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Cell function control by plasma induced active particles -Academic foundation for safe plasma medicine-

Research Project

Project/Area Number 16K08914
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied pharmacology
Research InstitutionGifu Pharmaceutical University

Principal Investigator

ADACHI tetsuo  岐阜薬科大学, 薬学部, 教授 (40137063)

Co-Investigator(Kenkyū-buntansha) 原 宏和  岐阜薬科大学, 薬学部, 准教授 (30305495)
神谷 哲朗  岐阜薬科大学, 薬学部, 講師 (60453057)
Research Collaborator ISHIKAWA kenji  
TANAKA hiromasa  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsプラズマ / ストレス / 細胞内シグナル伝達 / 活性酸素 / シグナル伝達 / プラズマ医療 / 活性粒子 / エピジェネティクス
Outline of Final Research Achievements

In order to advance the application of plasma irradiation to medicine, this study aimed to elucidate the dynamics of cellular response to plasma-activated medium (PAM) load and to provide information that serves as a bridge to the clinical application of PAM. It was found that the OH radical generated intracellularly by PAM loading to A549 cancer cells destroyed ferritin and released the stored iron ion to further induce cell death. On the other hand, when mild PAM prepared under mild plasma irradiation conditions is loaded on normal cells, resistance against oxidative stress is obtained by the enhanced expression of the antioxidant enzyme HO-1 through activation of the Keap1-Nrf2 system. I clarified plasma-activated lactated Ringer's solution (PAL) prepared in place of PAM for administration to humans showed stronger A549 cytotoxicity than PAM.

Academic Significance and Societal Importance of the Research Achievements

近年、プラズマ照射の医療への応用が急速に進み、有意な効果が示されているものの、その効果を証明するメカニズムについては未解明な部分が多い。本研究の成果は、人体にプラズマを直接的に照射する必要がない「より安心で安全なプラズマ医療」の確立、それに対する社会や国民の理解に繋がると思われる。また、プラズマ照射物質(培地や輸液など)を事前に製造保管し必要時に医療施設に普遍的に供給できる可能性を示すもので、臨床現場のみならず,医薬品産業界への波及効果は計りし得ない。さらに、臨床使用に向けての展開研究は,プラズマ発生装置や関連機器の機能向上、低コスト化などにも繋がり関連の理工学産業界にも効果が波及する。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (34 results)

All 2019 2018 2017 2016 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (24 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Sublethal treatment with plasma-activated medium induces senescence-like growth arrest of A549 cells: Involvement of intracellular mobile zinc2019

    • Author(s)
      Hara H, Kobayashi M, Shiiba M, Kamiya T, Adachi T
    • Journal Title

      J. Clin. Biochem. Nutr. in press

      Volume: -

    • NAID

      130007672102

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Non-thermal atmospheric pressure plasma-induced IL-8 expression is regulated via intracellular K+ loss and subsequent ERK activation in human keratinocyte HaCaT cells2018

    • Author(s)
      Hotta E, Hara H, Kamiya T, Adachi T
    • Journal Title

      Arch. Biochem. Biophys.

      Volume: 644 Pages: 64-71

    • DOI

      10.1016/j.abb.2018.03.005

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhanced ability of plasma-activated lactated Ringer's solution to induce A549 cell injury2018

    • Author(s)
      Matsuzaki T, Kano A, Kamiya T, Hara H, Adachi T
    • Journal Title

      Arch. Biochem. Biophys.

      Volume: 656 Pages: 19-30

    • DOI

      10.1016/j.abb.2018.08.011

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Introduction to serial reviews: Biomedical application of non-thermal atmospheric pressure plasma and its usefulness2017

    • Author(s)
      Adachi T
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 60 Issue: 1 Pages: 1-2

    • DOI

      10.3164/jcbn.16-78

    • NAID

      130005188905

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Differences in intracellular mobile zinc levels affect susceptibility to plasma-activated medium-induced cytotoxicity2017

    • Author(s)
      Hara H, Sueyoshi S, Taniguchi M, Kamiya T, Adachi T
    • Journal Title

      Free Rad. Res.

      Volume: - Issue: 3 Pages: 1-10

    • DOI

      10.1080/10715762.2017.1309527

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cytoprotective effects of mild plasma-activated medium against oxidative stress in human skin fibroblasts2017

    • Author(s)
      Horiba M, Kamiya T, Hara H, Adachi T
    • Journal Title

      Sci. Rep.

