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Cold atmospheric pressure plasma jet for the treatment of Aspergillus keratitis 冷常压等离子体喷射治疗曲霉菌性角膜炎
Clinical Plasma Medicine Pub Date : 2018-03-01 Epub Date: 2017-12-15 DOI: 10.1016/j.cpme.2017.12.075
Hamed Nikmaram , Mozhgan Rezaei Kanavi , Mahmood Ghoranneviss , Sahar Balagholi , Hamid Ahmadieh , Danial Roshandel , Maryam Amini
{"title":"Cold atmospheric pressure plasma jet for the treatment of Aspergillus keratitis","authors":"Hamed Nikmaram ,&nbsp;Mozhgan Rezaei Kanavi ,&nbsp;Mahmood Ghoranneviss ,&nbsp;Sahar Balagholi ,&nbsp;Hamid Ahmadieh ,&nbsp;Danial Roshandel ,&nbsp;Maryam Amini","doi":"10.1016/j.cpme.2017.12.075","DOIUrl":"10.1016/j.cpme.2017.12.075","url":null,"abstract":"<div><h3>Purpose</h3><p><span>In an in-vitro and in-vivo study, we investigated the effect of cold atmospheric pressure plasma jet (CAPPJ) in the treatment of </span><span><em>Aspergillus fumigatus</em></span> (<em>A. fumigatus)</em><span> keratitis.</span></p></div><div><h3>Methods</h3><p>In the in vitro phase, suspensions of <em>A. fumigatus</em> with 10<sup>6</sup><span> colony forming units (CFUs) were exposed to CAPPJ, 1, 2, 3, 4, and 5</span> <!-->min per day for 7 consecutive days. After culturing the post-treatment suspension in Saboraud dextrose agar, fungal colonies were counted. The same experiment was performed for fungal colonies cultivated on agar plates. Mean logarithm of CFUs were compared between the baseline and CAPPJ-treated groups and also between the exposure times by using Friedman and Bonferroni tests. In the in vivo phase, 3 rabbits with <em>A. fumigatus</em> keratitis were treated with CAPPJ, 5<!--> <!-->min daily for 3 days followed by microbiologic and histopathologic investigations on the excised corneas.</p></div><div><h3>Results</h3><p>Agar plate and broth media treatment assays disclosed a significant decreasing rate in mean logarithm of CFUs with increased exposure time as compared to the baseline (P = 0.010 and P = 0.012, respectively). This decrease in both treatment assays was statistically significant in the 5<!--> <!-->min-treatment group in comparison with the baseline (P = 0.016). However, in broth medium treatment assay, the decrease was slower and less than CAPPJ-treated agar plates. Direct application of the plasma jet in experimental model of rabbit <em>A. fumigatus</em> keratitis resulted in significant fungal inactivation evidenced by microbiologic and histopathologic investigations.</p></div><div><h3>Conclusion</h3><p>Both in vitro and in vivo results demonstrated that CAPPJ treatment was effective in inactivating fungal pathogens<span> and therefore it may be considered as a new treatment modality for fungal keratitis. However, further studies are required to investigate its long-term safety.</span></p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Pages 14-18"},"PeriodicalIF":0.0,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81090627","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: 10
Comparing two different plasma devices kINPen and Adtec SteriPlas regarding their molecular and cellular effects on wound healing 比较两种不同的等离子装置kINPen和Adtec SteriPlas对伤口愈合的分子和细胞作用
Clinical Plasma Medicine Pub Date : 2018-03-01 Epub Date: 2018-01-31 DOI: 10.1016/j.cpme.2018.01.002
Stephanie Arndt , Anke Schmidt , Sigrid Karrer , Thomas von Woedtke
