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Cellular and molecular mechanism of blood sludging/skimming. Causative role of cancer exosomes and their pathophysiological view points

Research Project

Project/Area Number 18K19587
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionKagoshima University

Principal Investigator

MARUYAMA Ikuro  鹿児島大学, 医歯学総合研究科, 特任教授 (20082282)

Co-Investigator(Kenkyū-buntansha) 山口 宗一  鹿児島大学, 医歯学域医学系, 准教授 (20325814)
原田 陽一郎  地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 糖鎖オンコロジー部主任研究員 (80464147)
伊藤 隆史  鹿児島大学, 医歯学総合研究科, 講師 (20381171)
山本 美佳  鹿児島大学, 医歯学総合研究科, 特任研究員 (70791507)
Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords血流動態異常 / Skimming / Sludging / T-TAS / 血栓・塞栓 / 出血 / 血漿成分 / 血球成分 / Exosome / Cancer Procoagulant / DIC / Thrombosis / Thrombomodulin / Trousseau syndrome / blood skimming / blood sludging / エクソソーム / 癌 / 血栓塞栓症 / 第Ⅶ因子 / 組織因子 / Blood skimming / Blood sludging / Thrombomodulin(TM) / exosome / sludging / skimming / shock
Outline of Final Research Achievements

We have previous created a total-Thrombus-Formation Analysis system(T-TAS), as a pre-, and prothrombotic states diagnostic instrument. This enabled that blood thrombotic ability not only by quantitatively but also qualitatively with the visualization of clot forming dynamics. under the microscope. Using this, we showed that blood skimming/sludging as a novel circulatory abnormality besides thrombosis/embolism and bleeding. The blood skimming is a rapid blood flow like as a skimmed liquid. The sludging flow is a peripheral flow of the red blood-rich fraction. Thus, we defined this blood flow with a skimming/sludging as a novel abnormal flow beside thrombosis/embolism and bleeding. These novel types of abnormal blood flow might play roles for such blood disturbances as shock, DIC, dehydration and so on.

Academic Significance and Societal Importance of the Research Achievements

血液の円滑な循環はダイナミックな生命活動の最重点基盤機能で、その異常病態は「血栓・塞栓」と「出血」であり循環領域最大のテーマである。本研究では申請者らが共同開発したTotal Thrombus Formation Analysis System(T-TAS)を用い、”Blood sludging, skimming” について研究した。この病的循環動態はこれまでも知られていたが、T-TAS 法で初めて可視化され、定量・定性的解析と診断が可能となった。この”Blood sludging, skimming(血流の上清化と泥流化)”は、血栓・塞栓、出血と並び、新たな血流動態の異常であると結論した。

Report

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

    (17 results)

All 2020 2019 2018

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 14 results,  Open Access: 12 results) Presentation (2 results) (of which Invited: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Leukocyte-derived extracellular DNA contributes to abnormal pressure elevation in the extracorporeal circulation circuit2020

    • Author(s)
      Yashima Nozomi、Ito Takashi、Kajiyama Kenji、Maeda Hiroyuki、Kakihana Yasuyuki、Maruyama Ikuro
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1

    • DOI

      10.1038/s41598-019-57173-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum histone H3 levels and platelet counts are potential markers for coagulopathy with high risk of death in septic patients: a single-center observational study2019

    • Author(s)
      Ito Takashi、Totoki Takaaki、Yokoyama Yayoi、Yasuda Tomotsugu、Furubeppu Hiroaki、Yamada Shingo、Maruyama Ikuro、Kakihana Yasuyuki
    • Journal Title

      Journal of Intensive Care

      Volume: 7 Issue: 1 Pages: 63-63

    • DOI

      10.1186/s40560-019-0420-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recombinant Thrombomodulin Suppresses Histone-Induced Neutrophil Extracellular Trap Formation2019

    • Author(s)
      Shrestha Binita、Ito Takashi、Kakuuchi Midori、Totoki Takaaki、Nagasato Tomoka、Yamamoto Mika、Maruyama Ikuro
    • Journal Title

      Frontiers in Immunology

      Volume: 10 Pages: 2535-2535

    • DOI

      10.3389/fimmu.2019.02535

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of glycemic control and hypoglycemia on Thrombus formation assessed using automated microchip flow chamber system: an exploratory observational study.2019

    • Author(s)
      Yamamoto K, Ito T, Nagasato T, Shinnakasu A, Kurano M, Arimura A, Arimura H, Hashiguchi H, Deguchi T, Maruyama I, Nishio Y.
    • Journal Title

      Thromb J.

      Volume: 17 Issue: 1

    • DOI

      10.1186/s12959-019-0206-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunological evidence for in vivo production of novel advanced glycation end-products from 1,5-anhydro-D-fructose, a glycogen metabolite2019

    • Author(s)
      Sakasai-Sakai Akiko、Takata Takanobu、Suzuki Hirokazu、Maruyama Ikuro、Motomiya Yoshihiro、Takeuchi Masayoshi
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 10194-10194

    • DOI

      10.1038/s41598-019-46333-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Application of high-mannose-type glycan-specific lectin from Oscillatoria Agardhii for affinity isolation of tumor-derived extracellular vesicles2019

    • Author(s)
      Yamamoto Mika、Harada Yoichiro、Suzuki Takehiro、Fukushige Tomoko、Yamakuchi Munekazu、Kanekura Takuro、Dohmae Naoshi、Hori Kanji、Maruyama Ikuro
    • Journal Title