      Volume: 7 Issue: 1 Pages: 42208-42208

    • DOI

      10.1038/srep42208

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Iron stimulates plasma-activated medium-induced A549 cell injury2016

    • Author(s)
      Adachi T, Nonomura S, Horiba M, Hirayama T, Kamiya T, Nagasawa H, HaraH
    • Journal Title

      Sci Reports

      Volume: 6 Issue: 1 Pages: 20928-20928

    • DOI

      10.1038/srep20928

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histone deacetylase inhibitors stimulate the susceptibility of A549 cells to a plasma-activated medium treatment2016

    • Author(s)
      Adachi T, Kano A, Nonomura S, Kamiya T, Hara H
    • Journal Title

      Arch. Biochem. Biophys.

      Volume: 606 Pages: 120-127

    • DOI

      10.1016/j.abb.2016.07.019

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] プラズマ照射培地とNAMPT阻害剤の併用によるがん細胞死増強作用2019

    • Author(s)
      長屋実咲,原 宏和,神谷哲朗,足立哲夫
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 大気圧低温プラズマのがん治療への応用2018

    • Author(s)
      足立哲夫
    • Organizer
      Biotech 2018
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] プラズマ照射培地による細胞増殖抑制機構-亜鉛依存性p53シグナルの関与-2018

    • Author(s)
      椎葉 萌,小林真理,原 宏和,神谷哲朗,足立哲夫
    • Organizer
      第64回日本薬学会東海支部大会
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Presentation] プラズマ照射培地によるA549細胞の細胞増殖抑制機構2018

    • Author(s)
      原 宏和,椎葉 萌,小林真理,神谷哲朗,足立哲夫
    • Organizer
      名大医薬系3部局交流シンポジウム~岐阜薬科大学・岐阜大学G-Chain・ラクオリア創薬合同シンポジウム~
    • Related Report
      2018 Annual Research Report
  • [Presentation] 低温大気圧プラズマ照射によるIL-8発現誘導における細胞内K+の関与2018

    • Author(s)
      原 宏和,堀田英美里,神谷哲朗,足立哲夫
    • Organizer
      日本酸化ストレス学会東海支部第6回学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] プラズマ照射乳酸リンゲル液負荷によるA549細胞の細胞傷害2018

    • Author(s)
      松崎 樹,神谷哲朗,原 宏和,足立哲夫
    • Organizer
      日本酸化ストレス学会東海支部第6回学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Contribution of Iintracellular Mobile Zinc to Anti-Cancer Effects of Plasma-Activated Medium2018

    • Author(s)
      Hirokazu Hara, Tetsuo Adachi
    • Organizer
      5th International Workshop on Plasma for Cancer Treatment
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] プラズマ照射培地によるA549細胞の細胞増殖抑制作用2018

    • Author(s)
      原 宏和,椎葉 萌,小林真理,神谷哲朗,足立哲夫
    • Organizer
      第71回日本酸化ストレス学会,第18回日本NO学会合同学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Intracellular Free Zinc Mediates Cellular Responses to PAM2017

    • Author(s)
      Hara H, Adachi T
    • Organizer
      The 1st International conference on plasma medical science innovation (ICPMSI2017)
    • Place of Presentation
      名古屋大学(愛知県、名古屋市)
    • Year and Date
      2017-02-27
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 大気圧プラズマ負荷に対するがん細胞応答機構2017

    • Author(s)
      原宏和,足立哲夫
    • Organizer
      日本薬学会第137年会
    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Invited
  • [Presentation] 大気圧プラズマを利用したがん治療の分子基盤の確立2017

    • Author(s)
      原 宏和,神谷哲朗,足立哲夫
    • Organizer
      名古屋大学3部局シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] マイルドプラズマ照射培地を負荷したヒト線維芽細胞の酸化ストレス抵抗性の獲得2017

    • Author(s)
      足立哲夫,堀場美の里,神谷哲朗,原 宏和
    • Organizer
      第70回日本酸化ストレス学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] プラズマ照射培地に対する細胞感受性に及ぼす細胞内亜鉛の影響2017

    • Author(s)
      原 宏和,末吉紗也子,谷口美紘,神谷哲朗,足立哲夫
    • Organizer
      第70回日本酸化ストレス学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] プラズマ照射培地によるIL-1β発現制御機構2017

    • Author(s)
      國吉真子,福留早貴,神谷哲朗,原 宏和,足立哲夫
    • Organizer
      第63回日本薬学会東海支部大会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒト表皮角化細胞株HaCaT細胞における大気圧低温プラズマ照射によるIL-8発現誘導2017

