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Effect of ectopically synthesized coagulation factor VII on venous thromboembolism and malignancy

Research Project

Project/Area Number 18K08346
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionKanagawa Cancer Center Research Institute

Principal Investigator

Koizume Shiro  地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), その他部局等, 副技幹・主任研究員 (60416063)

Co-Investigator(Kenkyū-buntansha) 宮城 洋平  地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), 臨床研究所, 所長 (00254194)
河内 利賢  日本大学, 医学部, 助教 (10328205)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords血栓塞栓症 / がん / 静脈血栓塞栓症 / がん関連血栓塞栓症 / 癌
Outline of Final Research Achievements

In this study, we examined effect of ectopically synthesized coagulation factor VII on cancer-associated thromboembolism (CAT) and malignancy. Cancer cells derived from CAT-prone cancer-types were transfected with FVII. Effect of FVII expression on cell proliferation, secretion of extracellular vesicles (EVs), and blood coagulation activity of EVs were tested. We found that FVII enhances EVs shedding and coagulation activity. We further performed immunohistochemistry of FVII using tissue specimen surgically removed from ovarian cancer patients. Relationship between FVII level and prognosis of patients were statistically evaluated.

Academic Significance and Societal Importance of the Research Achievements

がん関連血栓塞栓症はがんの主要な合併症であり、がん患者死因のおよそ一割を占める。しかしながら現在その発症予測は困難である。本研究により異所発現性血液凝固第7因子(FVII)ががん細胞より放出される細胞外小胞の血液凝固活性を増強させることを明らかにした。さらにFVIIのがん血栓塞栓症発症への役割を明らかにし、それを指標に血栓塞栓症発症の予測が可能となれば、がんの予後改善に繋が河ることが期待される。

Report

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

    (15 results)

All 2021 2020 2019 2018 Other

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (10 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Tissue factor pathway inhibitor 2 is specifically expressed in ovarian clear cell carcinoma tissues in the nucleus, cytoplasm and extracellular matrix2021

    • Author(s)
      Yukihide Ota, Shiro Koizume, Yoshiyasu Nakamura, Mitsuyo Yoshihara, Tomoko Takahashi, Shinya Sato, Shohei Myoba, Norihisa Ohtake, Hisamori Kato, Tomoyuki Yokose, Etsuko Miyagi, Yohei Miyagi
    • Journal Title

      Oncology Reports

      Volume: 45 Issue: 3 Pages: 1023-1032

    • DOI

      10.3892/or.2021.7944

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Drug screening Pelizaeus-Merzbacher disease by quantifying the total levels and membrane localization of PLP12019

    • Author(s)
      Kouga T, Koizume S, Aoki S, Jimbo E, Yamagata T, Inoue K, Osaka H.
    • Journal Title

      Mol Genet Metab Rep

      Volume: 20 Pages: 100474-100474

    • DOI

      10.1016/j.ymgmr.2019.100474

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cholesterol Starvation and Hypoxia Activate the FVII Gene via the SREBP1-GILZ Pathway in Ovarian Cancer Cells to Produce Procoagulant Microvesicles2019

    • Author(s)
      Koizume S, Takahashi T, Yoshihara M, Nakamura Y, Ruf W, Takenaka K, Miyagi E, and Miyagi Y.
    • Journal Title

      Thromb. Haemost.

      Volume: 印刷中 Issue: 07 Pages: 1058-1071

    • DOI

      10.1055/s-0039-1687876

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Hypoxia-driven CD69 synthesis enhances ovarian clear cell carcinoma cell survival via integrin-fibronectin interaction2020

    • Author(s)
      小井詰 史朗、太田 幸秀、中村 圭靖、吉原光代、佐藤 慎哉、横瀬智之、宮城悦子、宮城洋平
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Tissue factor pathway inhibitor-2 (TFPI-2) is a novel immunohistochemical biomarker in ovarian clear cell carcinoma.2020

    • Author(s)
      太田 幸秀、小井詰 史朗、佐藤 慎哉、中村 圭靖、宮城 悦子、宮城 洋平
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 胆道癌における血栓塞栓症リスクと血液中の組織因子との関連解析2019

    • Author(s)
      小井詰 史朗、小林 智、高橋 朋子、森本 学、上野 誠、宮城 洋平
    • Organizer
      第2回 日本腫瘍循環器学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 膵癌患者の血液中組織因子による血栓塞栓症発症予測2019

    • Author(s)
      小林 智、小井詰 史朗、上野 誠、宮城 洋平、森本 学
    • Organizer
      第2回 日本腫瘍循環器学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] HIF1 and SREBP1 collaborate to induce GILZ expression to produce procoagulant microvesicles in ovarian cancer cells2019

    • Author(s)
      小井詰 史朗、中村 圭靖、吉原光代、宮城 悦子、竹中 克也、宮城 洋平
    • Organizer
      第78回 日本癌学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Cancer progression by an enzyme expression under serum starvation and hypoxia2019

    • Author(s)
      竹中 克也、小森 由香子、中村 圭靖、小井詰 史朗、宮城 洋平
    • Organizer
      第78回 日本癌学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 低酸素、血清除去環境に暴露された卵巣癌細胞におけるCD69発現依存的タンパク質リン酸化の解析2018

    • Author(s)
      小井詰史朗、金山知彦、岡山明子、木村弥生、宮城洋平
    • Organizer
      第27回 日本癌転移学会学術集会・総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Ectopic synthesis of CD69 is important for intra-peritoneal survival of ovarian clear cell carcinoma cells2018

    • Author(s)
      小井詰史朗、中村圭靖、吉原光代、竹中克也、宮城洋平
    • Organizer
      第77回 日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Expression of an ATP-grasp superfamily enzyme under hypoxia2018

    • Author(s)
      竹中克也、小森由香子、中村圭靖、小井詰史朗、宮城洋平
    • Organizer
      第77回 日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 膵臓癌における血栓塞栓症リスクと血液中の組織因子との関連解析2018

    • Author(s)
      小井詰史朗、小林智、高橋朋子、森本学、上野誠、宮城洋平
    • Organizer
      第1回 日本腫瘍循環器学会学術集会
    • Related Report
      2018 Research-status Report
  • [Book] 腫瘍循環器学の現況と展望 クリニカルトピック・組織因子の機能調節メカニズム in BIO Clinica, 2019, vol 34, No. 102019

    • Author(s)
      小井詰史朗、宮城洋平
    • Total Pages
      6
    • Publisher
      北隆館
    • Related Report
      2019 Research-status Report
  • [Remarks] 神奈川県立がんセンター臨床研究所

    • URL

      http://kcch.kanagawa-pho.jp/kccri/index.html

    • Related Report
      2019 Research-status Report

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

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