Development of experimental model of Chronic Intestinal Pseudo-obstruction (CIPO) using iPS and drug discovery research

• Project/Area Number: 15K15292
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Osaka University
• Principal Investigator: Tsujii Masahiko 大阪大学, 医学系研究科, 招へい教授 (40303937)
• Co-Investigator(Kenkyū-buntansha): 渡部 健二 大阪大学, 医学部附属病院, 准教授 (50379244) ; 竹原 徹郎 大阪大学, 医学系研究科, 教授 (70335355) ; 林 義人 大阪大学, 医学系研究科, 助教 (80647123) ; 飯島 英樹 大阪大学, 医学系研究科, 准教授 (90444520)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 慢性偽性腸閉塞 / 便秘 / 過敏性腸症候群 / 慢性偽性腸閉塞症 / CIPO / APOB48 / カハール介在細胞 / ペーシング細胞 / iPS細胞 / APOB蛋白

Outline of Final Research Achievements

1) Clinical research of CIPO ( Chronic Intestinal Pseudo-obstruction)：An independent study of prospective multi center study analyzing prognostic factors of CIPO was accepted in 20 institutions (Osaka Gut Forum) led by Osaka University (endorsement number 13124). Fourteen cases have been enrolled to date: 10 females, 4 males. The large intestine was compromised in 13 cases. Four cases were treated with IVH, 6 were with surgery, and 5 were with decompression by endoscopy.
2) Analysis of concentration of serum protein APOB48: Concentration of serum protein APOB48 has been measured by immunoblotting analysis in 4 cases of CIPO, 3 cases of chronic constipation, and 3 healthy control.

Research Products

• [Journal Article] Evaluation of endoscopic entire 3D image acquisition of the digestive tract using a stereo endoscope (2017)
  • Author(s): Kayo Yoshimoto, Kenji Watabe, Tetsuji Fujinaga, Hideki Iijima, Masahiko Tsujii, Hideya Takahashi, Tetsuo Takehara, Kenji Yamada
  • Journal Title: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XV Volume: Proc. SPIE Pages: 10054-10054
  • DOI: 10.1117/12.2250774
  • Peer Reviewed
• [Journal Article] 臨床現場における睡眠時呼吸障害のスクリーニングのための非接触手法の検討 (2017)
  • Author(s): Yutaka Matsuura, Hieyong Jeong, Kenji Yamada, Kenji Watabe and Yuko Ohno
  • Journal Title: Journal of Robotics and Mechatronics Volume: 印刷中
  • Peer Reviewed
• [Journal Article] A novel pathogenesis of inflammatory bowel disease from the perspective of glyco-immunology. (2017)
  • Author(s): Shinzaki S, Iijima H, Fujii H, Kamada Y, Naka T, Takehara T, Miyoshi E.
  • Journal Title: J Biochem. Volume: 印刷中 Issue: 5 Pages: 409-415
  • DOI: 10.1093/jb/mvx010
  • Peer Reviewed
• [Journal Article] Cardiac metastasis from colon cancer effectively treated with 5-fluorouracil, leucovorin, and oxaliplatin (modified FOLFOX6) plus panitumumab: a case report. (2017)
  • Author(s): Tsujii Y, Hayashi Y, Maekawa A, Fujinaga T, Nagai K, Yoshii S, Sakatani A, Hiyama S, Shinzaki S, Iijima H, Takehara T.
  • Journal Title: BMC Cancer. Volume: 印刷中 Issue: 1
  • DOI: 10.1186/s12885-017-3147-2
  • Peer Reviewed
• [Journal Article] Age at onset is associated with the seasonal pattern of onset and exacerbation in inflammatory bowel disease (2017)
  • Author(s): Araki, M, Shinzaki, S., Yamada, T., Arimitsu S., Komori, M., Shibukawa, N., Mukai A., Nakajima, S., Kinoshita, K., Kitamura, S., Murayama, Y., Ogawa H., Yasunaga Y, Oshita, M., Fukui, H., Masuda E., Tsujii, M., Hiyama, S., Inoue, T., Iijima, H., Takehara, T.
