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The mechanism of malignant potential in digestive cancers based on intestinal metaplasia

Research Project

Project/Area Number 18H02791
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Tsuchiya Kiichiro  東京医科歯科大学, 医学部附属病院, 准教授 (40376786)

Co-Investigator(Kenkyū-buntansha) 渡辺 守  東京医科歯科大学, 高等研究院, 特別栄誉教授 (10175127)
赤星 径一  東京医科歯科大学, 医学部附属病院, 助教 (80749523)
伴 大輔  東京医科歯科大学, 大学院医歯学総合研究科, 講師 (40376736)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Keywords腸上皮化生 / IPMN / Atoh1 / 腸上皮形質 / 癌幹細胞 / スキルスがん / スキルス癌
Outline of Final Research Achievements

Pancreatic cancer is still intractable, but it is expected that the number of pancreatic cancers generated from intraductal papillary mucinous tumor (IPMN) will increase in the future. In IPMN, pancreatic cells are transformed into intestinal phenotype, but their involvement in carcinogenesis was unknown. In this study, we found that the expression of factors that regulate intestinal phenotype is increased in the process of developing pancreatic cancer of IPMN. Introducing the intestinal regulator into pancreatic cancer cells results in an intestinal type tumor with mucous traits, which grows, suggesting that intestinal phenotypes are associated with carcinogenesis of pancreatic cancer of IPMN.

Academic Significance and Societal Importance of the Research Achievements

膵癌は未だ難治ですが、今後膵管内乳頭粘液性腫瘍(IPMN)から癌化する膵癌の増加が予想されています。しかしながらがん化する病態は未だ不明です。IPMNは膵臓から腸の形質に変化するものが多いため、今回腸の形質が膵臓癌の癌化に関わる機序を解析しました。その結果、大腸癌の治療標的となる分子が膵臓癌においても発現していることを発見しました。大腸癌の治療が膵臓癌にも応用できることが期待されます。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (25 results)

All 2021 2020 2019 2018

All Journal Article (14 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 14 results,  Open Access: 11 results) Presentation (11 results) (of which Int'l Joint Research: 8 results,  Invited: 4 results)

  • [Journal Article] Schlafen 11 Is a Novel Target for Mucosal Regeneration in Ulcerative Colitis2021

    • Author(s)
      Watanabe Sho、Nishimura Ryu、Shirasaki Tomoaki、Katsukura Nobuhiro、Hibiya Shuji、Kirimura Susumu、Negi Mariko、Okamoto Ryuichi、Matsumoto Yuka、Nakamura Tetsuya、Watanabe Mamoru、Tsuchiya Kiichiro
    • Journal Title

      Journal of Crohn's and Colitis

      Volume: 15 Issue: 9 Pages: 1558

    • DOI

      10.1093/ecco-jcc/jjab032

    • URL

      https://localhost/en/publications/e3f94db8-6569-4d0c-ab84-c3c9e646147c

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intraepithelial Lymphocytes Suppress Intestinal Tumor Growth by Cell-to-Cell Contact via CD103/E-Cadherin Signal.2021

    • Author(s)
      Ryo Morikawa, Yasuhiro Nemoto, Yuki Yonemoto, Shohei Tanaka, Yuria Takei, Shigeru Oshima, Takashi Nagaishi, Kiichiro Tsuchiya, Kengo Nozaki , Tomohiro Mizutani, Tetsuya Nakamura, Mamoru Watanabe, Ryuichi Okamoto.
    • Journal Title

      Cell Mol Gastroenterol Hepatol.

      Volume: 11 Issue: 5 Pages: 1483-1503

    • DOI

      10.1016/j.jcmgh.2021.01.014

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Notch and TNF-α signaling promote cytoplasmic accumulation of OLFM4 in intestinal epithelium cells and exhibit a cell protective role in the inflamed mucosa of IBD patients2021

    • Author(s)
      Kuno Reiko、Ito Go、Kawamoto Ami、Hiraguri Yui、Sugihara Hady Yuki、Takeoka Sayaka、Nagata Sayaka、Takahashi Junichi、Tsuchiya Mao、Anzai Sho、Mizutani Tomohiro、Shimizu Hiromichi、Yui Shiro、Oshima Shigeru、Tsuchiya Kiichiro、Watanabe Mamoru、Okamoto Ryuichi
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 25 Pages: 100906-100906

