Development of novel therapy based on epigenetic alterations in Barrett's esophagus

• Project/Area Number: 25460923
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Asahikawa Medical College
• Principal Investigator: Moriichi Kentaro 旭川医科大学, 医学部, 講師 (70455715)
• Co-Investigator(Kenkyū-buntansha): 水上 裕輔 医療法人徳洲会札幌東徳洲会病院付属臨床研究センター, がん研究部, 部門長 (30400089) ; 藤谷 幹浩 旭川医科大学, 医学部, 准教授 (80322915)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: バレット食道

Outline of Final Research Achievements

We successfully established primary cell culture of patient-derived Barrett's esophageal cancer (BE ca) using conditioning reprogramming method. To investigate the carcinogenic mechanisms of BE ca, the primary cells were exposed to low pH bile acids. The exposures of low pH bile acid decreased mRNA expressions of p63 and CK5. It was speculated that the post-transcriptional regulations such as abnormal gene methylations or histone acetylations were involved in the altered expressions of these genes. However, treatments of demethylation or deacetylation did not change the expressions of these mRNA, indicating the other mechanisms are associated with the effects of the exposures of low pH bile acid. We are continuously analyzing the mechanisms. In parallel, our transcriptome analysis identified novel alterations of nine gene expressions which were epigenetically regulated in the process to develop BE ca. We are analyzing the roles of these gene alterations in the cancer development.

