本研究以小鼠皮膚黑色素瘤細胞B16-F10及纖維母細胞L929進行體外共培養，並以該共培養系統來評估非熱微電漿處理皮膚黑色素瘤之效益。腫瘤微環境中的癌細胞與纖維母細胞會因為細胞之間的交互作用而影響彼此的生長。因此，採用共培養系統能更實際的反應癌細胞及癌相關纖維母細胞(CAFs)於電漿處理後所會產生的細胞生理變化。電漿處理方面，本研究使用純氬氣(Pure Ar)以及氬氮氣(Ar + 1% N2)這兩種工作氣體的電漿，來比較其生成活性氧及活性氮(RONS)的差異，會如何改變電漿抑制黑色素瘤惡化的效益。另外，本研究也探討了分次治療模式能否提升電漿對於黑色素瘤的抑制效率。實驗結果顯示於電漿處理後，B16-F10於細胞週期的S phase, G2/M phase之停滯率較L929來的高，說明前者受到較高的細胞增生抑制程度。不過，於細胞存活及凋亡的實驗結果卻發現B16-F10具有比L929還低的凋亡率，因此推測B16-F10具有比L929還高的RONS耐受能力。實驗結果也顯示模擬腫瘤微環境的共培養系統會讓L929具有更多細胞內的氧化壓力，進而可能影響其受電漿處理後的增生及凋亡程度；反之，共培養系統下的B16-F10則有提升的增生率及存活率。上述現象則有可能是兩種細胞透過細胞間的交互作用，影響了彼此的細胞生理所導致的。Ar + 1% N2之電漿所生成的ROS會有下調的趨勢，而RNS則有上升的趨勢。該氣體組合下的電漿，其RONS之間所產生的協同效應比Pure Ar電漿還要顯著，進而能夠提升對細胞的增生抑制及凋亡程度。分次電漿處理下的細胞增生抑制及凋亡程度皆有提升的情形。因此，透過調整電漿氣體成分及採用分次處理皆能提升電漿抑制黑色素腫瘤惡化的情形。本研究呈現了黑色素癌細胞比纖維母細胞更耐受RONS的情況。於該情況下，欲以電漿選擇性抑制黑色素癌細胞之難度較高。但是，電漿能促進CAFs之凋亡及抑制黑色素癌細胞及CAFs的細胞增生，以上現象也能夠緩降黑色素腫瘤的進程。因而，本研究認為非熱微電漿仍具有成為黑色素癌之輔助治療之潛力。

In this study, an in vitro direct co-culture model of melanoma B16-F10 and fibroblast L929 was used to simulate a primary melanoma tumor, which would more realistically reflect on how cells would react to plasma treatment under the tumor microenvironment. Two combinations of plasma working gas, Pure Ar and Ar + N2, would be used during treatment to assess whether altering the RONS ratio could induce a higher attenuative effect on melanoma progression. Comparison between single and double treatment would also be made to evaluate whether adopting hyperfractionation in plasma treatment could improve treatment effectiveness. It was found that B16-F10 experience higher S phase and G2/M phase cell cycle arrest than L929, which resulted in relatively higher proliferation inhibition. However, B16-F10 had a lower apoptosis rate than L929 under the same plasma treatment dosage, which was probably due to B16-F10 having a higher RONS resistant. N2 addition to Ar plasma would decrease ROS levels and increase RNS levels, and a synergistic effect of RONS could induce higher proliferation inhibition and apoptosis on both cell lines. Double plasma treatments would also induce higher proliferation inhibition and apoptosis than single treatments. It was also observed that L929 in co-culture experienced higher oxidative stress than in mono-culture, while B16-F10 had an increase in proliferation and survival. These changes in cellular behavior might be caused by the cellular interactions between the two cell lines in co-culture. Overall, a case where melanoma cells were more resistant to RONS administration than fibroblast cells was given, hence the selective toxicity on melanoma may not be as prominent. However, it could be explained that through higher apoptosis induction of CAFs and proliferation inhibition of both melanomas and CAFs, tumor progression may still be limited, which could still consolidate the possibility of serving plasma as adjuvant therapy to current melanoma treatments.

[1] A. J. Miller and M. C. Mihm, "Melanoma," New England Journal of Medicine, vol. 355, no. 1, pp. 51-65, 2006.
[2] B. Domingues, J. M. Lopes, P. Soares, and H. Pópulo, "Melanoma treatment in review," (in eng), Immunotargets Ther, vol. 7, pp. 35-49, 2018.