  • Journal Title: Journal of Gastroenterology Volume: 印刷中 Issue: 11 Pages: 1149-1157
  • DOI: 10.1007/s00535-017-1313-6
  • Peer Reviewed
• [Journal Article] Indigo Naturalis ameliorates murine dextran sodium sulfate-induced colitis via aryl hydrocarbon receptor activation. (2017)
  • Author(s): Kawai S, Iijima H, Shinzaki S, Hiyama S, Yamaguchi T, Araki M, Iwatani S, Shiraishi E, Mukai A, Inoue T, Hayashi Y, Tsujii M, Motooka D, Nakamura S, Iida T, Takehara T.
  • Journal Title: J Gastroenterol. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Leucine-rich Alpha-2 Glycoprotein is a Serum Biomarker of Mucosal Healing in Ulcerative Colitis (2017)
  • Author(s): Shinzaki, S., Matsuoka, K., Iijima, H., Mizuno, S., Serada, S., Fujimoto, M., Arai, N. Koyama, N., Morii, E., Watanabe, M., Hibi, T., Kanai, T., Takehara, T., Naka, T.
  • Journal Title: Journal of Crohn's and Colitis Volume: 11(1) Issue: 1 Pages: 84-91
  • DOI: 10.1093/ecco-jcc/jjw132
  • Peer Reviewed
• [Journal Article] Clinical problems with antithrombotic therapy for endoscopic submucosal dissection for gastric neoplasms. (2016)
  • Author(s): Yoshio T, Nishida T, Hayashi Y, Iijima H, Tsujii M, Fujisaki J, Takehara T.
  • Journal Title: World J Gastrointest Endosc. Volume: 16 Issue: 20 Pages: 756-762
  • DOI: 10.4253/wjge.v8.i20.756
• [Journal Article] Narrow-band imaging with magnifying endoscopy for Peyer's patches is useful in predicting the recurrence of remissive patients with ulcerative colitis. (2016)
  • Author(s): Hiyama S, Iijima H, Kawai S, Mukai A, Shiraishi E, Iwatani S, Yamaguchi T, Araki M, Hayashi Y, Shinzaki S, Mizushima T, Tsujii M, Takehara T.
  • Journal Title: Intest Res. Volume: 14 Pages: 314-321
  • Peer Reviewed
• [Journal Article] p53 functional deficiency in human colon cancer cells promotes fibroblast-mediated angiogenesis and tumor growth. (2016)
  • Author(s): Hayashi Y, Tsujii M, Kodama T, Akasaka T, Kondo J, Hikita H, Inoue T, Tsujii Y, Maekawa A, Yoshii S, Shinzaki S, Watabe K, Tomita Y, Inoue M, Tatsumi T, Iijima H, Takehara T.
  • Journal Title: Carcinogenesis. Volume: 37 Issue: 10 Pages: 972-984
  • DOI: 10.1093/carcin/bgw085
  • Peer Reviewed
• [Journal Article] Core Fucosylation on T Cells, Required for Activation of T-Cell Receptor Signaling and Induction of Colitis in Mice, Is Increased in Patients With Inflammatory Bowel Disease. (2016)
  • Author(s): Fujii H, Shinzaki S, Iijima H, Wakamatsu K, Iwamoto C, Sobajima T, Kuwahara R, Hiyama S, Hayashi Y, Takamatsu S, Uozumi N, Kamada Y, Tsujii M, Taniguchi N, Takehara T, Miyoshi E.
  • Journal Title: Gastroenterology. Volume: 150 Pages: 1620-1632
  • NAID: 40021255019
  • Peer Reviewed
• [Journal Article] "Underwater" endoscopic submucosal dissection: a novel technique for complete resection of a rectal neuroendocrine tumor. (2016)
  • Author(s): Yoshii S, Hayashi Y, Matsui T, Aoi K, Tsujii Y, Iijima H, Takehara T.
  • Journal Title: Endoscopy. Volume: 48 Issue: S 01 Pages: E67-E68
  • DOI: 10.1055/s-0042-101855
  • Peer Reviewed
• [Journal Article] Role of aberrant IgG glycosylation in the pathogenesis of inflammatory bowel disease. (2016)
  • Author(s): Miyoshi E, Shinzaki S, Fujii H, Iijima H, Kamada Y, Takehara T.
