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Characteristics of colorectal carcinogenesis based on metabolic syndrome: molecular abnormality and alteration of miRNA expression

Research Project

Project/Area Number 17K15936
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionGifu University

Principal Investigator

Kubota Masaya  岐阜大学, 医学部附属病院, 助教 (90542407)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords肥満関連大腸発癌 / 大腸癌 / 化学予防 / 肥満 / メタボリック症候群 / APC / 糖尿病
Outline of Final Research Achievements

This study was conducted focusing on environmental factors such as lifestyle-related diseases and gene abnormalities in colorectal carcinogenesis. A novel obesity-related colorectal carcinogenesis model was constructed by crossing APC-mutated Min mouse and db/db mouse exhibiting obesity/type 2 diabetes. It was found that this mouse developed obesity, hyperglycemia, hyperinsulinemia, and dyslipidemia, and that the incidence of tumors in the intestinal tract increased significantly compared to the control. Administration of the anti-diabetic drug metformin and green tea catechin to the mice reduced the number of intestinal tumors. Moreover, development of colorectal neoplasms was suppressed by an anti-diabetic drug SGLT2 inhibitor in a colon carcinogenesis model using db/db mice. The results indicated the possibility that obesity-related colorectal carcinogenesis is suppressed by anti-diabetic agents and phytochemicals.

Academic Significance and Societal Importance of the Research Achievements

肥満や糖尿病をはじめとする生活習慣病患者の増加は重要な社会問題であり、また、これらの疾患を合併する大腸癌患者の増加が危惧されている。本研究結果は、臨床で使用されている糖尿病治療薬や日常生活で摂取可能な植物由来化学物質(phytochemical)が、肥満に関連する大腸発癌を抑制する上で有効であることを示しており、大腸発癌リスクの高い肥満や糖尿病を合併した患者の予後改善・再発予防への寄与が期待できる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (14 results)

All 2020 2019 2018 2017

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 9 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Alpha-Glucosidase Inhibitor Voglibose Suppresses Azoxymethane-Induced Colonic Preneoplastic Lesions in Diabetic and Obese Mice.2020

    • Author(s)
      Kato J, Shirakami Y, Mizutani T, Kubota M, Sakai H, Ibuka T, Shimizu M.
    • Journal Title

      Int J Mol Sci.

      Volume: 21 Issue: 6 Pages: 2226-2226

    • DOI

      10.3390/ijms21062226

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endoscopic and Pathological Characteristics of Helicobacter pylori Infection-Negative Early Gastric Cancer.2020

    • Author(s)
      Mizutani T, Araki H, Saigo C, Takada J, Kubota M, Ibuka T, Suzui N, Miyazaki T, Shimizu M.
    • Journal Title

      Dig Dis.

      Volume: 11 Issue: 6 Pages: 1-10

    • DOI

      10.1159/000506120

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppressive effects of the sodium-glucose cotransporter 2 inhibitor tofogliflozin on colorectal tumorigenesis in diabetic and obese mice.2019

    • Author(s)
      Kato J, Shirakami Y, Ohnishi M, Mizutani T, Kubota M, Sakai H, Ibuka T, Tanaka T, Shimizu M.
    • Journal Title

      Oncol Rep.

      Volume: 42 Pages: 2797-2805

    • DOI

      10.3892/or.2019.7357

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effective Treatment of Cytotoxic Agent Refractory Alpha-Fetoprotein-Producing Gastric Cancer with Ramucirumab: a Case Report and Review of the Literature.2019

    • Author(s)
      Takada J, Araki H, Ozawa N, Sugiyama T, Kubota M, Ibuka T, Shimizu M.
    • Journal Title

      J Gastrointest Cancer.

      Volume: 50 Issue: 3 Pages: 556-559

    • DOI

      10.1007/s12029-017-0043-6

    • Related Report
      2019 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acute cytomegalovirus infection in an immunocompetent patient with ulcerative colitis: A case report.2019

    • Author(s)
      Maeda T, Sakai H, Ozawa N, Sugiyama T, Takada J, Kubota M, Ibuka T, Shirakami Y, Araki H, Shimizu M.
    • Journal Title

      Exp Ther Med.