[3] L. A. von Schuckmann, M. C. B. Hughes, R. Ghiasvand, M. Malt, J. C. van der Pols, V. L. Beesley, K. Khosrotehrani, B. M. Smithers, and A. C. Green, "Risk of Melanoma Recurrence After Diagnosis of a High-Risk Primary Tumor," JAMA Dermatol, vol. 155, no. 6, pp. 688-693, Jun 1 2019.
[4] A. Fridman, Plasma Chemistry. New York, NY 10013-2473, USA: Cambridge University Press, 2008.
[5] N. De Geyter and R. Morent, "Nonthermal Plasma Sterilization of Living and Nonliving Surfaces," Annual Review of Biomedical Engineering, vol. 14, no. 1, pp. 255-274, 2012.
[6] P. L. Shao, J. D. Liao, T. W. Wong, Y. C. Wang, S. Leu, and H. K. Yip, "Enhancement of Wound Healing by Non-Thermal N2/Ar Micro-Plasma Exposure in Mice with Fractional-CO2-Laser-Induced Wounds," PLoS One, vol. 11, no. 6, p. e0156699, 2016.
[7] J. Schlegel, J. Köritzer, and V. Boxhammer, "Plasma in cancer treatment," Clinical Plasma Medicine, vol. 1, no. 2, pp. 2-7, 2013.
[8] K. D. Weltmann and T. von Woedtke, "Plasma medicine—current state of research and medical application," Plasma Physics and Controlled Fusion, vol. 59, no. 1, 2017.
[9] J. Duan, X. Lu, and G. He, "On the penetration depth of reactive oxygen and nitrogen species generated by a plasma jet through real biological tissue," Physics of Plasmas, vol. 24, no. 7, 2017.
[10] G. Pasqual-Melo, R. K. Gandhirajan, I. Stoffels, and S. Bekeschus, "Targeting malignant melanoma with physical plasmas," Clinical Plasma Medicine, vol. 10, pp. 1-8, 2018.
[11] T. F. Vandamme, "Use of rodents as models of human diseases," (in eng), J Pharm Bioallied Sci, vol. 6, no. 1, pp. 2-9, 2014.
[12] G. Xu, J. Liu, C. Yao, S. Chen, F. Lin, P. Li, X. Shi, and G.-J. Zhang, "Effects of atmospheric pressure plasma jet with floating electrode on murine melanoma and fibroblast cells," Physics of Plasmas, vol. 24, no. 8, 2017.
[13] G.-M. Xu, Y. Hao, M.-Y. Sun, J.-R. Liu, X.-M. Shi, and G.-J. Zhang, "Characteristics of Plasma Activated Medium Produced by Atmospheric Pressure Helium Plasma Jet and Its Selective Effect on Malignant Melanoma and Normal Fibroblast Cells," IEEE Transactions on Plasma Science, vol. 48, no. 2, pp. 587-595, 2020.
[14] A. Rafiei, F. Sohbatzadeh, S. Hadavi, S. Bekeschus, M. Alimohammadi, and R. Valadan, "Inhibition of murine melanoma tumor growth in vitro and in vivo using an argon-based plasma jet," Clinical Plasma Medicine, vol. 19-20, 2020.
[15] S. Bekeschus, K. Rodder, B. Fregin, O. Otto, M. Lippert, K. D. Weltmann, K. Wende, A. Schmidt, and R. K. Gandhirajan, "Toxicity and Immunogenicity in Murine Melanoma following Exposure to Physical Plasma-Derived Oxidants," Oxid Med Cell Longev, vol. 2017, p. 4396467, 2017.
[16] K. Mizuno, K. Yonetamari, Y. Shirakawa, T. Akiyama, and R. Ono, "Anti-tumor immune response induced by nanosecond pulsed streamer discharge in mice," Journal of Physics D: Applied Physics, vol. 50, no. 12, 2017.
[17] A. Lin, Y. Gorbanev, J. De Backer, J. Van Loenhout, W. Van Boxem, F. Lemiere, P. Cos, S. Dewilde, E. Smits, and A. Bogaerts, "Non-Thermal Plasma as a Unique Delivery System of Short-Lived Reactive Oxygen and Nitrogen Species for Immunogenic Cell Death in Melanoma Cells," Adv Sci (Weinh), vol. 6, no. 6, p. 1802062, Mar 20 2019.
[18] G. M. Fischer, Y. N. Vashisht Gopal, J. L. McQuade, W. Peng, R. J. DeBerardinis, and M. A. Davies, "Metabolic strategies of melanoma cells: Mechanisms, interactions with the tumor microenvironment, and therapeutic implications," Pigment Cell Melanoma Res, vol. 31, no. 1, pp. 11-30, Jan 2018.
