Clinical Plasma Medicine最新文献

{"title":"Plasma Elicits Immunogenic Death In Melanoma Cells","authors":"Abraham Lin ,&nbsp;Yury Gorbanev ,&nbsp;Paul Cos ,&nbsp;Evelien Smits ,&nbsp;Annemie Bogaerts","doi":"10.1016/j.cpme.2017.12.013","DOIUrl":"10.1016/j.cpme.2017.12.013","url":null,"abstract":"<div><p>Development of non-thermal plasma for cancer immunotherapeutic applications has received growing attention, namely for induction of immunogenic cancer cell<span> death (ICD). Cancer cells undergoing ICD emit signals known as damage-associated molecular patterns (DAMPs), that can attract and stimulate local immune cells<span><span><span> [1]. Of these, membrane-bound calreticulin is a key DAMP signal that facilitates engulfment of cancer cells by dendritic cells, a critical process for the development of a specific, anti-tumor immune response [2]. Several studies have shown that plasma </span>treatment of cancer cell lines increased the exposure of CRT on the cell surface [3, 4]. However, the mechanism by which plasma elicits ICD is not fully elucidated. We therefore studied the interaction of plasma with </span>melanoma cells, at ICD-inducing regimes.</span></span></p><p><span><span>The B16-F10 murine melanoma cell line and the A375 human melanoma cell line were treated with a microsecond-pulsed </span>dielectric<span><span> barrier discharge system over a range of energies and evaluated for CRT emission. We also studied changes to liquid chemistry following plasma treatment<span>, as cells were not treated under dry conditions. Using electron paramagnetic resonance spectroscopy and </span></span>colorimetric assays<span>, we identified the reactive oxygen and nitrogen species (RONS) present in the liquid after treatment with plasma. By comparing the trends between the exposure of CRT on the cell membrane<span> and the concentration of RONS in the liquid following increasing plasma treatment energies, we can gain insight into which species are most crucial for plasma-induction of ICD. Knowing this will facilitate the optimization of plasma systems for immunotherapy of cancers. Ongoing work includes evaluation of ICD induction of melanoma cells in an </span></span></span></span><em>in vivo</em> mouse model.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Page 9"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75108548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can We Achieve Selectivity In Plasma Medicine?","authors":"Kristian Wende ,&nbsp;Jan-Wilm Lackmann ,&nbsp;Helena Jablonowski ,&nbsp;Katharina Stapelmann ,&nbsp;Thomas von Woedtke ,&nbsp;Sander Bekeschus","doi":"10.1016/j.cpme.2017.12.067","DOIUrl":"10.1016/j.cpme.2017.12.067","url":null,"abstract":"<div><p>Cold physical plasmas have made a remarkable progress over the last few years and are increasingly established in clinics. Especially in chronic wound care and in palliative cancer treatment plasma has a firm foothold [1, 2]. However, the underlying mechanisms have not been completely understood [3, 4].</p><p>In the gas phase of cold plasmas, various chemical entities (electrons, ions, metastables, radicals) can be quantified which subsequently interact with an aqueous or biomolecule dominated interfacial layer. The prevailing secondary species of such encounter are matter of debate, with proposed short lived OH, 1O2, O, e-, H, medium lived NO, OCl-, O3, ONOO-, NO2-, and +/- persistent candidates NO3- or H2O2 for aqueous systems [5]. In the case of separate plasma treatment (creating plasma treated liquids) only a few species are stable enough to finally interact clinically or experimentally with a desired target [6, 7]. Similarly, in the case of the direct treatment, the resulting (or remaining) active species and their propagation in gel-like biomolecule matrices, seems to be limited to stable species. Contrasting these experimental results and conclusions, cold plasma has been deployed successfully in a number of completely different conditions. In all cases research points towards an interference with the cellular redox signaling cascade [8].</p><p>Accordingly, it must be asked if 1) a common biological denominator exist in all successful applications, if 2) the composition of the plasma treated liquid or the biomolecule matrix in direct treatment determines the effect of the plasma, if 3) the treated tissue itself determines the impact and effectivity of the treatment, or if all aspects add proportionately to the plasmas clinical effectivity. If one (or all) statements are true, it appears that i) plasma source design is subordinate, ii) selectivity is determined by the target and not the treatment, and iii) cold plasma delivers an impulse rather than a substantial dose.</p><p>To respond to these theses satisfactorily, our research applying multicellular organoid/animal models and complex biochemical models in order to seek for primary or secondary signs of redox signaling and its potential precursors or conditions [9]. Standardized protocols are used to determine the biochemical equivalence of different plasma sources and to infer on their clinical impact. It can be stated so far, that a cells or tissues properties, e.g. origin, protein content, or membrane composition, massively renders the biological impact of a plasma treatment. On the other hand, different chemical fingerprints have been obtained for various plasma sources, fueling engineering approaches to tailor selective plasma sources.