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Search for blood and fecal microRNA biomarkers that can estimate acute exposure to intestinal death

Research Project

Project/Area Number 17K19779
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Society medicine, Nursing, and related fields
Research InstitutionHirosaki University

Principal Investigator

Chiba Mitsuru  弘前大学, 保健学研究科, 講師 (20583735)

Co-Investigator(Kenkyū-buntansha) 門前 暁  弘前大学, 保健学研究科, 講師 (20514136)
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords放射線被ばく / 腸管障害 / microRNA / 血清 / 糞便 / バイオマーカー / 腸管損傷 / 腸管死 / 血液
Outline of Final Research Achievements

Exposure to high-dose radiation causes life-threatening serious intestinal damage. Here we focused on extracellular microRNA released from cells and investigated microRNA species that increased or decreased in serum and feces using a radiation-induced intestinal injury mouse model. MiRNAs increased more than 2.0-fold in serum or feces following a 10 Gy radiation exposure were 21 in serum and 119 in feces by microarray analysis. In this study, miR-375-3p detected in serum and feces was identified as the strongest candidate for a high-dose radiation biomarker in serum and/or feces using a radiation-induced intestinal injury model.

Academic Significance and Societal Importance of the Research Achievements

被ばくによる死因が腸管損傷であるかどうかは,死後の病理組織学的診断にゆだねられており,存命中に腸管損傷の程度を客観的に評価することは困難となっている。本研究成果は血液や糞便といった採取上患者への負担の少ない生体検体を使用して,これまで不可能であった腸管損傷の程度の判断を行うものである。このようなアイディアはこれまでの放射線生物学分野にないもので,従来の生物学的被ばく線量評価法の方向性を変える非常に斬新な着想であるといえる。また,腸管損傷を予防・軽減するための放射線防護剤の効果を判断する評価指標にも利用できる可能性があり,本研究構想の実現は被ばく腸管損傷の診断や治療上に大きな意義を持っている。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (51 results)

All 2019 2018 2017

All Journal Article (16 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 16 results,  Open Access: 12 results,  Acknowledgement Compliant: 1 results) Presentation (35 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] Malondialdehyde: a urinary toxic biomarker for unexpected exposure to high-dose ionizing radiation2019

    • Author(s)
      Satoru Monzen, Mitsuru Chiba, Yasushi Mariya
    • Journal Title

      Rinsho Byori

      Volume: 67 Pages: 212-215

    • NAID

      40021862154

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Injured pancreatic β cells enhance the release of miR?375?3p into the extracellular space2019

    • Author(s)
      Chiba Mitsuru、Niiyama Ikumi、Uehara Haruka、Kuwata Haruka
    • Journal Title

      Experimental and Therapeutic Medicine

      Volume: 17 Pages: 2815-2820

    • DOI

      10.3892/etm.2019.7276

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 血液検体による放射線応答性マイクロRNAの探索2018

    • Author(s)
      千葉 満、門前 暁
    • Journal Title

      Cytometry Research

      Volume: 28

    • NAID

      130007378938

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 生物学的評価による放射線治療線量の最適化のための基礎的検討2018

    • Author(s)
      上野達也、門前暁、千葉満、細川洋一郎
    • Journal Title

      Cytometry Research

      Volume: 28

    • NAID

      130007378939

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 膵β細胞障害は細胞外miR-375-3pを増加させる2018

    • Author(s)
      新井山 育未,上原 悠花,桑田 遥,千葉 満
    • Journal Title

      Journal of Health Sciences Research

      Volume: 8

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 疾患バイオマーカーとしての体液中マイクロRNAの探索研究2018

    • Author(s)
      千葉 満
    • Journal Title

      臨床化学

      Volume: 47

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 細胞外小胞の細胞内への取り込み機構2018

    • Author(s)
      千葉 満、久保田 栞、門前 暁
    • Journal Title

      細胞

      Volume: 50 Pages: 267-270

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serum miR-375-3p increase in mice exposed to a high dose of ionizing radiation2018