[19] P. R. Kumar, J. A. Moore, K. M. Bowles, S. A. Rushworth, and M. D. Moncrieff, "Mitochondrial oxidative phosphorylation in cutaneous melanoma," Br J Cancer, vol. 124, no. 1, pp. 115-123, Jan 2021.
[20] A. Indini, F. Grossi, M. Mandala, D. Taverna, and V. Audrito, "Metabolic Interplay between the Immune System and Melanoma Cells: Therapeutic Implications," Biomedicines, vol. 9, no. 6, May 26 2021.
[21] W. Sun, Y. Chen, Y. Wang, P. Luo, M. Zhang, H. Zhang, and P. Hu, "Interaction study of cancer cells and fibroblasts on a spatially confined oxygen gradient microfluidic chip to investigate the tumor microenvironment," Analyst, vol. 143, no. 22, pp. 5431-5437, Nov 5 2018.
[22] K. Ashok, H. Dwivedi, and N. Vijay, "Atmospheric Non-Thermal Plasma Sources," International Journal of Engineering, vol. 2, 02/01 2008.
[23] V. Scholtz, J. Pazlarova, H. Souskova, J. Khun, and J. Julak, "Nonthermal plasma--A tool for decontamination and disinfection," Biotechnol Adv, vol. 33, no. 6 Pt 2, pp. 1108-19, Nov 1 2015.
[24] X. Lu, M. Laroussi, and V. Puech, "On atmospheric-pressure non-equilibrium plasma jets and plasma bullets," Plasma Sources Science and Technology, vol. 21, no. 3, 2012.
[25] D. Brany, D. Dvorska, E. Halasova, and H. Skovierova, "Cold Atmospheric Plasma: A Powerful Tool for Modern Medicine," Int J Mol Sci, vol. 21, no. 8, Apr 22 2020.
[26] B. Smolkova, A. Frtus, M. Uzhytchak, M. Lunova, S. Kubinova, A. Dejneka, and O. Lunov, "Critical Analysis of Non-Thermal Plasma-Driven Modulation of Immune Cells from Clinical Perspective," Int J Mol Sci, vol. 21, no. 17, Aug 28 2020.
[27] N. K. Kaushik, B. Ghimire, Y. Li, M. Adhikari, M. Veerana, N. Kaushik, N. Jha, B. Adhikari, S. J. Lee, K. Masur, T. von Woedtke, K. D. Weltmann, and E. H. Choi, "Biological and medical applications of plasma-activated media, water and solutions," Biol Chem, vol. 400, no. 1, pp. 39-62, Dec 19 2018.
[28] N. Kurake, H. Tanaka, K. Ishikawa, T. Kondo, M. Sekine, K. Nakamura, H. Kajiyama, F. Kikkawa, M. Mizuno, and M. Hori, "Cell survival of glioblastoma grown in medium containing hydrogen peroxide and/or nitrite, or in plasma-activated medium," Arch Biochem Biophys, vol. 605, pp. 102-8, Sep 1 2016.
[29] Y. H. Kim, Y. J. Hong, K. Y. Baik, G. C. Kwon, J. J. Choi, G. S. Cho, H. S. Uhm, D. Y. Kim, and E. H. Choi, "Measurement of Reactive Hydroxyl Radical Species Inside the Biosolutions During Non-thermal Atmospheric Pressure Plasma Jet Bombardment onto the Solution," Plasma Chemistry and Plasma Processing, vol. 34, no. 3, pp. 457-472, 2014.
[30] S. Kalghatgi, C. M. Kelly, E. Cerchar, B. Torabi, O. Alekseev, A. Fridman, G. Friedman, and J. Azizkhan-Clifford, "Effects of non-thermal plasma on mammalian cells," PLoS One, vol. 6, no. 1, p. e16270, Jan 21 2011.
[31] X.-M. Shi, Z.-S. Chang, X.-L. Wu, G.-J. Zhang, Z.-Y. Peng, Z.-Y. Dong, and X.-J. Shao, "Inactivation Effect of Argon Atmospheric Pressure Low-Temperature Plasma Jet on Murine Melanoma Cells," Plasma Processes and Polymers, vol. 10, no. 9, pp. 808-816, 2013.
[32] F. Utsumi, H. Kajiyama, K. Nakamura, H. Tanaka, M. Mizuno, K. Ishikawa, H. Kondo, H. Kano, M. Hori, and F. Kikkawa, "Effect of indirect nonequilibrium atmospheric pressure plasma on anti-proliferative activity against chronic chemo-resistant ovarian cancer cells in vitro and in vivo," PLoS One, vol. 8, no. 12, p. e81576, 2013.