    • DOI

      10.1016/j.bbrep.2020.100906

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Functional analysis of isoflavones using patient-derived human colonic organoids2021

    • Author(s)
      Tsuchiya Mao、Ito Go、Hama Minami、Nagata Sayaka、Kawamoto Ami、Suzuki Kohei、Shimizu Hiromichi、Anzai Sho、Takahashi Junichi、Kuno Reiko、Takeoka Sayaka、Hiraguri Yui、Sugihara Hady Yuki、Mizutani Tomohiro、Yui Shiro、Oshima Shigeru、Tsuchiya Kiichiro、Watanabe Mamoru、Okamoto Ryuichi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 542 Pages: 40-47

    • DOI

      10.1016/j.bbrc.2021.01.021

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nickel ions attenuate autophagy flux and induce transglutaminase 2 (TG2) mediated post-translational modification of SQSTM1/p62.2020

    • Author(s)
      Emi Aonuma, Akiko Tamura, Hiroki Matsuda, Takehito Asakawa, Yuriko Sakamaki, Kana Otsubo, Yoichi Nibe, Michio Onizawa, Yasuhiro Nemoto, Takashi Nagaishi, Kiichiro Tsuchiya, Tetsuya Nakamura, Motohiro Uo, Mamoru Watanabe, Ryuichi Okamoto, Shigeru Oshima.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 542 Pages: 17-23

    • DOI

      10.1016/j.bbrc.2021.01.023

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intestinal phenotype is maintained by Atoh1 in the cancer region of intraductal papillary mucinous neoplasm2020

    • Author(s)
      Katsukura Nobuhiro、Watanabe Sho、Shirasaki Tomoaki、Hibiya Shuji、Kano Yoshihito、Akahoshi Keiichi、Tanabe Minoru、Kirimura Susumu、Akashi Takumi、Kitagawa Masanobu、Okamoto Ryuichi、Watanabe Mamoru、Tsuchiya Kiichiro
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 2 Pages: 932

    • DOI

      10.1111/cas.14755

    • URL

      https://localhost/en/publications/0b846b2e-755c-4577-9e18-e680b9f2f8f9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD8αα+ T cells show amoeboid shape and frequent morphological change in?vitro, and localize to small intestinal intraepithelial region in?vivo2020

    • Author(s)
      Takei Yuria、Nemoto Yasuhiro、Morikawa Ryo、Tanaka Shohei、Oshima Shigeru、Nagaishi Takashi、Okamoto Ryuichi、Tsuchiya Kiichiro、Nakamura Tetsuya、Watanabe Mamoru
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 523 Issue: 2 Pages: 328-335

    • DOI

      10.1016/j.bbrc.2019.12.021

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-fat diet-derived free fatty acids impair the intestinal immune system and increase sensitivity to intestinal epithelial damage2020

    • Author(s)
      Tanaka Shohei、Nemoto Yasuhiro、Takei Yuria、Morikawa Ryo、Oshima Shigeru、Nagaishi Takashi、Okamoto Ryuichi、Tsuchiya Kiichiro、Nakamura Tetsuya、Stutte Susanne、Watanabe Mamoru
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 522 Issue: 4 Pages: 971-977

    • DOI

      10.1016/j.bbrc.2019.11.158

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TP53 mutation by CRISPR system enhances the malignant potential of colon cancer.2019

    • Author(s)
      Watanabe S, Tsuchiya K, Nishimura R, Shirasaki T, Katsukura N, Hibiya S, Okamoto R, Nakamura T, Watanabe M
    • Journal Title

      Mol Cancer Res.

      Volume: in press Issue: 7 Pages: 1459-1467

    • DOI

      10.1158/1541-7786.mcr-18-1195

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A subset of diffuse-type gastric cancer is susceptible to mTOR inhibitors and checkpoint inhibitors2019

    • Author(s)
      Fukamachi H、Kim SK、Koh J、Lee HS、Sasaki Y、Yamashita K、Nishikawaji T、Shimada S、Akiyama Y、Byeon SJ、Bae DH、Okuno K、Nakagawa M、Tanioka T、Inokuchi M、Kawachi H、Tsuchiya K、Kojima K、Tokino Takashi、Eishi Y、Kim YS、Kim WH、Yuasa Y、Tanaka S
    • Journal Title

      Journal of Experimental & Clinical Cancer Research

      Volume: 38 Issue: 1 Pages: 127-127

    • DOI

      10.1186/s13046-019-1121-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Establishment of a system to evaluate the therapeutic effect and the dynamics of an investigational drug on ulcerative colitis using human colonic organoids.2019

    • Author(s)
      Nishimura R, Shirasaki T, Tsuchiya K, Miyake Y, Watanabe Y, Hibiya S, Watanabe S, Nakamura T, Watanabe M
    • Journal Title

      J Gastroenterol.

