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Immunogenic Potential Of Cold Atmospheric Plasma For The Treatment Of Pancreatic Cancer 低温常压血浆治疗胰腺癌的免疫原性潜力
Clinical Plasma Medicine Pub Date : 2018-02-01 DOI: 10.1016/j.cpme.2017.12.041
Jinthe Van Loenhout , Christophe Deben , Julie Jacobs , Jorrit De Waele , Jonas Van Audenaerde , Elly Marcq , Sylvia Dewilde , Annemie Bogaerts , Evelien Smits
{"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":null,"pages":null},"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}
引用次数: 3
Therapeutic Efficacy Of Plasma Activated Medium In 2d And 3d In Vitro Head And Neck Fadu Cancer Cell 血浆活化培养基对体外培养头颈部发度癌细胞的治疗效果
Clinical Plasma Medicine Pub Date : 2018-02-01 DOI: 10.1016/j.cpme.2017.12.063
Nofel Merbahi , Julie Chaivin , Florian Judée , Patricia Vicendo , Mohammed Yousfi
{"title":"Therapeutic Efficacy Of Plasma Activated Medium In 2d And 3d In Vitro Head And Neck Fadu Cancer Cell","authors":"Nofel Merbahi ,&nbsp;Julie Chaivin ,&nbsp;Florian Judée ,&nbsp;Patricia Vicendo ,&nbsp;Mohammed Yousfi","doi":"10.1016/j.cpme.2017.12.063","DOIUrl":"10.1016/j.cpme.2017.12.063","url":null,"abstract":"<div><p>Plasma Activated Media (PAM) has shown an increasing anticancer effect in the past few [1-3]. In <em>in vitro</em><span>, decrease in cell proliferation<span> [2.4], DNA damage [2;5] and apoptosis [6] were observed. The main advantage of PAM is its possibility to be prepared in advance and it can be used several weeks after activation by plasma jet when it is stored at the right temperature [2;7].</span></span></p><p><span>The aim of this work is to investigate the inhibitory effect of PAM and hydrogen peroxide H2O2 on Head and Neck cancerous cells (FaDu). The response of FaDu cells in monolayer cultures and Multi Cellular Tumor Spheroids<span> (MCTS) after treatment with different PAMs was compared. A homemade helium plasma jet was used to produce PAM. Helium plasma jet was generated using </span></span>dielectric<span> barrier discharge configuration. Helium was injected with flowmeter and the gas flow is fixed at 3L/min.</span></p><p>One treatment with PAM induces cell detachment from MTCs since the first day in a PAM exposure dependent manner. This is due to the presence of H2O2 in PAM. However, a rapid spheroids regrowth is observed attributed to a resistance of FaDu cells to H2O2. After multiple treatments of MCTS with PAM we obtained an inhibition of cell growth. MCTS is brought out with a comparison of PAM effect on 2D versus MCTS. Inversely, PAM induces cell death in the case of 2D cell culture. This result underlines the importance of working with MCTS instead of 2D cells.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75723344","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}
引用次数: 2
Immuno-modulatory effect of bio-plasma against cancer and other dreadful disease 生物血浆对癌症和其他可怕疾病的免疫调节作用
Clinical Plasma Medicine Pub Date : 2018-02-01 DOI: 10.1016/j.cpme.2017.12.024
Nagendra Kumar Kaushik * , Neha Kaushik , Manish Adhikari , Su-Jae Lee , Eun Ha Choi
{"title":"Immuno-modulatory effect of bio-plasma against cancer and other dreadful disease","authors":"Nagendra Kumar Kaushik * ,&nbsp;Neha Kaushik ,&nbsp;Manish Adhikari ,&nbsp;Su-Jae Lee ,&nbsp;Eun Ha Choi","doi":"10.1016/j.cpme.2017.12.024","DOIUrl":"10.1016/j.cpme.2017.12.024","url":null,"abstract":"<div><p><span><span>The application of plasma medicine technology has been actively explored over last several years. Recently, non-thermal plasma has demonstrated potential as a safe anticancer therapeutic approach that can kill various types of cancer targets [1-4]. There is the urgent need of new human health care’s technology against cancers based on immuno-modulations. Main target of our study is to enhance efficacy and selectivity of plasma on cancer cells<span> and cancer microenvironment by inducing immune-modulations. Fundamental insights on the cold plasma interactions with the immune cells<span><span> and cancer micro-environment can clarify the basic mechanisms of plasma induced immune-stimulation. Recent preliminary study suggests that plasma significantly modulated immune cells and can