[33] M. S. Mann, R. Tiede, K. Gavenis, G. Daeschlein, R. Bussiahn, K.-D. Weltmann, S. Emmert, T. v. Woedtke, and R. Ahmed, "Introduction to DIN-specification 91315 based on the characterization of the plasma jet kINPen® MED," Clinical Plasma Medicine, vol. 4, no. 2, pp. 35-45, 2016.
[34] C. Schneider, L. Gebhardt, S. Arndt, S. Karrer, J. L. Zimmermann, M. J. M. Fischer, and A. K. Bosserhoff, "Acidification is an Essential Process of Cold Atmospheric Plasma and Promotes the Anti-Cancer Effect on Malignant Melanoma Cells," Cancers (Basel), vol. 11, no. 5, May 14 2019.
[35] General requirements for plasma sources, DIN SPEC 91315:2014-06, German Institute for Standardization, 2014.
[36] L. Milkovic, A. Cipak Gasparovic, M. Cindric, P. A. Mouthuy, and N. Zarkovic, "Short Overview of ROS as Cell Function Regulators and Their Implications in Therapy Concepts," Cells, vol. 8, no. 8, Jul 30 2019.
[37] B. Halliwell, M. V. Clement, J. Ramalingam, and L. H. Long, "Hydrogen Peroxide. Ubiquitous in Cell Culture and In vivo?," IUBMB Life, vol. 50, no. 4-5, pp. 251-257, 2000.
[38] N. Di Marzo, E. Chisci, and R. Giovannoni, "The Role of Hydrogen Peroxide in Redox-Dependent Signaling: Homeostatic and Pathological Responses in Mammalian Cells," Cells, vol. 7, no. 10, Oct 4 2018.
[39] D. Erudaitius, A. Huang, S. Kazmi, G. R. Buettner, and V. G. Rodgers, "Peroxiporin Expression Is an Important Factor for Cancer Cell Susceptibility to Therapeutic H2O2: Implications for Pharmacological Ascorbate Therapy," PLoS One, vol. 12, no. 1, p. e0170442, 2017.
[40] B. Perillo, M. Di Donato, A. Pezone, E. Di Zazzo, P. Giovannelli, G. Galasso, G. Castoria, and A. Migliaccio, "ROS in cancer therapy: the bright side of the moon," Exp Mol Med, vol. 52, no. 2, pp. 192-203, Feb 2020.
[41] H. Sies, "Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress," (in eng), Redox Biol, vol. 11, pp. 613-619, 2017.
[42] M. Redza-Dutordoir and D. A. Averill-Bates, "Activation of apoptosis signalling pathways by reactive oxygen species," Biochim Biophys Acta, vol. 1863, no. 12, pp. 2977-2992, Dec 2016.
[43] M. J. Malone-Povolny, S. E. Maloney, and M. H. Schoenfisch, "Nitric Oxide Therapy for Diabetic Wound Healing," (in eng), Adv Healthc Mater, vol. 8, no. 12, pp. e1801210-e1801210, 2019.
[44] S. Di Meo, T. T. Reed, P. Venditti, and V. M. Victor, "Role of ROS and RNS Sources in Physiological and Pathological Conditions," Oxid Med Cell Longev, vol. 2016, p. 1245049, 2016.
[45] M. B. Witte and A. Barbul, "Role of nitric oxide in wound repair," The American Journal of Surgery, vol. 183, no. 4, pp. 406-412, 2002.
[46] P. K. M. Kim, R. Zamora, P. Petrosko, and T. R. Billiar, "The regulatory role of nitric oxide in apoptosis," International Immunopharmacology, vol. 1, no. 8, pp. 1421-1441, 2001.
[47] W. Xu, L. Z. Liu, M. Loizidou, M. Ahmed, and I. G. Charles, "The role of nitric oxide in cancer," Cell Research, vol. 12, no. 5, pp. 311-320, 2002.
[48] J. O. Lundberg, M. T. Gladwin, A. Ahluwalia, N. Benjamin, N. S. Bryan, A. Butler, P. Cabrales, A. Fago, M. Feelisch, P. C. Ford, B. A. Freeman, M. Frenneaux, J. Friedman, M. Kelm, C. G. Kevil, D. B. Kim-Shapiro, A. V. Kozlov, J. R. Lancaster, Jr., D. J. Lefer, K. McColl, K. McCurry, R. P. Patel, J. Petersson, T. Rassaf, V. P. Reutov, G. B. Richter-Addo, A. Schechter, S. Shiva, K. Tsuchiya, E. E. van Faassen, A. J. Webb, B. S. Zuckerbraun, J. L. Zweier, and E. Weitzberg, "Nitrate and nitrite in biology, nutrition and therapeutics," Nat Chem Biol, vol. 5, no. 12, pp. 865-9, Dec 2009.
