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

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659365
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Osaka 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
• Keywords: 胃癌 / ヘリコバクターピロリ / CagA

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.

Research Products

• [Journal Article] Amelioration of small bowel injury by switching from nonselective nonsteroidal anti-inflammatory drugs to celecoxib in rheumatoid arthritis patients : a pilot study (2014)
  • Author(s): Inoue T, Iijima H, Nishida T, Tsujii M, Takehara T.
  • Journal Title: Digestion Volume: 89 Pages: 124-132
  • DOI: 10.1159/000357229
• [Journal Article] Clinical features of post-polypectomy bleeding associated with heparin bridge therapy (2014)
  • Author(s): Inoue T, Nishida T, Iijima H, Tsujii M, Takehara T.
  • Journal Title: Dig Endosc Volume: 26 Pages: 243-249
  • DOI: 10.1111/den.12123
• [Journal Article] Esophageal pyogenic granuloma developed after short-term follow-up (2013)
  • Author(s): Saito Y, Nishida T, Iijima H, Tsujii M, Takehara T.
  • Journal Title: Dis Esophagus Volume: 26 Pages: 343-344
  • DOI: 10.1111/j.1442-2050.2012.01351.x
• [Journal Article] Acute suppurative pancreatic ductitis associated with pancreatic duct obstruction (2013)
  • Author(s): Fujinaga T, Nishida T, Iijima H, Tsujii M, Takehara T.
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  • DOI: 10.1055/s-0032-1326450
• [Journal Article] Choroidal and cutaneous metastasis from gastric adenocarcinoma (2013)
  • Author(s): Kawai S, Nishida T, Iijima H, Tsujii M, Takehara T.
  • Journal Title: World J Gastroenterol Volume: 19 Pages: 1485-1488
  • DOI: 10.3748/wjg.v19.i9.1485
• [Journal Article] Lectin-based immunoassay for aberrant IgG glycosylation as the biomarker for Crohn's disease (2013)
  • Author(s): Shinzaki S, Iijima H, Tsujii M, Takehara T.
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  • DOI: 10.1097/MIB.0b013e318280eade
• [Journal Article] Evaluation of endoscopic ultrasound image quality is necessary in endosonographic assessment of early gastric cancer invasion depth (2013)
  • Author(s): Yamamoto S, Nishida T, Iijima H, Tsujii M, Takehara T.
  • Journal Title: Gastroenterol Res Pract Pages: 164530
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/?term=endosonographic+assessment+of+yamamoto+s
• [Journal Article] CagA mediates epigenetic regulation to attenuate let-7 expression in Helicobacter pylori-related carcinogenesis (2013)
  • Author(s): Hayashi Y, Tsujii M, Nishida T, Iijima H, Takehara T.
  • Journal Title: Gut Volume: 62 Pages: 1536-1546
  • DOI: 10.1136/gutjnl-2011-301625
• [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 group (2013)
  • Author(s): Kato M, Nshida T, Iijima H, Tsujii M, Takehara T.
  • Journal Title: Gut Volume: 62 Pages: 1425-1432
  • DOI: 10.1136/gutjnl-2011-301647
• [Journal Article] Mucosa-associated lymphoid tissue (MALT) lymphoma of the esophagus (2013)
  • Author(s): Tsujii Y, Nishida T, Iijima H, Tsujii M, Takehara T.
  • Journal Title: Dis Esophagus Volume: 26 Pages: 349-350
  • DOI: 10.1111/j.1442-2050.2012.01387.x
• [Journal Article] Managing hepatitis B virus carriers with systemic chemotherapy or biologic therapy in the outpatient clinic (2013)
  • Author(s): Nishida T, Iijima H, Tsujii M, Takehara T.
  • Journal Title: Hepatol Res Volume: 43 Pages: 339-346
  • DOI: 10.1111/j.1872-034X.2012.01073.x
• [Journal Article] Post-transplant lymphoproliferative disorder of the ileum diagnosed by double-balloon enteroscopy (2013)
  • Author(s): Tawara S, Nishida T, Iijima H, Tsujii M, Takehara T.
  • Journal Title: Endoscopy Volume: 45 Pages: E380-381
  • DOI: 10.1055/s-0033-1344828
• [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, Iijima H, Tsujii M, Takehara T.
  • Journal Title: Gastroenterol Res Pract Pages: 365830
  • DOI: 10.1155/2013/365830
• [Journal Article] Narrow band imaging with magnifying endoscopy for Peyer's patches in patients with inflammatory bowel disease (2013)
  • Author(s): Hiyama S, Iijima H, Nishida T, Tsujii M, Takehara T.
  • Journal Title: Digestion Volume: 87 Pages: 269-280
  • DOI: 10.1159/000349953
• [Journal Article] Atypical duodenal ulcer and invagination caused by a large pedunculated duodenal Brunner's gland hamartoma (2013)
  • Author(s): Nakabori T, Nishida T, Iijima H, Tsujii M, Takehara T.
  • Journal Title: Gastrointest Endosc Volume: 79 Pages: 679-680
  • DOI: 10.1016/j.gie.2013.11.002
• [Journal Article] Epstein-Barr virus-associated early gastric cancer presenting as an elevated lesion (2012)
  • Author(s): Yamamoto S, Nishida T, Tsujii M, Takehara T
  • Journal Title: Endoscopy Pages: E222-223
  • DOI: 10.1055/s-0032-1309353
• [Journal Article] Altered oligosaccharide structures reduce colitis induction in mice defective inβ-1,4-galactosyltransferase (2012)
  • Author(s): Shinzaki S, Iijima H, Tsujii M, Takehara T
  • Journal Title: Gastroenter ology Volume: 142 Pages: 1172-1182
  • DOI: 10.1053/j.gastro.2012.02.008
• [Journal Article] Protective role of adiponectin against ethanol-induced gastric injury in mice (2012)
  • Author(s): Yamamoto S, Tsujii M, Takehara T
  • Journal Title: Am J Physiol Gastrointest Liver Physiol Volume: 302 Pages: G773-780
  • DOI: 10.1152/ajpgi.00324.2011
• [Journal Article] Deficiency of N-acetylgalactosamine in O-linked oligosaccharides of IgA is a novel biologic marker for Crohn's disease (2012)
  • Author(s): Inoue T, Iijima H, Nishida T, Tsujii M, Takehara T
  • Journal Title: Inflamm Bowel Dis Volume: 18 Pages: 1723-1734
  • DOI: 10.1002/ibd.22876
• [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
• [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
• [Presentation] Long-term outcomes of ESD for patients with early gastric cancer and liver cirrhosis : a multicenter study by Osaka University ESD Study Group (2012)
  • 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
  • Year and Date: 20120519-22
• [Presentation] Narrow band imaging with magnifying endoscopy for Peyer's patches in patients with inflammatory bowel disease (2012)
  • 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
  • Year and Date: 20120519-22
• [Presentation] Role of DNA methylation on epithelial mesenchymal transition (EMT)-like phenotype of colon cancer cells (2012)
  • 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
  • Year and Date: 20120519-22
• [Presentation] Clinical features of late bleeding associated with heparin replacement after endoscopic resection for colorectal neoplasms (2012)
  • 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
  • Year and Date: 20120519-22
• [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)
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  • Organizer: 第8回日本消化管学会
  • Place of Presentation: 仙台
  • Year and Date: 20120000
• [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)
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• [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)
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  • Organizer: 第83回日本消化器内視鏡学会総会
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