      Volume: 18 Pages: 2271-2277

    • DOI

      10.3892/etm.2019.7823

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Safety of Carbon Dioxide Insufflation during Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma2018

    • Author(s)
      Takada Jun、Araki Hiroshi、Mizutani Taku、Ozawa Noritaka、Sugiyama Tomohiko、Kubota Masaya、Ibuka Takashi、Shimizu Masahito
    • Journal Title

      Digestive Diseases

      Volume: 37 Issue: 2 Pages: 93-99

    • DOI

      10.1159/000492870

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibitory effects of pentoxifylline on inflammation-related tumorigenesis in rat colon2018

    • Author(s)
      Shirakami Yohei、Kochi Takahiro、Kubota Masaya、Sakai Hiroyasu、Ibuka Takashi、Yoshimi Kazuto、Kuramoto Takashi、Tanaka Takuji、Shimizu Masahito、Seishima Mitsuru
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 74 Pages: 33972-33981

    • DOI

      10.18632/oncotarget.26119

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Carbon dioxide insufflation reduces residual gas in the gastrointestinal tract following colorectal endoscopic submucosal dissection.2018

    • Author(s)
      Sugiyama T, Araki H, Ozawa N, Takada J, Kubota M, Ibuka T, Shimizu M.
    • Journal Title

      Biomed Rep

      Volume: 8 Pages: 257-263

    • DOI

      10.3892/br.2018.1044

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of an elderly patient with inverted Meckel's diverticulum with small intestinal bleeding detected using capsule and double-balloon endoscopies2017

    • Author(s)
      Ibuka T, Araki H, Sugiyama T, Takada J, Kubota M, Shirakami Y, Shiraki M, Shimizu M, Suzui N, Miyazaki T.
    • Journal Title

      Nippon Shokakibyo Gakkai Zasshi

      Volume: 114 Issue: 11 Pages: 2005-2011

    • DOI

      10.11405/nisshoshi.114.2005

    • NAID

      130007330949

    • ISSN
      0446-6586, 1349-7693
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Preventative Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice2017

    • Author(s)
      Fukuta K, Shirakami Y, Maruta A, Obara K, Iritani S, Nakamura N, Kochi T, Kubota M, Sakai H, Tanaka T, Shimizu M
    • Journal Title

      Int J Mol Sci

      Volume: 18(2) Issue: 2 Pages: 413-413

    • DOI

      10.3390/ijms18020413

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin on hepatoma cell lines and liver tumorigenesis2018

    • Author(s)
      Yohei Shirakami, Koki Obara, Masaya Kubota, Hiroyasu Sakai, Takuji Tanaka, Masahito Shimizu, Mitsuru Seishima
    • Organizer
      109th American Association for Cancer Research Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 当院における食道ESD後の狭窄予防および発生した狭窄に対する治療に関する検討2017

    • Author(s)
      久保田全哉、小島健太郎、小澤範高、杉山智彦、高田 淳、井深貴士、荒木寛司、清水雅仁
    • Organizer
      第93回日本消化器内視鏡学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 大腸発癌モデルにおけるペントキシフィリンの発癌抑制効果2017

    • Author(s)
      白上洋平、河内隆宏、久保田全哉、清水雅仁、清島 満
    • Organizer
      第49回日本臨床分子形態学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 胃Diffuse large B-cell lymphoma(DLBCL)の臨床病理学的検討2017

    • Author(s)
      久保田全哉、手塚隆一、前田俊英、小島健太郎、大西雅也、中村みき、小澤範高、長谷川恒輔、杉山智彦、華井竜徳、高田 淳、境 浩康、井深貴士、白上洋平、末次 淳、白木 亮、荒木寛司、清水雅仁
    • Organizer
      JDDW2017(第59回日本消化器病学会大会)
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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