COX-2 gene promoter methylation in patients infected with Helicobacter pylori.

• Project/Area Number: 23590928
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: YASUDA Hiroshi 聖マリアンナ医科大学, 医学部, 教授 (80262129)
• Co-Investigator(Kenkyū-buntansha): ITOH Fumio 聖マリアンナ医科大学, 医学部, 教授 (90223180)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 胃潰瘍 / COX-2 / DNAメチル化 / COX2 / ピロリ菌 / スナネズミ / 消化性潰瘍 / 胃癌

Research Abstract

[Aim] COX2 plays a critical role in peptic ulcer development. We evaluated COX2 methylation levels in the gastric mucosa. [Methods] DNA was extracted from endoscopic biopsy materials. The COX2 methylation levels were measured quantitatively by pyrosequencing. COX2 mRNA expression was measured using real-time PCR. [Results] COX2 methylation levels were significantly higher in H.pylori (HP)-positive cases than in HP-negative cases. COX2 methylation levels in patients in whom HP was successfully eradicated were significantly lower than that in HP-positive cases. COX2 mRNA expression was not observed in Kato III cells, despite the addition of the protein kinase C stimulator (PDBu). COX2 expression was observed after the addition of the demethylating agent and was enhanced by PDBu.
[Conclusion] HP infection caused a significant increase in the COX2 methylation levels in the gastric mucosa. In addition to transcriptional regulation, COX2 expression is regulated through epigenetic mechanisms.