      Volume: in press Issue: 7 Pages: 608-620

    • DOI

      10.1007/s00535-018-01540-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Predictors of mucosal healing during induction therapy in patients with acute moderate‐to‐severe ulcerative colitis2018

    • 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

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ubiquitin D is Upregulated by Synergy of Notch Signalling and TNF-α in the Inflamed Intestinal Epithelia of IBD Patients2018

    • 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

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Single cell analysis of Crohn’s disease patient-derived small intestinal organoids reveals disease activity-dependent modification of stem cell properties2018

    • 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

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] IBD病態から繙く再生医療研究への展開と臨床応用2020

    • Author(s)
      土屋輝一郎
    • Organizer
      第3回旭川CDワークショップ
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 炎症性腸疾患モデル構築から癌化モデルへの試み2019

    • Author(s)
      土屋輝一郎
    • Organizer
      第3回 がん三次元培養研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 小腸からIBDそして再生へ2019

    • Author(s)
      土屋輝一郎
    • Organizer
      Advanced GI & Liver Forum 15th
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Establishment of chronic inflammation model using human small intestinal and colonic organoids2019

    • Author(s)
      Shuji Hibiya, Kiichiro Tsuchiya, Ryu Nishimura, Sho Watanabe, Nobuhiro Katsukura, Tomoaki Shirasaki, Ryuichi Okamoto, Mamoru Watanabe
    • Organizer
      UEG Week 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Long-term inflammation model using human colonic organoids2019

    • Author(s)
      Shuji Hibiya, Kiichiro Tsuchiya, Ryu Nishimura, Tomoaki Shirasaki, Sho Watanabe, Nobuhiro Katsukura, Shigeru Oshima, Ryuichi Okamoto, Tetsuya Nakamura, Mamoru Watanabe
    • Organizer
      The 7th annual meeting of AOCC
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Organoid model for the carcinogenesis process of CAC2019

    • Author(s)
      Kiichiro Tsuchiya
    • Organizer
      IMKASID 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] TP53 mutation in human colonic organoids acquires resistance to in vitro long-term inflammation.2019

    • Author(s)
      Tsuchiya K, Watanabe S, Shirasaki T, Nishimura R, Katsukura N, Hibiya S, Okamoto R, Nakamura T, Watanabe M
    • Organizer
      ECCO2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Lesion-specific gene expression in the Epithelial cells of Crohn’s disease by comparing Small intestinal organoids from active and inactive Lesion in the same patient.2018

    • Author(s)
      Hibiya S, Tsuchiya K, Nishimura R, Shirasaki T, Watanabe S, Katsukura N, Okamoto R, Nakamura T, Watanabe M
    • Organizer
      UEGW 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tp53 mutation enhances cell proliferation and stemness in human colon epithelial organoids and promotes a resistance against long-term inflammation.2018

    • Author(s)
      Watanabe S, Tsuchiya K, Shirasaki T, Hibiya S, Nishimura S, Katsukura N, Oshima S, Okamoto R, Tetsuya N, Watanabe M
    • Organizer
      UEGW 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Human colonic organoid treated with inflammatory factors might mimic the pathophysiology of epithelial cells in ulcerative colitis.2018

    • Author(s)
      Hibiya S, Tsuchiya K, Watanabe S, Nishimura R, Shirasaki T, Oshima S, Okamoto R, Nakamura T, Watanabe M
    • Organizer
      DDW 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of lesion-specific epithelial function of ulcerative colitis by comparing colonic organoids from lesion and non-lesion parts of same patients.2018

    • Author(s)
      Shirasaki T, Tsuchiya K, Nishimura R, Watanabe S, Hibiya S, Katsukura N, Okamoto R, Nakamura T, Watanabe M
    • Organizer
      DDW 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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