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Crosstalk between CagA and inflammation in H. pylori-related gastric carcinogenesis.

Research Project

Project/Area Number 24659365
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionOsaka University

Principal Investigator

TSUJII Masahiko  大阪大学, 医学(系)研究科(研究院), 准教授 (40303937)

Co-Investigator(Kenkyū-buntansha) TAKEHARA Tetsuo  大阪大学, 大学院医学系研究科, 教授 (70335355)
IIJIMA Hideki  大阪大学, 大学院医学系研究科, 講師 (90444520)
NISHIDA Tsutomu  大阪大学, 大学院医学系研究科, 助教 (20467575)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords胃癌 / ヘリコバクターピロリ / CagA / 腸上皮化生 / 胃炎 / let-7 / 炎症
Research Abstract

In in vitro experiments, CagA significantly attenuated let-7 expression leading to Ras pathway activation. CagA enhanced c-myc, DNA methyltransferase 3B (DNMT3B) and Enhancer of Zeste homologue 2 (EZH2) expression and attenuated miR-26a and miR-101 expression, which resulted in the attenuation of let-7 expression by histone and DNA methylation. Experiments performed in CagA transgenic mice revealed that c-myc, EZH2 and DNMT3B expression were enhanced and let-7 expression was attenuated to induce Ras oncoprotein expression in the stomach, with no associated inflammation. It is concluded that H pylori CagA induces aberrant epigenetic silencing of let-7 expression, leading to Ras upregulation.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (35 results)

All 2014 2013 2012 Other

All Journal Article (27 results) (of which Peer Reviewed: 22 results) Presentation (8 results)

  • [Journal Article] Clinical features of post-polypectomy bleeding associated with heparin bridge therapy.2014

    • Author(s)
      Inoue T, Nishida T, Maekawa A, Tsujii Y, Akasaka T, Kato M, Hayashi Y, Yamamoto S, Kondo J, Yamada T, Shinzaki S, Iijima H, Tsujii M, Takehara T.
    • Journal Title

      Dig Endosc.

      Volume: 26 Issue: 2 Pages: 243-249

    • DOI

      10.1111/den.12123

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Atypical duodenal ulcer and invagination caused by a large pedunculated duodenal Brunner's gland hamartoma.2014

    • Author(s)
      Nakabori T, Shinzaki S, Yamada T, Nishida T, Iijima H, Tsujii M, Kurokawa Y, Mori M, Doki Y, Morii E, Takehara T.
    • Journal Title

      Gastrointest Endosc.

      Volume: 79 Issue: 4 Pages: 679-680

    • DOI

      10.1016/j.gie.2013.11.002

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Concomitant use of romiplostim and chemotherapy for advanced rectal cancer associated with idiopathic thrombocytopenic purpura2014

    • Author(s)
      Yamada M, Shinzaki S, Nishida T, Yamada T, Fujinaga T, Yakushijin T, Tatsumi T, Iijima H, Hiramatsu N, Tsujii M, Takehara T.
    • Journal Title

      日本消化器病学会雑誌

      Volume: 111 Pages: 521-528

    • NAID

      130003392015

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amelioration of Small Bowel Injury by Switching from Nonselective Nonsteroidal Anti-Inflammatory Drugs to Celecoxib in Rheumatoid Arthritis Patients: A Pilot Study2013

    • Author(s)
      Inoue, T., Iijima, H., Arimitsu, J., Hagihara, K., Kawai, S., Shiraishi, E., Hiyama, S., Mukai, A., Shinzaki, S., Nishida, T., Ogata, A., Tsujii, M., Takehara, T.
    • Journal Title

      Digestion

      Volume: 89 Issue: 2 Pages: 124-132

    • DOI

      10.1159/000357229

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Esophageal pyogenic granuloma developed after short-term fol low-up.2013

    • Author(s)
      Saito Y, Nishida T, Kato M, et al.
    • Journal Title

      Dis Esophagus

      Volume: 26(Epub 2012 May 9.) Issue: 3 Pages: 343-344

    • DOI

      10.1111/j.1442-2050.2012.01351.x

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acute suppurative pancreatic ductitis associated with pancreatic duct obstruction.2013

