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Elucidation of the mechanisms involved in development and suppression ofBarrett's esophagus: Results of joint Japan-U.S. research

Research Project

Project/Area Number 22590692
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionHyogo Medical University

Principal Investigator

WATARI Jiro  兵庫医科大学, 医学部, 教授 (10311531)

Co-Investigator(Kenkyū-buntansha) MIWA Hiroto  兵庫医科大学, 医学部, 教授 (80190833)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords上部消化管学(食道,胃,十二指腸) / バレット食道 / 特殊腸上皮化生 / 円柱上皮化生 / プロトンポンプ阻害薬 / メチル化異常 / マイクロサテライト不安定性 / Das-1抗体 / ゲノム不安定性 / Helicobacter pylori
Research Abstract

We evaluated several molecular alterations including microsatellite instability (MSI); the CpG island methylation status of hMLH1, p16, E-cadherin and APC genes; and monoclonal antibody Das-1, which specifically reacts with BE in specialized intestinal metaplasia (SIM), as well as in columnar lined epithelium (CLE) without SIM in BE mucosa. Additionally, we investigated changes in the above molecular markers in a randomized control trial, comparing PPI administration versus PPI non-administration groups. Our results showed no significant differences in the frequency of MSI, or methylation at any genes investigated in SIM or CLE. In contrast, Das-1 reactivity was significantly higher in SIM versus CLE. The frequency of methylation and Das-1 reactivity among Japanese was similar to that of BE in the U.S. population, a finding which corroborates previous reports. In patients administered PPI, MSI and hypermethylation at p16, E-cadherin, and APC genes disappeared following interventon, while patients without PPI did not show this tendency. These results indicate that CLE may be a precancerous lesion as well as SIM, and there is no difference in the molecular characteristics of BE between Japanese and U.S. populations. Furthermore, PPI may promote regression of the molecular alterations involved in BE.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (41 results)

All 2013 2012 2011 2010

All Journal Article (21 results) (of which Peer Reviewed: 11 results) Presentation (17 results) Book (3 results)

  • [Journal Article] わが国のGERDとバレット食道の関わり2012

    • Author(s)
      渡二郎、富田寿彦、大島忠之、他
    • Journal Title

      THEGIFOREFRONT

      Volume: 8巻 Pages: 36-39

    • Related Report
      2012 Final Research Report
  • [Journal Article] Barrett食道の分子病理学2012

    • Author(s)
      渡二郎、浅野晴紀、近藤隆、他
    • Journal Title

      消化器内科

      Volume: 54巻 Pages: 202-208

    • Related Report
      2012 Final Research Report
  • [Journal Article] Biomarkers predicting development of metachronous gastric cancer after endoscopic resection: An analysis of molecular pathology of Helicobacter pylori eradication.2012

    • Author(s)
      Watari J, Moriichi K, Tanabe H, Kashima S, Nomura Y, Fujiya M, Tomita T, Oshima T, Fukui H, Miwa H, Das KM, Kohgo Y.
    • Journal Title

      Int J Cancer.

      Volume: 15;130(10) Issue: 10 Pages: 2349-58

    • DOI

      10.1002/ijc.26275

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Barrett食道の分子病理学2012

    • Author(s)
      渡 二郎
    • Journal Title

      消化器内科

      Volume: 54 Pages: 202-208

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
  • [Journal Article] わが国のGERDとバレット食道の関わり2012

    • Author(s)
      渡 二郎
    • Journal Title

      THE GI FOREFRONT

      Volume: 8 Pages: 36-39

    • Related Report
      2012 Annual Research Report
  • [Journal Article] A prospective randomized controlled trial to compare the effects of omeprazole and famotidine in preventing delayed bleeding and promoting ulcer healing after endoscopic submucosal dissection2012

    • Author(s)
      Tomita T, Kim Y, Yamasaki T, Watari J, et al
    • Journal Title

      J Gastroenterol Hepatol

      Volume: 27 Issue: 9 Pages: 1441-1446

    • DOI

      10.1111/j.1440-1746.2012.07144.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A pseudosarcomatous lesion resembling a malignant tumor of the esophagocardiac junction, diagnosed by a total biopsy with endoscopic surgery2012

    • Author(s)
      Ando K, Fujiya M, Ito T, Watari J, et al
    • Journal Title

      Endoscopy

      Volume: 44 Issue: S 02 Pages: E21-E22

    • DOI

      10.1055/s-0031-1291502

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endoscopic and clinical features of gastric ulcers in Japanese patients with or without Helicobacter pylori infection who were using NSAIDs or low-doseaspirin2012

    • Author(s)
      Kim Y, Yokoyama S, Watari J, et al
    • Journal Title

      J Gastroenterol

      Volume: 47 Issue: 8 Pages: 904-911

    • DOI

      10.1007/s00535-012-0553-8

    • NAID

      10031051274

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autofluorescence imaging and the quantitative intensity of fluorescence for evaluating the dysplastic grade of colonic neoplasms2012

    • Author(s)
      Moriichi K, Fujiya M, Sato R, Watari J, et al
    • Journal Title

