研究者詳細 - 石川　健治

論文 - 石川　健治

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Plasma-activated medium (PAM) kills human cancer-initiating cells 査読有り Open Access

Ikeda, J; Tanaka, H; Ishikawa, K; Sakakita, H; Ikehara, Y; Hori, M

PATHOLOGY INTERNATIONAL 68 巻 ( 1 ) 頁： 23 - 30 2018年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Pathology International

Medical non-thermal plasma (NTP) treatments for various types of cancers have been reported. Cells with tumorigenic potential (cancer-initiating cells; CICs) are few in number in many types of tumors. CICs efficiently eliminate anti-cancer chemicals and exhibit high-level aldehyde dehydrogenase (ALDH) activity. We previously examined the effects of direct irradiation via NTP on cancer cells; even though we targeted CICs expressing high levels of ALDH, such treatment affected both non-CICs and CICs. Recent studies have shown that plasma-activated medium (PAM) (culture medium irradiated by NTP) selectively induces apoptotic death of cancer but not normal cells. Therefore, we explored the anti-cancer effects of PAM on CICs among endometrioid carcinoma and gastric cancer cells. PAM reduced the viability of cells expressing both low and high levels of ALDH. Combined PAM/cisplatin appeared to kill cancer cells more efficiently than did PAM or cisplatin alone. In a mouse tumor xenograft model, PAM exerted an anti-cancer effect on CICs. Thus, our results suggest that PAM effectively kills both non-CICs and CICs, as does NTP. Therefore, PAM may be a useful new anti-cancer therapy, targeting various cancer cells including CICs.

DOI： 10.1111/pin.12617

Selective production of reactive oxygen and nitrogen species in the plasma-treated water by using a nonthermal high-frequency plasma jet 査読有り

Uchida, G; Takenaka, K; Takeda, K; Ishikawa, K; Hori, M; Setsuhara, Y

JAPANESE JOURNAL OF APPLIED PHYSICS 57 巻 ( 1 ) 2018年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Journal of Applied Physics

We present the control of H<inf>2</inf>O<inf>2</inf> and NO<inf>2</inf> <sup>-</sup> productions in deionized water by using a high-frequency plasma jet driven by a 60 MHz voltage. In the gas phase, the high-frequency plasma jet has a high O (<sup>3</sup>P) atom density of 8 × 10<sup>14</sup> cm<sup>-3</sup>, which is two orders of magnitude higher than that of the low-frequency plasma jet driven by a 5 kHz voltage. Concerning the production of reactive oxygen and nitrogen species in the liquid phase, with the direct contact of the plasma jet to the liquid surface, the H<inf>2</inf>O<inf>2</inf> concentration is higher than the NO<inf>2</inf> <sup>-</sup> concentration. On the other hand, without the observable contact of the high-frequency plasm jet with high plasma density to the liquid surface, the NO<inf>2</inf> <sup>-</sup> concentration increases with the flow rate of N<inf>2</inf>(20%)O<inf>2</inf>(80%) gas added to the Ar discharge gas and becomes more dominant compared with H<inf>2</inf>O<inf>2</inf> in the plasma-treated water. H<inf>2</inf>O<inf>2</inf> and NO<inf>2</inf> <sup>-</sup> could be selectively produced in the plasma-treated water by using a nonthermal high-frequency plasma jet, which is a promising tool for biomedical applications.

DOI： 10.7567/JJAP.57.0102B4

Rapid growth of micron-sized graphene flakes using in-liquid plasma employing iron phthalocyanine-added ethanol 査読有り Open Access

Amano, T; Kondo, H; Ishikawa, K; Tsutsumi, T; Takeda, K; Hiramatsu, M; Sekine, M; Hori, M

APPLIED PHYSICS EXPRESS 11 巻 ( 1 ) 2018年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Applied Physics Express

Giant graphene flakes on the micron scale were synthesized and grown in plasmas in liquid-phase pure ethanol with added iron phthalocyanine (FePc) in a solvent. At atmospheric pressure, plasmas were generated in the gas phase filled with Ar and in the liquid phases comprising bubbles and liquid solutions. In the mixture of FePc in ethanol, nanographene sheets aggregated to form giant graphene flakes, as confirmed by the D, G, and 2D bands in the corresponding Raman spectra. Therefore, a bottom-up approach of graphite synthesis from pure ethanol with additives and a catalyst was realized by in-liquid plasma processing.