    • Author(s)
      Fujinaga T, Nishida T, Miyazaki M, Shigekawa M, Ikezawa K, Iwahashi K, Inoue T, Yamada T, Ezaki H, Shinzaki S, Yakushijin T, Iijima H, Tsujii M, Takehara T.
    • Journal Title

      Endoscopy

      Volume: 45 Issue: S 02 Pages: 135-135

    • DOI

      10.1055/s-0032-1326450

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Choroidal and cutaneous metastasis from gastric adenocmcinoma.2013

    • Author(s)
      Kawai S, Nishida T, Hayashi Y, et al.
    • Journal Title

      World J Gastroenterol

      Volume: 19 Issue: 9 Pages: 1485-1488

    • DOI

      10.3748/wjg.v19.i9.1485

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lectin-based immunoassay for aberrant IgG glycosylation as the biomarker for Crohn's disease.2013

    • Author(s)
      Shinzaki S, 他13名, Naka T, Plevy S E, Takehara T, Miyoshi E.
    • Journal Title

      Inflamm Bowel Dis.

      Volume: 19(2) Issue: 2 Pages: 321-31

    • DOI

      10.1097/mib.0b013e318280eade

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of endoscopic ultrasound image quality is necessary in endosonographic assessment of early gastric cancer invasion depth2013

    • Author(s)
      Yamamoto S, Nishida T, Iijima H, Tsujii M, Takehara T.
    • Journal Title

      Gastroenterol Res Pract

      Pages: 164530-164530

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/?term=endosonographic+assessment+of+yamamoto+s

    • Related Report
      2013 Final Research Report
  • [Journal Article] CagA mediates epigenetic regulation to attenuate let-7 expression in Helicobacter pylori-related carcinogenesis.2013

    • Author(s)
      Hayashi Y, Tsujii M, Wang J, Kondo J, Akasaka T, Jin Y, Li W, Nakamura T, Nishida T, Iijima H, Tsuji S, Kawano S, Hayashi N, Takehara T.
    • Journal Title

      GUT

      Volume: 62 Issue: 11 Pages: 1536-1546

    • DOI

      10.1136/gutjnl-2011-301625

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Scheduled endoscopic surveillance controls secondary cancer after curative endoscopic resection for early gastric cancer : a multicentre retrospective cohort study by Osaka University ESD study group2013

    • Author(s)
      Kato M, Nshida T, Iijima H, Tsujii M, Takehara T.
    • Journal Title

      Gut

      Volume: 62 Issue: 10 Pages: 1425-1432

    • DOI

      10.1136/gutjnl-2011-301647

    • Related Report
      2013 Final Research Report
  • [Journal Article] Mucosa-associated lymphoid tissue (MALT) lymphoma of the esophagus.2013

    • Author(s)
      Tsujii Y, Nishida T, Kato M, et al.
    • Journal Title

      Dis Esophagus. 2013 Apr : 26(3) : 349-50.

      Volume: 26.(Epub 2012 Aug 7.) Issue: 3 Pages: 349-350

    • DOI

      10.1111/j.1442-2050.2012.01387.x

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Managing hepatitis B virus carriers with systemic chemotherapy or biologic therapy in the outpatient clinic.2013

    • Author(s)
      Nishida T
    • Journal Title

      Hepatol Res.

      Volume: 43 Issue: 4 Pages: 339-346

    • DOI

      10.1111/j.1872-034x.2012.01073.x

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Post-transplant lymphoproliferative disorder of the ileum diagnosed by double-balloon enteroscopy.2013

    • Author(s)
      Tawara S, Shinzaki S, Nishida T, Kato M, Hiyama S, Inoue T, Iijima H, Tsujii M, Takehara T.
    • Journal Title

      Endoscopy.