induce cancer cell death in co-culture condition [5-7]. In one of our recent studies, using a monocyte<span> cell model, we show that cold plasma activates the differentiation of monocytes into a macrophage-like phenotype and can increase mitochondrial/lysosomal numbers, suggesting that plasma may stimulate macrophage differentiation or activation. In turn, the interaction of plasma-activated macrophage cells reduced pro-tumorigenic features such as epithelial-mesenchymal-transition (EMT) and the stem-like population of tumor cells. Furthermore, plasma targeted macrophage activity and consequently enhanced </span></span>apoptosis via expression of the TNF-α/NOS+ M1-like phenotype. In another study we have evaluated role of plasma induced damage associated molecular patterns/ </span></span></span>immunogenic cell death<span><span> in immune activation and cancer treatment<span> in skin and oral cancer models. We have also initiated a study on plasma induced immuno-modulations for treatment of atopic dermatitis </span></span>skin disorder. Present research work mainly comprises plasma induced activation of immune cells; which find applications for curing various kinds of resistant tumors and other dreadful diseases. Our main objectives are (i) to clarify basic mechanism on plasma induced immuno-modulations (ii) to develop immunomodulation based strategy for the treatment of various dreadful diseases including cancers (iii) to initiate </span></span>clinical trial based on pre-clinical study.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73137666","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}
引用次数: 0
Cold plasma treatment of in vitro gliomas and patient-derived tumors – Role of human myeloid cells 体外胶质瘤和患者源性肿瘤的冷等离子体治疗——人髓细胞的作用
Clinical Plasma Medicine Pub Date : 2018-02-01 DOI: 10.1016/j.cpme.2017.12.009
Sascha Marx , Frederik Kinnen , Juliane Moritz , Eric Freund , Mathias Stope , Sandra Bien-Möller , Bernhard H. Rauch , Christopher Ritter , Henry W.S. Schroeder , Sander Bekeschus
{"title":"Cold plasma treatment of in vitro gliomas and patient-derived tumors – Role of human myeloid cells","authors":"Sascha Marx ,&nbsp;Frederik Kinnen ,&nbsp;Juliane Moritz ,&nbsp;Eric Freund ,&nbsp;Mathias Stope ,&nbsp;Sandra Bien-Möller ,&nbsp;Bernhard H. Rauch ,&nbsp;Christopher Ritter ,&nbsp;Henry W.S. Schroeder ,&nbsp;Sander Bekeschus","doi":"10.1016/j.cpme.2017.12.009","DOIUrl":"10.1016/j.cpme.2017.12.009","url":null,"abstract":"<div><p><span><span>Tumor-associated macrophages (TAM) are the pre-dominant myeloid cells within </span>malignant glioma<span><span><span> and are a poor prognostic factor </span>in patients<span><span><span>. TAM in malignant glioma show a tumor-supporting, so-called M2 phenotype. The aim of this study was to characterize phenotype and relevant markers of monocytes/macrophages in the </span>tumor microenvironment following exposure to cold physical plasma Monocytes were enriched from </span>peripheral blood mononuclear cells derived from young healthy volunteers donating blood after </span></span>informed consent<span><span> and in accordance with the guidelines of the local ethics committee. Monocytes were co-cultured with a glioma cell line<span><span> (U87MG). The latter readily induced a M2 phenotype in these monocytes<span> as seen by an increase in CD163 expression. Prior to co-culture, either U87MG cells or monocytes were treated with an atmospheric pressure argon plasma jet (kINPen) for 15 seconds or 5 seconds, respectively. Non-treated co-cultures as well as single monocytes cultures served as controls. FACS immuno-phenotyping of monocytes/macrophages was performed for </span></span>CD55, CD97, CD162, CD163, CD169, CD204, CD276, HLA-DR, and HLA-ABC after 24h, 48h, and 72h. M2 polarization of monocytes by U87MG was neither attenuated nor reversed by plasma </span></span>treatment<span>. We next exposed primary glioblastoma patient material to cold physical plasma (kINPen) ex vivo. After treatment, tissues were incubated for 24h, and supernatants were collected. Multiplex cytokine analysis of supernatants. Results of five patients showed an absence of IFNα, IFNγ, IL12p70, IL17α, and IL23, and a presence of IL1β, TNFα, MCP1, IL6, IL8, IL10, IL18, and IL33 in samples. A mixed response was observed. For instance, both of the myeloid-cell interacting proteins MCP1 and IL1β are associated with glioma aggressiveness, and secretion of IL1β decreased after plasma treatment whereas MCP1 was increased. Glioma tissue sections will determine the distribution of myeloid cells within the tumor after plasma treatment compared to controls.