Development of the prediction system for relapse in Crohn's disease

• Project/Area Number: 17K09370
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Ohtsuka Kazuo 東京医科歯科大学, 医学部附属病院, 准教授 (00338443)
• Co-Investigator(Kenkyū-buntansha): 土屋 輝一郎 東京医科歯科大学, 医学部附属病院, 准教授 (40376786) ; 渡辺 守 東京医科歯科大学, 高等研究院, 特別栄誉教授 (10175127)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: クローン病 / 小腸オルガノイド / 再燃予測 / 病態解明 / 炎症応答評価 / 分子マーカー

Outline of Final Research Achievements

The Crohn's disease that is one of inflammatory bowel diseases has an intractable ulcer lesion in the small intestine and colon, resulting in the decrease of QOL due to bleeding, stenosis and fistula. Therefore it is important to keep healthy small intestine for the increase of QOL. In this study, I aimed to establish the new revival prediction score based on a new revival molecules marker. I successfully established organoid from the lesion and the non-lesion of the Crohn disease patient, respectively. Finally, I identified a lesion-specific expression gene by microarray analysis.

Academic Significance and Societal Importance of the Research Achievements

クローン病の再燃メカニズムに着目し、持続刺激における過剰応答からの細胞形質転換を主にヒトの検体、細胞、遺伝子を用いヒトを主眼において進めてきた独創性の高い研究である点に加え、得られた成果により最終的にはクローン病患者での個別医療として「再燃危険度」を評価することで再燃予測を可能にし、「再燃標的オーダーメイド治療」の開発を行うという新たな理論基盤を創出する可能性が期待される。