      Volume: 45 Issue: S 02 Pages: 380-381

    • DOI

      10.1055/s-0033-1344828

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gastric ESD under Heparin Replacement at High-Risk Patients of Thromboembolism Is Technically Feasible but Has a High Risk of Delayed Bleeding: Osaka University ESD Study Group.2013

    • Author(s)
      Yoshio T, Nishida T, Kawai N, Yuguchi K, Yamada T, Yabuta T, Komori M, Yamaguchi S, Kitamura S, Iijima H, Tsutsui S, Michida T, Mita E, Tsujii M, Takehara T.
    • Journal Title

      Gastroenterol Res Pract.

      Volume: 2013 Pages: 365830-365830

    • DOI

      10.1155/2013/365830

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Narrow Band Imaging with Magnifying Endoscopy for Peyer's Patches in Patients with Inflammatory Bowel Disease2013

    • Author(s)
      Hiyama, S., Iijima, H., Shinzaki, S., Mukai, A., Inoue, T., Shiraishi, E., Kawai, S., Yamada, T., Nishida, T., Tsujii, M., Takehara, T.
    • Journal Title

      Digestion

      Volume: 87 Issue: 4 Pages: 269-80

    • DOI

      10.1159/000349953

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hemobilia into a metallic biliary stent due to pseudoaneurysm: a case report2013

    • Author(s)
      Morishita N, Nishida T, Hayashi Y, Iwahashi K, Ikezawa K, Shigekawa M, Shinzaki S, Yamada T, Kakita N, Ezaki H, Miyazaki M, Yakushijin T, Tatsumi T, Iijima H, Kiso S, Hiramatsu N, Tsujii M, Osuga K, Terashima K, Takehara T.
    • Journal Title

      日本消化器病学会雑誌

      Volume: 110 Pages: 2127-2135

    • NAID

      130003383333

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclooxygenase, cancer stem cells and DNA methylation play important roles in colorectal carcinogenesis2013

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

      Digestion

      Volume: 87 Issue: 2 Pages: 12-16

    • DOI

      10.1159/000334678

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Functional Network between Bone and Organs. Gastrointestinal diseases and bone2013

    • Author(s)
      Iijima, H. Tsujii, M. Takehara, T.
    • Journal Title

      Clin Calcium

      Volume: 23 Pages: 243-248

    • Related Report
      2012 Research-status Report
  • [Journal Article] Epste in-Barr virus-associated early gastric cancer presenting as an elevated lesion.2012

    • Author(s)
      Yamamoto S, Nishida T, Tsujii M, et al.
    • Journal Title

      Endoscopy

      Volume: 44(Epub 2012 May 23.) Issue: S 02 Pages: 222-223

    • DOI

      10.1055/s-0032-1309353

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Altered oligosaccharide structures contribute to ameliorate murine colitis defective in beta 1,4 galactosyltransferase I.2012

    • Author(s)
      Shinzaki S, Miyoshi E, et al.
    • Journal Title

      Gastroenterology

      Volume: 142(5) Issue: 5 Pages: 1172-82

    • DOI

      10.1053/j.gastro.2012.02.008

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protective role of adiponec t in against ethanol-induced gastric injury in mice.2012

    • Author(s)
      Yamamoto S, ffatabe K, Araki H, et al.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol.

      Volume: 302(Epub 2012 Feb 9) Issue: 8 Pages: G773-G780

    • DOI

      10.1152/ajpgi.00324.2011

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Deficiency of N-acetylgalactosamine in O-linked oligosaccharides of IgA is a novel biologic marker for inflammatory bowel diseases.2012

    • Author(s)
      InoueT, Miyoshi E, et al.
    • Journal Title

      IBD Journal

      Volume: 18(9) Issue: 9 Pages: 1723-34

    • DOI

      10.1002/ibd.22876

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of endoscopic ultrasound image quality is necessary in endosonographic assessment of early gastric cancer invasion depth2012

    • Author(s)
      Yamamoto, S. Nishida, T. Kato, M. et al.
    • Journal Title

      Gastroenterol Res Pract

      Volume: 2012 Pages: 194530-194530

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biomarkers in the diagnosis and therapy of inflammatory bowel diseases2012

