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Investigation of APE-1 regulation induced by gamma/delta T cells in intestinal cells

Research Project

Project/Area Number 17590686
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionNippon Medical School

Principal Investigator

FUTAGAMI Seiji  Nippon Medical School, Internal Medicine, Division of Gastroenterology, Assistant Professor (50247011)

Co-Investigator(Kenkyū-buntansha) SAKAMOTO Choitsu  Nippon Medical School, Internal Medicine, Division of Gastroenterology, Professor (30196092)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,140,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsAPE-1 / intestinal metaplasia / Cdx2 / MCP-1 / CD40 / CD4OL / COX-2 / gamma delta T cell / prostaglandinsE2 / COX-2(cyclooxygenase-2) / mucosal defense / cyclooxygenase-2 / V deltal T cell / V delta2 T cell
Research Abstract

BACKGROUND : Recent studies have reported that expression of monocyte chemoattractant protein 1 (MCP-1) and its receptor (CCR2) and CD40 ligation on mesenchymal cells play important roles in tumor development. Cyclooxygenase 2 (COX-2) has also been shown to contribute to tumor angiogenesis. We examined the interaction between MCP-1 and CD40 ligation in mesenchymal cells in gastric cancer to determine the effect of these factors on vascular endothelial growth factor (VEGF) production via upregulation of COX-2 expression. METHODS : COX-2, prostaglandin E2 (PGE2), and VEGF production were evaluated in CD40 ligand (CD4OL)-stimulated macrophages. CD4OL and MCP-1 mRNA levels in gastric cancer tissues were evaluated by real-time polymerase chain reaction (PCR). Localizations of MCP-1, CD4OL, CD34, CD40, and CCR2 in 34 gastric cancer tissue specimens were evaluated by single-or double-label immunohistochemistry. RESULTS : COX-2 expression levels were significantly higher in CD40L-stimulated macrophages and correlated with increased PGE2 and VEGF production. Addition of MCP-1 to CD4OL-stimulated macrophages had a synergistic effect on COX-2 expression and subsequent PGE2 and VEGF production. CD4OL and MCP-1 mRNA levels were significantly higher in poorly differentiated gastric cancers than in H. pylori-infected gastritis patients. High microvessel density was significantly associated with MCP-1 and CCR2 scores and lymph node metastasis. CONCLUSIONS : MCP-1 and CD4OL had a synergistic effect on COX-2 expression and subsequent VEGF production in gastric cancer.

Report

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

    (26 results)

All 2008 2007 2006 2005 Other

All Journal Article (20 results) (of which Peer Reviewed: 6 results) Presentation (3 results) Book (3 results)

  • [Journal Article] COX-2 and CCR2 induced by CD40 ligand and MCP-1 are linked to VEGF production in endothelial cells2008

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

      Prostaglandins Leukot Essent Fatty Acids 78

      Pages: 137-146

    • 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] MCP-1 and CD40 ligation have a synergistic effect on VEGF production through COX-2 upregulation in gastric cancer2008

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

      J Gastroenterol 43

      Pages: 31-39

    • 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 apurinic/apyrimidinic endonuclease-1(APE-1)in H.pylori associated gastritis,gastric adenoma,and gastric cancer2008

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

      Helicobacter (In press)

    • 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] COX-2 and CCR2 induced by CD40 ligand and MCP-1 are linked to VEGF production in endothelial cells.2008

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

      Prostaglandins Leukot Essent Fatty Acids 78

      Pages: 137-146

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] MCP-1 and CD40 ligation have a synergistic effect on VEGF production through COX-2 upregulation in gastric cancer.2008

    • Author(s)
      Futagami, S., Tatsuguchi, A., Hiratsuka, T., et. al.
    • Journal Title

      J Gastroenterol 43

      Pages: 31-39

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] COX-2 and CCR2 induced by CD40 ligand and MCP-1 are linked to VEGF production in endothelial cells.2008

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

      Prostaglandins Leukot Essent Fatty Acids 78

      Pages: 137-146

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MCP-1 and CD40 ligation have a synergistic effect on VEGF production through COX-2 upregulation in gastric cancer.2008

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

      J Gastroenterol 43

      Pages: 31-39

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of apurinic/apyrimidinic endonuclease-1(APE-1)in H. pylori associated gastritis, gastric adenoma, and gastric cancer.2008

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

      Helicobacter (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemopreventative effect of celecoxib in gastric cancer.2007

    • Author(s)
      Futagami S, Suzuki K, Hiratsuka T, et al.
    • Journal Title

      Inflammopharmacology 15

      Pages: 1-4

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Gammadelta T cells increase with gastric mucosal interleukin(IL)-7, IL-1beta, and Helicobacter pylori urease specific immunoglobulin levels via CCR2 upregulation in Helicobacter pylori gastritis.2006

