Study on the pathogenesis of Barrett's esophagus based on stem cell biopsy

2009 Fiscal Year Final Research Report

• Project/Area Number: 19590723
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Shimane University
• Principal Investigator: KINOSHITA Yoshikazu Shimane University, 医学部, 教授 (30243306)
• Project Period (FY): 2007 – 2009
• Keywords: バレット食道 / 胃食道逆流症 / 幹細胞 / 分化 / 腸上皮化生

Research Abstract

We have investigated the pathogenesis of Barrett's esophagus focusing on the cellular origin and abnormal differentiation of the original cells. Esophageal fibroblasts, when exposed to acidic gastric contents, secrete various growth factors and cytokines. Especially HB-EGF produced by these acid exposed fibroblasts induced abnormal differentiation of immature esophageal squamous cells to intestinal type columnar cells by inducing Cdx2 expression. Furthermore squamous epithelial cells exposed to bile acids started to differentiate to columnar epithelial cells by the mutual interaction of Cdx1 and Cdx2.

Research Products

• [Journal Article] 前癌病変としてのBarrett食道. (2010)
  • Author(s): 木下芳一、数森秀章、石村典久
  • Journal Title: G.I. Reseach 18 Pages: 45-52
• [Journal Article] Roles of caudal-related homeobox gene Cdx1 in oesophageal epithelial cells in Barrett's epithelium development. (2009)
  • Author(s): Kazumori H, Ishihara S, Kinoshita Y.
  • Journal Title: Gut. 58(5) Pages: 620-628
  • Peer Reviewed
• [Journal Article] Architectural roles of multiple chromatin insulators at the human apolipoprotein gene cluster. (2009)
  • Author(s): Mishiro T, Ishihara K, Hino S, Tsutsumi S, Aburatani H, Shirahige K, Kinoshita Y, Nakao M.
  • Journal Title: EMBO J. 28(9) Pages: 1234-1245
  • Peer Reviewed
• [Journal Article] Half-solidification of nutrient does not decrease gastro-esophageal reflux events in patients fed via percutaneous endoscopic gastrostomy. (2009)
  • Author(s): Adachi K, Furuta K, Morita T, Nakata S, Ohara S, Tanimura T, Koshino K, Miki M, Ishimura N, Inoue Y, Ryuko K, Umegae N, Ohhata S, Katoh S, Yamamoto K, Nariai Y, Hashimoto Y, Sumi A, Kawaguchi M, Kinoshita Y.
  • Journal Title: Clin Nutr. 28 Pages: 648-651
  • Peer Reviewed
• [Journal Article] Asymmetrical circumferential distribution of esophagogastric junctional lesions: anatomical and physiological considerations. (2009)
  • Author(s): Kinoshita Y, Furuta K, Adachi K, Amano Y.
  • Journal Title: J Gastroenterol. 44 Pages: 812-818
  • Peer Reviewed
• [Journal Article] Endoscopic definition of esophagogastric junction for diagnosis of Barrett's esophagus: importance of systematic education and training. (2009)
  • Author(s): Ishimura N, Amano Y, Kinoshita Y.
  • Journal Title: Digestive Endoscopy 21 Pages: 213-218
  • Peer Reviewed
• [Journal Article] IGICS study group. A questionnaire-based survey of GERD and related diseases by physicians in East Asian countries in 2008. (2009)
  • Author(s): Fujiwara Y, Takahashi S, Arakawa T, Sollano JD, Zhu Q, Kachintorn U, Rani AA, Hahm KB, Joh T, Kinoshita Y, Matsumoto T, Naito Y, Takeuchi K, Terano A
  • Journal Title: Digestion 80 Pages: 119-128
  • Peer Reviewed
• [Journal Article] Barrett食道癌予防を目的とした本邦独自のサーベイランス法の確立およびPPI投与による発癌予防効果についての検討 (2009)
  • Author(s): 石村典久、天野祐二、木下芳一
  • Journal Title: The GI Forefront 5 Pages: 114-117
• [Journal Article] REG1αprotein expression in Barrett's esophagus. (2008)