Research Products

• [Journal Article] Polyphosphate Derived from Lactobacillus brevis Inhibits Colon Cancer Progression Through Induction of Cell Apoptosis. (2016)
  • Author(s): Sakatani A, Fujiya M, Ueno N, Kashima S, Sasajima J, Moriichi K, Ikuta K, Tanabe H, Kohgo Y
  • Journal Title: Anticancer Research Volume: 36 Pages: 591-598
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Efficacy and adverse events of EMR and endoscopic submucosal dissection for the treatment of colon neoplasms: a meta-analysis of studies comparing EMR and endoscopic submucosal dissection. (2015)
  • Author(s): Fujiya M, Tanaka K, Dokoshi T, Tominaga M, Ueno N, Inaba Y, Ito T, Moriichi K, Kohgo Y.
  • Journal Title: Gastrointest Endosc. Volume: 81 Issue: 3 Pages: 583-95
  • DOI: 10.1016/j.gie.2014.07.034
  • Peer Reviewed
• [Journal Article] A randomized study on the effectiveness of prophylactic clipping during endoscopic resection of colon polyps for the prevention of delayed bleeding. (2015)
  • Author(s): Dokoshi T, Fujiya M, Tanaka K, Sakatani A, Inaba Y, Ueno N, Kashima S, Goto T, Sasajima J, Tominaga M, Ito T, Moriichi K, Tanabe H, Ikuta K, Ohtake T, Kohgo Y.
  • Journal Title: Biomed Res Int. Volume: in press Pages: 1-6
  • DOI: 10.1155/2015/490272
  • NAID: 120005607948
  • Peer Reviewed
• [Journal Article] Polyphosphate, an active molecule derived from probiotic Lactobacillus brevis, improves the fibrosis in murine colitis. (2015)
  • Author(s): Kashima S, Fujiya M, Konishi H, Ueno N, Inaba Y, Moriichi K, Tanabe H, Ikuta K, Ohtake T, Kohgo Y.
  • Journal Title: Transl Res. Volume: in press Issue: 2 Pages: 00069-9
  • DOI: 10.1016/j.trsl.2015.02.002
  • NAID: 120005837997
  • Peer Reviewed / Open Access
• [Journal Article] Intraductal cholangioscopic visualization of moving Fasciola hepatica. (2015)
  • Author(s): Fujibayashi S, Goto T, Sasajima J, Utsumi T, Dokoshi T, Sakatani A, Tanaka K, Nomura Y, Ueno N, Kashima S, Inaba Y, Moriichi K, Fujiya M, Kohgo Y.
  • Journal Title: Gastrointest Endosc. Volume: in press Issue: 6 Pages: 1485-1486
  • DOI: 10.1016/j.gie.2014.12.014
  • Peer Reviewed
• [Journal Article] Decreased vessel networks and irregular vessel on narrow band imaging are useful findings to distinguish intestinal lymphoma from lymphoid hyperplasia. (2014)
  • Author(s): Fujiya M, Kashima S, Ikuta K, Dokoshi T, Sakatani A, Tanaka K, Ando K, Ueno N, Tominaga M, Inaba Y, Ito T, Moriichi K, Tanabe H, Saitoh Y, Kohgo Y.
  • Journal Title: Gastrointestinal Endoscopy Volume: in press Issue: 6 Pages: 1064-71
  • DOI: 10.1016/j.gie.2014.03.030
  • Peer Reviewed
• [Presentation] バレット食道表在癌の臨床的検討 (2014)
  • Author(s): 内海 辰哉，盛一健太郎，藤谷幹浩，田中一之，坂谷 慧，堂腰達矢，藤林周吾，安藤勝祥，上野伸展，嘉島 伸，後藤拓磨，笹島順平，稲場勇平，伊藤貴博，高後 裕
  • Organizer: 日本消化器関連学会週間（JDDW 2014）
  • Place of Presentation: 神戸
  • Year and Date: 2014-10-23 – 2014-10-26
• [Presentation] Quantitative autofluorescence imaging is useful for assessing the severity of ulcerative colitis (2014)
  • Author(s): Moriichi K, Fujiya M, Ijiri M, Tanaka K, Sakatani A, Doukoshi T, Ando K, Ueno N, Kashima S, Inaba Y, Ito T, Kohgo Y.
  • Organizer: United European Gastroenterology Week 2014
  • Place of Presentation: Vienna
  • Year and Date: 2014-10-18 – 2014-10-22
• [Presentation] A probiotic-derived polyphosphate improves the fibrosis in a murine model of chronic colitis via the regulation of inflammation- and fibrosis-associated mediators. (2014)
  • Author(s): Fujiya M, Konishi H, Ueno N, Inaba Y, Moriichi K, Kohgo Y.
  • Organizer: GI Research Academy 2014
  • Place of Presentation: Tokyo
  • Year and Date: 2014-06-06
• [Presentation] 潰瘍性大腸炎の活動性評価における自家蛍光内視鏡検査の有用性 (2014)
  • Author(s): 盛一健太郎，藤谷幹浩，高後 裕
  • Organizer: 第87回日本消化器内視鏡学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-15 – 2014-05-17
• [Presentation] Long-term oral dietary administration of a new probiotic, Lactobacillus brevis SBC8803, alters gut the microbiota and ameliorates DSS-induced colitis in mice. (2014)
  • Author(s): Ueno N, Fujiya M, Segawa S, Konishi H, Sakatani A, Tanaka K, Dokoshi T, Ando K, Kashima S, Inaba Y, Ito T, Moriichi K, Shigyo T, Kohgo Y.
  • Organizer: DDW 2014
  • Place of Presentation: Chicago
  • Year and Date: 2014-05-03 – 2014-05-06
• [Presentation] Comparison of the efficacy and adverse events of endoscopic mucosal resection and submucosal dissection for the treatment of colon neoplasms –Based on the results of our institute experience and a meta-analysis of comparative studies (2014)
  • Author(s): Tanaka K, Fujiya M, Dokoshi T, Tominaga M, Ueno N, Inaba Y, Ito T, Moriichi K, Kohgo Y.
  • Organizer: DDW 2014
  • Place of Presentation: Chicago
  • Year and Date: 2014-05-03 – 2014-05-06
• [Presentation] Usefulness of NBI for differentiating colon neoplasms from non-neoplasms: Based on results of our institutional experience and a meta-analysis of comparative studies. (2014)
  • Author(s): Sakatani A, Fujiya M, Tanaka K, Dokoshi T, Fujibayashi S, Ando K, Ueno N, Goto T,Kashima S, Sasajima J, Inaba Y, Ito T, Moriichi K, Sato R, Kohgo Y.
  • Organizer: DDW 2014
  • Place of Presentation: Chicago
  • Year and Date: 2014-05-03 – 2014-05-06