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Elucidation of molecular network-regulating mechanisms on pancreatic tumor microenvironment suppression by fucoxanthin

Research Project

Project/Area Number 20K05879
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 38050:Food sciences-related
Research InstitutionHealth Sciences University of Hokkaido

Principal Investigator

TERASAKI Masaru  北海道医療大学, 薬学部, 准教授 (10391195)

Co-Investigator(Kenkyū-buntansha) 小島 弘幸  北海道医療大学, 薬学部, 教授 (10414286)
武藤 倫弘  京都府立医科大学, 医学(系)研究科(研究院), 教授 (30392335)
高橋 真美  国立研究開発法人国立がん研究センター, 研究所, ユニット長 (90214973)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywordsカロテノイド / フコキサンチン / 海藻 / がん化学予防 / 腫瘍微小環境 / 膵臓がん / フコキサンチノール / 膵癌 / 癌化学予防 / 癌幹細胞 / がん予防 / 膵臓癌
Outline of Research at the Start

膵癌予防については、食品やその含有成分は極めて有望な候補であるが、腫瘍微小環境を標的とした研究はほとんど進んでいない。申請者は、最近、フコキサンチン(Fx)を投与した大腸発癌モデルマウスにおける腫瘍微小環境形成抑制効果を初めて発見した。本研究では、大腸と同様、Fxによる腫瘍微小環境形成抑制効果が膵臓で見られるかを検討するため、Fxを投与した膵癌モデル動物における膵臓PCSCsやTregs等の細胞応答機序と細胞間の相互作用を調べ、膵臓腫瘍微小環境形成において主要な役割を果たす細胞間の分子Network制御に対するFxによる制御機構の解明を目指す。

Outline of Final Research Achievements

Fucoxanthin (Fx) contained in brown algae such as Undaria pinnatifida has potent anticancer activity. Pancreatic cancer (PC) represents the stepwise progress from formation of tumor microenvironment to development of tumor volume in pancreatic tissue. Foods and foods-derived compounds are attractive candidates on the PC prevention. However, there are little information on the preventive researches of foods and foods-derived compounds targeting PC tumor microenvironment. Recently, we have reported cancer chemopreventive effects of Fx on a colorectal cancer murine model through suppressions of tumor microenvironment. In the present study, we investigated the suppressive molecular mechanisms of tumor microenvironment network in PC animal models with Fx administration.

Academic Significance and Societal Importance of the Research Achievements

Fxは、日常的な海藻摂取生活でヒト癌予防効果が得られる可能性の高い化合物であるが、腫瘍微小環境制御に関する知見はほとんどない。本研究は、Fxの癌予防効果の観点からは不明であった腫瘍微小環境形成抑制の分子Network制御の解明に取り組んだ先駆的研究になる。さらに、本研究は、ヒト膵癌の組織形態と分子制御に近いモデル動物として、現在使用可能な膵癌同種同所移植モデルマウスあるいはハムスターを用い、包括的にFxによる膵臓腫瘍微小環境制御の解明を目指す極めて独自性の高い研究と言える。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (35 results)

All 2023 2022 2021 2020

All Journal Article (17 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 17 results,  Open Access: 13 results) Presentation (18 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Effects of benzotriazole UV stabilizers, UV-PS and UV-P, on the differentiation of splenic regulatory T cells via aryl hydrocarbon receptor2022

    • Author(s)
      Kubota Atsuhito、Terasaki Masaru、Sakuragi Yuuta、Muromoto Ryuta、Ikeda-Araki Atsuko、Takada Hideshige、Kojima Hiroyuki
    • Journal Title

      Ecotoxicology and Environmental Safety

      Volume: 238 Pages: 113549-113549

    • DOI

      10.1016/j.ecoenv.2022.113549

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Biscuit Containing Fucoxanthin Prevents Colorectal Carcinogenesis in Mice2022

    • Author(s)
      Terasaki Masaru、Murase Wataru、Kamakura Yukino、Kawakami Serina、Kubota Atsuhito、Kojima Hiroyuki、Ohta Tohru、Tanaka Takuji、Maeda Hayato、Miyashita Kazuo、Mutoh Michihiro
    • Journal Title

      Nutrition and Cancer

      Volume: 74 Issue: 10 Pages: 3651-3661

    • DOI

      10.1080/01635581.2022.2086703

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Requirement of CLIC4 Expression in Human Colorectal Cancer Cells for Sensitivity to Growth Inhibition by Fucoxanthinol2022

