Elucidating mechanisms of tumor development and histological typing of gastric cancer based on the analysis of molecular mechanism of gastric differentiation

• Project/Area Number: 25460381
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Yamamichi Nobutake 東京大学, 医学部附属病院, 助教 (30463897)
• Co-Investigator(Renkei-kenkyūsha): INADA Kenichi 藤田保健衛生大学, 医学部, 教授 (70246081)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 消化管分化 / 胃癌 / 胃分化 / 腸上皮化生 / 腸分化 / 胃がん / MUC5AC / gastric cancer / gut differentiation / gene regulation / gli

Outline of Final Research Achievements

We identified Cathepsin E (CTSE) as a new gastric marker, and also as an useful marker for signet-ring cell carcionoma of stomach. We also found the conserved upstream 15 bp sequence of MUC5AC plays a critical role on MUC5AC expression via the recruitment of Gli transcription factor to this region.

Research Products

• [Journal Article] Comparative analysis of upper gastrointestinal endoscopy, double-contrast upper gastrointestinal barium X-ray radiography, and the titer of serum anti-Helicobacter pylori IgG focusing on the diagnosis of atrophic gastritis (2016)
  • Author(s): Yamamichi N, Hirano C, Takahashi Y, Minatsuki C, Nakayama C, Matsuda R, Shimamoto T, Takeuchi C, Kodashima S, Ono S, Tsuji Y, Fujishiro M, Wada R, Mitsushima T, Koike K.
  • Journal Title: Gastric Cancer. Volume: 19 Issue: 2 Pages: 670
  • DOI: 10.1007/s10120-015-0515-y
  • NAID: 40020836534
  • Peer Reviewed
• [Journal Article] Atrophic gastritis and enlarged gastric folds diagnosed by double-contrast upper gastrointestinal barium X-ray radiography are useful to predict future gastric cancer development based on the 3-year prospective observation (2016)
  • Author(s): Yamamichi N, Hirano C, Ichinose M, Takahashi Y, Minatsuki C, Matsuda R, Nakayama C, Shimamoto T, Kodashima S, Ono S, Tsuji Y, Niimi K, Sakaguchi Y, Kataoka Y, Saito I, Asada-Hirayama I, Takeuchi C, Yakabi S, Kaikimoto H, Matsumoto Y, Yamaguchi D, Kageyama-Yahara N, Fujishiro M, Wada R, Mitsushima T, Koike K
  • Journal Title: Gastric Cancer Volume: 印刷中
  • NAID: 40020882076
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Gastric polyps diagnosed by double-contrast upper gastrointestinal barium X-ray radiography mostly arise from the Helicobacter pylori-negative stomach with low risk of gastric cancer in Japan (2016)
  • Author(s): Takeuchi C, Yamamichi N, Shimamoto T, Takahashi Y, Mitsushima T, Koike K
  • Journal Title: Gastric Cancer Volume: 印刷中
  • NAID: 40021129497
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Scheduled second-look endoscopy is not recommended after endoscopic submucosal dissection for gastric neoplasms (the SAFE trial): A multicentre prospective randomised controlled non-inferiority trial (2015)
  • Author(s): Mochizuki S, Uedo N, Oda I, Kaneko K, Yamamoto Y, Yamashina T, Suzuki H, Kodashima S, Yano T, Yamamichi N, Goto O, Shimamoto T, Fujishiro M, Koike K; SAFE Trial Study Group
  • Journal Title: GUT Volume: 64 Issue: 3 Pages: 397
  • DOI: 10.1136/gutjnl-2014-307552
  • Peer Reviewed / Open Access
• [Journal Article] Demonstration of the usefulness of epigenetic cancer risk prediction by a multicentre prospective cohort study (2015)
  • Author(s): Asada K, Nakajima T, Shimazu T, Yamamichi N, Maekita T, Yokoi C, Oda I, Ando T, Yoshida T, Nanjo S, Fujishiro M, Gotoda T, Ichinose M, Ushijima T
  • Journal Title: GUT Volume: 64 Issue: 3 Pages: 388-396
  • DOI: 10.1136/gutjnl-2014-307094
  • Peer Reviewed / Open Access
• [Journal Article] Trend and risk factors of diverticulosis in Japan: Age, gender, and lifestyle/metabolic-related factors may cooperatively affect on the colorectal diverticula formation (2015)
  • Author(s): Yamamichi N, Shimamoto T, Takahashi Y, Sakaguchi Y, Kakimoto H, Matsuda R, Kataoka Y, Saito I, Tsuji Y, Yakabi S, Takeuchi C, Minatsuki C, Niimi K, Asada-Hirayama I, Nakayama C, Ono S, Kodashima S, Yamaguchi D, Fujishiro M, Yamaji Y, Wada R, Mitsushima T, Koike K.