    • Author(s)
      Chiba Mitsuru、Monzen Satoru、Iwaya Chihiro、Kashiwagi Yuri、Yamada Sunao、Hosokawa Yoichiro、Mariya Yasushi、Nakamura Toshiya、Wojcik Andrzej
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 1302-1302

    • DOI

      10.1038/s41598-018-19763-7

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exosomal natural antisense transcripts in culture supernatants released from colorectal cancer SW480 cells2018

    • Author(s)
      Mitsuru Chiba
    • Journal Title

      Biomedical Research

      Volume: 29

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] がん放射線療法における線量最適化のためのバイオマーカー探索2018

    • Author(s)
      上野 達也, 門前 暁, 千葉 満, 森野 友貴, 細川 洋一郎
    • Journal Title

      日本放射線技術学雑誌

      Volume: 74

    • NAID

      130006742922

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 緊急時放射線被ばく線量推定のための尿中バイオマーカー8-Hydroxy-2'-Deoxyguanosineの検討2018

    • Author(s)
      門前暁、多和田侑介、千葉満、高坂望美、森野友貴、山屋大樹、上野達也、Andrzej Wojcik
    • Journal Title

      Cytometry Research

      Volume: 28

    • NAID

      130007378932

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A radioresistant fraction of acute promyelocytic leukemia cells exhibit CD38 cell-surface antigen and mRNA expression2018

    • Author(s)
      Monzen Satoru、Chiba Mitsuru、Ueno Tatsuya、Morino Yuki、Terada Kenji、Yamaya Hiroki、Hosokawa Yoichiro
    • Journal Title

      Oncology Letters

      Volume: 15(5) Pages: 6709-6714

    • DOI

      10.3892/ol.2018.8099

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] がん細胞由来エキソソームの間質細胞への影響2017

    • Author(s)
      千葉満、門前暁
    • Journal Title

      細胞

      Volume: 49 Pages: 40-43

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anti-tumor and anti-invasion effects of a combination of 4-methylumbelliferone and ionizing radiation in human fibrosarcoma cells.2017

    • Author(s)
      Saga R, Monzen S, Chiba M, Yoshino H, Nakamura T, Hosokawa Y.
    • Journal Title

      Oncol Lett.

      Volume: 13(1) Issue: 1 Pages: 410-416

    • DOI

      10.3892/ol.2016.5385

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Anthocyanin-rich blackcurrant extract inhibits proliferation of the MCF10A healthy human breast epithelial cell line through induction of G0/G1 arrest and apoptosis2017

    • Author(s)
      Nanashima Naoki、Horie Kayo、Chiba Mitsuru、Nakano Manabu、Maeda Hayato、Nakamura Toshiya
    • Journal Title

      Molecular Medicine Reports

      Volume: 16 Issue: 5 Pages: 6134-6141

    • DOI

      10.3892/mmr.2017.7391

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antisense RNA transcripts in the blood may be novel diagnostic markers for colorectal cancer2017

    • Author(s)
      Tomohiro Kurokawa, Keisuke Kohno, Kentaro Nagai, Mitsuru Chiba, Sugiru Pak, Soichiro Murata, Kiyoshi Fukunaga, Hiroshi Yasue, Nobuhiro Ohkohchi
    • Journal Title

      Oncology Letters

      Volume: 14 Issue: 3 Pages: 3487-3493

    • DOI

      10.3892/ol.2017.6572

    • NAID

      120007134844

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Investigation of Urinary Metabolic Molecules for Radiation Biodosimetry and Its Functional Analysis2018

    • Author(s)
      Kenji Terada,Yusuke Tawata,Mitsuru Chiba, Yasushi Mariya,Satoru Monzen
    • Organizer
      第74回日本放射線技術学会総会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 膵β細胞傷害は細胞外miR-375-3pを増加させる2018

    • Author(s)
      千葉 満,門前 暁
    • Organizer
      第28回日本サイトメトリー学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 放射線被ばくマウスにおける造血細胞の変化と損傷2018