    • Author(s)
      YOKOYAMA REO、KUSHIBIKI AYUMI、YAMADA SHIORI、KUBOTA ATSUHITO、KOJIMA HIROYUKI、OHTA TOHRU、HAMADA JUNICHI、MAEDA HAYATO、MUTOH MICHIHIRO、TERASAKI MASARU
    • Journal Title

      Cancer Genomics - Proteomics

      Volume: 19 Issue: 4 Pages: 428-444

    • DOI

      10.21873/cgp.20330

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fucoxanthinol Promotes Apoptosis in MCF-7 and MDA-MB-231 Cells by Attenuating Laminins?Integrins Axis2022

    • Author(s)
      Yasuda Ayaka、Wagatsuma Momoka、Murase Wataru、Kubota Atsuhito、Kojima Hiroyuki、Ohta Tohru、Hamada Junichi、Maeda Hayato、Terasaki Masaru
    • Journal Title

      Onco

      Volume: 2 Issue: 3 Pages: 145-163

    • DOI

      10.3390/onco2030010

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Stable isotope ratios of carbon, nitrogen, oxygen, and mercury concentrations in north pacific baleen whales and the comparison of their calves with toothed whale calves2022

    • Author(s)
      Endo Tetsuya、Terasaki Masaru、Kimura Osamu
    • Journal Title

      Journal of Veterinary Science & Medicine

      Volume: 10 Pages: 1-10

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Induction of DNA Damage in Mouse Colorectum by Administration of Colibactin-producing Escherichia coli, Isolated from a Patient With Colorectal Cancer2022

    • Author(s)
      NARITA TAKUMI、TSUNEMATSU YUTA、MIYOSHI NORIYUKI、KOMIYA MASAMI、HAMOYA TAKAHIRO、FUJII GEN、YOSHIKAWA YUKO、SATO MICHIO、KAWANISHI MASANOBU、SUGIMURA HARUHIKO、IWASHITA YUJI、TOTSUKA YUKARI、TERASAKI MASARU、WATANABE KENJI、WAKABAYASHI KEIJI、MUTOH MICHIHIRO
    • Journal Title

      In Vivo

      Volume: 36 Issue: 2 Pages: 628-634

    • DOI

      10.21873/invivo.12746

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppression of C-C chemokine receptor 1 is a key regulation for colon cancer chemoprevention in AOM/DSS mice by fucoxanthin2022

    • Author(s)
      Terasaki Masaru、Ono Shion、Hashimoto Saki、Kubota Atsuhito、Kojima Hiroyuki、Ohta Tohru、Tanaka Takuji、Maeda Hayato、Miyashita Kazuo、Mutoh Michihiro
    • Journal Title

      The Journal of Nutritional Biochemistry

      Volume: 99 Pages: 108871-108871

    • DOI

      10.1016/j.jnutbio.2021.108871

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fucoxanthin Prevents Pancreatic Tumorigenesis in C57BL/6J Mice That Received Allogenic and Orthotopic Transplants of Cancer Cells2021

    • Author(s)
      Murase Wataru、Kamakura Yukino、Kawakami Serina、Yasuda Ayaka、Wagatsuma Momoka、Kubota Atsuhito、Kojima Hiroyuki、Ohta Tohru、Takahashi Mami、Mutoh Michihiro、Tanaka Takuji、Maeda Hayato、Miyashita Kazuo、Terasaki Masaru
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 24 Pages: 13620-13620

    • DOI

      10.3390/ijms222413620

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 5-Aminosalicylic Acid, A Weak Agonist for Aryl Hydrocarbon Receptor That Induces Splenic Regulatory T Cells2021

    • Author(s)
      Kubota Atsuhito、Terasaki Masaru、Takai Rie、Kobayashi Masaki、Muromoto Ryuta、Kojima Hiroyuki
    • Journal Title

      Pharmacology

      Volume: 107 Issue: 1-2 Pages: 28-34

    • DOI

      10.1159/000520404

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of Cells Displaying High Expression of CLIC4 in Tumor Tissue of Patients With Colorectal Cancer2021

    • Author(s)
      YOKOYAMA REO、KUBOTA ATSUHITO、KOJIMA HIROYUKI、TANAKA TAKUJI、MUTOH MICHIHIRO、TERASAKI MASARU
    • Journal Title