DOI： 10.7567/APEX.11.015102

Cell Deposition Microchip with Micropipette Control over Liquid Interface Motion. 査読有り

Onoshima D, Hattori Y, Yukawa H, Ishikawa K, Hori M, Baba Y

Cell medicine 10 巻頁： 2155179017733152 2018年

Isotropic atomic level etching of tungsten using formation and desorption of tungsten fluoride 査読有り

Shinoda, K; Miyoshi, N; Kobayashi, H; Hanaoka, Y; Kawamura, K; Izawa, M; Ishikawa, K; Hori, M

ADVANCED ETCH TECHNOLOGY FOR NANOPATTERNING VII 10589 巻 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Proceedings of SPIE the International Society for Optical Engineering

A selective, rapid thermal-cyclic atomic-level etching (ALE) of tungsten is developed. The first step of this process is exposing the surface of tungsten with hydrofluorocarbon plasma at -22°C to form a tungsten fluoride-based surface modified layer on the tungsten surface. The second step is rapid thermal annealing with infrared (IR) irradiation to remove the surface modified layer. Tungsten 4f peaks and a fluorine 1s peak, which were assigned to tungsten fluoride, were observed by in-situ x-ray photoelectron spectroscopy immediately after plasma exposure. The peaks that originated from tungsten fluoride disappeared after the samples were annealed. Cyclic etching tests were carried out by repeating plasma exposure and IR irradiation with a 300-mm ALE tool. Films of tungsten, TiN, and SiO<inf>2</inf> were used as sample materials. The amount of etched tungsten increased as the number of cycle repetitions increased. The etched amount per cycle for tungsten was 0.8 nm. In comparison, etching of TiN and SiO<inf>2</inf> was not detected. Conformal etching profiles of patterned samples after 60 cycles were obtained. Furthermore, the etched amount per cycle showed saturation behavior with regard to plasma exposure time. Selective, rapid thermal cyclic ALE of tungsten was thus successfully demonstrated.

DOI： 10.1117/12.2297241

Glioblastoma Cell Lines Display Different Sensitivities to Plasma-Activated Medium 査読有り

Tanaka H., Mizuno M., Ishikawa K., Takeda K., Hashizume H., Nakamura K., Utsumi F., Kajiyama H., Okazaki Y., Toyokuni S., Akiyama S., Maruyama S., Kikkawa F., Hori M.

IEEE Transactions on Radiation and Plasma Medical Sciences 2 巻 ( 2 ) 頁： 99 - 102 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：IEEE Transactions on Radiation and Plasma Medical Sciences

Plasma-activated medium (PAM) is a novel chemotherapy that induces reactive oxygen species (ROS) and cell death in a wide range of cancer cell types, suggesting that PAM may be a promising therapeutic option for cancer treatment. However, dose response experiments suggest that PAM sensitivity is cell line specific. We examined the sensitivities of three glioblastoma cell lines to PAM, and found a wide variation in cell killing that was linked to differences in PAM induced ROS and apoptosis. These results indicate that the PAM sensitivity of glioblastoma cells, and potentially cancer cells more generally, is heterogeneous and likely to be dependent on the regulation of apoptosis and antioxidant pathways in target cells.

DOI： 10.1109/trpms.2017.2721973

Oncogene mutation analysis of circulating tumor cells using single-cell membrane separation and DNA amplification 査読有り

Onoshima D., Kuboyama D., Kihara N., Tanaka H., Hase T., Yukawa H., Ishikawa K., Odaka H., Hasegawa Y., Hori M., Baba Y.

22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences Microtas 2018 3 巻頁： 1291 - 1293 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences Microtas 2018

We present a study of genomic profiling for circulating tumor cells (CTCs) using a blood microfiltration system. DNA amplification of CTCs was performed with a microfilter for single cancer cells in a clinical setting. This strategy was successfully used to detect the driver mutations in epidermal growth factor (EGF) receptor oncogenes by quantitative PCR and characterize the dosing effect of molecularly targeted drug for lung cancer.

Exosome isolation toward cancer diagnosis using glass filter with nanoporous structure 査読有り Open Access

Aoki K., Yukawa H., Onoshima D., Yamazaki S., Kihara N., Koguchi R., Takahashi K., Odaka H., Ishikawa K., Hori M., Baba Y.