  • Journal Title: PLoS One. Volume: 10 Issue: 4 Pages: e0123688-e0123688
  • DOI: 10.1371/journal.pone.0123688
  • Peer Reviewed / Open Access
• [Journal Article] Polyglycolic acid sheets with fibrin glue can prevent esophageal stricture after endoscopic submucosal dissection (2015)
  • Author(s): Sakaguchi Y, Tsuji Y, Ono S, Saito I, Kataoka Y, Takahashi Y, Nakayama C, Shichijo S, Matsuda R, Minatsuki C, Asada-Hirayama I, Niimi K, Kodashima S, Yamamichi N, Fujishiro M, Koike K.
  • Journal Title: Endoscopy. Volume: 41 Issue: 4 Pages: 336-340
  • DOI: 10.1055/s-0034-1390787
  • Peer Reviewed
• [Journal Article] Polyglycolic acid sheets and fibrin glue decrease the risk of bleeding after endoscopic submucosal dissection of gastric neoplasms (with video) (2015)
  • Author(s): Tsuji Y, Fujishiro M, Kodashima S, Ono S, Niimi K, Mochizuki S, Asada-Hirayama I, Matsuda R, Minatsuki C, Nakayama C, Takahashi Y, Sakaguchi Y, Yamamichi N, Koike K.
  • Journal Title: Gastrointest Endosc. Volume: 81 Issue: 4 Pages: 906
  • DOI: 10.1016/j.gie.2014.08.028
  • URL: https://pure.teikyo.jp/en/publications/4263d93b-9f2b-4185-ae6a-6578b13f4d05
  • Peer Reviewed
• [Journal Article] Video of the Month (2015)
  • Author(s): Niimi K, Aikou S, Kodashima S, Yagi K, Oya S, Yamaguchi D, Yamashita H, Yamamichi N, Fujishiro M, Koike K, Seto Y.
  • Journal Title: Am J Gastroenterol. Volume: 110 Issue: 11 Pages: 1535
  • DOI: 10.1038/ajg.2015.226
  • Peer Reviewed
• [Journal Article] Associated factors of atrophic gastritis diagnosed by double-contrast upper gastrointestinal barium X-ray radiography: A cross-sectional study analyzing 6,901 in Japan (2014)
  • Author(s): Yamamichi N, Hirano C, Shimamoto T, Minatsuki C, Takahashi Y, Nakayama C, Matsuda R, Fujishiro M, Konno-Shimizu M, Kato J, Kodashima S, Ono S, Niimi K, Mochizuki S, Tsuji Y, Sakaguchi Y, Asada-Hirayama I, Takeuchi C, Yakabi S, Kakimoto H, Wada R, Mitsushima T, Ichinose M, Koike K
  • Journal Title: PLoS One Volume: 9 Issue: 10 Pages: e111359-e111359
  • DOI: 10.1371/journal.pone.0111359
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Gli regulates MUC5AC transcription in human gastrointestinal cells (2014)
  • Author(s): Kageyama-Yahara N, Yamamichi N, Takahashi Y, Nakayama C, Shiogama K, Inada K, Konno-Shimizu M, Kodashima S, Fujishiro M, Tsutsumi Y, Ichinose M, Koike K
  • Journal Title: PLoS One Volume: 9 Issue: 8 Pages: e106106-e106106
  • DOI: 10.1371/journal.pone.0106106
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Evaluation of preferable insertion routes for esophagogastroduodenoscopy using ultrathin endoscopes (2014)
  • Author(s): Ono S, Niimi K, Fujishiro M, Takahashi Yu, Sakaguchi Y, Nakayama C, Minatsuki C, Matsuda R, Hirayama-Asada I, Tsuji Y, Mochizuki S, Kodashima S, Yamamichi N, Ozeki A, Matsumoto L, Ohike Y, Yamazaki T, Koike K.
  • Journal Title: World J Gastroenterol. Volume: 20 Issue: 17 Pages: 5045
  • DOI: 10.3748/wjg.v20.i17.5045
  • Peer Reviewed / Open Access
• [Journal Article] An effective technique for delivery of polyglycolic acid sheet after endoscopic submucosal dissection of the esophagus: The clip and pull method (2014)
  • Author(s): Ono S, Tsuji Y, Fujishiro M, Kodashima S, Yamamichi N, Koike K.
