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飽和脂肪酸摂取による膜リン脂質アシル基飽和化を介した前立腺癌発症進展機序

Research Project

Project/Area Number 20K18084
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56030:Urology-related
Research InstitutionAkita University

Principal Investigator

小泉 淳  秋田大学, 医学部附属病院, 助教 (50813987)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Discontinued (Fiscal Year 2021)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords前立腺癌 / 肥満 / 脂質 / 脂質代謝 / 高脂肪食
Outline of Research at the Start

高脂肪食および肥満は前立腺癌発症・進展の危険因子とされるが、詳細な分子生物学的機序は不明である。我々は膜リン脂質であるイノシトールリン脂質(以下PIPs)に着目し、マウス前立腺癌モデル、ヒト前立腺癌組織において非癌組織と比較しPIPsプロファイルが異なることを証明した。さらに、癌組織ではPIPsの脂肪酸飽和度が亢進していることを確認しており、各脂質の飽和化と癌増悪進展の関連に特に注目している。本研究は高脂肪食および肥満下の前立腺癌発症進展に重要な脂質代謝産物および関連脂質代謝酵素を同定し、更にその代謝産物、関連分子を標的とした新規治療効果について解析することを目的としている。

Outline of Annual Research Achievements

前立腺癌は本邦男性において最も罹患率の高い癌であり、社会的に注目されている。高脂肪食およびそれに伴って引き起こされる肥満は前立腺癌発症・進展の危険因子とされ、また前立腺癌腫瘍内では脂質代謝亢進が報告されるが、外因性脂質、内因性脂質代謝と前立腺癌増悪進展の関連は不明である。私達は膜リン脂質であるイノシトールリン脂質(以下PIPs)に着目し、マウス前立腺癌モデル、ヒト前立腺組織のPIPs発現プロファイルを明らかにし、PIPsの脂肪酸飽和度が非癌組織より亢進し、癌増悪に関連している可能性を見出している。これまでの成果を踏まえて、本研究では外因性脂肪や肥満が前立腺癌脂質代謝を制御し、癌発症進展に影響すると仮説を立てた。特異的な脂質が前立腺癌増悪進展に関与するかを細胞株、動物モデル、臨床検体を用いた検討から解析し、特に前立腺内脂質代謝変化を中心とした分子生物学的機序解明を目的とした。本年度は高脂肪食が前立腺癌細胞ゼノグラフトの増殖を促進し、その腫瘍細胞の細胞内脂質代謝産物の変化を網羅的に解析しリン脂質プロファイル解析を行った。これによりPIP3のいくつかのサブクラスが高脂肪食摂取下の前立腺癌ゼノグラフトで増加していることを見出した。また関連分子候補FASNを同定し、この分子を薬剤で阻害した際のリン脂質プロファイルも同時に解析し、PIP1,PIP2,PIP3が低下していることを見出した。同時に特定の脂質(ラード食、魚油食)の違う食餌による前立腺癌増殖変化マウスモデルも確立しており、研究は順調に進んでいる。

Report

(2 results)
  • 2021 Annual Research Report
  • 2020 Research-status Report
  • Research Products

    (27 results)

All 2021 2020

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 4 results) Presentation (18 results) (of which Int'l Joint Research: 9 results)

  • [Journal Article] Impact of Nerve-Sparing Status on Positive Surgical Margin Location and Biochemical Recurrence in Patients with Prostate Cancer Post Radical Prostatectomy2021

    • Author(s)
      Matsuda Yoshinori、Narita Shintaro、Okubo Teppei、Mitsuzuka Koji、Hatakeyama Shingo、Koizumi Atsushi、Koie Takuya、Kawamura Sadafumi、Tochigi Tatsuo、Ito Akihiro、Oyama Chikara、Arai Yoichi、Habuchi Tomonori
    • Journal Title

      Annals of Surgical Oncology

      Volume: 28 Issue: 9 Pages: 5341-5348

    • DOI

      10.1245/s10434-021-10281-x

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Macrophage inhibitory cytokine‐1 induced by a high‐fat diet promotes prostate cancer progression by stimulating tumor‐promoting cytokine production from tumor stromal cells2021

    • Author(s)
      Huang Mingguo、Narita Shintaro、Koizumi Atsushi、Nara Taketoshi、Numakura Kazuyuki、Satoh Shigeru、Nanjo Hiroshi、Habuchi Tomonori
    • Journal Title

      Cancer Communications

      Volume: 41 Issue: 5 Pages: 389-403

    • DOI

      10.1002/cac2.12137

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Short-term outcomes of risk-adapted upfront docetaxel administration in patients with metastatic hormone-sensitive prostate cancer: a multicenter prospective study in Japan2021