</span></span></span></span><span><figure><span><img><ol><li><span>Download : <span>Download high-res image (136KB)</span></span></li><li><span>Download : <span>Download full-size image</span></span></li></ol></span></figure></span></p><p>Figure 1: Fold change of several chemokines/cytokines in kINPen plasma-treated primary human glioblastoma samples compared to untreated glioma tissue.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84057020","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}
引用次数: 0
Plasma-Activated Medium Inhibites Metastatic Activities Of Ovarian Cancer Cells In Vitro Via Repressing Mapk Pathway 血浆活化培养基通过抑制Mapk通路抑制卵巢癌细胞的体外转移活性
Clinical Plasma Medicine Pub Date : 2018-02-01 DOI: 10.1016/j.cpme.2017.12.065
Yang Peng , Hiroaki Kajiyama , Kae Nakamura , Fumi Utsumi , Nobuhisa Yoshikawa , Hiromasa Tanaka , Masaaki Mizuno , Shinya Toyokuni , Masaru Hori , Fumitaka Kikkawa
{"title":"Plasma-Activated Medium Inhibites Metastatic Activities Of Ovarian Cancer Cells In Vitro Via Repressing Mapk Pathway","authors":"Yang Peng ,&nbsp;Hiroaki Kajiyama ,&nbsp;Kae Nakamura ,&nbsp;Fumi Utsumi ,&nbsp;Nobuhisa Yoshikawa ,&nbsp;Hiromasa Tanaka ,&nbsp;Masaaki Mizuno ,&nbsp;Shinya Toyokuni ,&nbsp;Masaru Hori ,&nbsp;Fumitaka Kikkawa","doi":"10.1016/j.cpme.2017.12.065","DOIUrl":"10.1016/j.cpme.2017.12.065","url":null,"abstract":"<div><p>Ovarian cancer is among the most malignant gynecologic cancers<span> since peritoneal dissemination often occurs at the diagnosis of these patients. The 5-year survival rate is less than 50%. Recently, non-equilibrium atmospheric pressure plasma (NEAPP) has been introduced in medical field. We have already demonstrated the cytotoxic effect of the direct plasma exposure to ovarian cancer cells. However, it is difficult to expose cancer cells to plasma gas intraperitoneally. Thus, we established the system of plasma-activated medium (PAM) to treat ovarian cancer indirectly instead of a direct exposure to plasma [1].</span></p><p>In our previous works, it was demonstrated that PAM significantly inhibited proliferation ability of ovarian cancer cells, with fibroblast cells remaining unaffected though. Both <em>in vitro</em> and <em>in vivo</em><span> study had confirmed the cytotoxic effect of PAM to ovarian cancer. However, it still remains unknown whether PAM can affect metastasis of ovarian cancer cells, which is the fatal problem of ovarian cancer patients [2].</span></p><p>In this study, we tried to investigate PAM’s anti-metastasis effect <em>in vitro</em><span><span> and the underneath mechanism. Firstly, we performed wound-healing and transwell assay on ES2, one of ovarian cancer cell lines. We found that the cell migration and invasion abilities were significantly inhibited by PAM. Secondly, we established a co-culture system by seeding ES2 cells onto monolayer of peritoneal </span>mesothelial cells<span>, which models the initial step of ovarian cancer cells metastasis in human peritoneal cavity<span>, and it was found that PAM significantly repressed ES2 cells to implant onto mesothelial cells. Moreover, mechanism study showed both mRNA and protein levels of MMP-9 were inhibited by PAM. And PAM significantly inhibited the phosphorylation of JNK1/2 MAPK and p38 MAPK (figure 1), which indicated that inhibition of MMP-9 was dependent on MAPK pathway [3].</span></span></span></p><p>In summary, it is indicated in this work that PAM presents efficient inhibitory effect towards ovarian cancer cells metastasis <em>in vitro</em><span>. Moreover, PAM’s anti-metastasis effect is implemented by repressing the activation MAPK pathway, resulting in de-activation of downstream target MMP-9, thus leading to suppression of cell migration and invasion. In the near future, it might be a new clinical strategy for metastatic ovarian cancer patients to choose PAM therapy via intaperitoneal treatment.</span><span><figure><span><img><ol><li><span>Download : <span>Download high-res image (86KB)</span></span></li><li><span>Download : <span>Download full-size image</span></span></li></ol></span></figure></span></p><p>Fig. 1</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79434310","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}