22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences Microtas 2018 3 巻頁： 1409 - 1410 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences Microtas 2018

We present a study of centrifugal filtration device toward easy-to-use approach of non-invasive liquid biopsy for cancer diagnosis by cell-derived nanoscale vesicles (exosomes). A phase-dispersed glass filter having nanoporous structure was embedded into a spin column to trap exosomes with small centrifuge. This device enabled over 90% exosome isolation from biological samples within 10 minutes.

DOI： 10.1088/1361-6595/ac12bf

Dynamic analysis of reactive oxygen nitrogen species in plasma-activated culture medium by UV absorption spectroscopy 査読有り国際共著

Brubaker, TR; Ishikawa, K; Takeda, K; Oh, JS; Kondo, H; Hashizume, H; Tanaka, H; Knecht, SD; Bilén, SG; Hori, M

JOURNAL OF APPLIED PHYSICS 122 巻 ( 21 ) 2017年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Applied Physics

The liquid-phase chemical kinetics of a cell culture basal medium during treatment by an argon-fed, non-equilibrium atmospheric-pressure plasma source were investigated using real-time ultraviolet absorption spectroscopy and colorimetric assays. Depth- and time-resolved NO2- and NO3- concentrations were strongly inhomogeneous and primarily driven by convection during and after plasma-liquid interactions. H<inf>2</inf>O<inf>2</inf> concentrations determined from deconvolved optical depth spectra were found to compensate for the optical depth spectra of excluded reactive species and changes in dissolved gas content. Plasma-activated media remained weakly basic due to NaHCO<inf>3</inf> buffering, preventing the H<sup>+</sup>-catalyzed decomposition of NO2- seen in acidic plasma-activated water. An initial increase in pH may indicate CO<inf>2</inf> sparging. Furthermore, the pH-dependency of UV optical depth spectra illustrated the need for pH compensation in the fitting of optical depth data.

DOI： 10.1063/1.4999256

Dependence of absolute photon flux on infrared absorbance alteration and surface roughness on photoresist polymers irradiated with vacuum ultraviolet photons emitted from HBr plasma 査読有り

Zhang, Y; Takeuchi, T; Ishikawa, K; Hayashi, T; Takeda, K; Sekine, M; Hori, M

JAPANESE JOURNAL OF APPLIED PHYSICS 56 巻 ( 12 ) 2017年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Journal of Applied Physics

The absolute fluxes of vacuum ultraviolet (VUV) photons emitted from HBr plasma were analyzed and the effects of VUV photons on a photoresist polymer in ArF-excimer-laser (193 nm) lithography were quantitatively investigated on the basis of the infrared spectra attributed to the C=O region. The spectral peak intensity assigned to the methacrylic acid (MAA) in the photoresist drastically decreased owing to the loss of this monomer caused by the irradiation of VUV photons at dosages below 16 - 10<sup>16</sup> photons/cm<sup>2</sup>. X-ray photoelectron spectroscopy observation showed that the removed monomer moved to the surface and generated volatile products that induced a decrease in film thickness. As a consequence, the surface became rough during the early-stage irradiation at dosages lower than 16 - 10<sup>16</sup> photons/cm<sup>2</sup> owing to the monomer loss of MAA with volatile product formation and subsequent cross-linking reactions.

DOI： 10.7567/JJAP.56.126503

State of the art in medical applications using non-thermal atmospheric pressure plasma 査読有り国際共著

Tanaka H., Ishikawa K., Mizuno M., Toyokuni S., Kajiyama H., Kikkawa F., Metelmann H.R., Hori M.

Reviews of Modern Plasma Physics 1 巻 ( 1 ) 2017年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Reviews of Modern Plasma Physics

Plasma medical science is a novel interdisciplinary field that combines studies on plasma science and medical science, with the anticipation that understanding the scientific principles governing plasma medical science will lead to innovations in the field. Non-thermal atmospheric pressure plasma has been used for medical treatments, such as for cancer, blood coagulation, and wound healing. The interactions that occur between plasma and cells/tissues have been analyzed extensively. Direct and indirect treatment of cells with plasma has broadened the applications of non-thermal atmospheric pressure plasma in medicine. Examples of indirect treatment include plasma-assisted immune-therapy and plasma-activated medium. Controlling intracellular redox balance may be key in plasma cancer treatment. Animal studies are required to test the effectiveness and safety of these treatments for future clinical applications.

