Cancer treatments using plasma activated liquids and elucidating the mechanisms

• Project/Area Number: 15H05430
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Plasma electronics
• Research Institution: Nagoya University
• Principal Investigator: Tanaka Hiromasa 名古屋大学, 未来社会創造機構, 特任講師 (00508129)
• Co-Investigator(Renkei-kenkyūsha): ISHIKAWA KENJI 名古屋大学, プラズマナノ工学研究センター, 特任教授 (60417384)
• Research Collaborator: NAKAMURA KAE 名古屋大学, 医学研究科, 研究員 ; KANO HIROYUKI NUエコエンジニアリング株式会社, 社長
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2016: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2015: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
• Keywords: プラズマ医療 / 癌治療 / プラズマがん治療

Outline of Final Research Achievements

Recently, medical applications using non-thermal atmospheric pressure plasmas have attracted attention in the field of medicine. We have developed non-thermal atmospheric pressure plasma sources, and applied for cancer therapy. We found anti-tumor effects by plasma treated medium, which we termed “plasma-activated medium or PAM”. In this study, we further developed plasma-activated Ringer’s lactate solution or PAL, and we found that plasma-treated L-sodium lactate is an anti-tumor factor in the PAL. Based on these results, we proposed that PAL is promising as a novel chemotherapy for cancers such as peritoneally disseminated cancers.

Research Products

• [Journal Article] Effects of OH and NO radicals in the aqueous phase on H2O2 and NO2- generated in plasma-activated medium (2017)
  • Author(s): Naoyuki Kurake, Hiromasa Tanaka, Kenji Ishikawa, Keigo Takeda, Hiroshi Hashizume, Kae Nakamura, Hiroaki Kajiyama, Takashi Kondo, Fumitaka Kikkawa, Masaaki Mizuno and Masaru Hori
  • Journal Title: J. Phys. D: Appl. Phys. Volume: 50 Issue: 15 Pages: 155201-155201
  • DOI: 10.1088/1361-6463/aa5f1d
  • Peer Reviewed
• [Journal Article] Intraperitoneal Administration of Plasma-Activated Medium: Proposal of a Novel Treatment Option for Peritoneal Metastasis From Gastric Cancer (2017)
  • Author(s): Shigeomi Takeda, Suguru Yamada, Norifumi Hattori, Kae Nakamura, Hiromasa Tanaka, Hiroaki Kajiyama, Mitsuro Kanda, Daisuke Kobayashi, Chie Tanaka, Tsutomu Fujii, Michitaka Fujiwara, Masaaki Mizuno, Masaru Hori, Yasuhiro Kodera
  • Journal Title: Annals of Surgical Oncology Volume: 24 Issue: 5 Pages: 1188-1194
  • DOI: 10.1245/s10434-016-5759-1
  • Peer Reviewed
• [Journal Article] Behavior of absolute densities of atomic oxygen in the gas phase near an object surface in an AC-excited atmospheric pressure He plasma jet (2017)
  • Author(s): Keigo Takeda Takumi Kumakura, Kenji Ishikawa, Hiromasa Tanaka3 Makoto Sekine Masaru Hori
  • Journal Title: Applied Physics Express Volume: 10 Issue: 3 Pages: 036201-036201
  • DOI: 10.7567/apex.10.036201
  • NAID: 210000135797
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Medical applications of non-thermal atmospheric pressure plasma (2017)
  • Author(s): Tanaka H, Hori M
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 60 Issue: 1 Pages: 29-32
  • DOI: 10.3164/jcbn.16-67
  • NAID: 130005188915
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Future perspective of strategic non-thermal plasma therapy for cancer treatment (2017)
  • Author(s): Kajiyama H, Utsumi F, Nakamura K, Tanaka H, Toyokuni S, Hori M, Kikkawa F
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 60 Issue: 1 Pages: 33-38
  • DOI: 10.3164/jcbn.16-65
  • NAID: 130005188914