Research Products

• [Journal Article] Small Bowel Healing Detected by Endoscopy in Patients With Crohn’s Disease After Treatment With Antibodies Against Tumor Necrosis Factor (2019)
  • Author(s): Takenaka Kento、Fujii Toshimitsu、Suzuki Kohei、Shimizu Hiromichi、Motobayashi Maiko、Hibiya Shuji、Saito Eiko、Nagahori Masakazu、Watanabe Mamoru、Ohtsuka Kazuo
  • Journal Title: Clinical Gastroenterology and Hepatology Volume: inpress Issue: 7 Pages: 1545-1552
  • DOI: 10.1016/j.cgh.2019.08.024
  • Peer Reviewed / Open Access
• [Journal Article] Long‐term effect of NUDT15 R139C on hematologic indices in inflammatory bowel disease patients treated with thiopurine (2019)
  • Author(s): Akiyama Shintaro、Takenaka Kento、et al
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: 34 Issue: 10 Pages: 1751-1757
  • DOI: 10.1111/jgh.14693
  • Peer Reviewed / Open Access
• [Journal Article] Crohn Disease: A 5-Point MR Enterocolonography Classification Using Enteroscopic Findings (2019)
  • Author(s): Kitazume Yoshio、Fujioka Tomoyuki、Takenaka Kento、Oyama Jun、Ohtsuka Kazuo、Fujii Toshimitsu、Tateisi Ukihide
  • Journal Title: American Journal of Roentgenology Volume: 212 Issue: 1 Pages: 67-76
  • DOI: 10.2214/ajr.17.18897
  • Peer Reviewed
• [Journal Article] Predictors of mucosal healing during induction therapy in patients with acute moderate‐to‐severe ulcerative colitis (2018)
  • Author(s): Motobayashi Maiko、Matsuoka Katsuyoshi、Takenaka Kento、Fujii Toshimitsu、Nagahori Masakazu、Ohtsuka Kazuo、Iwamoto Fumihiko、Tsuchiya Kiichiro、Negi Mariko、Eishi Yoshinobu、Watanabe Mamoru
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: in press Issue: 6 Pages: 1004-1010
  • DOI: 10.1111/jgh.14565
  • Peer Reviewed
• [Journal Article] Ubiquitin D is Upregulated by Synergy of Notch Signalling and TNF-α in the Inflamed Intestinal Epithelia of IBD Patients (2018)
  • Author(s): Kawamoto Ami、Nagata Sayaka、Anzai Sho、Takahashi Junichi、Kawai Mao、Hama Minami、Nogawa Daichi、Yamamoto Kouhei、Kuno Reiko、Suzuki Kohei、Shimizu Hiromichi、Hiraguri Yui、Yui Shiro、Oshima Shigeru、Tsuchiya Kiichiro、Nakamura Tetsuya、Ohtsuka Kazuo、Kitagawa Masanobu、Okamoto Ryuichi、Watanabe Mamoru
  • Journal Title: Journal of Crohn's and Colitis Volume: 13 Issue: 4 Pages: 495-509
  • DOI: 10.1093/ecco-jcc/jjy180
  • Peer Reviewed
• [Journal Article] Prediction of disease activity of Crohn's disease through fecal calprotectin evaluated by balloon‐assisted endoscopy (2018)
  • Author(s): Iwamoto Fumihiko、Matsuoka Katsuyoshi、Motobayashi Maiko、Takenaka Kento、Kuno Toru、Tanaka Keisuke、Tsukui Yuya、Kobayashi Shoji、Yoshida Takashi、Fujii Toshimitsu、Saito Eiko、Yamaguchi Tatsuya、Nagahori Masakazu、Sato Tadashi、Ohtsuka Kazuo、Enomoto Nobuyuki、Watanabe Mamoru
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: 33 Issue: 12 Pages: 1984-1989
  • DOI: 10.1111/jgh.14310
  • Peer Reviewed
• [Journal Article] Single cell analysis of Crohn’s disease patient-derived small intestinal organoids reveals disease activity-dependent modification of stem cell properties (2018)
  • Author(s): Suzuki Kohei、Murano Tatsuro、Shimizu Hiromichi、Ito Go、Nakata Toru、Fujii Satoru、Ishibashi Fumiaki、Kawamoto Ami、Anzai Sho、Kuno Reiko、Kuwabara Konomi、Takahashi Junichi、Tsuchiya Kiichiro、Nakamura Tetsuya、Ohtsuka Kazuo、Watanabe Mamoru、Okamoto Ryuichi
  • Journal Title: Journal of Gastroenterology Volume: 印刷中 Issue: 9 Pages: 1035-1047
  • DOI: 10.1007/s00535-018-1437-3
  • Peer Reviewed / Open Access
• [Journal Article] Utility of Magnetic Resonance Enterography For Small Bowel Endoscopic Healing in Patients With Crohn’s Disease (2017)
  • Author(s): Takenaka Kento、Ohtsuka Kazuo、Kitazume Yoshio、Matsuoka Katsuyoshi、Nagahori Masakazu、Fujii Toshimitsu、Saito Eiko、Kimura Maiko、Fujioka Tomoyuki、Watanabe Mamoru
  • Journal Title: The American Journal of Gastroenterology Volume: 113 Issue: 2 Pages: 283-294
  • DOI: 10.1038/ajg.2017.464
  • Peer Reviewed
• [Journal Article] Chronic Enteropathy Associated With SLCO2A1 Gene [CEAS]-Characterisation of an Enteric Disorder to be Considered in the Differential Diagnosis of Crohn’s Disease (2017)