      In Vivo

      Volume: 35 Issue: 6 Pages: 3165-3173

    • DOI

      10.21873/invivo.12611

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Downregulated expression of organic anion transporting polypeptide (Oatp) 2b1 in the small intestine of rats with acute kidney injury2021

    • Author(s)
      Takeda Fuyo、Oda Masako、Terasaki Masaru、Kubota Atsuhito、Asada Keita、Ichimura Yuichi、Kojima Hiroyuki、Saitoh Hiroshi
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 40 Pages: 100411-100411

    • DOI

      10.1016/j.dmpk.2021.100411

    • NAID

      210000166019

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nine Cases of SARS-CoV-2-PCR-positive Samples Showed No Increase of Antibodies Against SARS-CoV-22021

    • Author(s)
      Kitagawa T, Kobayashi M, Ohta T, Terasaki M, Tsukamoto Y, Takai R, Ishizumi R, Uehara O, Nakagawa K, Akino K, Asaka M, Kuramitsu Y.
    • Journal Title

      In Vivo

      Volume: 35 Issue: 5 Pages: 2947-2949

    • DOI

      10.21873/invivo.12587

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An analytical survey of benzotriazole UV stabilizers in plastic products and their endocrine-disrupting potential via human estrogen and androgen receptors2021

    • Author(s)
      Sakuragi Yuuta、Takada Hideshige、Sato Hiroya、Kubota Atsuhito、Terasaki Masaru、Takeuchi Shinji、Ikeda-Araki Atsuko、Watanabe Yoko、Kitamura Shigeyuki、Kojima Hiroyuki
    • Journal Title

      Science of The Total Environment

      Volume: 800 Pages: 149374-149374

    • DOI

      10.1016/j.scitotenv.2021.149374

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fucoxanthin and Colorectal Cancer Prevention2021

    • Author(s)
      Terasaki Masaru、Kubota Atsuhito、Kojima Hiroyuki、Maeda Hayato、Miyashita Kazuo、Kawagoe Chikara、Mutoh Michihiro、Tanaka Takuji
    • Journal Title

      Cancers

      Volume: 13 Issue: 10 Pages: 2379-2379

    • DOI

      10.3390/cancers13102379

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fucoxanthin Prevents Colorectal Cancer Development in Dextran Sodium Sulfate-treated Apc Min/+ Mice2021

    • Author(s)
      Terasaki M, Hamoya T, Kubota A, Kojima H, Tanaka T, Maeda H, Miyashita K, Mutoh M
    • Journal Title

      Anticancer Research

      Volume: 41 Issue: 3 Pages: 1299-1305

    • DOI

      10.21873/anticanres.14887

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A fucoxanthinol induces apoptosis in a pancreatic  intraepithelial neoplasia cells.2021

    • Author(s)
      Terasaki, M., Takuya Inoue, T., Murase, W., Atsuhito Kubota, A., Kojma, H., Kojoma, M., Ohta, T., Maeda, H., Miyashita, K., Mutoh, M., Takahashi, M.
    • Journal Title

      Cancer Genomics Proteomics

      Volume: 18 Issue: 2 Pages: 133-146

    • DOI

      10.21873/cgp.20248

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Marine Carotenoid of Fucoxanthinol Accelerates the Growth of Human Pancreatic Cancer PANC-1 Cells2021

    • Author(s)
      Terasaki M, Takahashi S, Nishimura R, Kubota A, Kojima H, Ohta T, Hamada J, Kuramitsu Y, Maeda H, Miyashita K, Takahashi M, Mutoh M
    • Journal Title

      Nutrition and Cancer

      Volume: 16 Issue: 1 Pages: 1-16

    • DOI

      10.1080/01635581.2020.1863994

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 幼若期ストレス負荷うつ病モデル動物の脳機能発達における遺伝子発現の異常2023

    • Author(s)
      進藤 つぐみ、脇田 征太朗、寺崎 将、鹿内 浩樹、尾崎 和音、大橋 敦子、泉剛
    • Organizer
      日本薬学会 第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 同所移植マウス膵がんモデルにおけるFucoxanthinによるがん化学予防2022

    • Author(s)
      村瀬渉, 窪田篤人, 小島弘幸, 寺崎将
    • Organizer
      日本薬学会 第142年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ucoxanthinolによるCLIC4依存性がん細胞アポトーシス誘導機構2022

