プラズマによるゲノム応答生物学の確立と治療への展開

• Project Area: Plasma medical innovation
• Project/Area Number: 25108503
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: University of Toyama
• Principal Investigator: 近藤 隆 富山大学, 大学院医学薬学研究部(医学), 教授 (40143937)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000); Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 大気圧プラズマ / 活性酸素種 / 放射線 / アポトーシス / 遺伝子発現 / OHラジカル / イオン化エネルギー / スピン捕捉法

Outline of Annual Research Achievements

大気圧低温プラズマと細胞との相互作用について、気相・液相・細胞の各水準で生成する活性種を検討し、その定量的評価を実施した。次に放射線を指標として、細胞内外に生成する活性酸素量を比較した。 また、Arプラズマに窒素を添加した場合の生物影響を調べた。
水溶液中の活性種はEPR-スピン捕捉法によるラジカル種の測定を行い、OHラジカルおよびH原子を同定した。Arプラズマ照射ではヒトリンパ腫細胞株のU937のアポトーシスを指標にし、15％水準で比較した時、放射線に比べて、約30倍多いOHラジカルが水溶液中に生成した。核酸やアミノ酸等のラジカル付加体の測定からも、プラズマによるOHラジカル生成が重要であることが判明した。また、細胞内に生成する活性種をフローサイトメータで調べたところ、プラズマ照射細胞内にOHラジカル、OCl-、過酸化水素の生成を認めた。スーパーオキシド生成も認めたが僅かであった。Arプラズマに窒素を添加した場合、水溶液中のOHラジカル生成は半減し、細胞死も抑制された。網羅的遺伝子解析を行ったところ、熱ショックタンパク質遺伝子を主とする細胞保護遺伝子の発現増加を認めた。
以上より、Arプラズマ照射は細胞外に相対的に多くのOHラジカルを生成するが、細胞内においては、二次的に生成する活性種が重要と思われる。今後は、目的に応じたプラズマ照射の最適化を図るために用量の測定法を確立する必要がある。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Isofraxidin, a potent reactive oxygen species (ROS) scavenger, protects human leukemia cells from radiation-induced apoptosis via ROS/mitochondria pathway in p53-independent manner (2014)
  • Author(s): Li P., Zhao Q. L., Wu L. H., Jawaid P., Jiao Y. F., Kadowaki M., Kondo T.
  • Journal Title: Apoptosis Volume: 19 Issue: 6 Pages: 1043-1053
  • DOI: 10.1007/s10495-014-0984-1
  • Peer Reviewed
• [Journal Article] Effects of SOD/catalase mimitic platinum nanoparticles on radiation-induced apoptosis in human lymphoma U937 cells (2014)
  • Author(s): Jawaid P et al.
  • Journal Title: Apoptosis Volume: 19 Issue: 6 Pages: 1006-1016
  • DOI: 10.1007/s10495-014-0972-5
  • Peer Reviewed
• [Journal Article] A microRNA-27a mimic sensitizes human oral squamous cell carcinoma HSC-4 cells to hyperthermia through down-regulation of Hsp110 and Hsp90 (2014)
  • Author(s): Kariya A et al.
  • Journal Title: Int J Mol Med Volume: 34 Issue: 1 Pages: 334-340
  • DOI: 10.3892/ijmm.2014.1758
  • Peer Reviewed
• [Journal Article] Molecular mechanisms of hyperthermia-induced apoptosis enhanced by docosahexaenoic acid: Implication for cancer therapy. (2014)
  • Author(s): Cui ZG, Piao JL, Kondo T, Ogawa R, Tsuneyama K, Zhao QL, Feril LB Jr, Inadera H.
  • Journal Title: Chem Biol Interact Volume: in press Pages: 46-53
  • DOI: 10.1016/j.cbi.2014.03.005
  • Peer Reviewed
• [Journal Article] Effects of therpeutic ultrasound on the nucleus and genomic DNA (2014)
  • Author(s): Furusawa Y et al.