{"title":"Comparing two different plasma devices kINPen and Adtec SteriPlas regarding their molecular and cellular effects on wound healing","authors":"Stephanie Arndt ,&nbsp;Anke Schmidt ,&nbsp;Sigrid Karrer ,&nbsp;Thomas von Woedtke","doi":"10.1016/j.cpme.2018.01.002","DOIUrl":"10.1016/j.cpme.2018.01.002","url":null,"abstract":"<div><h3>Background</h3><p>Over the past years, plasma medicine has developed from an unknown and little accepted medical field into an integral part of medical research<span> and subsequently of clinical treatment. The cellular mechanisms mediated by plasma treatment in wound healing are well investigated, and plasma sources specifically developed for treating wound healing disorders are already available. Nevertheless, the treatment results obtained with one plasma source cannot be simply transferred to another plasma device. The reason for this non-transferability is the biological effects caused by the ‘cocktail’ of reactive species, radiation (above all ultraviolet light), the electrical current flow from plasma to the body, the flow of working gas, and the heat transfer to the treated surface, depending on the plasma generation technology. Therefore, to avoid toxic, mutagenic, or otherwise damaging effects, the physical and biomedical performance parameters of each plasma device need to be comprehensively evaluated before the device can be used as a medicinal product.</span></p></div><div><h3>Objective</h3><p>This article compared the most important molecular and cellular mechanisms investigated <em>in vitro</em> and <em>in vivo</em> in the context of wound healing.</p></div><div><h3>Methods</h3><p>This study compared two plasma devices that are CE-certified medical devices class IIa, the kINPen®MED including the experimental predecessor devices kINPen09 and kINPen11 (summarized below under kINPen, plasma jet, neoplas and neoplas tools GmbH, Greifswald, Germany) and the MicroPlaSter/Adtec SteriPlas (plasma torch, Adtec Plasma Technology/Adtec Europe, Hiroshima, Japan/Hunslow, UK).</p></div><div><h3>Results</h3><p>The kINPen and the MicroPlaSter are ̶ both optically and technically ̶ completely different plasma devices. The two devices are almost comparable with regard to their cellular effects such as collagen expression, induction of wound healing-relevant cytokines and growth factors, activation of immune cells<span> and other protective mechanisms, as well as improved wound healing. The two devices differ with regard to their effect on cell proliferation and migration, probably due to different treatment times and modalities such as different mechanisms of action of the plasma devices, as well as sources of the cells.</span></p></div><div><h3>Conclusions</h3><p>This comparative study showed that cold atmospheric plasma has several positive effects on wound healing and that kINPen and MicroPlaSter are two devices with substantial, comparable basic research.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Pages 24-33"},"PeriodicalIF":0.0,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2018.01.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73642446","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: 47
Cold Physical Plasma Does Not Promote Metastasis-Like Spread In Human Pancreatic Cancer Cell Lines 冷物理血浆不会促进人胰腺癌细胞系的转移样扩散
Clinical Plasma Medicine Pub Date : 2018-02-01 Epub Date: 2018-04-10 DOI: 10.1016/j.cpme.2017.12.039
Chiara Spadola , Sander Bekeschus , Christine Hackbarth , Claus-Dieter Heidecke , Lars-Ivo Partecke , André Käding
{"title":"Cold Physical Plasma Does Not Promote Metastasis-Like Spread In Human Pancreatic Cancer Cell Lines","authors":"Chiara Spadola ,&nbsp;Sander Bekeschus ,&nbsp;Christine Hackbarth ,&nbsp;Claus-Dieter Heidecke ,&nbsp;Lars-Ivo Partecke ,&nbsp;André Käding","doi":"10.1016/j.cpme.2017.12.039","DOIUrl":"10.1016/j.cpme.2017.12.039","url":null,"abstract":"<div><h3>1. Purpose/Background</h3><p><span>Up to 76% of pancreatic resections show histologically positive resection margins leaving patients with residual tumor load after surgery. Cold Physical Plasma (CPP) has shown antitumor effects inducing apoptosis. The application of CPP after resection of </span>pancreatic cancer<span> could significantly decrease the local microscopic tumor load. Yet, it is unknown whether plasmas may support tumor metastasis<span>. Hence, the aim of this study was to characterize the influence of CPP on possible tumor cell spread. The cell adhesion<span> profile of four different human pancreatic cancer cell lines was analyzed. In addition, the effects of CPP on Epithelial-to-Mesenchymal-Transition (EMT) of pancreatic cancer cells were investigated, especially the relation between ZEB-1 and E-Cadherin.