      Int J Colorectal Dis

      Volume: 27 Issue: 3 Pages: 325-330

    • DOI

      10.1007/s00384-011-1311-8

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Helicobacter pylori infection on genetic instability, the aberrant CpG island methylation status and the cellular phenotype in Barrett's esophagus in a Japanese population2011

    • Author(s)
      Moriichi K, Watari J, Das KM, et al.
    • Journal Title

      Recent advances and research updates

      Volume: 12 Pages: 213-226

    • Related Report
      2012 Final Research Report
  • [Journal Article] Morphological changes of colonic Dieulafoy's lesion : a case that could be retrospectively reviewed in a patient without treatment2011

    • Author(s)
      Watari J, Yamasaki T, Kondo T, et al
    • Journal Title

      Clin J Gastroenterol

      Volume: 4 Issue: 5 Pages: 351-354

    • DOI

      10.1007/s12328-011-0254-5

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Helicobacter pylori infection on genetic instability, the aberrant CpG island methylation status and the cellular phenotype in Barrett's esophagus in a Japanese population2011

    • Author(s)
      Moriichi K, Watari J, Das KM, et al
    • Journal Title

      Eecent advances and research updates

      Volume: 12 Pages: 213-226

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Endoscopically treated Cronkhite-Canada syndrome associated with minute intramucosal gastric cancer : an analysis of molecular pathology2011

    • Author(s)
      Watari J, Morita T, Sakurai J, et al
    • Journal Title

      Dig Endosc

      Volume: 23 Pages: 319-323

    • NAID

      120004872626

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Is a patient with asymptomatic esophagitis really in hyposensitivity to acid and distension?2011

    • Author(s)
      Yamasaki T, Watari J, Oshima T, et al
    • Journal Title

      J Neurogastroenterol Motil

      Volume: 17 Issue: 3 Pages: 318-319

    • DOI

      10.5056/jnm.2011.17.3.318

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multiple Gastric Polypoid Lesions with Protein-losing Enteropathy2011

    • Author(s)
      Sakurai J, Watari J, Oshima T, et al
    • Journal Title

      Internal Medicine

      Volume: 50 Issue: 14 Pages: 1497-1498

    • DOI

      10.2169/internalmedicine.50.5519

    • NAID

      130000969429

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The diagnostic accuracy of high-resolution endoscopy, autofluorescence imaging and narrow-band imaging for differentially diagnosing colon adenoma2011

    • Author(s)
      Sato R, Fujiya M, Watari J, et al
    • Journal Title

      Endoscopy

      Volume: 43 Issue: 10 Pages: 862-868

    • DOI

      10.1055/s-0030-1256510

    • NAID

      10031131117

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 肥満・メタボリックシンドロームと胃食道逆流症2011

    • Author(s)
      渡二郎, 三輪洋人
    • Journal Title

      BIO Clinica

      Volume: 26 Pages: 125-129

    • Related Report
      2010 Annual Research Report
  • [Journal Article] A case of early Barrett's adenocarcinoma repeatedly developing multiple metachronous lesions shortly after endoscopic therapy : an analysis for genetic and epigenetic alterations.2010

    • Author(s)
      Watari J, Sakurai J, Morita T, et. al.
    • Journal Title

      Gastrointest Endosc

      Volume: 72 Pages: 1303-1307

    • NAID

      120004138816

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] バレット食道の定義:見直しの時期-腸上皮化生は忘れ去られるか?2010

    • Author(s)
      渡二郎
    • Journal Title

      THE GI FOREFRONT

      Volume: 6 Pages: 67-68

    • Related Report
      2010 Annual Research Report
  • [Journal Article] 食道円柱上皮におけるgeneticおよびepigenetic異常とその解析法2010

    • Author(s)
      盛一健太郎, 渡二郎, 藤谷幹浩, 高後裕
    • Journal Title

      分子消化器病

      Volume: 7 Pages: 274-280

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Barrett食道/癌の発生にエピジェネチクス異常はどうかかわるか2010

    • Author(s)
      盛一健太郎, 渡二郎, 藤谷幹浩, 高後裕
    • Journal Title

      分子消化器病

      Volume: 7 Pages: 355-362

    • Related Report
      2010 Annual Research Report
  • [Presentation] Barrett食道の発生に肥満は関連するか2013

    • Author(s)
      渡二郎、堀和敏、豊島史彦、他、日本人の
    • Organizer
      第3回肥満と消化器疾患研究会
    • Place of Presentation
      鹿児島
    • Year and Date
      2013-03-23
    • Related Report
      2012 Final Research Report
  • [Presentation] 日本人のBarrett食道の発生に肥満は関連するのか?2013

    • Author(s)
      渡 二郎
    • Organizer
      第3回肥満と消化器疾患研究会
    • Place of Presentation
      鹿児島
    • Related Report
      2012 Annual Research Report
  • [Presentation] 肥満とBarrett食道に関する疫学調査?pilot研究2012

    • Author(s)
      渡二郎、浅野晴紀、近藤隆、他
    • Organizer
      第2回肥満と消化器疾患研究会
    • Place of Presentation
      東京
    • Year and Date
      2012-04-12
    • Related Report
      2012 Final Research Report
  • [Presentation] 胃癌の前癌病変とその治療2012