引用次数: 2
Contribution Of Intracellular Mobile Zinc To Anti-Cancer Effects Of Plasma-Activated Medium 细胞内移动锌对血浆活化培养基抗癌作用的贡献
Clinical Plasma Medicine Pub Date : 2018-02-01 DOI: 10.1016/j.cpme.2017.12.023
Hirokazu Hara, Tetsuo Adachi
{"title":"Contribution Of Intracellular Mobile Zinc To Anti-Cancer Effects Of Plasma-Activated Medium","authors":"Hirokazu Hara,&nbsp;Tetsuo Adachi","doi":"10.1016/j.cpme.2017.12.023","DOIUrl":"10.1016/j.cpme.2017.12.023","url":null,"abstract":"<div><p><span>Non-thermal plasma (NTP) irradiation has been reported to have a broad array of biological effects, and has been found to preferentially kill cancer cells<span>. Therefore, NTP is a promising approach for cancer therapy. The indirect NTP irradiation method using plasma-activated medium (PAM) induces cancer cell death<span> to the same extent as the direct NTP irradiation method. The anti-cancer effects of PAM are thought to be attributed to reactive oxygen species (ROS), mainly H</span></span></span><sub>2</sub>O<sub>2</sub><span>. On the other hand, oxidative stress caused by ROS has been demonstrated to induce the liberation of zinc (Zn</span><sup>2+</sup>) from intracellular Zn<sup>2+</sup> pools and Zn<sup>2+</sup>-dependent cell death. Zn<sup>2+</sup> is thought to function as a second messenger activated by oxidative stress. We previously reported that PAM rapidly triggered intracellular Zn<sup>2+</sup><span> liberation in human neuroblastoma SH-SY5Y cells, and that the liberated Zn</span><sup>2+</sup> induced activation of poly(ADP-ribose) polymerase 1 (PARP-1) and subsequent loss of cellular NAD<sup>+</sup><span> and ATP, resulting in cell death associated with energy exhaustion. Recently, we also found that normal human fibroblasts were less sensitive to PAM cytotoxicity compared with SH-SY5Y cells. PAM decreased intracellular NAD</span><sup>+</sup> levels in both cell types, whereas the depletion of ATP and mitochondrial ROS generation were hardly observed in fibroblasts. The addition of Zn<sup>2+</sup> augmented PAM-induced cell death and ATP depletion in fibroblasts. The levels of PAM-induced Zn<sup>2+</sup> liberation were lower in fibroblasts than in SH-SY5Y cells. These findings suggest the possibility that cells with high intracellular mobile Zn<sup>2+</sup><span> are susceptible to PAM cytotoxicity. Moreover, PAM promoted G2/M growth arrest of lung adenocarcinoma A549 cells via activation of the ATM-p53 pathway and the Zn</span><sup>2+</sup><span> chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) suppressed these events. Thus, we consider intracellular mobile Zn</span><sup>2+</sup> to play a key role in the anti-cancer effects of PAM.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83643369","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}
引用次数: 1
Cold Atmospheric Plasma Suppresses Ovarian Cancer Cell Activity With Concurrent Secretion Of Heat Shock Protein 27 Affecting Monocyte Fate 低温大气血浆抑制卵巢癌细胞活性,同时分泌影响单核细胞命运的热休克蛋白27
Clinical Plasma Medicine Pub Date : 2018-02-01 DOI: 10.1016/j.cpme.2017.12.040
Matthias B. Stope , Dominique Koensgen , Can Wulff , Ilma Besic , Denis Gümbel , Anne Kaul , Martin Weiss , Karoline Diesing , Axel Kramer , Alexander Mustea , Sander Bekeschus