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Page 43"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79470652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection And Regulation Of Radical Production In Plasma Treated Liquids","authors":"Helena Jablonowski ,&nbsp;Ansgar Schmidt-Bleker ,&nbsp;Sander Bekeschus ,&nbsp;Klaus-Dieter Weltmann ,&nbsp;Kristian Wende","doi":"10.1016/j.cpme.2017.12.059","DOIUrl":"10.1016/j.cpme.2017.12.059","url":null,"abstract":"<div><p>The optimization of a plasma source regarding the species production is of high relevance for a tailored therapeutic application [1]. Especially for treatment of cancer versus healthy cells, a selective impact of the plasma is desired [2]. It can be achieved either by varying concentrations of an active species or, in some cases, by different reactive species. In order to regulate the species output, species densities generated in plasma treated liquids have to be determined. Furthermore, the impact of the plasma parameters on the yielded concentrations need to be known. Therefore, the influence of the plasma parameters on ROS and RNS levels in physiologic liquids were investigated for the argon plasma jet kINPen09, which is quite similar to the certified medical product, the kINPen® MED.</p><p>For instance, the impact of molecular gas admixtures to the feed gas, treatment distance, treatment time as well as liquid ingredients were analyzed for different reactive oxygen or reactive nitrogen species. As the more stable species such as nitrite, nitrate, and hydrogen peroxide were already investigated in several studies[3-5] the focus was set on the short-lived species: radicals such as hydroxyl radicals (•OH), superoxide anion radicals (O2•-), or nitric oxide (•NO). In addition, also highly reactive non-radicals such as singlet delta oxygen (1O2) or ozone (O3) were analyzed. These species are well known as relevant for biomedical application [6], furthermore, they are also known to be generated during plasma treatment of liquids in primary as well as in secondary and tertiary reactions [5].</p><p>By the use of different spin probes and spin traps, these radicals and non-radicals, generated during plasma treatment, were detected by electron paramagnetic resonance spectroscopy (EPR). The results obtained from the EPR, colorimetric and ion chromatographic measurements were compared with gas phase studies of a similar plasma source [7, 8] to determine their origin and potential adjustability.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Page 38"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73579204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On The Penetration Depth Of Reactive Oxygen And Nitrogen Species Generated By A Plasma Jet Through Real Biological Tissue","authors":"L. Nie ,&nbsp;J. Duan ,&nbsp;X. Lu","doi":"10.1016/j.cpme.2017.12.051","DOIUrl":"10.1016/j.cpme.2017.12.051","url":null,"abstract":"<div><p>In this work, an actual biological tissue is used to investigate how thick the RONS produced by a plasma jet can penetrate through the tissue. This is one of the most critical questions in plasma medicine. The concentration of reactive oxygen and nitrogen species (RONS) (O₃, H₂O₂, OH, NO₂^-, NO₂^-+NO₃^-) produced by the plasma jet penetrating through different thickness of the tissue are measured. It is found that the reactive oxygen species (ROS) produced by the plasma are significantly consumed by the tissue. For the tissue thickness of 500μm, there is only about five percent or even less of the ROS (O₃, H₂O₂, and OH) penetrating through the tissue. On the other hand, more than eighty percent of the RNS (NO₂^-+NO₃^-) are able to penetrate through the 500μm biological tissue. Furthermore, under certain experiment conditions, some of the RONS can penetrate through 1.25mm of the biological tissue. Finally, besides H₂O₂, NO₂^- and NO₃^-, there is some other unknown RONS that penetrate through the biological tissue.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Page 32"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82147420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma as adjuvant in melanoma treatment via mitochondrial targeting","authors":"Gabriella Pasqual-Melo,&nbsp;Rajesh Gandhirajan,&nbsp;Thomas von Woedtke,&nbsp;Sander Bekeschus","doi":"10.1016/j.cpme.2017.12.034","DOIUrl":"10.1016/j.cpme.2017.12.034","url":null,"abstract":"<div><p>Cutaneous melanoma<span><span><span><span><span> is a highly aggressive malignancy and has rapidly increased over the past several decades [1]. Although the clinical biology and pathogenesis of </span>melanoma<span> are well understood, the prognosis remains poor with limited therapeutic options in the metastatic stage of the disease [2]. Reactive oxygen