  • Journal Title: Ultrason Sonochem Volume: 21 Issue: 6 Pages: 2061-2068
  • DOI: 10.1016/j.ultsonch.2014.02.028
  • Peer Reviewed
• [Journal Article] Common gene expression patterns responsive to mild temperature hyperthermia in normal human fibroblastic cells. (2013)
  • Author(s): Tabuchi Y, Furusawa Y, Kariya A, Wada S, Ohtsuka K, Kondo T.
  • Journal Title: Int J Hyperthermia Volume: 29 Issue: 1 Pages: 38-50
  • DOI: 10.3109/02656736.2012.753163
  • Peer Reviewed
• [Journal Article] Inactivation of DNA-dependent protein kinase promotes heat-induced apoptosis independently of heat-shock protein induction in human cancer cell lines (2013)
  • Author(s): Okazawa S, Furusawa Y, Kariya A,Hassan MA, Arai M, Hayashi R, TabuchiY, Kondo T, Tobe K
  • Journal Title: PLos One Volume: 8(3) Issue: 3 Pages: e58325-e58325
  • DOI: 10.1371/journal.pone.0058325
  • Peer Reviewed
• [Journal Article] Genes responsive to low-intensity pulsed ultrasound in MC3T3-E1 preosteoblast cells (2013)
  • Author(s): Tabuchi Y, Sugahara Y, Ikegame M, Suzuki N, Kitamura K, Kondo T
  • Journal Title: Int. J. Mol. Sci Volume: Vol.14,No.11 Issue: 11 Pages: 22721-22740
  • DOI: 10.3390/ijms141122721
  • Peer Reviewed
• [Journal Article] TAK1 promotes cell survival by TNFAIP3 and IL-8 dependent and NF-κB independent pathway in HeLa cells exposed to heat stress. (2013)
  • Author(s): Li P, Furusawa Y, Wei ZL, Sakurai H, Tabuchi Y, Zhao QL, Saiki I, Kondo T.
  • Journal Title: Int J Hyperthermia. Volume: 29 Issue: 7 Pages: 688-695
  • DOI: 10.3109/02656736.2013.828104
  • Peer Reviewed
• [Journal Article] The molecular mechanisms and gene expression profiling for shikonin-induced apoptotic and necroptotic cell death in U937 cells (2013)
  • Author(s): Piao J. L., Cui Z. G., Furusawa Y., Ahmed K., Rehman M. U., Tabuchi Y., Kadowaki M., Kondo T.
  • Journal Title: Chemico-Biological Interactions Volume: 205 Issue: 2 Pages: 119-127
  • DOI: 10.1016/j.cbi.2013.06.011
  • Peer Reviewed
• [Journal Article] Identification of common gene networks responsive to mild hyperthermia in human cancer cells (2013)
  • Author(s): Kariya A, Tabuchi Y, Yunoki T, Kondo T
  • Journal Title: Int. J. Mol. Med Volume: Vol.32,No.1 Issue: 1 Pages: 195-202
  • DOI: 10.3892/ijmm.2013.1366
  • Peer Reviewed
• [Journal Article] Regulation of gene expression in human prostate cancer cells with artificially constructed promoters that are activated in response to ultrasound stimulation (2012)
  • Author(s): Ogawa R., A. Morii, A. Watanabe, Z. G. Cui, G. Kagiya, T. Kondo, N. Doi, L. B. Feril
  • Journal Title: Ultrason Sonochem Volume: 20 Issue: 1 Pages: 460-467
  • DOI: 10.1016/j.ultsonch.2012.05.007
  • Peer Reviewed
• [Presentation] Inhibiting heat shock transcription facor 1 and its related genes for novel hyperthermia therapy. Symposium 2 Impact of HSPs-Revisit &Perspective- (2014)
  • Author(s): Tabuchi Y et al.