  • Author(s): Hosoe Naoki、Ohmiya Naoki、Yano Tomonori、Okita Yoshiki、Araki Toshimitsu、Saruta Masayuki、Ohtsuka Kazuo、CEAS Atlas Group
  • Journal Title: Journal of Crohn's and Colitis Volume: 11 Issue: 10 Pages: 1277-1281
  • DOI: 10.1093/ecco-jcc/jjx068
  • Peer Reviewed
• [Journal Article] Endoscopic features and genetic background of inflammatory bowel disease complicated with Takayasu arteritis. (2017)
  • Author(s): Akiyama S, Fujii T, Matsuoka K, Yusuke E, Negi M, Takenaka K, Nagahori M, Ohtsuka K, Isobe M, Watanabe M.
  • Journal Title: J Gastroenterol Hepatol. Volume: 32 Issue: 5 Pages: 1011-1017
  • DOI: 10.1111/jgh.13640
  • Peer Reviewed
• [Presentation] Intolerance to 5-aminosalicylate is a risk of poor prognosis in Ulcerative colitis patients (2020)
  • Author(s): Toshimitsu Fujii, Shuji Hibiya, Chiaki Maeyashiki, Eiko Saito, Kento Takenaka, Maiko Motobayashi, Hiromichi Shimizu, Masakazu Nagahori, Kazuo Ohtsuka, Masayuki Kurosaki, Tsunehito Yauchi, Mamoru Watanabe.
  • Organizer: ECCO2020
  • Int'l Joint Research
• [Presentation] クローン病小腸病変 に対するアプローチ. (2019)
  • Author(s): 竹中健人、大塚和朗、渡辺 守.
  • Organizer: JDDW2019
• [Presentation] 当院でのバルーン内視鏡によるクローン病小腸病変評価方法. (2018)
  • Author(s): 竹中健人、大塚和朗、渡辺 守.
  • Organizer: 第95 回日本消化器内視鏡学会総会
• [Presentation] 当院でのクローン病に対するシングルバルーン内視鏡 (2018)
  • Author(s): 鈴木康平、大塚和朗、渡辺 守
  • Organizer: JDDW2018
• [Presentation] クローン病における小腸内視鏡的重症度の検討. (2018)
  • Author(s): 竹中健人、大塚和朗、渡辺 守
  • Organizer: JDDW2018
• [Presentation] Usefulness of single-balloon enteroscopy: from a single center 990 experiences. (2018)
  • Author(s): Ohtsuka K, Takenaka K, Suzuki K, Fujii T, Nagahori M, Matsuoka K, Saito E, Katsukura N, Fukuda M, Araki A, Watanabe M
  • Organizer: DDW2018
  • Int'l Joint Research
• [Presentation] Small bowel mucosal healing of Crohn’s disease treated with anti-TNF antibodies. (2018)
  • Author(s): Takenaka K, Ohtsuka K, Fujii T, Nagahori M, Saito E, Motobayashi M, Suzuki K, Watanabe M.
  • Organizer: FALK symposium
  • Int'l Joint Research
• [Presentation] Simplified MR enterocolonography Classification Based on Endoscopic Findings for Activity Assessment of Crohn’s Disease. (2018)
  • Author(s): Fujii T, Kitazume Y, Takenaka K, Kimura M, Saito E, Matsuoka K, Nagahori M, Ohtsuka K, Watanabe M.
  • Organizer: UEGW2017
  • Int'l Joint Research
• [Presentation] Utility of Magnetic Resonance Evaluation for Small Bowel Endoscopic Healing in Patients with Crohn’s Disease. (2018)
  • Author(s): Takenaka K, Ohtsuka K, Kitazume Y, Fujii T, Matsuoka K, Kimura M, Nagahori M, Watanabe M.
  • Organizer: UEGW2017
  • Int'l Joint Research
• [Presentation] クローン病評価における小腸内視鏡の有用性と限界. (2017)
  • Author(s): 竹中健人、大塚和朗、北詰良雄、鈴木康平、木村麻衣子、藤岡友之、福田将義、藤井俊光、齋藤詠子、松岡克善、長堀正和、渡辺 守
  • Organizer: 第55回日本小腸学会学術集会
• [Presentation] クローン病活動性モニタリングにおける小腸内視鏡とMREの役割 (2017)
  • Author(s): 大塚和朗、 竹中健人、 渡辺 守.
  • Organizer: JDDW 2017
• [Presentation] Magnetic resonance enterography for small bowel mucosal healing in patients with Crohn’s disease. (2017)
  • Author(s): Takenaka K, Ohtsuka K, Kitazume Y, Matsuoka K, Fujii T, Nagahori M, Kimura M, Watanabe M.
  • Organizer: APDW2017
  • Int'l Joint Research
• [Presentation] The 5-point MR enterocolonography classification based on endoscopic findings for activity assessment of Crohn's disease. (2017)
  • Author(s): Fujii T, Kitazume Y, Takenaka K, Kimura M, Matsuoka K, Nagahori M, Ohtsuka K, Watanabe M.
  • Organizer: AOCC2017
  • Int'l Joint Research
• [Presentation] Magnetic resonance evaluation for small bowel endoscopic remission in patients with crohn’s disease (2017)
  • Author(s): Kento Takenaka, Kazuo Ohtsuka, Yoshio Kitazume, Katsuyoshi Matsuoka, Toshimitsu Fujii, Masakazu Nagahori, Maiko Kimura, Mamoru Watanabe.
  • Organizer: AOCC2017
  • Int'l Joint Research
• [Presentation] クローン病におけるシングルバルーン内視鏡所見と患者予後との関係に関する検討. (2017)
  • Author(s): 竹中健人、大塚和朗、渡辺 守.
  • Organizer: 第93回日本消化器内視鏡学会総会
  • Int'l Joint Research
• [Presentation] クローン病小腸病変に対するMRI によるEndoscopic remission 評価. (2017)
  • Author(s): 竹中健人、大塚和朗、渡辺 守.
  • Organizer: 第103回日本消化器病学会総会