species<span><span> (ROS) may be drivers of carcinogenesis and may cause oxidative damage to several cellular components, so it is generally considered to be deleterious [3]. However, ROS, as well as the products generated during </span>redox reactions<span><span><span> can act as second messengers and participates of signaling pathways, activating redox-sensitive transcription factors and gene expressions leading to </span>cell proliferation, </span>metastasis, and therapy resistance [4]. Although antioxidants can prevent the onset of melanoma [5], studies have shown that a systemic </span></span></span></span>pro oxidant status is necessary to prevent </span>distant metastases<span><span><span> [6]. Consequently, some therapies aim at the generation of ROS as a mechanism of death [7]. Despite advances in chemotherapy, immunotherapy, and radiotherapy, the success in drug </span>treatment<span> of disseminated disease<span> remains limited. The large number of side effects and resistance to treatment are the main causes of unsuccessful therapy. Thus, it is necessary to search for new strategies that can increase patient survival and quality of life. Cold plasma is a partially ionized gas proved its effectiveness for different applications in </span></span></span>health care and medicine. It has been shown to exert various biologic effects to living tissue and cells ranging from cytoprotective to cytotoxic potency depending on the applied technique [8]. The gas generates reactive oxygen and nitrogen species [9] that are being deposited in cell culture media [10]. Such oxidant-enriched media selectively kills </span></span>cancer cells in vitro by targeting the mitochondrial network [11], but the exact mechanism is still unclear. We aim at therapeutic strategies combining chemotherapy/radiotherapy with cold plasma as a strategy against melanoma. In addition, we studied the mitochondrial action mechanism of plasma, elucidating its possible target.</span></p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Pages 21-22"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87644183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasmas, membranes, and transport across the membranes","authors":"Lluis M. Mir","doi":"10.1016/j.cpme.2017.12.011","DOIUrl":"10.1016/j.cpme.2017.12.011","url":null,"abstract":"<div><p><span>Physical agents, like cold plasma, may affect the cells at various levels, amongst which the cell membrane. Cell or “plasma” membrane is a vital “organ” for the cell. Indeed if cell membrane integrity is affected, transports from cell outside to cell inside and from cell inside to cell outside can no longer be regulated [1]. It is essential for the cell physiology and survival to keep fully regulated the transport across the cell membrane of ions (Na</span>⁺, Ca⁺⁺, K⁺, Cl^-<span><span>), of small molecules (sugars, ATP, aminoacids, </span>drugs – amongst many other xenobiotics) and even of large molecules such as regulatory RNAs (e.g. siRNA) or even proteins, DNAs, …</span></p><p>The way in which physical agents can modify/perturb the cell membrane [2] to cause these changes in the molecules transport across the membrane are even less well known that the changes occurring in the molecules transport. The methods used to analyze cell membrane perturbations have to be very sophisticated due to the dimensions of this element of the cell (the phospholipid bilayer has a thickness of 5 nm). They include nonlinear optical methods such as Raman microspectroscopy [3, 4].</p><p>In the presentation, these issues (changes in membrane structure and changes in transport across the membrane) will be presented in spite of a still fragmentary knowledge. They will be discussed comparing the action of various physical agents (plasma, electromagnetic fields<span>, ultrasounds) to the electric pulses effects for which a deeper knowledge has been accumulated. [1-4], and analyzing their potentialities to cause cell death and to develop in new cancer treatments.</span></p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Pages 7-8"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91010233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenic Potential Of Cold Atmospheric Plasma For The Treatment Of Pancreatic Cancer","authors":"Jinthe Van Loenhout ,&nbsp;Christophe Deben ,&nbsp;Julie Jacobs ,&nbsp;Jorrit De Waele ,&nbsp;Jonas Van Audenaerde ,&nbsp;Elly Marcq ,&nbsp;Sylvia Dewilde ,&nbsp;Annemie Bogaerts ,&nbsp;Evelien Smits","doi":"10.1016/j.cpme.2017.12.041","DOIUrl":"10.1016/j.cpme.2017.12.041","url":null,"abstract":"<div><p>Pancreatic ductal adenocarcinoma<span><span><span> (PDAC) forms the third leading cause of cancer related deaths in western countries. PDAC is a tumor with a fibroblastic stroma compartment that consists of </span>pancreatic stellate cells<span> (PSC) which play a complex role in supporting carcinogenesis, immunosuppression and therapy resistance. Therefore, the 5-year survival rate for PDAC patients remains below a disappointing 8%, stressing the need for new and more effective </span></span>treatments [1]. Recently, cold atmospheric plasma (CAP) has emerged as a potent treatment option for cancer [2]. Although, CAP is being investigated for several years [3], the involvement of the immune system after CAP treatment remains poorly understood.