    • Author(s)
      渡二郎
    • Organizer
      第14回日本消化器病学会北海道支部教育講演会
    • Place of Presentation
      札幌市(招待講演)
    • Year and Date
      2012-03-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] Abdominal obesity and risk of Barrett's esophagus: a pilot study in Japanese referral centers2012

    • Author(s)
      Tamura A, Watari J, Hara K, et al.
    • Organizer
      13th World Congress of the International Society for the Diseases of the Esophagus (ISDE)
    • Place of Presentation
      Venice/Italy
    • Related Report
      2012 Final Research Report
  • [Presentation] Shortsegmentバレット食道での分子異常と内視鏡診断の対応2012

    • Author(s)
      渡二郎、盛一健太郎、三輪洋人
    • Organizer
      第83回日本消化器内視鏡学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report
  • [Presentation] 肥満とBarrett食道に関する疫学調査-pilot研究2012

    • Author(s)
      渡 二郎
    • Organizer
      第2回肥満と消化器疾患研究会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] Short segmentバレット食道での分子異常と内視鏡診断の対応2012

    • Author(s)
      渡 二郎
    • Organizer
      第83回日本消化器内視鏡学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] Abdominal obesity and risk of Barrett’s esophagus: a pilot study in Japanese referral centers2012

    • Author(s)
      Tamura A
    • Organizer
      13th World Congress of the SIDE
    • Place of Presentation
      Venice/Italy
    • Related Report
      2012 Annual Research Report
  • [Presentation] 最新の胃癌内視鏡診断と内視鏡治療2011

    • Author(s)
      渡二郎
    • Organizer
      第25回日本消化器内視鏡学会近畿セミナー
    • Place of Presentation
      西宮市(招待講演)
    • Year and Date
      2011-12-05
    • Related Report
      2011 Annual Research Report
  • [Presentation] Biomarkers predicting development of metachronous gastric cancer after endoscopic resection : an analysis of molecular pathology on Helicobacter pylori eradication2011

    • Author(s)
      Watari J, Moriichi K, Tanabe H, et al
    • Organizer
      UEGW 2011
    • Place of Presentation
      Stockholm
    • Year and Date
      2011-10-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] Image Enhanced and Magnifying Colonoscopy : Clinical evaluation of endoscopic trimodal imaging for the differentiation of colon neoplastic from non-neoplastic polyp2011

    • Author(s)
      Sato R, Fujiya M, Watari J
    • Organizer
      WEO-OMED/JGES Joint Symposium
    • Place of Presentation
      Nagoya
    • Year and Date
      2011-08-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] 本邦におけるBarrett粘膜形成における分子異常とHelicobacter pylori感染の関与に関する検討2011

    • Author(s)
      野村好紀, 藤谷幹浩, 盛一健太郎, 渡二郎, 田邊裕貴, 高後裕
    • Organizer
      第17回日本ヘリコバクター学会
    • Place of Presentation
      富山市
    • Year and Date
      2011-06-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] Barrett食道における分子病理学的検討2011

    • Author(s)
      渡二郎, 盛一健太郎, 高後裕
    • Organizer
      第97回日本消化器病学会総会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] H.pylori感染からみたバレット食道におけるCDX2発現とメチル化異常の検討2010

    • Author(s)
      渡二郎, 三輪洋人
    • Organizer
      第93回日本消化器病学会近畿支部例会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] Molecular alterations, the cellular phenotype and proliferation in Barrett's esophagus in a Japanese population with H. pylori infection2010

    • Author(s)
      Watari J, Moriichi K, Tanabe H, et. al.
    • Organizer
      World congress of international society for diseases of the esophagus
    • Place of Presentation
      鹿児島
    • Year and Date
      2010-09-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] H.pylori感染からみたバレット粘膜と慢性胃炎での腸上皮化生における細胞増殖能の比較検討2010

    • Author(s)
      渡二郎, 盛一健太郎, 野村好紀, 他
    • Organizer
      第96回日本消化器病学会総会
    • Place of Presentation
      新潟
    • Year and Date
      2010-04-24
    • Related Report
      2010 Annual Research Report
  • [Book] Intestinal metaplasia related togastric cancer: an outcome analysis ofbiomarkers for early detection. CurrentTopics in Gastritis - 2012, edited by GyulaMozsik2012

    • Author(s)
      Watari J, Moriichi K, Tanabe H, et al.Chapter 6
    • Publisher
      Published by InTech, Croatia
    • Related Report
      2012 Final Research Report
  • [Book] Gastritis and Gastric cancer-New insights in gastroprotection, diagnosis and treatmenys2011

    • Author(s)
      Watari J, Tanabe H, Moriichi K, et al
    • Total Pages
      296
    • Publisher
      InTech
    • Related Report
      2011 Annual Research Report
  • [Book] 肥満と消化器疾患2010

    • Author(s)
      渡二郎, 三輪洋人
    • Total Pages
      224
    • Publisher
      金原出版
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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