DOI： 10.1007/s41614-017-0004-3

Intracellular responses to reactive oxygen and nitrogen species, and lipid peroxidation in apoptotic cells cultivated in plasma-activated medium 査読有り

Furuta, R; Kurake, N; Ishikawa, K; Takeda, K; Hashizume, H; Tanaka, H; Kondo, H; Sekine, M; Hori, M

PLASMA PROCESSES AND POLYMERS 14 巻 ( 11 ) 2017年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Plasma Processes and Polymers

A mechanism of the cytotoxicity of plasma-activated medium (PAM) is revealed by examining the intracellular effects of reactive oxygen nitrogen species (RONS) and lipid oxidation. PAM is cell culture medium activated by irradiation using non-equilibrium atmospheric-pressure plasma using pure Ar gas in ambient air. Extracellular RONS in PAM induced the apoptotic death of HeLa cells. Temporal changes in intracellular RONS, such as ONOO<sup>−</sup>, NO, and (Formula presented.), were analyzed. Intracellular RONS generation in HeLa cells following incubation in PAM triggered activation of the caspase cascade pathway and lipid peroxidation of intracellular membranes to induce apoptosis.

DOI： 10.1002/ppap.201700123

Surface roughening of photoresist after change of the photon/radical and ion treatment sequence 査読有り

Zhang, Y; Takeuchi, T; Ishikawa, K; Takeda, K; Kondo, H; Sekine, M; Hori, M

JOURNAL OF VACUUM SCIENCE & TECHNOLOGY A 35 巻 ( 6 ) 2017年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Vacuum Science and Technology A Vacuum Surfaces and Films

The formation of surface roughness during ion irradiation was suppressed by photon/radical pretreatment of a photoresist with HBr or H<inf>2</inf> plasmas. The opposite sequence of treatment after ion irradiation enhanced the surface roughness. The enhancement of roughness after post-treatment was not correlated with a decrease in the film thickness, reactions of Br radicals at the surface, or with the presence of the amorphous carbon-like layer generated by ion irradiation because similar modification was observed for the pretreatment. Fourier transform infrared spectroscopy analysis revealed that the intensities of peaks originated from the C=O absorption of methacrylic acid and methacrylate groups were decreased by irradiation with vacuum ultraviolet light at wavelengths in the range between 115 and 170 nm emitted from HBr or H<inf>2</inf> plasmas. The removal of the C=O groups possibly generated dangling bonds and induced crosslinking reactions of the photoresist polymers. The nonuniformity of crosslinking reactions on the roughened photoresist intensively increased the surface roughness.

DOI： 10.1116/1.4994218

最先端プラズマバイオ技術招待有り査読有り Open Access

堀勝，石川健治，近藤隆，田中宏昌，橋爪博司

放射線化学頁： 3 - 14 2017年10月

Crystallization of calcium oxalate dihydrate in a buffered calcium-containing glucose solution by irradiation with non-equilibrium atmospheric pressure plasma 査読有り

Kurake, N; Tanaka, H; Ishikawa, K; Nakamura, K; Kajiyama, H; Kikkawa, F; Mizuno, M; Ikehara, Y; Hori, M

JOURNAL OF APPLIED PHYSICS 122 巻 ( 14 ) 2017年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Applied Physics

Oxalate was synthesized in the glucose solution by irradiation with non-equilibrium atmospheric pressure plasma (NEAPP), in which the NEAPP plume contacted the solution surface, via the generation of several intermediate organic products such as gluconic acid. A thermodynamically unstable phase of calcium oxalate dihydrate crystallized rapidly during incubation of a NEAPP-irradiated glucose solution that contained calcium ions and was buffered at neutral pH. Longer irradiation times increased the growth rate and the number of seed crystals.

DOI： 10.1063/1.5006598

High-durability catalytic electrode composed of Pt nanoparticle-supported carbon nanowalls synthesized by radical-injection plasma-enhanced chemical vapor deposition 査読有り

Imai, S; Kondo, H; Cho, H; Kano, H; Ishikawa, K; Sekine, M; Hiramatsu, M; Ito, M; Hori, M

JOURNAL OF PHYSICS D-APPLIED PHYSICS 50 巻 ( 40 ) 2017年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Physics D Applied Physics

For polymer electrolyte fuel cell applications, carbon nanowalls (CNWs) were synthesized by radical-injection plasma-enhanced chemical vapor deposition, and a high density of Pt nanoparticles (>10<sup>12</sup> cm<sup>-2</sup>) was supported on the CNWs using a supercritical fluid deposition system. The high potential cycle tests were applied and the electrochemical surface area of the Pt nanoparticle-supported CNWs did not change significantly, even after 20 000 high potential cycles. According to transmission electron microscopy observations, the mean diameter of Pt changed slightly after the cycle tests, while the crystallinity of the CNWs evaluated using Raman spectroscopy showed almost no change.