  • Journal Title: Endoscopy Volume: 46 Issue: SUPPL 1 Pages: E44-E45
  • DOI: 10.1055/s-0033-1359125
  • Peer Reviewed
• [Journal Article] Categorization of upper gastrointestinal symptoms is useful in predicting background factors and studying effects and usages of digestive drugs (2014)
  • Author(s): Yamamichi N, Shimamoto T, Sakaguchi Y, Takahashi Y, Kodashima S, Nakayama C, Minatsuki C, Ono S, Mochizuki S, Matsuda R, Asada-Hirayama I, Niimi K, Fujishiro M, Tsuji Y, Takeuchi C, Kakimoto H, Goto O, Mitsushima T, Koike K.
  • Journal Title: PLoS One Volume: 9 Issue: 2 Pages: e88277-e88277
  • DOI: 10.1371/journal.pone.0088277
  • Peer Reviewed / Open Access
• [Journal Article] Endoscopic tissue shielding method with polyglycolic acid sheets and fibrin glue to cover wounds after colorectal endoscopic submucosal dissection (with video). (2014)
  • Author(s): Tsuji Y, Ohata K, Gunji T, Shozushima M, Hamanaka J, Ohno A, Ito T, Yamamichi N, Fujishiro M, Matsuhashi N, Koike K.
  • Journal Title: Gastrointest Endosc. Volume: 79 Issue: 1 Pages: 151-155
  • DOI: 10.1016/j.gie.2013.08.041
  • Peer Reviewed / Open Access
• [Journal Article] Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer. (2014)
  • Author(s): Yoshida T, Kato J, Inoue I, Yoshimura N, Deguchi H, Mukoubayashi C, Oka M, Watanabe M, Enomoto S, Niwa T, Maekita T, Iguchi M, Tamai H, Utsunomiya H, Yamamichi N, Fujishiro M, Iwane M, Takeshita T, Ushijima T, Ichinose M
  • Journal Title: Int J Cancer Volume: 134 Issue: 6 Pages: 1445-1457
  • DOI: 10.1002/ijc.28470
  • Peer Reviewed / Open Access
• [Journal Article] Helicobacter pylori infection is positively associated with gallstones: A large-scale cross-sectional study in Japan (2014)
  • Author(s): Takahashi Y, Yamamichi N, Shimamoto T, Mochizuki S, Fujishiro M, Takeuchi C, Sakaguchi Y, Niimi K, Ono S, Kodashima S, Mitsushima T, Koike K.
  • Journal Title: J Gastroenterol Volume: 49 Issue: 5 Pages: 882
  • DOI: 10.1007/s00535-013-0832-z
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Evaluation of a new image-enhanced endoscopic technology using band-limited light for detection of esophageal squamous cell carcinoma (2014)
  • Author(s): Kodashima S, Fujishiro M, Ono S, Niimi K, Mochizuki S, Asada-Hirayama I, Konno-Shimizu M, Matsuda R, Minatsuki C, Nakayama C, Takahashi Y, Sakaguchi Y, Yamamichi N, Tanaka C, Koike K.
  • Journal Title: Dig Endosc. Volume: 26 Issue: 2 Pages: 164
  • DOI: 10.1111/den.12108
  • Peer Reviewed / Open Access
• [Journal Article] Cathepsin E Is a Marker of Gastric Differentiation and Signet-Ring Cell Carcinoma of Stomach: A Novel Suggestion on Gastric Tumorigenesis (2013)
  • Author(s): Konno-Shimizu M
  • Journal Title: PLoS ONE Volume: 8 Issue: 2 Pages: e56766-e56766
  • DOI: 10.1371/journal.pone.0056766
  • Peer Reviewed
• [Journal Article] Background Factors of Reflux Esophagitis and Non-Erosive Reflux Disease: A Cross-Sectional Study of 10,837 Subjects in Japan (2013)
  • Author(s): Minatsuki C, Yamamichi N, Shimamoto T, Kakimoto H, Takahashi Y, Fujishiro M, Sakaguchi Y, Nakayama C, Konno-Shimizu M, Matsuda R, Mochizuki S, Asada-Hirayama I, Tsuji Y, Kodashima S, Ono S, Niimi K, Mitsushima T, Koike K.