</span></p><p><span><span>The immunogenic cell death<span> (ICD) concept describes that the killing of cancer cells leads to direct activation of the immune system. Cancer cells dying in such an immunogenic fashion release so-called ‘danger-associated molecular patterns’ that are able to induce a specific antitumoral immune response. ICD can be elicited by several physical means such as irradiation and </span></span>photodynamic therapy, providing a rationale for the induction of ICD after CAP treatment [4]. The aim of this study is to investigate the induction of a specific antitumoral immune response after CAP treatment in PDAC, </span><em>in vitro</em>.</p><p><span><span>Phosphate-buffered saline (PBS) was treated with CAP, generated by the kINPenIND®, and subsequently added to the monocultures of both pancreatic cancer cell (PCC) lines and PSC lines. To evaluate the four most important hallmarks of ICD, being membrane exposure of calreticulin, secretion of </span>ATP<span><span><span> and release of HMGB1 and type I interferon, the treatment parameters were optimized (i.e. treatment time, </span>gas flow and gap distance) to obtain 50% </span>cell death. The cellular difference in sensitivity between these two cell types for CAP treatment was assessed through cytotoxic analysis. After attaining the optimal treatment parameters, we investigated the translocation of calreticulin onto the cell surface with flow cytometry. ATP secretion was investigated with a </span></span>bioluminescence assay, while ELISA was used to monitor the release of HMGB1 and interferon type I in the extracellular compartment.</p><p>Our data report a cytotoxic and immunogenic effect of CAP treatment <em>in vitro</em> on both PCC and PSC cell lines. These results warrant further <em>in vivo</em> validation to refine the involvement of the immune system after CAP treatment.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Page 26"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80399906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigations Of A Helium Plasma Jet In Interaction With Biological Liquids","authors":"Delia Ciubotaru * ,&nbsp;Ioana Cristina Gerber ,&nbsp;Ilarion Mihaila ,&nbsp;Valentin Pohoata ,&nbsp;Ionut Topala","doi":"10.1016/j.cpme.2017.12.055","DOIUrl":"10.1016/j.cpme.2017.12.055","url":null,"abstract":"<div><p>For the plasma medicine community<span><span> it is of high interest to understand the physicochemical mechanisms concerning the effects of plasmas on living cells and cancerous cells, in particular. A first step is to study the effects produced upon biological liquids, as they represent the exchange environment for most biological process. After plasma exposure of liquids, minor changes of the basic parameters such as pH, ionic </span>strength<span> or chemical composition can lead to a major biological impact. Thus, this indirect effect of plasma treatment on cells behaviour must also be addressed during plasma cancer studies, together with direct exposure.</span></span></p><p><span>In this context, the present experiments are focused on the plasma production and transfer of oxygen and nitrogen reactive species to a liquid target, e.g. ultra pure water or phosphate-buffered saline. The plasma source consists of a helium plasma jet in a barrier discharge configuration, operated at atmospheric pressure which interacts with solutions up to 40 minutes. Electrical and optical monitoring of the plasma jet was performed over the entire exposure duration, using high speed techniques, in order to assess the plasma jet warm-up period and settling time [1], with and without liquid target. Molecular beam mass spectrometry of the jet confirmed the presence in the various negative and positive ions based on oxygen and nitrogen species [2].</span><span><figure><span><img><ol><li><span>Download : <span>Download high-res image (303KB)</span></span></li><li><span>Download : <span>Download full-size image</span></span></li></ol></span></figure></span></p><p>Fig. 1. Influence of elapsed time on peak values of the current (I_max), time (t_Imax) and O (777 nm) line integral intensity.</p><p><span>The ultraviolet absorption spectra of liquids, in the 200 - 400 nm wavelength range, were acquired immediately after exposure and they were repeated up to 14 days, in order to monitor the liquid chemistry evolution. Using spectral deconvolution, we monitored the variation of absorption bands corresponding to the following species: O</span>₂, NO₂^-, NO₃^<del>-</del>, H₂O₂ and O₃. We observed an increase of the O₂ and NO₂ ^- bands, while the absorption bands related to all other species remain unchanged.