[49] S. L. Fink and B. T. Cookson, "Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells," (in eng), Infect Immun, vol. 73, no. 4, pp. 1907-1916, 2005.
[50] J. E. Gershenwald, R. A. Scolyer, K. R. Hess, V. K. Sondak, G. V. Long, M. I. Ross, A. J. Lazar, M. B. Faries, J. M. Kirkwood, G. A. McArthur, L. E. Haydu, A. M. M. Eggermont, K. T. Flaherty, C. M. Balch, J. F. Thompson, P. for members of the American Joint Committee on Cancer Melanoma Expert, D. the International Melanoma, and P. Discovery, "Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual," CA: A Cancer Journal for Clinicians, vol. 67, no. 6, pp. 472-492, 2017.
[51] L. E. Davis, S. C. Shalin, and A. J. Tackett, "Current state of melanoma diagnosis and treatment," Cancer Biol Ther, vol. 20, no. 11, pp. 1366-1379, 2019.
[52] R. Haq, J. Shoag, P. Andreu-Perez, S. Yokoyama, H. Edelman, G. C. Rowe, D. T. Frederick, A. D. Hurley, A. Nellore, A. L. Kung, J. A. Wargo, J. S. Song, D. E. Fisher, Z. Arany, and H. R. Widlund, "Oncogenic BRAF regulates oxidative metabolism via PGC1alpha and MITF," Cancer Cell, vol. 23, no. 3, pp. 302-15, Mar 18 2013.
[53] L. Wang, R. Leite de Oliveira, S. Huijberts, E. Bosdriesz, N. Pencheva, D. Brunen, A. Bosma, J. Y. Song, J. Zevenhoven, G. T. Los-de Vries, H. Horlings, B. Nuijen, J. H. Beijnen, J. H. M. Schellens, and R. Bernards, "An Acquired Vulnerability of Drug-Resistant Melanoma with Therapeutic Potential," Cell, vol. 173, no. 6, pp. 1413-1425 e14, May 31 2018.
[54] P. Corazao-Rozas, P. Guerreschi, M. Jendoubi, F. André, A. Jonneaux, C. Scalbert, G. Garçon, M. Malet-Martino, S. Balayssac, S. Rocchi, A. Savina, P. Formstecher, L. Mortier, J. Kluza, and P. Marchetti, "Mitochondrial oxidative stress is the Achille's heel of melanoma cells resistant to Braf-mutant inhibitor," (in eng), Oncotarget, vol. 4, no. 11, pp. 1986-1998, 2013.
[55] I. J. Fidler, "Biological Behavior of Malignant Melanoma Cells Correlated to Their Survival in Vivo," Cancer Research, vol. 35, no. 1, p. 218, 1975.
[56] V. Mathieu, M. Le Mercier, N. De Neve, S. Sauvage, T. Gras, I. Roland, F. Lefranc, and R. Kiss, "Galectin-1 knockdown increases sensitivity to temozolomide in a B16F10 mouse metastatic melanoma model," J Invest Dermatol, vol. 127, no. 10, pp. 2399-410, Oct 2007.
[57] J. Lee, T. G. Molley, C. H. Seward, A. A. Abdeen, H. Zhang, X. Wang, H. Gandhi, J. L. Yang, K. Gaus, and K. A. Kilian, "Geometric regulation of histone state directs melanoma reprogramming," Commun Biol, vol. 3, no. 1, p. 341, Jul 3 2020.
[58] X.-M. Shi, G.-J. Zhang, Z.-S. Chang, X.-L. Wu, W.-L. Liao, and N. Li, "Viability Reduction of Melanoma Cells by Plasma Jet via Inducing G1/S and G2/M Cell Cycle Arrest and Cell Apoptosis," IEEE Transactions on Plasma Science, vol. 42, no. 6, pp. 1640-1647, 2014.
[59] L. Lin, L. Wang, Y. Liu, C. Xu, Y. Tu, and J. Zhou, "Non‑thermal plasma inhibits tumor growth and proliferation and enhances the sensitivity to radiation in vitro and in vivo," Oncol Rep, vol. 40, no. 6, pp. 3405-3415, 2018.
[60] J. Vaquero, F. Judée, M. Vallette, H. Decauchy, A. Arbelaiz, L. Aoudjehane, O. Scatton, E. Gonzalez-Sanchez, F. Merabtene, J. Augustin, C. Housset, T. Dufour, and L. Fouassier, "Cold-Atmospheric Plasma Induces Tumor Cell Death in Preclinical In Vivo and In Vitro Models of Human Cholangiocarcinoma," Cancers, vol. 12, no. 5, 2020.
