter heilmannii infection in C57BL/6 mice2007

    • Author(s)
      Nakamura, M., Matsui, H., Murayama, S. Y., Matsumoto, T., Yamada, H., Takahashi, S., Tsuchimoto, K
    • Journal Title

      Inflammopharmacology 15

      Pages: 115-118

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Increased apoptosis and angiogenesis in gastric low-grade mucosa-associated lymphoid tissue-type lymphoma by Helicobacter heilmannii infection in C57/BL6 mice2007

    • Author(s)
      Nishikawa, K.
    • Journal Title

      FEMS Immunol. Med. Microbiol 50

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LGnsoprαzole Novel Effecfor Sifes Reveled by Autoradiography:Relation to Helicobacter pylori, Colon, Esophagus and Others2007

    • Author(s)
      Nakamura, M.
    • Journal Title

      J.Clin.Biochem.Nutr. 41

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] L-Lactic acid secreted from gastric mucosal cells enhances growth of Helicobacter pylori2007

    • Author(s)
      Takahashi, T.
    • Journal Title

      Helicobacter 12

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Candidatus Helicobacter heilmemnii from Cynomcbus Monloy about gastric Inc...2007

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

      Infect. Immun. 75・3

      Pages: 1214-1222

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Interaction of VEGF to gastric low grade MALT lymhimo by Helicobictev heilmannii.2007

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

      Inflammopharmacology 15(in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Co-infection of Helico bacter plyori and Nelsseria subflava is clrsely associated with lymgh follia...2006

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

      Aliment Pharmacol. Ther. Symp. ser 2

      Pages: 207-213

    • Related Report
      2006 Annual Research Report
  • [Presentation] MALTリンパ腫症例の半数近くにH.heilmanniiとH.pyloriの混合感染を確認2007

    • Author(s)
      中村 正彦
    • Organizer
      第13回日本ヘリコバクター学会
    • Place of Presentation
      大津
    • Year and Date
      2007-06-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] Inreraction of VEGF on formation of microcirculatory network of MALT lymphoma by Helicobacter heilmannii infection2007

    • Author(s)
      Nakamura, M.
    • Organizer
      Digestive Disease Week 2007
    • Place of Presentation
      Washington,D.C.
    • Year and Date
      2007-05-19
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Newly-designed PCR Study has revealed one third of MALT lymphoma cases doubly positive to Helicobacter heilmannii-like organism and Hp in Japan2007

    • Author(s)
      Nakamura, M., Matsui, H., Murayama, S. Y., Aikawa, C., Sekiya, Y., Serizawa, H., Suzuki, H., Suzuki, M., Takahashi, S., Hibi, T., Tsuchimoto, K
    • Organizer
      DDW 2007 Ma
    • Place of Presentation
      Washington D. C., USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 消化器疾患アプローチのための解剖生理,病気と薬 パーフェクトbook,2008

    • Author(s)
      中村 正彦
    • Publisher
      南山堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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