DOI： 10.1088/1361-6463/aa8131

Cold atmospheric helium plasma causes synergistic enhancement in cell death with hyperthermia and an additive enhancement with radiation 査読有り Open Access

Moniruzzaman, R; Rehman, MU; Zhao, QL; Jawaid, P; Takeda, K; Ishikawa, K; Hori, M; Tomihara, K; Noguchi, K; Kondo, T; Noguchi, M

SCIENTIFIC REPORTS 7 巻 ( 1 ) 頁： 11659 2017年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Scientific Reports

Cold atmospheric plasmas (CAPs) have been proposed as a novel therapeutic method for its anti-cancer potential. However, its biological effects in combination with other physical modalities remain elusive. Therefore, this study examined the effects of cold atmospheric helium plasma (He-CAP) in combination with hyperthermia (HT) 42 °C or radiation 5 Gy. Synergistic enhancement in the cell death with HT and an additive enhancement with radiation were observed following He-CAP treatment. The synergistic effects were accompanied by increased intracellular reactive oxygen species (ROS) production. Hydrogen peroxide (H<inf>2</inf>O<inf>2</inf>) and superoxide (O<inf>2</inf> <sup>•-</sup>) generation was increased immediately after He-CAP treatment, but fails to initiate cell death process. Interestingly, at late hour's He-CAP-induced O<inf>2</inf> <sup>•-</sup> generation subsides, however the combined treatment showed sustained increased intracellular O<inf>2</inf> <sup>•-</sup> level, and enhanced cell death than either treatment alone. He-CAP caused marked induction of ROS in the aqueous medium, but He-CAP-induced ROS seems insufficient or not completely incorporated intra-cellularly to activate cell death machinery. The observed synergistic effects were due to the HT effects on membrane fluidity which facilitate the incorporation of He-CAP-induced ROS into the cells, thus results in the enhanced cancer cell death following combined treatment. These findings would be helpful when establishing a therapeutic strategy for CAP in combination with HT or radiation.

DOI： 10.1038/s41598-017-11877-8

Lipid droplets exhaustion with caspases activation in HeLa cells cultured in plasma-activated medium observed by multiplex coherent anti-Stokes Raman scattering microscopy 査読有り

Furuta, R; Kurake, N; Takeda, K; Ishikawa, K; Ohta, T; Ito, M; Hashizume, H; Tanaka, H; Kondo, H; Sekine, M; Hori, M

BIOINTERPHASES 12 巻 ( 3 ) 頁： 031006 2017年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Biointerphases

The multiplex coherent anti-Stokes Raman scattering microscopy allowed label-free visualization of cytoplasmic lipid droplets (LDs). The LDs, which act to conserve energy storage, are usually accumulated during the normal apoptosis of HeLa cells with activation of caspase-3/7 leading to downregulation of the fatty acid catabolism pathways. During cultivating in nonthermal plasmaactivated medium (PAM), while the activation of caspase-3/7 was induced, the authors found that a dynamic exhaustion of the intracellular LDs, underlying the metabolic mechanism of the PAMinduced apoptotic cell death of HeLa cells.

DOI： 10.1116/1.4997170

高温での窒化ガリウム低損傷塩素エッチング査読有り

石川健治, 劉沢成, 今村真人, 堤隆嘉, 小田修, 近藤博基, 関根誠, 堀勝

応用物理学会学術講演会講演予稿集 2017.2 巻 ( 0 ) 頁： 1758 - 1758 2017年8月

Laser diagnostics of properties of atmospheric pressure plasmas 査読有り

Ishikawa Kenji, Lin YuChun, Ando Atsushi, Wang Meng-Jiy, Hori Masaru

JSAP Annual Meetings Extended Abstracts 2017.2 巻 ( 0 ) 頁： 1701 - 1701 2017年8月

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