[61] J. R. Liu, L. G. Gao, Y. M. Wu, G. M. Xu, Y. Ma, Y. Hao, X. M. Shi, and G. J. Zhang, "Low‐temperature plasma‐activated medium inhibited invasion and metastasis of melanoma cells via suppressing the Wnt/β‐catenin pathway," Plasma Processes and Polymers, vol. 17, no. 1, 2019.
[62] G. Daeschlein, A. Hillmann, D. Gümbel, C. Sicher, S. v. Podewils, M. B. Stope, and M. Jünger, "Enhanced Anticancer Efficacy by Drug Chemotherapy and Cold Atmospheric Plasma Against Melanoma and Glioblastoma Cell Lines In Vitro," IEEE Transactions on Radiation and Plasma Medical Sciences, vol. 2, no. 2, pp. 153-159, 2018.
[63] M. Keidar, R. Walk, A. Shashurin, P. Srinivasan, A. Sandler, S. Dasgupta, R. Ravi, R. Guerrero-Preston, and B. Trink, "Cold plasma selectivity and the possibility of a paradigm shift in cancer therapy," Br J Cancer, vol. 105, no. 9, pp. 1295-301, Oct 25 2011.
[64] D. Yan, L. Lin, J. H. Sherman, J. Canady, B. Trink, and M. Keidar, "The Correlation Between the Cytotoxicity of Cold Atmospheric Plasma and the Extracellular H2O2-Scavenging Rate," IEEE Transactions on Radiation and Plasma Medical Sciences, vol. 2, no. 6, pp. 618-623, 2018.
[65] A. Schmidt, S. Bekeschus, T. von Woedtke, and S. Hasse, "Cell migration and adhesion of a human melanoma cell line is decreased by cold plasma treatment," Clinical Plasma Medicine, vol. 3, no. 1, pp. 24-31, 2015.
[66] R. K. Gandhirajan, K. Rodder, Y. Bodnar, G. Pasqual-Melo, S. Emmert, C. E. Griguer, K. D. Weltmann, and S. Bekeschus, "Cytochrome C oxidase Inhibition and Cold Plasma-derived Oxidants Synergize in Melanoma Cell Death Induction," Sci Rep, vol. 8, no. 1, p. 12734, Aug 24 2018.
[67] X. Li, Z. Feng, S. Pu, Y. Yang, X. Shi, and Z. Xu, "Cold atmospheric Plasma Jet-Generated Oxidized Derivatives of Tryptophan and Their Selective Effects on Murine Melanoma and Fibroblast Cells," Plasma Chemistry and Plasma Processing, vol. 38, no. 5, pp. 919-936, 2018.
[68] M. Alimohammadi, M. Golpur, F. Sohbatzadeh, S. Hadavi, S. Bekeschus, H. A. Niaki, R. Valadan, and A. Rafiei, "Cold Atmospheric Plasma Is a Potent Tool to Improve Chemotherapy in Melanoma In Vitro and In Vivo," Biomolecules, vol. 10, no. 7, Jul 8 2020.
[69] J. R. Liu, G. M. Xu, X. M. Shi, and G. J. Zhang, "Low temperature plasma promoting fibroblast proliferation by activating the NF-kappaB pathway and increasing cyclinD1 expression," Sci Rep, vol. 7, no. 1, p. 11698, Sep 15 2017.
[70] K. Mokhtari, A. Perez-Jimenez, L. Garcia-Salguero, A. L. J, and E. E. Rufino-Palomares, "Unveiling the Differential Antioxidant Activity of Maslinic Acid in Murine Melanoma Cells and in Rat Embryonic Healthy Cells Following Treatment with Hydrogen Peroxide," Molecules, vol. 25, no. 17, Sep 3 2020.
[71] G. M. Jose, M. Raghavankutty, and G. M. Kurup, "Attenuation of hydrogenperoxide-induced oxidative damages in L929 fibroblast cells by sulfated polysaccharides isolated from the edible marine algae Padina tetrastromatica," Journal of Bioactive and Compatible Polymers, vol. 34, no. 2, pp. 150-162, 2019.
[72] S. Ivankovic, S. Music, M. Gotic, and N. Ljubesic, "Cytotoxicity of nanosize V(2)O(5) particles to selected fibroblast and tumor cells," Toxicol In Vitro, vol. 20, no. 3, pp. 286-94, Apr 2006.