      Analytical Biochemistry

      Volume: 580 Pages: 21-29

    • DOI

      10.1016/j.ab.2019.06.001

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamics of Soluble Thrombomodulin and Circulating miRNAs in Patients with Atrial Fibrillation Undergoing Radiofrequency Catheter Ablation2019

    • Author(s)
      Namino F, Yamakuchi M, Iriki Y, Okui H, Ichiki H, Maenosono R, Oketani N, Masamoto I, Miyata M, Horiuchi M, Hashiguchi T, Ohishi M, Maruyama I
    • Journal Title

      Clin Appl Thromb Hemost

      Volume: 25 Pages: 107602961985157-107602961985157

    • DOI

      10.1177/1076029619851570

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] N‐glycome inheritance from cells to extracellular vesicles in B16 melanomas2019

    • Author(s)
      Harada Yoichiro、Kizuka Yasuhiko、Tokoro Yuko、Kondo Kiyotaka、Yagi Hirokazu、Kato Koichi、Inoue Hiromasa、Taniguchi Naoyuki、Maruyama Ikuro
    • Journal Title

      FEBS Letters

      Volume: 印刷中 Issue: 9 Pages: 942-951

    • DOI

      10.1002/1873-3468.13377

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of the heterogeneity of extracellular vesicles by membrane organization and sorting machineries2019

    • Author(s)
      Harada Yoichiro、Suzuki Takehiro、Fukushige Tomoko、Kizuka Yasuhiko、Yagi Hirokazu、Yamamoto Mika、Kondo Kiyotaka、Inoue Hiromasa、Kato Koichi、Taniguchi Naoyuki、Kanekura Takuro、Dohmae Naoshi、Maruyama Ikuro
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - General Subjects

      Volume: 1863 Issue: 4 Pages: 681-691

    • DOI

      10.1016/j.bbagen.2019.01.015

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Circulating histone H3 levels in septic patients are associated with coagulopathy, multiple organ failure, and death: a single-center observational study2019

    • Author(s)
      Yokoyama Yayoi、Ito Takashi、Yasuda Tomotsugu、Furubeppu Hiroaki、Kamikokuryo Chinatsu、Yamada Shingo、Maruyama Ikuro、Kakihana Yasuyuki
    • Journal Title

      Thrombosis Journal

      Volume: 17 Issue: 1 Pages: 1-1

    • DOI

      10.1186/s12959-018-0190-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison between blood coagulability in the intra-atrial and peripheral regions during the acute phase after rapid atrial pacing2019

    • Author(s)
      Yamada S, Hirao D, Miura N, Iwanaga T, Kawaguchi T, Yoshimura A, Oomori T, Nagasato T, Maruyama I, Fukushima R
    • Journal Title

      Experimental Animals

      Volume: 68 Issue: 2 Pages: 137-146

    • DOI

      10.1538/expanim.18-0100

    • NAID

      130007642989

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating histone H3 levels are increased in septic mice in a neutrophil-dependent manner: preclinical evaluation of a novel sandwich ELISA for histone H32018

    • Author(s)
      Ito Takashi、Nakahara Mayumi、Masuda Yoshiki、Ono Sachie、Yamada Shingo、Ishikura Hiroyasu、Imaizumi Hitoshi、Kamikokuryo Chinatsu、Kakihana Yasuyuki、Maruyama Ikuro
    • Journal Title

      Journal of Intensive Care

      Volume: 6 Issue: 1 Pages: 79-79

    • DOI

      10.1186/s40560-018-0348-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating activated protein C levels are not increased in septic patients treated with recombinant human soluble thrombomodulin2018

    • Author(s)
      Arishima Takuro、Ito Takashi、Yasuda Tomotsugu、Yashima Nozomi、Furubeppu Hiroaki、Kamikokuryo Chinatsu、Futatsuki Takahiro、Madokoro Yutaro、Miyamoto Shotaro、Eguchi Tomohiro、Haraura Hiroyuki、Maruyama Ikuro、Kakihana Yasuyuki
    • Journal Title

      Thrombosis Journal

      Volume: 16 Issue: 1 Pages: 24-24

    • DOI

      10.1186/s12959-018-0178-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of chronological changes in blood characteristics in the atrium and peripheral vessels after the development of non-valvular atrial fibrilation2018

    • Author(s)
      Yamada S,Hirao D, Miura N, Iwanaga T, Kawaguchi T,Yoshimura A, Oomori T, Nagasato T, Maruyama I, Fukushima R
    • Journal Title

      Thrombosis Reserch

      Volume: 171 Pages: 31-37

    • DOI

      10.1016/j.thromres.2018.09.040

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 急性血液浄化の新視点:exosomeとRAMPMs2018

    • Author(s)
      丸山 征郎
    • Organizer
      第29回日本急性血液浄化学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 病態拡大の新しい使者:exosomeが参画した新しいショック病像2018

    • Author(s)
      丸山 征郎
    • Organizer
      第33回日本Shock学会総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] 癌の診断デバイス2018

    • Inventor(s)
      堀貫治、平山真、丸山征郎、田口好弘、黒川洋、水口博義、小林謙也
    • Industrial Property Rights Holder
      広島大学、鹿児島大学、アルプスアルパイン、京都モノテック
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-092557
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2021-02-19  

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