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Page 35"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73345768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptation Of Operational Parameters Of Cold Atmospheric Plasma And Their Role In Cancer Therapy","authors":"Eda Gjika ,&nbsp;Sonali Pal-Ghosh ,&nbsp;Li Lin ,&nbsp;Gauri Tadvalkar ,&nbsp;Zhitong Chen ,&nbsp;Colin Young ,&nbsp;Jerome Canady ,&nbsp;Jonathan Sherman ,&nbsp;Mary Ann Stepp ,&nbsp;Michael Keidar","doi":"10.1016/j.cpme.2017.12.026","DOIUrl":"10.1016/j.cpme.2017.12.026","url":null,"abstract":"<div><p><span><span>The evaluation of CAP in cancer treatment has been significantly fueled by the growing demand for more effective therapies. CAP has been reported as a selective treatment method with a higher affinity of inducing </span>cell death in </span>cancer cells<span><span> while leaving normal cells unharmed. However, the extent of its effectiveness varies significantly per cancer type. Studies have revealed that different types of cancers exhibit different response to treatment when exposed to the same CAP conditions. Therefore, an understanding of the immediate effect of CAP on cancer cells may enable improvement of treatment outcomes [1]. We demonstrated that instantaneous CAP response can be monitored in real-time by RealTime-Glo Assay with results interpreted as </span>cell viability. This creates the possibility for developing an adaptive CAP approach platform which could enable real-time modification of the plasma treatment condition. In particular, the composition of reactive oxygen and nitrogen species (RONS) and the intensity of CAP, which is effected by discharge voltage and length of treatment, can be optimized with a feedback system at regular intervals to minimize the predicted viability of cancer cells [1, 2].</span></p><p>In an <em>in vitro</em><span> proof-of-concept study conducted in glioblastoma<span> and breast cancer cells, we showed that CAP reduced cell viability in a dose dependent manner as a function of treatment duration and plasma discharge voltage. In fact, a 30-60 second increase in treatment duration and/or a discharge voltage adjustment from 3.16 to 3.71 kV, was consistently accompanied with a significant reduction in cell viability. Therefore, these two operational parameters can be utilized for adjusting plasma composition and improving treatment outcomes. In addition to the cell viability findings, we determined that CAP inhibited cancer cell proliferation and triggered apoptosis via damage to the mitochondrial membrane<span> and deregulation of the protein synthesis mechanism [2]. The work completed in this study will serve as the foundation for the development of the adaptive CAP platform. The novel platform will intend to propel CAP therapy forefront other well-established therapies associated with cancer treatment.</span></span></span></p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Pages 16-17"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90591954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cold Atmospheric Plasma Selectively Induces Apoptosis In Renal Adenocarcinoma","authors":"Warren J Rowe III ,&nbsp;Xiaoqian Cheng ,&nbsp;Lawan Ly ,&nbsp;Giacomo Basadonna ,&nbsp;Barry Trink ,&nbsp;Michael Keidar ,&nbsp;Jerome Canady","doi":"10.1016/j.cpme.2017.12.047","DOIUrl":"10.1016/j.cpme.2017.12.047","url":null,"abstract":"<div><p><span>The application of cold atmospheric plasma (CAP) in the selective treatment of cancer<span> has drawn increasing attention. However, very few studies have focused on the selective effect of CAP towards cancer compared to the corresponding normal cells, among which the results have been mixed. Guerrero-Preston has shown that CAP selectively kills head and neck squamous cell carcinoma. While the normal </span></span>oral cavity<span><span> epithelial cells were killed to some degree, the mechanism of selectivity was not reported [1]. Breast cancer has been shown to be selectively killed relative to mesenchymal stem cells<span> (MSCs) [2], however, no selectivity was found when compared to normal breast epithelial cells [3]. CAP induces apoptosis of lung cancer without affecting bronchial epithelial cells, but no apoptotic pathways were identified or proposed [4]. Ishaq et al. proposed </span></span>NADPH oxidase<span> (Nox2) as the endogenous ROS<span> source which mediates the ROS level in different types of colon cancer<span> and further induces various degrees of cell death, but this proposed pathway was not verified in normal colon cells [5].</span></span></span></span></p><p>We study the effects of helium cold atmospheric plasma using the Canady Helios Cold Plasma Scalpel on established renal adenocarcinoma<span><span> and renal epithelial cell lines. Our data demonstrates that kidney adenocarcinoma (769-P) is selectively killed compared to renal epithelial cells (HPRCEC). DR4 (TRAIL-R1) expression was found to be significantly increased following CAP </span>treatment, and may contribute to the selective induction of apoptosis. Differences in DR4 expression following CAP treatment may explain the inconsistent responses of various cell lines to CAP.</span></p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Pages 29-30"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76570985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}