    • Author(s)
      Iijima, H. Shinzaki, S. Tsujii, M. et al.
    • Journal Title

      日本臨床

      Volume: 70 Pages: 869-873

    • NAID

      40019297884

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of anergy-related ubiquitin E3 ligase, GRAIL, in murine models of colitis and patients with Crohn's disease

    • Author(s)
      Mukai A, Iijima H, H, Nishida T, Tsujii M, Takehara T.
    • Journal Title

      J Gastroenterol

      Volume: (in press)

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/24356810

    • Related Report
      2013 Final Research Report
  • [Journal Article] Peyer's Patches Play a Protective Role in Nonsteroidal Anti-inflammatory Drug-induced Enteropathy in Mice

    • Author(s)
      Hiyama S, Iijima H, Tsujii M, Takehara T.
    • Journal Title

      Inflamm Bowel Dis

      Volume: (in press)

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/24651581

    • Related Report
      2013 Final Research Report
  • [Presentation] Cyclooxygenase-2の癌幹細胞バイオロジー、DNA異常メチル化に及ぼす影響.ワークショップ;消化管がん分子病態診断学の進歩2012

    • Author(s)
      辻井正彦,近藤純平,赤坂智史,林義人,金瑛,加藤元彦,山本俊祐,井上拓也,山田拓哉,西田勉,渡部健二,飯島英樹,竹原徹郎
    • Organizer
      第8回日本消化管学会
    • Place of Presentation
      仙台
    • Related Report
      2013 Final Research Report
  • [Presentation] ESD後の適切なフォローアップ方法~多発胃癌に対するサーベイランスの観点から~ESDフォーラム; Where is our destination?2012

    • Author(s)
      加藤元彦,西田勉,山本克己,北村信次,由雄敏之,中村剛之,小森真人,河相直樹,西原彰浩,中西文彦,中原征則,荻山秀治,木下和郎,辻井正彦,竹原徹郎
    • Organizer
      第8回日本消化管学会
    • Place of Presentation
      仙台
    • Related Report
      2013 Final Research Report
  • [Presentation] ヘパリン置換療法下での大腸内視鏡的粘膜切除後出血の検討.シンポジウム;抗凝固薬・抗血小板薬服用患者の内視鏡診療を検証する2012

    • Author(s)
      井上拓也,辻井正彦,竹原徹郎
    • Organizer
      第83回日本消化器内視鏡学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] Long-term outcomes of ESD for patients with early gastric cancer and liver cirrhosis : a multicenter study by Osaka University ESD Study Group2012

    • Author(s)
      Kato M, Tsujii M, Takehara T.
    • Organizer
      2012 Digestive Disease Week and the Annual Meeting of the American Society for Gastrointestinal Endoscopy
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Narrow band imaging with magnifying endoscopy for Peyer's patches in patients with inflammatory bowel disease2012

    • Author(s)
      Hiyama S, Nishida T, Tsujii M, Takehara T.
    • Organizer
      2012 Digestive Disease Week and the Annual Meeting of the American Society for Gastrointestinal Endoscopy
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of DNA methylation on epithelial mesenchymal transition (EMT)-like phenotype of colon cancer cells2012

    • Author(s)
      Kondo J, Nishida T, Watabe K, Tsujii M, Takehara T.
    • Organizer
      2012 Digestive Disease Week and the Annual Meeting of the American Society for Gastrointestinal Endoscopy
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Clinical features of late bleeding associated with heparin replacement after endoscopic resection for colorectal neoplasms2012

    • Author(s)
      Inoue T, Iijima H, Tsujii M, Takehara T.
    • Organizer
      2012 Digestive Disease Week and the Annual Meeting of the American Society for Gastrointestinal Endoscopy
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] 胃癌発生と腸上皮化生H.pylori起因性胃発癌におけるCagAと腸上皮化生の役割2012

    • Author(s)
      林 義人、辻井正彦、竹原徹郎
    • Organizer
      日本消化器関連学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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