    • Author(s)
      森野友貴、千葉満、Wojcik Andrzej、門前暁
    • Organizer
      第28回日本サイトメトリー学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 高線量率被ばくマウスの骨髄中造血前駆細胞の損傷の特徴2018

    • Author(s)
      森野友貴、寺田賢司、佐藤孝徳、千葉満、WOJCIK Andrzej、門前暁
    • Organizer
      日本放射線影響学会第61回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 膵β細胞傷害はmiR-375-3pの細胞外への放出を増加させる2018

    • Author(s)
      千葉満、門前暁
    • Organizer
      日本放射線影響学会第61回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 急性放射線障害に対する医療技術の検討 ~骨髄障害の重症化軽減を目指して~2018

    • Author(s)
      森野 友貴, 千葉 満, Andrzej Wojcik, 真里谷 靖, 門前 暁
    • Organizer
      平成30年度放射線安全取扱部会年次大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 放射線治療における生物学的な情報を含めた線量の最適化のための基礎的検討2017

    • Author(s)
      上野達也、門前暁、千葉満、細川洋一郎
    • Organizer
      第73回日本放射線技術学会総会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 致死線量放射線被ばくバイオマーカーとしての血中循環microRNA2017

    • Author(s)
      千葉満、門前暁
    • Organizer
      第27回日本サイトメトリー学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 放射線被ばく線量推定のための尿中バイオマーカーの探索2017

    • Author(s)
      門前暁、多和田侑介、千葉満、高坂望美、森野友貴、山屋大樹、上野達也、Andrzej Wojcik
    • Organizer
      第27回日本サイトメトリー学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 生物学的評価による放射線治療線量の最適化のための基礎的検討2017

    • Author(s)
      上野達也、門前暁、千葉満、細川洋一郎
    • Organizer
      第27回日本サイトメトリー学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 放射線被ばくバイオマーカーとしての尿中8-OHdGの検討2017

    • Author(s)
      千葉満
    • Organizer
      第66回日本医学検査学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 子ども期の低線量放射線被ばくによる血中成分変化2017

    • Author(s)
      桑田 遥、上原 悠花、新井山 育未、千葉 満
    • Organizer
      第12回日本臨床検査学教育学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 急性被ばく腸管障害を予測できる血液・糞便中microRNAバイオマーカーの探索2017

    • Author(s)
      上原 悠花、桑田 遥、新井山 育未、千葉 満
    • Organizer
      第12回日本臨床検査学教育学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Serum microRNAs for early diagnosis of acute radiation syndrome2017

    • Author(s)
      Mitsuru Chiba, Satoru Monzen
    • Organizer
      第9回日本RNAi研究会・第4回日本細胞外小胞学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 膵β細胞障害は細胞外miR-375-3pを増加させる2017

    • Author(s)
      新井山 育未、上原 悠花、桑田 遥、千葉 満
    • Organizer
      第4回保健科学研究発表会
    • Related Report
      2017 Research-status Report
  • [Presentation] 放射線被ばくバイオマーカーとしての核酸代謝物の検討2017

    • Author(s)
      千葉 満
    • Organizer
      日本臨床検査自動化学会第49回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Serum microRNAs for early diagnosis of acute radiation syndrome2017

    • Author(s)
      Mitsuru Chiba, Satoru Monzen, Chihiro Iwaya, Yuri Kashiwagi, Sunao Yamada, Yoichiro Hosokawa, Yasushi Mariya, Toshiya Nakamura, and Andrzej Wojcik
    • Organizer
      4th Educational Symposium on RADIATION AND HEALTH by young scientists (ESRAH2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Radiosensitivity regulation in fibrosarcoma cells by anti-inflammatory agents2017

    • Author(s)
      Ryo Saga, Kosho Murata, Mitsuru Chiba, Natsu Shibata, Toshiya Nakamura, Yoichiro Hosokawa
    • Organizer
      4th Educational Symposium on RADIATION AND HEALTH by young scientists (ESRAH2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Optimization of radiotherapy using extracellular microRNA expression2017

