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The development of chemoprevention for colorectal cancer by the combination of metformin and aspirin

Research Project

Project/Area Number 19KK0412
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))

Allocation TypeMulti-year Fund
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionYokohama City University

Principal Investigator

HIGURASHI Takuma  横浜市立大学, 医学部, 講師 (90622580)

Project Period (FY) 2020 – 2021
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
Keywords大腸癌 / 化学予防 / アスピリン / オルガノイド / メトホルミン / 大腸発癌
Outline of Research at the Start

大腸癌は全世界的に増加傾向であり早急な対策が求められる。これまで大腸癌の予防法としては、検診で早期発見や早期治療を行うことが重点的におこなわれていたが、死亡率の低下は限定的であった。近年は多くの疾患が対策型の治療から疾病予防へとシフトしてきており、大腸癌においても罹患予防を進めていく必要がある。メトホルミンやアスピリンは大腸癌予防効果の報告があるが、機序が十分解明されていないため、新規培養技術であるオルガノイドを用いて、薬剤がどのように抗大腸腫瘍効果を発揮するのかを解明し、その有効性を証明し臨床応用につなげることで、増加し続ける大腸癌の罹患率・死亡率を減少させることを目標としている。

Outline of Final Research Achievements

This research was conducted with Prof. Andrew T chan, the cheaf of Clinical and Translational Epidemiology unit, Harvard medical school, Massachusetts general hospital.
Aspirin revealed chemopreventive effect by the decrease of PGE2 via the supression of COX1/COX2. Metformin also revealed chemopreventive effect by the supression of mTOR via the activation of AMPK. The combination of metformin and aspirin showed higher efficacy for colorectal cancer chemprevention.

Academic Significance and Societal Importance of the Research Achievements

大腸癌は全世界的に増加傾向であり、早急な対策が求められている。分子標的薬や免疫チェックポイント阻害薬、新規抗がん剤などの進歩により大腸癌の生存期間の延長や、死亡率の低下は認めているものの、比例して医療費の増大も著しい。また、便潜血による健診や、内視鏡検査によるポリープ切除は大腸癌の死亡率を下げることが報告されているが、大腸ポリープや癌を内視鏡治療した患者はその後も再発/新規発生が多いことが知られており問題となっている。本研究は根本的な対策である一次予防(健康増進/疾病予防)であり今後の大腸癌の罹患/死亡率の抑制や、高騰する医療費の抑制により重要となるものであり、社会的意義が大きい。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (10 results)

All 2022 2021 2020

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (1 results) (of which Invited: 1 results)

  • [Int'l Joint Research] Harvard medical school, Massachusetts general hospital(米国)2020

    • Year and Date
      2020-04-01
    • Related Report
      2021 Annual Research Report
  • [Journal Article] Comparison of the diagnostic performance of NBI, Laser-BLI and LED-BLI: a randomized controlled noninferiority trial2022

    • Author(s)
      Higurashi Takuma、Ashikari Keiichi、Tamura Shigeki、Takatsu Tomohiro、Misawa Noboru、Yoshihara Tsutomu、Ninomiya Yuki、Okamoto Yuki、Taguri Masataka、Sakamoto Taku、Oka Shiro、Nakajima Atsushi、Tanaka Shinji、Matsuda Takahisa
    • Journal Title

      Surgical Endoscopy

      Volume: epub Issue: 10 Pages: 7577-7587

    • DOI

      10.1007/s00464-022-09197-8

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gastrointestinal Cancer Stage at Diagnosis Before and During the COVID-19 Pandemic in Japan2021

    • Author(s)
      Kuzuu Kento、Misawa Noboru、Ashikari Keiichi、Kessoku Takaomi、Kato Shingo、Hosono Kunihiro、Yoneda Masato、Nonaka Takashi、Matsushima Shozo、Komatsu Tatsuji、Nakajima Atsushi、Higurashi Takuma
    • Journal Title

      JAMA Network Open

      Volume: 4 Issue: 9 Pages: 2126334-2126334

    • DOI

      10.1001/jamanetworkopen.2021.26334

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of obesity in colorectal endoscopic submucosal dissection: single-center retrospective cohort study2021