  • Author(s): Chinuki D, Amano Y, Ishihara S, Moriyama N, Ishimura N, Kazumori H, Kadowaki Y, Takasawa S, Okamoto H, Kinoshita Y.
  • Journal Title: J. Gastroenterol Hepatol. 23 Pages: 296-302
  • Peer Reviewed
• [Journal Article] Prolactin induces MFG-E8 production in macrophages via transcription factor C/EBPβ-dependent pathway. (2008)
  • Author(s): Aziz MM, Ihishra S, Rumi MAK, Mishima Y, Oshima N, Kadota C, Moriyama I, Yong-Yu Li, Farzana Binte Rahman, Otani A, Oka A, Ishimura N, Kadowaki Y, Amano Y, Kinoshita Y.
  • Journal Title: Apoptosis. 13 Pages: 609-620
  • Peer Reviewed
• [Journal Article] Barrett's esophagus in Japanese patients: its prevalence, form, and elongation. (2008)
  • Author(s): Okita K, Amano Y, Takahashi Y, Mishima Y, Moriyama N, Ishimura N, Ishihara S, Kinoshita Y.
  • Journal Title: J Gastroenterol. 43(12) Pages: 928-934
  • Peer Reviewed
• [Journal Article] Esophageal epithelial surface in patients with gastroesophageal reflux disease: an electron microscopic study. (2008)
  • Author(s): Azumi T, Adachi K, Furuta K, Nakata S, Ohara S, Koshino K, Miki M, Morita T, Tanimura T, Ashizawa N, Kinoshita Y.
  • Journal Title: World J Gastroenterol. 14(37) Pages: 5712-5716
  • Peer Reviewed
• [Journal Article] Causes and therapeutic approaches for PPI-resistant GERD in Asia. (2008)
  • Author(s): Kinoshita Y, Ishihara S.
  • Journal Title: Therapeutic Advances in Gastroenterology. 1 Pages: 191-199
  • Peer Reviewed
• [Journal Article] What is the clinical significance of stromal angiogenesis in Barrett's esophagus? (2008)
  • Author(s): Moriyama N, Amano Y, Mishima Y, Okita K, Takahashi Y, Yuki T, Ishimura N, Ishihara S, Kinoshita Y.
  • Journal Title: J Gastroenterol Hepatol. 23(Suppl2) Pages: S210-S215
  • Peer Reviewed
• [Journal Article] バレット食道および食道腺癌の診断 (2008)
  • Author(s): 天野祐二、木下芳一
  • Journal Title: 治療 90 Pages: 1950-1955
• [Journal Article] Barrett食道の発生機序における胆汁酸の役割 (2007)
  • Author(s): 数森秀章、木下芳一
  • Journal Title: 日本消化器病学会雑誌 104 Pages: 10-16
  • Peer Reviewed
• [Journal Article] In vivo evidence for the role of RegIin gastric regeneration: transgenic overexpression of RegIaccelerates the healing of experimental gastric ulcers
  • Author(s): Fukuhara H, Kadowaki Y, Ose T, Aziz MM, Ishihara S, Takasawa S, Kinoshita Y.
  • Journal Title: Lab Invest (in press)
  • Peer Reviewed
• [Journal Article] Fibroblast derived HB-EGF promotes Cdx2 expression in esophageal squamous cells.
  • Author(s): Rahman F, Kadowaki Y, Ishihara S, Tobita H, Imaoka H, Fukuhara H, Aziz M, Furuta K, Amano Y, Kinoshita Y.
  • Journal Title: Lab Invest (in press)
  • Peer Reviewed
• [Journal Article] Effectiveness of crystal violet chromoendoscopy with mucosal pit pattern diagnosi for surveillance of Barrett's esophagus.
  • Author(s): Ishimura N, Amano Y, Yuki T, Takahashi Y, Kinoshita Y.
  • Journal Title: Digestion (in press)
  • Peer Reviewed
• [Journal Article] Comparison of the effects of omeprazole and famotidine in treatment of upper abdominal symptoms in patients with reflux esophagitis.
  • Author(s): Kusunoki H, Kusaka M, Kido S, Yamauchi R, Fujimura Y, Watanabe Y, Kobori M, Miwa H, Tomita T, Kin Y, Hori K, Tano N, Sugimoto K, Nakamura Y, Fujimoto K, Oza N, Matsunobu A, Ono N, Fuyuno S, Kinoshita Y, Adachi K, Yuki M, Fujisawa T, Haruma K.
  • Journal Title: J Gastroenterol. 44(4) Pages: 261-270
  • Peer Reviewed