  • Journal Title: Proteomics Clinical Applications Volume: 未定 Issue: 4 Pages: 384-390
  • DOI: 10.1002/prca.201500089
  • Peer Reviewed
• [Journal Article] N-Acetylglucosaminyltransferase V exacerbates murine colitis with macrophage dysfunction and enhances colitic tumorigenesis. (2016)
  • Author(s): Shinzaki S, Ishii M, Fujii H, Iijima H, Wakamatsu K, Kawai S, Shiraishi E, Hiyama S, Inoue T, Hayashi Y, Kuwahara R, Takamatsu S, Kamada Y, Morii E, Tsujii M, Takehara T, Miyoshi E.
  • Journal Title: J Gastroenterol. Volume: 51 Issue: 4 Pages: 357-369
  • DOI: 10.1007/s00535-015-1119-3
  • Peer Reviewed
• [Journal Article] N-Acetylglucosaminyltransferase V exacerbates murine colitis with macrophage dysfunction and enhances colitic tumorigenesis. (2016)
  • Author(s): Shinzaki S, Ishii M, Fujii H, Iijima H, Wakamatsu K, Kawai S, Shiraishi E, Hiyama S, Inoue T, Hayashi Y, Kuwahara R, Takamatsu S, Kamada Y, Morii E, Tsujii M, Takehara T, Miyoshi E.
  • Journal Title: J Gastroenterol Volume: 51 Issue: 4 Pages: 357-69
  • DOI: 10.1007/s00535-015-1112-x
  • Peer Reviewed
• [Journal Article] Esophagogastric junctional adenocarcinoma originating from endoscopically unrecognizable Barrett's epithelium. (2016)
  • Author(s): Nagai K, Tsujii Y, Matsui T, Yoshii S, Fujinaga T, Maekawa A, Inoue T, Hayashi Y, Shinzaki S, Iijima H, Tsujii M, Morii E, Takehara T.
  • Journal Title: Dis Esophagus. Volume: 29 Issue: 8 Pages: 1164-1166
  • DOI: 10.1111/dote.12396
  • Peer Reviewed
• [Journal Article] Core Fucosylation on T cells, Required for Activation of T-cell Receptor Signaling and Induction of Colitis in Mice, is Increased in Patients with Inflammatory Bowel Disease. (2016)
  • Author(s): Fujii H, Shinzaki S, Iijima H, Wakamatsu K, Iwamoto C, Sobajima T, Kuwahara R, Hiyama S, Hayashi Y, Takamatsu S, Uozumi N, Kamada Y, Tsujii M, Taniguchi N, Takehara T, Miyoshi E
  • Journal Title: Gastroenterology Volume: 未定 Issue: 7 Pages: 00297-3
  • DOI: 10.1053/j.gastro.2016.03.002
  • NAID: 40021255019
  • Peer Reviewed
• [Journal Article] Percutaneous endoscopic gastrostomy under steady pressure automatically controlled endoscopy: First clinical series. (2016)
  • Author(s): Imaeda H, Nakajima K, Hosoe N, Nakahara M, Zushi S, Kato M, Kashiwagi K, Matsumoto Y, Kimura K, Nakamura R, Wada N, Tsujii M, Yahagi N, Hibi T, Kanai T, Takehara T, Ogata H.
  • Journal Title: World J Gastrointest Endosc. Volume: in press Issue: 3 Pages: 186-186
  • DOI: 10.4253/wjge.v8.i3.186
  • Peer Reviewed
• [Journal Article] Renal dysfunction is an independent risk factor for bleeding after gastric ESD. (2015)
  • Author(s): Yoshioka T, Nishida T, Tsujii M, Kato M, Hayashi Y, Komori M, Yoshihara H, Nakamura T, Egawa S, Yoshio T, Yamada T, Yabuta T, Yamamoto K, Kinoshita K, Kawai N, Ogiyama H, Nishihara A, Michida T, Iijima H, Shintani A, Takehara T.
  • Journal Title: Endosc Int Open. Volume: 3 Issue: 01 Pages: E39-E45
  • DOI: 10.1055/s-0034-1390762
  • Peer Reviewed
• [Journal Article] Endoscopic submucosal dissection in early gastric cancer in elderly patients and comorbid conditions. (2015)
  • Author(s): Nishida T, Kato M, Yoshio T, Akasaka T, Yoshioka T, Michida T, Yamamoto M, Hayashi S, Hayashi Y, Tsujii M, Takehara T.