    • Author(s)
      Tachikawa Jun、Chiba Hideyuki、Okada Naoya、Arimoto Jun、Ashikari Keiichi、Kuwabara Hiroki、Nakaoka Michiko、Higurashi Takuma、Goto Toru、Nakajima Atsushi
    • Journal Title

      BMC Gastroenterology

      Volume: 21 Issue: 1 Pages: 74-74

    • DOI

      10.1186/s12876-021-01652-5

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy of sedation with dexmedetomidine plus propofol during esophageal endoscopic submucosal dissection2021

    • Author(s)
      Ashikari Keiichi、Nonaka Takashi、Higurashi Takuma、Takatsu Tomohiro、Yoshihara Tsutomu、Misawa Noboru、Arimoto Jun、Kanoshima Kenji、Matsuura Tetsuya、Fuyuki Akiko、Ohkubo Hidenori、Chiba Hideyuki、Nakajima Atsushi
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: 36 Issue: 7 Pages: 1920-1926

    • DOI

      10.1111/jgh.15417

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A prospective interventional trial on the effect of periodontal treatment on Fusobacterium nucleatum abundance in patients with colorectal tumours2021

    • Author(s)
      Yoshihara Tsutomu、Kioi Mitomu、Baba Junichi、Usuda Haruki、Kessoku Takaomi、Iwaki Michihiro、Takatsu Tomohiro、Misawa Noboru、Ashikari Keiichi、Matsuura Tetsuya、Fuyuki Akiko、Ohkubo Hidenori、Matsumoto Mitsuharu、Wada Koichiro、Nakajima Atsushi、Higurashi Takuma
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 23719-23719

    • DOI

      10.1038/s41598-021-03083-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Precision modeling of gall bladder cancer patients in mice based on orthotopic implantation of organoid-derived tumor buds2021

    • Author(s)
      Kato Shingo、Fushimi Kentaro、Yabuki Yuichiro、Maru Yoshiaki、Hasegawa Sho、Matsuura Tetsuya、Kurotaki Daisuke、Suzuki Akihiro、Kobayashi Noritoshi、Yoneda Masato、Higurashi Takuma、Enaka Makiko、Tamura Tomohiko、Hippo Yoshitaka、Nakajima Atsushi
    • Journal Title

      Oncogenesis

      Volume: 10 Issue: 4 Pages: 30-30

    • DOI

      10.1038/s41389-021-00322-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The efficacy of aspirin and metformin combination therapy in patients with rectal aberrant crypt foci: a double-blinded randomized controlled trial2020

    • Author(s)
      Higurashi Takuma、Arimoto Jun、Ashikari Keiichi、Takatsu Tomohiro、Misawa Noboru、Yoshihara Tsutomu、Matsuura Tetsuya、Fuyuki Akiko、Ohkubo Hidenori、Nakajima Atsushi
    • Journal Title

      BMC Cancer

      Volume: 20 Issue: 1 Pages: 1043-1043

    • DOI

      10.1186/s12885-020-07564-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The efficacy of a leukotriene receptor antagonist in the treatment of human rectal aberrant crypt foci: a nonrandomized, open-label, controlled trial2020

    • Author(s)
      Higurashi Takuma、Arimoto Jun、Ashikari Keiichi、Takatsu Tomohiro、Misawa Noboru、Yoshihara Tsutomu、Matsuura Tetsuya、Fuyuki Akiko、Ohkubo Hidenori、Nakajima Atsushi
    • Journal Title

      BMC Cancer

      Volume: 20 Issue: 1 Pages: 770-770

    • DOI

      10.1186/s12885-020-07266-6

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 大腸癌死を防げ~基礎と臨床からの取り組み~2021

    • Author(s)
      日暮琢磨
    • Organizer
      ボストン日本人研究者交流会 (BJRF) 第190回 講演会(オンライン開催)
    • Related Report
      2021 Annual Research Report
    • Invited

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Published: 2020-02-06   Modified: 2023-01-30  

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