{"title":"Cold Atmospheric Plasma Suppresses Ovarian Cancer Cell Activity With Concurrent Secretion Of Heat Shock Protein 27 Affecting Monocyte Fate","authors":"Matthias B. Stope ,&nbsp;Dominique Koensgen ,&nbsp;Can Wulff ,&nbsp;Ilma Besic ,&nbsp;Denis Gümbel ,&nbsp;Anne Kaul ,&nbsp;Martin Weiss ,&nbsp;Karoline Diesing ,&nbsp;Axel Kramer ,&nbsp;Alexander Mustea ,&nbsp;Sander Bekeschus","doi":"10.1016/j.cpme.2017.12.040","DOIUrl":"10.1016/j.cpme.2017.12.040","url":null,"abstract":"<div><h3>Background</h3><p><span><span>Ovarian cancer (OC) is a gynecologic tumor with poor prognosis. Despite radical </span>cytoreductive surgery<span><span> and platinum-based adjuvant systemic treatment, </span>OC relapses<span> in the majority of the cases. Several studies have suggested profound antitumor activity of cold atmospheric plasma (CAP). CAP is an ionized gas that mainly mediates its effects via the release of a variety of reactive oxygen and nitrogen species. Evidence of CAP treatment on </span></span></span>OC cells is scarce, and accordingly we investigated their biological responses following exposure to plasma.</p></div><div><h3>Materials and Methods</h3><p><span><span><span>We tested the activity of CAP and CAP-treated medium to inactivate OC cell lines, and investigated their secretory products following CAP treatment. </span>Cell proliferation and </span>cell motility<span><span> was measured. The presence of HSP27 was measured by </span>Western blotting<span> and enzyme-linked immunosorbent assay (ELISA). Supernatants of plasma-treated OC cells were added to the human THP-1 monocytic cell line. Cellular oxidation, viability, growth, morphology, surface marker expression, and </span></span></span>cytokine release were monitored over up to 4 days of culture with supernatants of untreated and plasma-treated cancer cells.</p></div><div><h3>Results</h3><p><span><span>CAP treatment led to an attenuation of OC cell growth and motility. Incubation with CAP-treated cell culture medium gave similar effects. Results were consistent in four OC cell lines. Notably, CAP treatment of OC cells led to a decrease of intracellular HSP27 accompanied by an increase of extracellular HSP27 in the cell culture supernatant. These supernatants did not cause oxidation or blunted cell growth in THP-1 monocytes. Cell morphology was rather unaffected whereas from 12 </span>cell surface markers screened, two (CD271 and CD55) gave a significant increase in plasma-treated OC cell supernatants compared to untreated controls. HSP27 alone led to a decrease of both markers. Likewise, a screening of 13 cytokines release from THP-1 revealed a differential regulation of a number of targets, for example, an upregulation of </span>interleukin 8 in plasma-treated samples compared to untreated controls.</p></div><div><h3>Conclusion</h3><p>Plasma treatment was cytotoxic in ovarian cancer cell lines with functional and phenotypical consequences in human monocytes. The role of extracellular HSP27 induced by CAP treatment may represent immunomodulating mechanisms, which will be characterized more detailed in future.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87874756","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}
引用次数: 0
5th International Workshop on Plasma for Cancer Treatment (IWPCT 2018) Greifswald, Germany, 20-21 March 2018 第五届血浆癌症治疗国际研讨会(IWPCT 2018)于2018年3月20日至21日在德国Greifswald举行
Clinical Plasma Medicine Pub Date : 2018-02-01 DOI: 10.1016/j.cpme.2018.02.002
{"title":"5th International Workshop on Plasma for Cancer Treatment (IWPCT 2018) Greifswald, Germany, 20-21 March 2018","authors":"","doi":"10.1016/j.cpme.2018.02.002","DOIUrl":"https://doi.org/10.1016/j.cpme.2018.02.002","url":null,"abstract":"","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2018.02.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137433547","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}
引用次数: 0
Biologically Active NOx Production By Nano-Second Pin-Plate Discharge In Air 空气中纳秒引脚板放电产生生物活性氮氧化物
Clinical Plasma Medicine Pub Date : 2018-02-01 DOI: 10.1016/j.cpme.2017.12.064
Xuekai Pei, Dogan Gidon, David B. Graves