    • Author(s)
      横山怜央, 窪田篤人, 小島弘幸, 寺崎将
    • Organizer
      日本薬学会 第142年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] レポーター遺伝子アッセイ法を用いた下水処理水及び河川水中の内分泌かく乱活性の測定2022

    • Author(s)
      窪田篤人, 中田典秀, 高田秀重, 五味茉尋, 寺崎将, 小島弘幸
    • Organizer
      日本薬学会 第142年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Gene expression profiles in human HepaRG liver cells treated with perfluorooctanoic acid (PFOA)2022

    • Author(s)
      Atsuhito Kubota, Masaru Terasaki, Yuri Kimura, Atsuko Ikeda-Araki, Reiko Kishi, Hiroyuki Kojima
    • Organizer
      International Society for Environmental Epidemiology Asia and Western Pacific Chapter & International Society for Exposure Science Asia Chapter Joint Conference 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fucoxanthin suppresses development of pancreatic cancer in allogenic and orthotopic murine model2022

    • Author(s)
      Wataru Murase, Takuji Tanaka, Mami Takahashi and Michihiro Mutoh, Masaru Terasaki
    • Organizer
      The 81st Annual Meeting of the Japanese Cancer Association
    • Related Report
      2022 Annual Research Report
  • [Presentation] フコキサンチンによる膵がん予防に対する免疫関連分子制御の検討2022

    • Author(s)
      村瀬渉、寺崎将、窪田篤人、安田彩夏、植原治、田中卓二、高橋真美、小島弘幸
    • Organizer
      第29回 日本免疫毒性学会学術年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] フコキサンチンによるマウス大腸がん及び膵臓がん化学予防機序2022

    • Author(s)
      寺崎 将
    • Organizer
      日本脂質栄養学会 第31回大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] プラスチック添加剤・ベンゾトリアゾール系UV吸収剤によるAhR活性化を介した免疫毒性作用2021

    • Author(s)
      小島弘幸、窪田篤人、寺崎将、室本竜太、高田秀重
    • Organizer
      第48回日本毒性学会学術年会
    • Related Report
      2021 Research-status Report
  • [Presentation] Fucoxanthin suppresses an onset of colorectal adenocarcinoma in AOM/DSS mice through alteration of fecal microbiota2021

    • Author(s)
      Masaru Terasaki, Takuji Tanaka and Michihiro Mutoh
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] フコキサンチンによるマウス大腸がん予防作用2021

    • Author(s)
      寺崎将
    • Organizer
      第72回日本電気泳動学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] ベンゾトリアゾール系UV吸収剤によるAhR活性化を介した制御性T細胞の誘導2021

    • Author(s)
      窪田篤人、寺崎将、室本竜太、高田秀重、小島弘幸
    • Organizer
      日本免疫毒性学会第28学術年会
    • Related Report
      2021 Research-status Report
  • [Presentation] FucoxanthinolによるCLIC4依存性がん細胞アポトーシス誘導機構2021

    • Author(s)
      横山怜央、窪田篤人、小島弘幸、寺崎将
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 同種同所マウス膵がんモデルにおけるFucoxanthinによるがん予防2021

    • Author(s)
      村瀬渉、窪田篤人、小島弘幸、寺崎将
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Research-status Report
  • [Presentation] フコキサンチンによる大腸がん予防制御機序2021

    • Author(s)
      寺崎 将
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Cell-besed assay法を用いたUV吸収剤のホルモン受容体を介したエストロゲン・抗アンドロゲン作用の検出2020

    • Author(s)
      桜木優太、寺崎将、小島弘幸
    • Organizer
      第147回日本薬学会北海道支部例会
    • Related Report
      2020 Research-status Report
  • [Presentation] Fucoxanthinolによるがん幹細胞上皮間葉転換抑制作用と相関するマーカー代謝物2020

    • Author(s)
      寺崎 将、浜田淳一
    • Organizer
      がん予防学術大会2020
    • Related Report
      2020 Research-status Report
  • [Presentation] Fucoxanthin induces anoikis in AOM/DSS-produced colorectal adenocarcinoma through suppressing integrin signals in mice2020

    • Author(s)
      Masaru Terasaki, Takuji Tanaka, Michihiro Mutoh
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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