    • Author(s)
      Tatsuya Ueno, Satoru Monzen, Mitsuru Chiba, Yoichiro Hosokawa
    • Organizer
      4th Educational Symposium on RADIATION AND HEALTH by young scientists (ESRAH2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Investigation of urinary metabolic molecules for radiation biodosimetry2017

    • Author(s)
      Kenji Terada, Yusuke Tawada, Mitsuru Chiba, Yasushi Mariya, Satoru Monzen
    • Organizer
      4th Educational Symposium on RADIATION AND HEALTH by young scientists (ESRAH2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Serum miR-375-3p as potential biomarkers of acute radiation syndrome in mice exposed to lethal dose2017

    • Author(s)
      Mitsuru Chiba
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Serum miR-375-3p as potential biomarkers of acute radiation syndrome in mice exposed to lethal dose2017

    • Author(s)
      千葉 満
    • Organizer
      第57回日本臨床化学会年次学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 子ども期の低線量放射線被ばくによる血中成分変化2017

    • Author(s)
      桑田 遥、上原 悠花、新井山 育未、千葉 満
    • Organizer
      第6回日臨技北日本支部医学検査学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 膵β細胞障害は細胞外miR-375-3pを増加させる2017

    • Author(s)
      新井山 育未、上原 悠花、桑田 遥、千葉 満
    • Organizer
      第6回日臨技北日本支部医学検査学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 急性被ばく腸管障害を予測できる血液・糞便中microRNAバイオマーカーの探索2017

    • Author(s)
      上原 悠花、桑田 遥、新井山 育未、千葉 満
    • Organizer
      第6回日臨技北日本支部医学検査学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Serum miR-375-3p as potential biomarkers of acute radiation syndrome in mice exposed to lethal dose2017

    • Author(s)
      千葉 満、門前 暁
    • Organizer
      日本放射線影響学会第60回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 尿中代謝産物に着目した放射線被ばくマーカーの探索2017

    • Author(s)
      寺田 賢司、多和田 侑介、千葉 満、真里谷 靖、門前 暁
    • Organizer
      日本放射線影響学会第60回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 放射線治療の線量最適化のための細胞外microRNA発現の利用検討2017

    • Author(s)
      上野達也、門前 暁、千葉 満、細川洋一郎
    • Organizer
      日本放射線影響学会第60回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] A biomarker of acute radiation syndrome: miR-375-3p increases in mouse serum by exposure to lethal/sublethal dose2017

    • Author(s)
      Mitsuru Chiba, Satoru Monzen, Yasushi Mariya
    • Organizer
      第29回世界病理臨床検査医学会連合会議(WASPaLM2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Urinary biomarkers of lethal/sublethal ionizing radiation doses2017

    • Author(s)
      Satoru Monzen, Mitsuru Chiba, Yasushi Mariya
    • Organizer
      第29回世界病理臨床検査医学会連合会議(WASPaLM2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 去勢抵抗性前立腺癌骨転移患者に対するRa-223内照射と腫瘍・骨代謝・酸化ストレスマーカーの経時的推移2017

    • Author(s)
      真里谷 靖、門前 暁、千葉 満
    • Organizer
      第64回日本臨床検査医学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 尿中代謝産物をバイオマーカーとした放射線被ばく影響の評価2017

    • Author(s)
      門前 暁、千葉 満、真里谷 靖
    • Organizer
      第64回日本臨床検査医学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 被ばくバイオマーカーとしての血中循環microRNAの検討2017

    • Author(s)
      千葉 満、門前 暁、真里谷 靖
    • Organizer
      第64回日本臨床検査医学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 尿中代謝物に着目した放射線被ばくの線量評価マーカーの探索2017

    • Author(s)
      門前 暁、寺田 賢司、多和田 侑介、真里谷 靖、千葉 満、Andrzej Wojcik
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Research-status Report
  • [Presentation] 急性放射線症候群の初期診断のための血清中マイクロRNA2017

    • Author(s)
      Mitsuru Chiba
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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