[73] G. Bauer, D. Sersenova, D. B. Graves, and Z. Machala, "Cold Atmospheric Plasma and Plasma-Activated Medium Trigger RONS-Based Tumor Cell Apoptosis," Sci Rep, vol. 9, no. 1, p. 14210, Oct 2 2019.
[74] I. Yagi, Y. Shirakawa, K. Hirakata, T. Akiyama, S. Yonemori, K. Mizuno, R. Ono, and T. Oda, "Measurement of OH, O, and NO densities and their correlations with mouse melanoma cell death rate treated by a nanosecond pulsed streamer discharge," Journal of Physics D: Applied Physics, vol. 48, no. 42, 2015.
[75] P. M. Girard, A. Arbabian, M. Fleury, G. Bauville, V. Puech, M. Dutreix, and J. S. Sousa, "Synergistic Effect of H2O2 and NO2 in Cell Death Induced by Cold Atmospheric He Plasma," Sci Rep, vol. 6, p. 29098, Jul 1 2016.
[76] Y. Tabuchi, H. Uchiyama, Q. L. Zhao, T. Yunoki, G. Andocs, N. Nojima, K. Takeda, K. Ishikawa, M. Hori, and T. Kondo, "Effects of nitrogen on the apoptosis of and changes in gene expression in human lymphoma U937 cells exposed to argon-based cold atmospheric pressure plasma," Int J Mol Med, vol. 37, no. 6, pp. 1706-14, Jun 2016.
[77] A. Pankaj, P. Ji Hoon, A. Anser, and C. Eun Ha, "How Does Plasma Activated Media Treatment Differ From Direct Cold Plasma Treatment?," Anti-Cancer Agents in Medicinal Chemistry, vol. 18, no. 6, pp. 805-814, 2018.
[78] S. Vermeylen, J. De Waele, S. Vanuytsel, J. De Backer, J. Van der Paal, M. Ramakers, K. Leyssens, E. Marcq, J. Van Audenaerde, E. L. J. Smits, S. Dewilde, and A. Bogaerts, "Cold atmospheric plasma treatment of melanoma and glioblastoma cancer cells," Plasma Processes and Polymers, vol. 13, no. 12, pp. 1195-1205, 2016.
[79] K. A. Ahmed, C. R. Correa, T. J. Dilling, N. G. Rao, R. Shridhar, A. M. Trotti, R. B. Wilder, and J. J. Caudell, "Altered Fractionation Schedules in Radiation Treatment: A Review," Seminars in Oncology, vol. 41, no. 6, pp. 730-750, 2014.
[80] H. D. Thames, Jr., L. T. Peters, H. R. Withers, and G. H. Fletcher, "Accelerated fractionation vs hyperfractionation: Rationales for several treatments per day," International Journal of Radiation Oncology, Biology, Physics, vol. 9, no. 2, pp. 127-138, 1983.
[81] Y. Ma, C. S. Ha, S. W. Hwang, H. J. Lee, G. C. Kim, K. W. Lee, and K. Song, "Non-thermal atmospheric pressure plasma preferentially induces apoptosis in p53-mutated cancer cells by activating ROS stress-response pathways," PLoS One, vol. 9, no. 4, p. e91947, 2014.
[82] Y. Binenbaum, G. Ben-David, Z. Gil, Y. Z. Slutsker, M. A. Ryzhkov, J. Felsteiner, Y. E. Krasik, and J. T. Cohen, "Cold Atmospheric Plasma, Created at the Tip of an Elongated Flexible Capillary Using Low Electric Current, Can Slow the Progression of Melanoma," PLoS One, vol. 12, no. 1, p. e0169457, 2017.
[83] U. E. Martinez-Outschoorn, Z. Lin, C. Trimmer, N. Flomenberg, C. Wang, S. Pavlides, R. G. Pestell, A. Howell, F. Sotgia, and M. P. Lisanti, "Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxide, driving the Warburg effect: implications for PET imaging of human tumors," Cell Cycle, vol. 10, no. 15, pp. 2504-20, Aug 1 2011.
[84] S. Pavlides, D. Whitaker-Menezes, R. Castello-Cros, N. Flomenberg, A. K. Witkiewicz, P. G. Frank, M. C. Casimiro, C. Wang, P. Fortina, S. Addya, R. G. Pestell, U. E. Martinez-Outschoorn, F. Sotgia, and M. P. Lisanti, "The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma," Cell Cycle, vol. 8, no. 23, pp. 3984-4001, Dec 2009.
[85] L. Wilde, M. Roche, M. Domingo-Vidal, K. Tanson, N. Philp, J. Curry, and U. Martinez-Outschoorn, "Metabolic coupling and the Reverse Warburg Effect in cancer: Implications for novel biomarker and anticancer agent development," Semin Oncol, vol. 44, no. 3, pp. 198-203, Jun 2017.