    • Author(s)
      堀田英美里,原 宏和,神谷哲朗,足立哲夫
    • Organizer
      生命科学系学会合同年次大会2017
    • Related Report
      2017 Research-status Report
  • [Presentation] プラズマ照射に対する細胞応答の分子機構2016

    • Author(s)
      堀場美の里,加納綾女,神谷哲朗,原 宏和,足立哲夫
    • Organizer
      新学術領域「プラズマ医療科学の創成」全体会議
    • Place of Presentation
      大宰府館(福岡県、大宰府市)
    • Year and Date
      2016-12-23
    • Related Report
      2016 Research-status Report
  • [Presentation] プラズマ照射培地負荷によるがん細胞死に対するヒストン脱アセチル化酵素阻害剤の増強効果2016

    • Author(s)
      加納綾女,野々村早帆,神谷哲朗,原 宏和,足立哲夫
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2016
    • Place of Presentation
      長良川国際会議場(岐阜県、岐阜市)
    • Year and Date
      2016-10-30
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒト表皮角化細胞HaCaTにおけるプラズマ照射によるIL-8発現誘導機構2016

    • Author(s)
      堀田英美里,原 宏和,神谷哲朗,足立哲夫
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2016
    • Place of Presentation
      長良川国際会議場(岐阜県、岐阜市)
    • Year and Date
      2016-10-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Intracellular Free Zinc Plays an Important Role in Plasma-Activated Medium-Induced Cell Death2016

    • Author(s)
      Hara H, Taniguchi M, Kobayasi K, Sueyoshi S, Kamiya T, Adachi T
    • Organizer
      6th International Conference on Plasma Medicine (ICPM-6)
    • Place of Presentation
      Bratislava (Slovakia)
    • Year and Date
      2016-09-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒストン脱アセチル化酵素阻害剤はがん細胞のプラズマ照射培地に対する感受性を増強する2016

    • Author(s)
      足立哲夫,加納綾女,野々村早帆,神谷哲朗,原 宏和
    • Organizer
      第69回日本酸化ストレス学会学術集会
    • Place of Presentation
      仙台国際センター(宮城県、仙台市)
    • Year and Date
      2016-08-30
    • Related Report
      2016 Research-status Report
  • [Presentation] プラズマ照射培地より惹起されるA549細胞増殖抑制における細胞内亜鉛の関与2016

    • Author(s)
      小林真理,原 宏和,末吉紗也子,神谷哲朗,足立哲夫
    • Organizer
      第62回日本薬学会東海支部大会
    • Place of Presentation
      愛知学院大学(愛知県、名古屋市)
    • Year and Date
      2016-07-02
    • Related Report
      2016 Research-status Report
  • [Presentation] ホルボールエステル誘導性の炎症反応に対するプラズマ照射培地の影響2016

    • Author(s)
      福留早貴,國吉真子,神谷哲朗,原宏和,足立哲夫
    • Organizer
      第62回日本薬学会東海支部大会
    • Place of Presentation
      愛知学院大学(愛知県、名古屋市)
    • Year and Date
      2016-07-02
    • Related Report
      2016 Research-status Report
  • [Presentation] プラズマ照射培地による細胞傷害と細胞内亜鉛動態の関連性2016

    • Author(s)
      末吉紗也子, 原 宏和, 谷口美紘, 神谷哲朗, 足立哲夫
    • Organizer
      日本生化学会中部支部例会・シンポジウム
    • Place of Presentation
      三重大学(三重県、津市)
    • Year and Date
      2016-05-21
    • Related Report
      2016 Research-status Report
  • [Presentation] プラズマ照射に対する細胞応答ダイナミクス2016

    • Author(s)
      足立哲夫,野々村早帆,堀場美の里,神谷哲朗,原 宏和
    • Organizer
      名古屋大学「プラズマ科学プラットフォーム」開所記念講演会
    • Place of Presentation
      名古屋大学(愛知県、名古屋市)
    • Year and Date
      2016-04-26
    • Related Report
      2016 Research-status Report
  • [Book] Plasma Medical Science, Chapter 3-5, Molecular Mechanism of Cellular Responses to Nonthermal Plasma2018

    • Author(s)
      Adachi T
    • Total Pages
      458
    • Publisher
      Academic Press
    • ISBN
      9780128150047
    • Related Report
      2018 Annual Research Report
  • [Remarks] 岐阜薬科大学臨床薬剤学研究室ホームページ

    • URL

      http://www.gifu-pu.ac.jp/lab/rinyaku/

    • Related Report
      2018 Annual Research Report 2017 Research-status Report 2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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