  • Journal Title: World J Gastrointest Endosc. Volume: 7 Issue: 5 Pages: 524-531
  • DOI: 10.4253/wjge.v7.i5.524
  • Peer Reviewed
• [Journal Article] Localized gastric amyloidosis mimicking a submucosal tumor-like gastric cancer. (2015)
  • Author(s): Yamaguchi T, Inoue T, Nishida T, Kato M, Hayashi Y, Tsujii Y, Maekawa A, Kawai S, Fujinaga T, Araki M, Nagai K, Yoshii S, Hiyama S, Shinzaki S, Iijima H, Tsujii M, Takehara T.
  • Journal Title: Gastrointest Endosc. Volume: 82 Issue: 1 Pages: 175-177
  • DOI: 10.1016/j.gie.2015.01.043
  • Peer Reviewed
• [Journal Article] Integrated diagnostic strategy for the invasion depth of early gastric cancer by conventional endoscopy and EUS. (2015)
  • Author(s): sujii Y, Kato M, Inoue T, Yoshii S, Nagai K, Fujinaga T, Maekawa A, Hayashi Y, Akasaka T, Shinzaki S, Watabe K, Nishida T, Iijima H, Tsujii M, Takehara T.
  • Journal Title: Gastrointest Endosc. Volume: 15 Issue: 3 Pages: 452-459
  • DOI: 10.1016/j.gie.2015.01.022
  • Peer Reviewed
• [Journal Article] Effectiveness of anti-tumor necrosis factor-α therapy in Crohn's disease with abscesses around the sigmoid colon: a case report (2015)
  • Author(s): Nagai K, Shinzaki S, Kato M, Hiyama S, Yakushijin T, Nishida T, Iijima H, Ookawa K, Tsujii M, Takehara T.
  • Journal Title: Nippon Shokakibyo Gakkai Zasshi Volume: 112 Issue: 4 Pages: 707-713
  • DOI: 10.11405/nisshoshi.112.707
  • NAID: 130005060962
  • ISSN: 0446-6586, 1349-7693
  • Peer Reviewed
• [Journal Article] Solitary Fibrous Tumor of the Liver from Development to Resection (2015)
  • Author(s): Makino Y, Miyazaki M, Shigekawa M, Ezaki H, Sakamori R, Yakushijin T, Ohkawa K, Kato M, Akasaka T, Shinzaki S, Nishida T, Miyake Y, Hama N, Nagano H, Honma K, Morii E, Wakasa K, Hikita H, Tatsumi T, Iijima H, Hiramatsu N, Tsujii M, Takehara T.
  • Journal Title: Internal Medicine Volume: 54 Issue: 7 Pages: 765-770
  • DOI: 10.2169/internalmedicine.54.3053
  • NAID: 130005063222
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] Clinical outcomes of endoscopic submucosal dissection for superficial esophageal neoplasms: a multicenter retrospective cohort study. (2015)
  • Author(s): Tsujii Y, Nishida T, Nishiyama O, Yamamoto K, Kawai N, Yamaguchi S, Yamada T, Yoshio T, Kitamura S, Nakamura T, Nishihara A, Ogiyama H, Nakahara M, Komori M, Kato M, Hayashi Y, Shinzaki S, Iijima H, Michida T, Tsujii M, Takehara T.
  • Journal Title: Endoscopy Volume: 47 Issue: 09 Pages: 775-783
  • DOI: 10.1055/s-0034-1391844
  • Peer Reviewed
• [Journal Article] Chemoradiotherapy is effective for primary esophageal adenosquamous cell carcinoma but ineffective for the metastatic adenocarcinoma component (2015)
  • Author(s): Nozaki Y, Nishida T, Hori Y, Shinzaki S, Kato M, Yakushijin T, Iijima H, Tsujii M, Morii E, Takehara T.
  • Journal Title: Nippon Shokakibyo Gakkai Zasshi Volume: 112 Issue: 2 Pages: 278-286
  • DOI: 10.11405/nisshoshi.112.278
  • NAID: 130004776875
  • ISSN: 0446-6586, 1349-7693
  • Peer Reviewed
• [Journal Article] The effectiveness of an anti-human IL-6 receptor monoclonal antibody combined with chemotherapy to target colon cancer stem-like cells. (2015)
  • Author(s): Ying J, Tsujii M, Kondo J, Hayashi Y, Kato M, Akasaka T, Inoue T, Shiraishi E, Inoue T, Hiyama S, Tsujii Y, Maekawa A, Kawai S, Fujinaga T, Araki M, Shinzaki S, Watabe K, Nishida T, Iijima H, Takehara T.