    • Author(s)
      Muto Yumina、Narita Shintaro、Hatakeyama Shingo、Maita Shinya、Chiba Shuji、Kubo Kyohei、Aoyama Yuu、Ito Ryuichi、Takahashi Yoshiko、Takahashi Shuhei、Nakamura Kumiko、Honma Naoko、Sato Hiromi、Ohyama Chikara、Habuchi Tomonori
    • Journal Title

      Medical Oncology

      Volume: 38 Issue: 4 Pages: 37-37

    • DOI

      10.1007/s12032-021-01480-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Altering phosphoinositides in high‐fat diet‐associated prostate tumor xenograft growth2021

    • Author(s)
      Huang Mingguo、Koizumi Atsushi、Narita Shintaro、Nakanishi Hiroki、Sato Hiromi、Kashima Soki、Nara Taketoshi、Kanda Sohei、Numakura Kazuyuki、Saito Mitsuru、Satoh Shigeru、Nanjo Hiroshi、Sasaki Takehiko、Habuchi Tomonori
    • Journal Title

      MedComm

      Volume: 2 Issue: 4 Pages: 756-764

    • DOI

      10.1002/mco2.89

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of Nuclear YAP1 Expression in Residual Cancer After Neoadjuvant Chemohormonal Therapy With Docetaxel for High-Risk Localized Prostate Cancer2020

    • Author(s)
      Yoshinori Matsuda, Shintaro Narita, Taketoshi Nara, Huang Mingguo, Hiromi Sato, Atsushi Koizumi, Sohei Kanda, Kazuyuki Numakura, Mitsuru Saito, Takamitsu Inoue, Yuko Hiroshima, Hiroshi Nanji, Shigeru Satoh, Norihiko Tsuchiya, Tomonori Habuchi
    • Journal Title

      BMC Cancer

      Volume: 20 Issue: 1 Pages: 2034-2034

    • DOI

      10.1186/s12885-020-06844-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Does the Addition of Abiraterone to Castration Affect the Reduction in Bone Mineral Density?2020

    • Author(s)
      NAKAJIMA SHIORI、INOUE TAKAMITSU、HUANG MINGGUO、TAKAYAMA KOICHIRO、KASHIMA SOKI、YAMAMOTO RYOHEI、KOIZUMI ATSUSHI、NARA TAKETOSHI、NUMAKURA KAZUYUKI、SAITO MITSURU、NARITA SHINTARO、MIURA MASATOMO、SATOH SHIGERU、HABUCHI TOMONORI
    • Journal Title

      In Vivo

      Volume: 34 Issue: 6 Pages: 3291-3299

    • DOI

      10.21873/invivo.12167

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognostic value of plasminogen activator inhibitor‐1 in biomarker exploration using multiplex immunoassay in patients with metastatic renal cell carcinoma treated with axitinib2020

    • Author(s)
      Honma Naoko、Inoue Takamitsu、Tsuchiya Norihiko、Koizumi Atsushi、Yamamoto Ryohei、Nara Taketoshi、Kanda Sohei、Huang Mingguo、Numakura Kazuyuki、Saito Mitsuru、Narita Shintaro、Satoh Shigeru、Habuchi Tomonori
    • Journal Title

      Health Science Reports

      Volume: 3 Issue: 4 Pages: 197-197

    • DOI

      10.1002/hsr2.197

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical outcomes and prognostic factors in patients with newly diagnosed metastatic prostate cancer initially treated with androgen deprivation therapy: a retrospective multicenter study in Japan2020

    • Author(s)
      Narita Shintaro、Hatakeyama Shingo、Takahashi Masahiro、Sakurai Toshihiko、Kawamura Sadafumi、Hoshi Senji、Ishida Masanori、Kawaguchi Toshiaki、Ishidoya Shigeto、Shimoda Jiro、Sato Hiromi、Koizumi Atsushi、Mitsuzuka Koji、Tochigi Tatsuo、Tsuchiya Norihiko、Ohyama Chikara、Arai Yoichi、Nomura Kyoko、Habuchi Tomonori
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 25 Issue: 5 Pages: 912-920

    • DOI

      10.1007/s10147-019-01614-8

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acute kidney injury and its impact on renal prognosis after robot‐assisted laparoscopic radical prostatectomy2020

    • Author(s)
      Sato Hiromi、Narita Shintaro、Saito Mitsuru、Yamamoto Ryohei、Koizumi Atsushi、Nara Taketoshi、Kanda Sohei、Numakura Kazuyuki、Inoue Takamitsu、Satoh Shigeru、Abe Kyoko、Habuchi Tomonori
    • Journal Title