[86] G. Gambara, M. Gaebler, C. Regenbrecht, and A. Silvestri, "From Chemotherapy to Combined Targeted Therapeutics: In Vitro and in Vivo Models to Decipher Intra-tumor Heterogeneity," Frontiers in Pharmacology, vol. 9, 02/14 2018.
[87] L. Kemény, Z. Kurgyis, T. Buknicz, G. Groma, Á. Jakab, K. Zänker, T. Dittmar, and I. Nemeth, "Melanoma Cells Can Adopt the Phenotype of Stromal Fibroblasts and Macrophages by Spontaneous Cell Fusion in Vitro," International Journal of Molecular Sciences, vol. 17, p. 826, 06/02 2016.
[88] A. Marconi, M. Quadri, A. Saltari, and C. Pincelli, "Progress in melanoma modelling in vitro," Experimental Dermatology, vol. 27, no. 5, pp. 578-586, 2018.
[89] M. Oparka, J. Walczak, D. Malinska, L. van Oppen, J. Szczepanowska, W. J. H. Koopman, and M. R. Wieckowski, "Quantifying ROS levels using CM-H2DCFDA and HyPer," Methods, vol. 109, pp. 3-11, Oct 15 2016.
[90] M. T. Ahlen, A. Husebekk, M. K. Killie, B. Skogen, and T. B. Stuge, "T-cell responses associated with neonatal alloimmune thrombocytopenia: isolation of HPA-1a-specific, HLA-DRB3*0101-restricted CD4+ T cells," Blood, vol. 113, no. 16, pp. 3838-44, Apr 16 2009.
[91] J. L. Suthar and J. R. Laghari, "Dielectric breakdown studies of Teflon perfluoroalkoxy at high temperature," Journal of Materials Science, vol. 27, no. 7, pp. 1795-1800, 1992/04/01 1992.
[92] C. R. Kruse, M. Singh, S. Targosinski, I. Sinha, J. A. Sørensen, E. Eriksson, and K. Nuutila, "The effect of pH on cell viability, cell migration, cell proliferation, wound closure, and wound reepithelialization: In vitro and in vivo study," Wound Repair and Regeneration, vol. 25, no. 2, pp. 260-269, 2017.
[93] A. Jo, H. M. Joh, J. W. Chung, and T. H. Chung, "Cell viability and measurement of reactive species in gas- and liquid-phase exposed by a microwave-excited atmospheric pressure argon plasma jet," Current Applied Physics, vol. 20, no. 4, pp. 562-571, 2020.
[94] H. J. Ahn, K. I. Kim, N. N. Hoan, C. H. Kim, E. Moon, K. S. Choi, S. S. Yang, and J.-S. Lee, "Targeting Cancer Cells with Reactive Oxygen and Nitrogen Species Generated by Atmospheric-Pressure Air Plasma," PLOS ONE, vol. 9, no. 1, p. e86173, 2014.
[95] A. Samouilov, Y. Y. Woldman, J. L. Zweier, and V. V. Khramtsov, "Magnetic resonance study of the transmembrane nitrite diffusion," (in eng), Nitric Oxide, vol. 16, no. 3, pp. 362-370, 2007.
[96] M. N. Möller and A. Denicola, "Diffusion of nitric oxide and oxygen in lipoproteins and membranes studied by pyrene fluorescence quenching," Free Radical Biology and Medicine, vol. 128, pp. 137-143, 2018.
[97] X. Zhou, D. Yuan, M. Wang, and P. He, "H2O2-induced endothelial NO production contributes to vascular cell apoptosis and increased permeability in rat venules," (in eng), Am J Physiol Heart Circ Physiol, vol. 304, no. 1, pp. H82-H93, 2013.
[98] M. A. Wallig and E. B. Janovitz, "Chapter 4 - Morphologic Manifestations of Toxic Cell Injury," in Haschek and Rousseaux's Handbook of Toxicologic Pathology (Third Edition), W. M. Haschek, C. G. Rousseaux, and M. A. Wallig, Eds. Boston: Academic Press, 2013, pp. 77-105.
[99] M. Fischer, C. V. Dang, and J. A. DeCaprio, "Chapter 17 - Control of Cell Division," in Hematology (Seventh Edition), R. Hoffman et al., Eds.: Elsevier, 2018, pp. 176-185.
[100] J. H. Chung, Y. Zhang, and F. Bunz, "Checkpoint bypass and cell viability," Cell Cycle, vol. 9, no. 11, pp. 2102-2107, 2010.