{"title":"Biologically Active NOx Production By Nano-Second Pin-Plate Discharge In Air","authors":"Xuekai Pei,&nbsp;Dogan Gidon,&nbsp;David B. Graves","doi":"10.1016/j.cpme.2017.12.064","DOIUrl":"10.1016/j.cpme.2017.12.064","url":null,"abstract":"<div><p>Atmospheric pressure air plasma discharges can generate abundance of biologically actives such as nitrogen oxides NO<sub>x</sub> (NO, NO<sub>2</sub> etc) which are known as very important reactive oxygen and nitrogen species (RONS) in biomedical applications.[1-2] In this work, we focus on the study of NO<sub>x</sub> synthesis by nanosecond pin-plate discharge in atmospheric pressure air. The fourier transform infrared (FTIR) spectrum shows the primary species produced by this discharge only include NO<sub>,</sub> NO<sub>2</sub>, and HONO. The energy costs of NO<sub>x</sub> production decrease with increasing pulse width (in the range of 100ns to 260ns) from ~2400 GJ/tN (gigajoules per metric ton) to ~1000 GJ/tN. Detailed investigation of power consumption and NO<sub>x</sub> production throughout the pulse gives hints regarding the mechanisms of efficient NO<sub>x</sub> synthesis, namely that the initial and inefficient breakdown process is the main sink of energy. We show late-pulse, 2 mm gap NO<sub>x</sub> production energy cost may be as low as ~ 300 GJ/tN(~1.4 x 10<sup>17</sup> molecules/J)which is something similar with gliding arc discharge results [3]. A simple 0D post-discharge kinetic model is able to reproduce the experimentally observed trends, assuming the main driver for NO<sub>x</sub> production is electronically excited nitrogen species N2,e*. The model implies an initial increasing trend for efficiency with increased N2,e* concentration which may explain the increase in efficiency we observe with increasing pulse width.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74923134","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}
引用次数: 2
Plasma-Derived Oxidants And The Modulation Of Immunsuppression In Melanoma 血浆来源的氧化剂和黑色素瘤免疫抑制的调节
Clinical Plasma Medicine Pub Date : 2018-02-01 DOI: 10.1016/j.cpme.2017.12.017
Juliane Moritz , Ingo Stoffels , Iris Helfrich , Sander Bekeschus
{"title":"Plasma-Derived Oxidants And The Modulation Of Immunsuppression In Melanoma","authors":"Juliane Moritz ,&nbsp;Ingo Stoffels ,&nbsp;Iris Helfrich ,&nbsp;Sander Bekeschus","doi":"10.1016/j.cpme.2017.12.017","DOIUrl":"10.1016/j.cpme.2017.12.017","url":null,"abstract":"<div><p><span><span>Many diseases are based on dysregulated immune responses. For instance, cancers benefit from immunosuppression [1]. Tumor cells initiate tolerance mechanisms e.g. by expression of inhibitory surface molecules, blunting antitumor immune responses. Similar receptors are often upregulated in </span>immunosuppressive<span><span> immune cells<span><span> in the tumor microenvironment as well [2]. These receptors can contribute to the tumor growth and progression and are associated with a poor prognosis [3]. </span>Reactive oxygen species<span><span> were identified to be involved in the differentiation of hematopoietic lineages and in the regulation of the tumor environment [4, 5]. At the same time, cold physical plasmas were found to be a promising approach in cancer therapy and immunomodulation [6]. Therefore, plasma-derived </span>oxidants may contribute to alter the immunosuppressive potential of immune or </span></span></span>cancer cells<span><span>. Treatment of melanoma and immune cells by plasma was followed by flow cytometric measurements of key immunomodulatory surface markers and their immunosuppressive secretion products. Moreover, immunosuppressive cells release distinct types and amounts of </span>chemokines or cytokines compared to the immune active cells. With the help of these molecules, immunosuppression is spread in the tumor environment. We analyzed the culture supernatants of patient-derived skin cancer samples treated </span></span></span><span><em>ex vivo</em></span> with cold physical plasma. With regard to the immunosuppression, distinct cytokine profiles were shown in plasma-treated clinical samples compared to the controls. In addition, <em>in vitro</em> co-culture assays with melanoma and immune cells verified the potential of plasma in modulating the immunosuppression. This study illustrates the importance and potential of utilizes plasmas to manipulate the redox environment for tumor immune control.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75716265","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}
引用次数: 0
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