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Synthesis of calcium oxalate crystals in culture medium irradiated with non-equilibrium atmospheric-pressure plasma (2016)
  • Author(s): N. Kurake., et. al.,
  • Journal Title: Applied Physics Express Volume: 9 Issue: 9 Pages: 096201-096201
  • DOI: 10.7567/apex.9.096201
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Non-Thermal atmospheric pressure plasma activated lactate in Ringer’s solution for anti-tumor effects (2016)
  • Author(s): H.Tanaka, K.Nakamura, M.Mizuno, K.Ishikawa, K.Takeda, h.Kajiyama, F.Utsumi, F.Kikkawa, M.Hori
  • Journal Title: Scientific Report Volume: 6 Issue: 1 Pages: 36282-36282
  • DOI: 10.1038/srep36282
  • Peer Reviewed / Open Access
• [Journal Article] Microfluidic Transport Through Microsized Holes Treated by Nonequilibrium Atmospheric-Pressure Plasma (2016)
  • Author(s): Takumi Ito, Kenji Ishikawa,Daisuke Onoshima, Naoto Kihara,Kentaro Tatsukoshi Hidefumi Odaka, Hiroshi Hashizume,Hiromasa Tanaka,Hiroshi Yukawa, Keigo Takeda Hiroki Kondo, Makoto Sekine, Yoshinobu Baba, Masaru Hori
  • Journal Title: IEEE Transactions on Plasma Science Volume: PP Issue: 12 Pages: 3060-3065
  • DOI: 10.1109/tps.2016.2571721
  • NAID: 120005981198
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Plasma-Activated Medium Selectively Eliminates Undifferentiated Human Induced Pluripotent Stem Cells (2016)
  • Author(s): R. Matsumoto, K. Shimizu, T. Nagashima, H. Tanaka, M. Mizuno, F. Kikkawa, M. Hori, and H. Honda
  • Journal Title: Regenerative Therapy Volume: 5 Pages: 55-63
  • DOI: 10.1016/j.reth.2016.07.001
  • Peer Reviewed
• [Journal Article] Non-thermal plasma prevents progression of endometriosis in mice (2016)
  • Author(s): C. Ishida, M. Mori, K. Nakamura, H. Tanaka, M. Mizuno, M. Hori, A. Iwase, F. Kikkawa, and S. Toyokuni
  • Journal Title: Free Radical Research Volume: 50 Issue: 10 Pages: 1131-1139
  • DOI: 10.1080/10715762.2016.1211273
  • NAID: 120005971254
  • Peer Reviewed
• [Journal Article] Possible therapeutic option of aqueous plasma for refractory ovarian cancer (2016)
  • Author(s): H. Kajiyama, F. Utsumi, K. Nakamura, H. Tanaka, M. Mizuno, S. Toyokuni, M. Hori, and F. Kikkawa
  • Journal Title: Clinical Plasma Medicine Volume: 4 Issue: 1 Pages: 14-18
  • DOI: 10.1016/j.cpme.2015.12.002
  • Peer Reviewed
• [Journal Article] Cell survival of glioblastoma grown in medium containing hydrogen peroxide and/or nitrite, or in plasma-activated medium (2016)
  • Author(s): Kurake N, Tanaka H, Ishikawa K, Kondo T, Sekine M, Nakamura K, Kajiyama Hi, Kikkaw F, Mizun M, Hori M
  • Journal Title: Arch Biochem Biophys Volume: 未定 Pages: 102-108
  • DOI: 10.1016/j.abb.2016.01.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Variable susceptibility of ovarian cancer cells to non-thermal plasma-activated medium. (2016)
  • Author(s): Utsumi F, Kajiyama H, Nakamura K, Tanaka H, Mizuno M, Toyokuni S, Hori M, Kikkawa F.
  • Journal Title: Oncol Rep. Volume: in press Issue: 6 Pages: 3169-3177
  • DOI: 10.3892/or.2016.4726
  • Peer Reviewed / Open Access
• [Journal Article] Biphasic effects of l-ascorbate on the tumoricidal activity of non-thermal plasma against malignant mesothelioma cells (2016)
  • Author(s): Shi L, Wang Y, Ito F, Okazaki Y, Tanaka H, Mizuno M, Hori M, Richardson DR, Toyokuni S
  • Journal Title: Arch. Biochem. Biophys. Volume: 605 Pages: 109-116
  • DOI: 10.1016/j.abb.2016.05.016
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effectiveness of plasma treatment on pancreatic cancer cells (2015)