    • Author(s)
      Futagami, S., Hiratsuka, T., Suzuki, K., et. al.
    • Journal Title

      Gastroenterol Hepatol 21

      Pages: 32-40

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Gamma delta T cells increase with gastric mucosal interleukin(IL)-7, IL-1β and Helicobacter pylori urease specific immunoglobulin levels via CCR2 upregulation in Helicobacter pylori gastritis.2006

    • Author(s)
      Futagami S, Hiratsuka T, Suzuki K, et al.
    • Journal Title

      J Gastroenterol Heaptol 21

      Pages: 32-40

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Helicobacter pylori infection induces accumulation of Vdelta 1 T cells via CCR2 upregulation2006

    • Author(s)
      Futagami S, Hiratsuka T, Shindo T, et al.
    • Journal Title

      Aliment Pharmacol Ther 2006 Suppl 4

      Pages: 8-15

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Celecoxib inhibits Cdx2 expression and prevents gastric cancer in Helicobacter pylori-infected Mongolina gerbils.2006

    • Author(s)
      Futagami S, Suzuki K, Hiratsuka T, et al.
    • Journal Title

      Digestion 74

      Pages: 187-198

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Gamma delta T cells increase with gastric mucosal interleukin-7, IL-1beta, and Helicobacter pylori urease specific immunoglobulin levels via CCR2 upregulation in Helicobacter pylori gastritis.2006

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

      Journal of Gastroenterology and Hepatology 21

      Pages: 32-40

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Helicobacter pylori infection induces accumulation of Vdelta1 T cells via CCR2 upregulation.2006

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

      Alimentary pharmacology & Therapeutics (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Monocyte chemoattractant protein 1 and macrophage cyclooxygenase 2 expression in colonic adenoma.2006

    • Author(s)
      Tanaka S, Tatsuguchi A, Futagami S, et al.
    • Journal Title

      Gut 55

      Pages: 54-61

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Rebamipide reduces indomethacin-induce gastrlc injury in mice via down-regulation of ICAM-1 expression.2005

    • Author(s)
      Hiratsuka T, Futagami S, et al.
    • Journal Title

      Dig Bis Sci 50

    • Related Report
      2005 Annual Research Report
  • [Journal Article] COX-1 and COX-2 conversely promote and suppress ischemia-reperfusion gastric injury in mice.2005

    • Author(s)
      Hiratsuka T, Futagami S, et al.
    • Journal Title

      Scand J Gastroenterol 40

      Pages: 903-913

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Heregulin-alpha and heregulin beta expression is linked to a COX-2 PGE2 pathway in human gastric fibroblasts.2005

    • Author(s)
      Nagata K, Wada K, Tatsuguchi A, Futagami S, et al.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol 15

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Celecoxib inhibits Cdx2 expression and prevents gastric cancer in Helicobacter pylori-infected Mongolian gerbils.

    • Author(s)
      Futagami, S., Suzuki, K., Hiratsuka T, et. al.
    • Journal Title

      Celecoxib inhibits Cdx2 expression and prevents gastric cancer in Helicobacter pylori-infected Mongolian gerbils.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 選択的COX-2阻害剤によるH.pylori感染胃癌モデルによるHPG発現抑制の検討2008

    • Author(s)
      二神 生爾, ほか
    • Organizer
      日本消化管学会
    • Place of Presentation
      大阪
    • 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
  • [Presentation] 選択的COX-2阻害剤を用いたcelecoxibによる胃癌発生抑制の検討2007

    • Author(s)
      二神 生爾, ほか
    • Organizer
      第13回日本ヘリコバクター学会
    • Place of Presentation
      大津
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Helicobacter pylori infection induces accumulation of Vdelta1 T cells via CCR2 upregulation.

    • Author(s)
      Futagami, S., Hiratsuka, T., et. al.
    • Place of Presentation
      AGA, Los Angeles, USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Helicobacter pylori感染の最近の知見-Helicobacter感染動物モデルの有用性2008

    • Author(s)
      二神 生爾, ほか
    • Publisher
      北隆社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Helicobacter pylori感染の最近の知見-Helicobacter感染動物モデルの有用性2008

    • Author(s)
      二神 生爾、ほか
    • Publisher
      北隆社
    • Related Report
      2007 Annual Research Report
  • [Book] H.pylori除菌と消化性潰瘍・関連疾患-基礎と臨床研究のアップデート-胃粘膜中IL-7, IL-1beta発現とgamma delta T cell浸潤の検討2005

    • Author(s)
      二神生爾, 坂本長逸
    • Publisher
      日本臨床
    • Related Report
      2005 Annual Research Report

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

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