  • Organizer: The 6th Asian Congress of Hyperthermic Oncology & the 31st Japanease Congress of Thermal Medicine
  • Place of Presentation: Fukui
  • Year and Date: 2014-09-05 – 2014-09-06
  • Invited
• [Presentation] Spiuchostatin-B, a nevel histone deacyltylase inhibitor enhanced apoptosis induced by hyperthermia. Workshop 2 Hyperthermia Up to Date in Asia-Clinical Case Reports and Biology- (2014)
  • Author(s): Rehman MU et al.
  • Organizer: The 6ht Asian Congress of Hyperthermic Oncology & the 31st Japanease Congress of Thermal Medicine,
  • Place of Presentation: Fukui
  • Year and Date: 2014-09-05 – 2014-09-06
• [Presentation] 大気圧プラズマによる細胞内外の活性酸素生成-EPR-スピン捕捉法およびフローサイトメトリーによる検討- (2014)
  • Author(s): 近藤 隆 他
  • Organizer: 第67回日本酸化ストレス学会
  • Place of Presentation: 京都
  • Year and Date: 2014-09-04 – 2014-09-05
• [Presentation] Free radical generation by cold atmospheric argon plasma in aqueous solutions. An ESR spin trapping ttudy. (2014)
  • Author(s): Uchiyama H et al.
  • Organizer: 5th Iternational Congress of Plasma Medicine
  • Place of Presentation: Nara
  • Year and Date: 2014-05-18 – 2014-05-21
• [Presentation] The biological and sonochemical effects of microbubbles. Impact of formulation. (2014)
  • Author(s): Hassan MA et al.
  • Organizer: The 6th Asian Conference on Ultrasound Contrast Imaging
  • Place of Presentation: Yokohama
  • Year and Date: 2014-05-10
  • Invited
• [Presentation] Roles of intracellular oxidative stress in DNA damage and apoptosis induced by different physical stressors; ultrasound, hyperthermia and ionizing radiation (2013)
  • Author(s): Kondo T, Hassan MA, Zhao QL, Ogawa R, Tabuchi Y, and Furusawa Y
  • Organizer: 1st Asia-Oceania Sonochemical Society Meeting
  • Place of Presentation: Melbourne
  • Invited
• [Presentation] DNA double strand breaks induced by ultrasound and DNA damage responce (2013)
  • Author(s): Kondo T, Hassan MA, Zhao QL, Ogawa R, Tabuchi Y, and Furusawa Y
  • Organizer: International Conference of Biomedical Ultrasound
  • Place of Presentation: Ｔａｉｐｅｉ
• [Presentation] Arbutin protects ionizing radiation-induced apoptosis in U937 cells (2013)
  • Author(s): Li P, Wu LH, Jiao YF, Zhao QL, KondoT
  • Organizer: The 3rd Asian Congress of Radiation Reserach
  • Place of Presentation: Beijin,
• [Presentation] Tempo enhanced radiation- or heat- induced apoptosis (2013)
  • Author(s): Zhao QL, Fuijiwara Y, KondoT
  • Organizer: The 3rd Asian Congress of Radiation Reserach
  • Place of Presentation: Beijin
• [Presentation] Identification of gene networks involved in apoptosis induced by low-intensity pulsed ultrasound in human lyphoma U937 cells (2013)
  • Author(s): Yunoki T, Tabuchi Y, and Kondo T
  • Organizer: International Conference of Biomedical Ultrasound
  • Place of Presentation: Taipei
• [Book] 酸化ストレスの医学, 改訂第２版 (2014)
  • Author(s): 近藤 隆, 櫻井宏明, 田渕圭章
  • Total Pages: 8
  • Publisher: 診断と治療社
• [Book] Cellular Response to Physical Stress and Therapeutic Applications (2013)
  • Author(s): KondoT
  • Total Pages: 14
  • Publisher: Nova Science Publishers
• [Remarks] 富山大学大学院医学薬学研究部（医学）放射線基礎医学講座
  • URL: http://www.med.u-toyama.ac.jp/radsci/index.html
• [Remarks] 富山大学大学院医学薬学研究部（医学）放射線基礎医学講座
  • URL: http://www.med.u-toyama.ac.jp/radsci/admission.html