  • Author(s): N. Hattori, S. Yamada, K. Torii, S. Takeda, K. Nakamura, H. Tanaka, H. Kajiyama, M. Kanda, T. Fujii, G. Nakayama, H. Sugimoto, M. Koike, S. Nomoto, M. Fujiwara, M. Mizuno, M. Hori, Y. Kodera
  • Journal Title: International journal of oncology Volume: 47 Issue: 5 Pages: 1655-1662
  • DOI: 10.3892/ijo.2015.3149
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Plasma with high electron density and plasma-activated medium for cancer treatment (2015)
  • Author(s): H. Tanaka, M. Mizuno, K. Ishikawa, H. Kondo, K. Takeda, H. Hashizume, K. Nakamura, F. Utsumi, H. Kajiyama, H. Kano, Y. Okazaki, S. Toyokuni, S. Akiyama, S. Maruyama, S. Yamada, Y. Kodera, H. Kaneko, H. Terasaki, H. Hara, T. Adachi, M. Iida, I. Yajima, M. Kato, F. Kikkawa, M. Hori
  • Journal Title: Clinical Plasma Medicine Volume: 3 Issue: 2 Pages: 72-76
  • DOI: 10.1016/j.cpme.2015.09.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cancer therapy using non-thermal atmospheric pressure plasma with ultra-highelectron density (2015)
  • Author(s): H. Tanaka, M. Mizuno, S. Toyokuni, S. Maruyama, Y. Kodera, H. Terasaki, T. Adachi, M. Kato, F. Kikkawa, M. Hori
  • Journal Title: Phys Plasmas Volume: 22 Issue: 12 Pages: 122004-122004
  • DOI: 10.1063/1.4933402
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Plasma-activated medium and Cancer (2016)
  • Author(s): H. Tanaka, M. Mizuno, K. Ishikawa, K. Takeda, H. Kondo, H. Hashizume, K. Nakamura, H. Kajiyama, H. Kano, Y. Okazaki, S. Toyokuni, S. Maruyama, F. Kikkawa, and M. Hori
  • Organizer: ICPM6
  • Place of Presentation: Slovak University of Technology
  • Year and Date: 2016-09-04
  • Int'l Joint Research / Invited
• [Presentation] ドライプロセスと医療 (2016)
  • Author(s): 田中 宏昌、堀 勝
  • Organizer: 夏季実習セミナー（II)“ドライプロセスの基礎と薄膜作製”
  • Place of Presentation: 千葉工業大学
  • Year and Date: 2016-08-25
  • Invited
• [Presentation] Plasma-activated medium as a novel cancer therapeutic approach (2016)
  • Author(s): H. Tanaka, M. Mizuno, F. Kikkawa, and M. Hori
  • Organizer: ISPB2016
  • Place of Presentation: BEXCO
  • Year and Date: 2016-08-21
  • Int'l Joint Research / Invited
• [Presentation] Plasma-Activated Medium and its Medical and Biological Applications (2016)
  • Author(s): H. Tanaka, M. Mizuno, F. Kikkawa, M. Hori
  • Organizer: 43rd IEEE International Conference on Plasma Science
  • Place of Presentation: Banff
  • Year and Date: 2016-06-19
  • Int'l Joint Research
• [Presentation] INTRACELLULAR MOLECULAR MECHANISMS OF CANCER CELL DEATH USING PLASMA-ACTIVATED MEDIUM (2016)
  • Author(s): Hiromasa Tanaka, Masaaki Mizuno, Kenji Ishikawa, Keigo Takeda, Hiroshi Hashizume, Kae Nakamura, Fumi Utsumi, Hiroaki Kajiyama, Hiroyuki Kano, Yasumasa Okazaki, Shinya Toyokuni, Shoichi Maruyama, Tetsuo Adachi, Hiroki Kaneko, Hiroko Terasaki, Yasuhiro Kodera, Fumitaka Kikkawa, and Masaru Hori
  • Organizer: IWPCT2016
  • Place of Presentation: Embassy Suites by Hilton Washington DC Convention Center
  • Year and Date: 2016-04-11
  • Int'l Joint Research / Invited
• [Presentation] 非熱大気圧プラズマのがん治療への応用とその細胞内分子機構 (2016)
  • Author(s): 田中 宏昌、水野 正明、豊國 伸哉、丸山 彰一、小寺 泰弘、寺崎 浩子、足立 哲夫、加藤 昌志、吉川 史隆 、堀 勝
  • Organizer: 第19回 若手科学者によるプラズマ研究会
  • Place of Presentation: 那珂
  • Year and Date: 2016-03-15
  • Invited
• [Presentation] がん細胞へのプラズマ影響 (2016)
  • Author(s): 田中 宏昌、堀 勝
  • Organizer: 153委員会 プラズマスクール---プラズマ医療の基礎と応用
  • Place of Presentation: 東京
  • Year and Date: 2016-02-08
  • Invited
• [Presentation] 大気圧プラズマを利用したがん治療 (2016)
  • Author(s): 田中 宏昌、水野 正明、吉川 史隆、堀 勝
  • Organizer: 第18回癌治療増感研究会シンポジウム
  • Place of Presentation: 奈良