      The International Journal of Medical Robotics and Computer Assisted Surgery

      Volume: 16 Issue: 5 Pages: 1-7

    • DOI

      10.1002/rcs.2117

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] Cellular retinoic acid-binding protein 2 enhances saturated fatty acid-induced prostate cancer progression.2021

    • Author(s)
      Hiromi Sato
    • Organizer
      AACR Annual Meeting 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Lard diet accelerates prostate cancer development with modulation of systematic and local inflammation and gut microbiota alteration in a Pten-deficient mouse model.2021

    • Author(s)
      Hiromi Sato
    • Organizer
      EAU2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Changes in conditional net survival and dynamic prognostic factors in patients with newly diagnosed metastatic prostate cancer2021

    • Author(s)
      Shintaro Narita
    • Organizer
      The 116th Annual Meeting of the American Urological Association
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Comparison of clinical outcomes in patients with metastatic castration sensitive prostate cancer treated with upfront abiraterone or docetaxel: a propensity score matching analysis2021

    • Author(s)
      Shintaro Narita
    • Organizer
      The 37th, Korea-Japan Urological Congress
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 2種の免疫応答性マウスモデルにおける飽和脂肪酸の前立腺癌発症・進展に対する影響2021

    • Author(s)
      佐藤 博美
    • Organizer
      第30回泌尿器分子・細胞研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 細胞内レチノイン酸結合蛋白2は飽和脂肪酸誘導性の前立腺癌進展を促進する2021

    • Author(s)
      佐藤 博美
    • Organizer
      第36回前立腺シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] ロボット支援腹腔鏡下と後腹膜鏡下前立腺全摘除術後における急性腎障害発症の比較2021

    • Author(s)
      佐藤 博美
    • Organizer
      第35回日本泌尿器内視鏡学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Cellular retinoic acid-binding protein 2 (CRABP2) enhances saturated fatty acid-induced prostate cancer progression.2021

    • Author(s)
      Hiromi Sato
    • Organizer
      日本癌学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 2種の免疫応答性マウスモデルにおける飽和脂肪酸の前立腺癌発症・進展に対する影響2021

    • Author(s)
      佐藤 博美
    • Organizer
      第109回日本泌尿器科学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Increased fatty acyl saturation of phosphatidylinositol phosphate in prostate cancer progression.2020

    • Author(s)
      Atsushi Koizumi
    • Organizer
      The 115th Annual Meeting of the American Urological Association
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] ホスホイノシタイド(PIPs)アシル基飽和度が前立腺癌進展に与える影響2020

    • Author(s)
      小泉 淳
    • Organizer
      第108回日本泌尿器科学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Fish -oil diet attenuates prostate cancer development with systematic inflammation protection and gut microbiota alteration in a Pten-deficient mouse model.2020

    • Author(s)
      Hriomi Sato
    • Organizer
      The 115th Annual Meeting of the American Urological Association
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] The impact of specific fat-diets and obesity on prostate cancer initiation and progression using two different immunocompetent mouse models.2020

    • Author(s)
      Hiromi Sato
    • Organizer
      The 35th Annual EAU congress
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] PTENノックアウト前立腺癌マウスモデルにおいてラード食は全身炎症と腸内細菌叢の変化を介して前立腺癌進展を促進する.2020

    • Author(s)
      佐藤 博美
    • Organizer
      第24回腸内細菌学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 2種の免疫応答性マウスモデルにおける特定の脂肪食が前立腺癌発症・進展に及ぼす影響.2020

    • Author(s)
      佐藤 博美
    • Organizer
      第79回日本癌学会
    • Related Report
      2020 Research-status Report
  • [Presentation] The impact of phosphatidylinositol phosphate and its associated enzyme levels on clinical outcomes in patients with renal cell carcinoma who underwent surgery.2020

    • Author(s)
      Shintaro Narita
    • Organizer
      The 35th Annual European Association of Urology Congress
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Prognostic impact of phosphatidylinositol phosphate and its associated enzyme levels in patients with renal cell carcinoma treated surgically2020

    • Author(s)
      Shintaro Narita
    • Organizer
      The 115th Annual Meeting of the American Urological Association
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Short-term outcomes of risk-adapted upfront docetaxel administration in patients with metastatic hormone-sensitive prostate cancer: a multicenter prospective study in Japan.2020

    • Author(s)
      Shintaro Narita
    • Organizer
      第58回日本癌治療学会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2022-12-28  

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