Research Products

• [Journal Article] An updated review of gastric cancer in the next-generation sequencing era : Insights from bench to bedside and vice versa (2014)
  • Author(s): Yamamoto H (他14名), Nosho K, Shinomura Y
  • Journal Title: World J Gastroenterol Volume: 20 Issue: 14 Pages: 3927-3937
  • DOI: 10.3748/wjg.v20.i14.3927
  • Peer Reviewed / Open Access
• [Journal Article] COX-2 gene promoter methylation in patients infected with Helicobacter pylori (2013)
  • Author(s): Michikawa Y, Yasuda H, Watanabe Y, Oikawa R, Ohishi Y, Maehata T, Itoh F
  • Journal Title: Clinical Medicine Insights : Gastroenterology Volume: 6 Pages: 13-19
  • Peer Reviewed
• [Journal Article] Aberrant DNA methylation status of DNA repair ge- nes in breast cancer treated with neoadjuvant chemotherapy (2013)
  • Author(s): Watanabe Y, Maeda I, Oikawa R, Wu W, Tsuchiya K, Miyoshi Y, Itoh F, Tsugawa K, Ohta T
  • Journal Title: Genes Cells Volume: 18 Pages: 1120-1130
  • Peer Reviewed
• [Journal Article] COX-2 gene promoter methylation in patients infected with Helicobacter pylori. (2013)
  • Author(s): Michikawa Y, Yasuda H, Watanabe Y, Oikawa R, Ohishi Y, Maehata T, Itoh F
  • Journal Title: Clinical Medicine Insights: Gastroenterology Volume: 6 Pages: 13-19
  • DOI: 10.4137/cgast.s11917
  • Peer Reviewed
• [Journal Article] Evaluation of magnifying colonoscopy in the diagnosis of serrated polyps (2012)
  • Author(s): Ishigoooka S, Nomoto M, Obinata N, Oishi Y, Sato Y, Nakatsu S, Suzuki M, Ikeda Y, Maehata T, Kimura T, Watanabe Y, Nakajima T, Yamano HO, Yasuda H, Itoh F
  • Journal Title: World J Gastroenterol Volume: 18 Pages: 4308-16
  • Peer Reviewed
• [Journal Article] A New Detection Method for Integration of Hepatitis B virus DNA in PLC/PRF/5 Cells (2012)
  • Author(s): Hiraishi T, Watanabe Y, Oikawa R, Hara M, Kiyokawa H, Yoshida Y, Yamada N, Okuse C, Suzuki M, Yotsuyanagi H, Itoh F
  • Journal Title: Journal of St.Marianna University Volume: 3 Pages: 63-72
  • Peer Reviewed
• [Journal Article] Change in levels of hepatitis B virus in patients positive for low-titer hepatitis B surface antigen (2012)
  • Author(s): Okuse C, Yotsuyanagi H, Yamada N, Ikeda H, Kobayashi M, Fukuda Y, Takahashi H, Matsunaga K, Matsumoto N, Okamoto M, Ishii T, Sato A, Koike K, Suzuki M, Itoh F
  • Journal Title: Hepatol Res Volume: 42 Pages: 1236-1240
  • Peer Reviewed
• [Journal Article] Characterization of DNA hypermethylation in two cases of peritoneal mesothelioma (2012)
  • Author(s): Hama R, Watanabe Y, Shinada K, Yamada Y, Ogata Y, Yoshida Y, Tamura T, Hiraishi T, Oikawa R, Sakurai J, Maehata T, Koizumi H, Itoh F
  • Journal Title: Tumor Biol Volume: 33 Pages: 2031-2040
  • Peer Reviewed
• [Journal Article] Hypermethylation of Sox17 gene is useful as a molecular diagnostic application in early gastric cancer (2012)
  • Author(s): Oishi Y, Watanabe Y, Yoshida Y, Sato Y, Hiraishi T, Oikawa R, Maehata T, Suzuki H, Toyota M, Niwa H, Suzuki M, Itoh F
  • Journal Title: Tumor Biol Volume: 33 Pages: 383-393
  • Peer Reviewed
• [Journal Article] Evaluation of magnifying colonoscopy in the diagnosis of serrated polyps. (2012)
  • Author(s): Ishigoooka S, Nomoto M, Obinata N, Oishi Y, Sato Y, Nakatsu S, Suzuki M, Ikeda Y, Maehata T, Kimura T, Watanabe Y, Nakajima T, Yamano HO, Yasuda H, Itoh F.
  • Journal Title: World Journal of Gastroenterology Volume: 18 Issue: 32 Pages: 4308-4316
  • DOI: 10.3748/wjg.v18.i32.4308
  • Peer Reviewed
• [Journal Article] プロトンポンプ阻害剤と抗血小板薬クロピドグレル, プラスグレルの最近の話題・消化器内科の立場から(PPI併用慎重派) (2011)
  • Author(s): 安田宏
  • Journal Title: 臨床薬理 Volume: 42 Pages: 369-373
• [Journal Article] Safety and efficacy of clopidogrel before surgery (2011)
  • Author(s): Yasuda H
  • Journal Title: Clinical Medicine Insights : Therapeutics Volume: 3
  • Peer Reviewed
• [Journal Article] Comparison of the effects of omeprazole and rabeprazole on ticlopidine metabolism in vitro (2011)
  • Author(s): Kinoshita Y,Matsumoto N,Watanabe M,Takeba Y,Yoshida Y,Ohba K,Suzuki S,Itoh F,Kobayashi S
  • Journal Title: J Pharm Sci Volume: 117 Pages: 19-26
  • Peer Reviewed
• [Journal Article] Frequent alteration of MLL3 frameshift mutations in microsatellite deficient colorectal cancer (2011)
  • Author(s): Watanabe Y, Castro RJ, Kim HS, North B, Oikawa R, Hiraishi T, Ahmed SS, Chung W, Cho MY, Toyota M, Itoh F, Estecio MR, Shen L, Jelinek J, Issa JP
  • Journal Title: PLos One Volume: 6
  • Peer Reviewed
• [Journal Article] Gastric wash-based molecular testing for antibiotic resistance in Helicobacter pylori (2011)
  • Author(s): Baba S, Oishi Y, Watanabe Y, Oikawa R, Morita R, Yoshida Y, Hiraishi T, Maehata T, Nagase Y, Fukuda Y, Nakazawa M, Ishigouoka S, Hattori N, Suzuki H, Toyota M, Niwa H, Suzuki M, Itoh F
  • Journal Title: Digestion Volume: 84 Pages: 299-305
  • Peer Reviewed
• [Journal Article] Safety and efficacy of clopidogrel before surgery. (2011)
  • Author(s): Yasuda H
  • Journal Title: Clinical Medicine Insights: Therapeutics Volume: 3 Pages: 3103-3111
  • Peer Reviewed
• [Presentation] COX-2メチル化とHP感染 (2012)
  • Author(s): 安田宏, 渡邊嘉行, 伊東文生
  • Organizer: 第8回日本消化管学会, 会長特別企画
  • Place of Presentation: 仙台
  • Year and Date: 2012-02-10
• [Presentation] 内視鏡処置症例における抗血栓薬服用例についての検討 (2012)
  • Author(s): 佐藤義典、前畑忠輝、安田宏
  • Organizer: 第83回日本消化器内視鏡学会プレナリーセッション
  • Place of Presentation: 東京
• [Presentation] COX-2メチル化とHP感染 (2012)
  • Author(s): 安田宏、渡邊嘉行、伊東文生
  • Organizer: 第８回日本消化管学会
  • Place of Presentation: 仙台（仙台国際センター）
• [Presentation] NSAID潰瘍のなりやすさの予測:胃前庭部生検組織からの分子診断 (2011)
  • Author(s): 路川陽介, 渡邊嘉行, 安田宏
  • Organizer: 第81回日本消化器内視鏡学会ワークショップ
  • Place of Presentation: 名古屋
  • Year and Date: 2011-08-17
• [Presentation] (2011)
  • Author(s): 安田宏, 渡邊嘉行, 伊東文生
  • Organizer: 第17回日本ヘリコバクター学会
  • Place of Presentation: 富山
  • Year and Date: 2011-06-25
• [Presentation] COX-2 hypermethylation in H. pylori-positive NSAID-induced gastric ulcer patients (2011)
  • Author(s): Yasuda H, Watanabe Y, Itoh F
  • Organizer: AGA Research Forum
  • Place of Presentation: Chicago
  • Year and Date: 2011-05-10
• [Presentation] NSAID服用者に対する予防的除菌療法:COX-2 DNAメチル化からみたエビデンス (2011)
  • Author(s): 安田宏, 渡邊嘉行, 大石嘉恭, 佐藤義典, 前畑忠輝, 伊東文生
  • Organizer: 第7回日本消化管学会ワークショップ
  • Place of Presentation: 京都
  • Year and Date: 2011-02-19
• [Presentation] COX2 hypermethylation in HP-positive GU patients. (2011)
  • Author(s): Yasuda H, Watanabe Y, Itoh F
  • Organizer: American Gastroenterological Association
  • Place of Presentation: Chicago, USA
• [Book] 浅香正博編「消化性潰瘍」 (2012)
  • Author(s): 安田宏（分担執筆）
  • Total Pages: 249
  • Publisher: 最新医学社
• [Book] 門脇孝・永井良三総編集 「カラー版 内科学」 (2012)
  • Author(s): 安田宏 （分担執筆）
  • Total Pages: 1929
  • Publisher: 西村書店
• [Book] Cell Signaling & Molecular Targets in Cancer (2011)
  • Author(s): Yasuda H, Itoh F
  • Total Pages: 328
  • Publisher: Springer