  • Year and Date: 2016-02-05
  • Invited
• [Presentation] プラズマ科学と生命科学の融合 (2016)
  • Author(s): 田中 宏昌
  • Organizer: 熊本大学大学院自然科学研究科プロゼミ
  • Place of Presentation: 熊本大学
  • Invited
• [Presentation] Progress of Plasma Medical Science Innovation (2015)
  • Author(s): H. Tanaka, M. Mizuno, F. Kikkawa, and M. Hori
  • Organizer: Sungkyunkwan University (SKKU)& Nagoya University (NU) Joint Symposium 2015
  • Place of Presentation: Nagoya
  • Year and Date: 2015-11-25
  • Int'l Joint Research / Invited
• [Presentation] Responses of cells in plasma-activated medium (2015)
  • Author(s): Hiromasa Tanaka, Masaaki Mizuno, Kenji Ishikawa, Keigo Takeda, Hiroshi Hashizume, Kae Nakamura, Hiroaki Kajiyama, Hiroyuki Kano, Yasumasa Okazaki, Shinya Toyokuni, Shoichi Maruyama, Yasuhiro Kodera, Hiroko Terasaki, Tetsuo Adachi, Masashi Kato, Fumitaka Kikkawa, and Masaru Hori
  • Organizer: 68th Annual Gaseous Electronics Conference/9th International Conference on Reactive Plasmas/33rd Symposium on Plasma Processing
  • Place of Presentation: Hawaii
  • Year and Date: 2015-10-12
  • Int'l Joint Research
• [Presentation] Cellular And Molecular Responses Of Plasma-activated Medium Treated Cells (2015)
  • Author(s): Hiromasa Tanaka, Masaaki Mizuno, Kenji Ishikawa, Keigo Takeda, Hiroshi Hashizume, Kae Nakamura, Hiroaki Kajiyama, Hiroyuki Kano, Yasumasa Okazaki, Shinya Toyokuni, Fumitaka Kikkawa, and Masaru Hori
  • Organizer: The 10th Asian-European International Conference On Plasma Surface Engineering
  • Place of Presentation: Jeju
  • Year and Date: 2015-09-20
  • Int'l Joint Research
• [Presentation] Interactions between plasma- activated medium and cancer cells (2015)
  • Author(s): H. Tanaka, M. Mizuno, F. Kikkawa, M. Hori
  • Organizer: Bioplasmas and Plasmas with Liquids
  • Place of Presentation: Bertinoro
  • Year and Date: 2015-09-13
  • Int'l Joint Research / Invited
• [Presentation] 大気圧プラズマによるがん治療 (2015)
  • Author(s): 田中 宏昌、水野 正明、豊國 伸哉、丸山 彰一、小寺 泰弘、足立 哲夫、寺崎 浩子、加藤 昌志、吉川 史隆、堀 勝
  • Organizer: 第68回日本酸化ストレス学会学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2015-06-11
  • Invited
• [Book] 「ドライプロセスと医療」、ドライプロセスによる表面処理・薄膜形成の応用 12.2 (2016)
  • Author(s): 田中 宏昌、堀 勝
  • Total Pages: 318
  • Publisher: コロナ社
• [Remarks] 堀・関根研究室 へようこそ！
  • URL: http://horilab.nuee.nagoya-u.ac.jp/
• [Patent(Industrial Property Rights)] シュウ酸の製造方法 (2016)
  • Inventor(s): 石川 健治、堀 勝、倉家 尚之、田中 宏昌
  • Industrial Property Rights Holder: 石川 健治、堀 勝、倉家 尚之、田中 宏昌
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-10-08
• [Patent(Industrial Property Rights)] 成長促進水溶液…農作物および魚類の生産方法 (2016)
  • Inventor(s): 堀 勝、橋爪 博司、田中 宏昌、秋山 真一
  • Industrial Property Rights Holder: 堀 勝、橋爪 博司、田中 宏昌、秋山 真一
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-11-08
• [Patent(Industrial Property Rights)] 分化細胞の生産方法およびｉＰＳ細胞の未分化細胞の除去方法 (2015)
  • Inventor(s): 本多 裕之、清水 一憲、堀 勝、田中 宏昌、他3名
  • Industrial Property Rights Holder: 本多 裕之、清水 一憲、堀 勝、田中 宏昌、他3名
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-155312
  • Filing Date: 2015-08-05
• [Patent(Industrial Property Rights)] 魚類の生産方法および稚魚の成長促進方法および魚類の成長促進剤 (2015)
  • Inventor(s): 堀 勝、水野 正明、秋山 真一、田中 宏昌、他3名
  • Industrial Property Rights Holder: 堀 勝、水野 正明、秋山 真一、田中 宏昌、他3名
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-155525
  • Filing Date: 2015-08-05
• [Patent(Industrial Property Rights)] 抗癌剤および輸液とそれらの製造方法ならびに抗癌物質 (2015)
  • Inventor(s): 水野 正明、堀 勝、吉川 史隆、田中 宏昌、他6名
  • Industrial Property Rights Holder: 水野 正明、堀 勝、吉川 史隆、田中 宏昌、他6名
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-12-23
  • Overseas