  • Journal Title: Int J Oncol. Volume: 46 Issue: 4 Pages: 1151-1159
  • DOI: 10.3892/ijo.2015.2851
  • Peer Reviewed
• [Journal Article] Polyglycolic acid sheets for repair of refractory esophageal fistula. (2015)
  • Author(s): Tsujii Y, Kato M, Shinzaki S, Takigawa A, Hayashi Y, Nishida T, Iijima H, Tsujii M, Takehara T.
  • Journal Title: Endoscopy. Volume: 47 Issue: S 01 Pages: 39-40
  • DOI: 10.1055/s-0034-1390914
  • Peer Reviewed
• [Journal Article] Gastric endoscopic submucosal dissection under steady pressure automatically controlled endoscopy (SPACE); a multicenter randomized preclinical trial. (2015)
  • Author(s): Yamada T, Hirota M, Tsutsui S, Kato M, Takahashi T, Yasuda K, Sumiyama K, Tsujii M, Takehara T, Mori M, Doki Y, Nakajima K.
  • Journal Title: Surg Endosc. Volume: 29 Issue: 9 Pages: 2748-2755
  • DOI: 10.1007/s00464-014-4001-0
  • Peer Reviewed
• [Journal Article] 5FU resistance abrogates the amplified cytotoxic effects induced by inhibiting checkpoint kinase 1 in p53‑mutated colon cancer cells. (2015)
  • Author(s): Akasaka T, Tsujii M, Kondo J, Hayashi Y, Ying J, Lu Y, Kato M, Yamada T, Yamamoto S, Inoue T, Tsujii Y, Maekawa A, Fujinaga T, Shiraishi E, Hiyama S, Inoue T, Shinzaki S, Watabe K, Nishida T, Iijima H, Takehara T.
  • Journal Title: Int J Oncol. Volume: 46 Issue: 1 Pages: 63-70
  • DOI: 10.3892/ijo.2014.2693
  • Peer Reviewed
• [Presentation] 大腸カプセル内視鏡の病変検出率と大腸内視 鏡検査法における位置づけの検討 (2016)
  • Author(s): 前阪 和城,小森 真人,辻井 正彦
  • Organizer: 第91回日本消化器内視鏡学会総会
  • Place of Presentation: グランドプリンスホテル新高輪・国際館パミール
  • Year and Date: 2016-05-12
• [Presentation] 内視鏡検査におけるプロポフォールによる静 脈麻酔の有用性 (2016)
  • Author(s): 福岡 誠,小森 真人,奥山 直木,工藤 慎之輔,前阪 和城, 白井 久美子,木村 晋也,大西 幸作,楠本 侑宏,末吉 由佳, 松本 健吾,平尾 元宏,法水 淳,辻井 正彦
  • Organizer: 第91回日本消化器内視鏡学会総会
  • Place of Presentation: グランドプリンスホテル新高輪・国際館パミール
  • Year and Date: 2016-05-12
• [Presentation] 中下部悪性胆道狭窄に対するSEMS(EGIS Biliary Stent、Double Bare typeおよびDou- ble Covered type)の使用経験 (2016)
  • Author(s): 福岡 誠,小森 真人,奥山 直木,工藤 慎之輔,前阪 和城, 白井 久美子,木村 晋也,大西 幸作,楠本 侑宏,末吉 由佳, 松本 健吾,平尾 元宏,法水 淳,辻井 正彦
  • Organizer: 第91回日本消化器内視鏡学会総会
  • Place of Presentation: グランドプリンスホテル新高輪・国際館パミール
  • Year and Date: 2016-05-12
• [Presentation] ３D内視鏡システムを用いた消化管病変の大きさ測定 (2015)
  • Author(s): 辻井正彦、渡部健二、吉本佳代子、飯島英樹、加藤元彦、西田勉、林 義人、竹原徹郎
  • Organizer: 日本消化器内視鏡学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-05-30