  • Journal Title: PLoS One Volume: 8 Issue: 7 Pages: e69891-e69891
  • DOI: 10.1371/journal.pone.0069891
  • Peer Reviewed
• [Journal Article] Elevated risk of recurrent colorectal neoplasia with Helicobacter pylori-associated chronic atrophic gastritis: A follow-up study of patients with endoscopically resected colorectal neoplasia. (2013)
  • Author(s): Inoue I, Kato J, Yoshimura N, Maeda Y, Moribata K, Shingaki N, Deguchi H, Enomoto S, Maekita T, Ueda K, Iguchi M, Tamai H, Fujishiro M, Yamamichi N, Takeshita T, Ichinose M.
  • Journal Title: Mol Clin Oncol. Volume: 1 Pages: 75-82
  • Peer Reviewed
• [Journal Article] No Association of Coffee Consumption with Gastric Ulcer, Duodenal Ulcer, Reflux Esophagitis, and Non-Erosive Reflux Disease: A Cross-Sectional Study of 8,013 Healthy Subjects in Japan (2013)
  • Author(s): Shimamoto T, Yamamichi N, Kodashima S, Takahashi Y, Fujishiro M, Oka M, Mitsushima T, Koike K.
  • Journal Title: PLoS One Volume: 8 Issue: 6 Pages: e65996-e65996
  • DOI: 10.1371/journal.pone.0065996
  • Peer Reviewed
• [Presentation] 胃Ｘ線検査における萎縮性胃炎・ヒダ肥厚とピロリ菌感染・胃癌発症との関連 (2015)
  • Author(s): 山道信毅
  • Organizer: JDDW2015
  • Place of Presentation: グランドプリンスホテル新高輪（東京都千代田区）
  • Year and Date: 2015-10-08
• [Presentation] 我が国の大腸憩室の疫学的動向、ならびに、生活習慣関連因子との関連 (2015)
  • Author(s): 山道信毅
  • Organizer: 第101回日本消化器病学会総会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2015-04-24
• [Presentation] 非乳頭部十二指腸上皮性腫瘍における臨床病理学的検討 (2014)
  • Author(s): 皆月ちひろ, 山道信毅, 稲田健一, 高橋悠, 中山千恵美, 藤城光弘, 小池和彦
  • Organizer: JDDW2014
  • Place of Presentation: 神戸
  • Year and Date: 2014-10-26
• [Presentation] 胃バリウムＸ線検査（MDL）判定「慢性胃炎」の背景因子の解析 (2014)
  • Author(s): 山道信毅, 光島徹, 小池和彦
  • Organizer: JDDW2014
  • Place of Presentation: 神戸
  • Year and Date: 2014-10-23
• [Presentation] 腸への分化誘導による胃癌抑制効果の検証 (2014)
  • Author(s): 中山千恵美, 山道信毅, 稲田健一, 高橋悠, 小田島慎也, 藤城光弘, 堤寛, 小池和彦
  • Organizer: JDDW2014
  • Place of Presentation: 神戸
  • Year and Date: 2014-10-23
• [Presentation] Gli1による胃型粘液形質マーカー遺伝子MUC5ACの発現制御の解明 (2013)
  • Author(s): 山道信毅
  • Organizer: JDDW2013
  • Place of Presentation: 東京
• [Presentation] 大規模健常者コホートを用いた上部消化管諸症状のクラスター分析と奏功薬剤の予測 (2013)
  • Author(s): 山道信毅
  • Organizer: JDDW2013
  • Place of Presentation: 東京
  • Invited
• [Presentation] ピロリ菌による慢性萎縮性胃炎に対する胃Ｘ線検査・上部消化管内視鏡検査の診断能の比較 (2013)
  • Author(s): 山道信毅
  • Organizer: JDDW2013
  • Place of Presentation: 東京
• [Remarks] 東京大学消化器内科消化管グループ：基礎研究、疫学研究
  • URL: http://www.todai-shoukakan.com/cont5/main.html
• [Remarks] 東京大学消化器内科消化管グループ：臨床研究の紹介
  • URL: http://www.todai-shoukakan.com/cont4/main.html
• [Remarks] 東京大学消化器内科消化管グループ：108研の基礎研究
  • URL: http://www.todai-shoukakan.com/cont5/33.html
• [Remarks] 東京大学消化器内科消化管グループ：108研の疫学研究
  • URL: http://www.todai-shoukakan.com/cont5/34.html
• [Remarks] 東京大学消化器内科消化管グループ
  • URL: http://www.todai-shoukakan.com/
• [Remarks] 東京大学消化器内科消化管グループ＿108研：基礎研究
  • URL: http://www.todai-shoukakan.com/cont5/33.html
• [Remarks] http://gastro.m.u-tokyo.ac.jp/med/0202A3.htm