</span></span></span></p><p>To complete the <em>in-vitro</em><span> studies, the chicken chorioallantoic membrane model was used as an </span><em>in-vivo</em><span> model. In relation to preliminary experiments, the cell adhesion molecules as well as the tumor cell spread were characterized for each cell line.</span></p></div><div><h3>2. Methods</h3><p>Using flow cytometry, the pancreatic cancer cell lines PA-TU-8988-T, PA-TU-8988-S, MIA-PaCa-2, PANC-1 were analyzed for CD324 (E-Cadherin), CD326 (EpCam), CD49b (Integrin α-2) and CD49d (Integrin α-4) as well as ZEB-1 after 60sec of CPP treatment<span><span>. Furthermore, metabolic activity was investigated. All experiments were carried out in a 96-well plate in which adherent cells and supernatants (possibly containing floating cells) were observed. CPP treatment was performed employing the atmospheric pressure argon plasma jet kINPen 11. Examining the mechanic influence of the </span>gas flow was done employing argon gas treatment without plasma.</span></p></div><div><h3>3. Results/Conclusion</h3><p><span>CPP reduced viability and metastasis potential of aggressive </span>pancreatic carcinoma cell lines, whereas less aggressive cell lines were less affected. PATU-T showed significantly decreased viability after 60s of CPP treatment compared to controls (p= 0.0304), whereas PATU-S was less affected (p=0.3372). CPP-treatment increased the expression of E-Cadherin (p=0.0001) in PATU-T and MIA-PaCa-2 (p=0.0001) compared to untreated controls. This might affect potential metastasis in these cell lines whereas PATU-S and PANC-1 were not significantly affected.</p><p>Analyzing the number of viable cells after 4 days (as offspring of detached but viable floating tumor after plasma treatment) in all four cell lines, no changes between treated and non-treated cells were observed (p=0.8478).</p><p>These results confirm the antitumor effect of Cold Physical Plasma in pancreatic cancer. Furthermore, the results are promising, that CPP is a safe treatment option which may reduce local reoccurrence and moreover has no promoting effects on tumor cell spread.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Page 25"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80646726","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
Intraperitoneal Treatment With Plasma-Activated Liquid Inhibits Peritoneal Metastasis In Ovarian Cancer Mouse Model 腹腔注射血浆活化液抑制卵巢癌小鼠腹膜转移模型
Clinical Plasma Medicine Pub Date : 2018-02-01 Epub Date: 2018-04-10 DOI: 10.1016/j.cpme.2017.12.073
Kae Nakamura , Hiroaki Kajiyama , Yang Peng , Fumi Utsumi , Nobuhisa Yoshikawa , Hiromasa Tanaka , Masaaki Mizuno , Shinya Toyokuni , Masaru Hori , Fumitaka Kikkawa
{"title":"Intraperitoneal Treatment With Plasma-Activated Liquid Inhibits Peritoneal Metastasis In Ovarian Cancer Mouse Model","authors":"Kae Nakamura ,&nbsp;Hiroaki Kajiyama ,&nbsp;Yang Peng ,&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.2017.12.073","DOIUrl":"10.1016/j.cpme.2017.12.073","url":null,"abstract":"<div><p><span>Non-thermal plasma in the medical field is a novel approach having various beneficial applications, such as sterilization, blood coagulation<span><span><span><span>, tissue regeneration and cancer </span>treatment. Recently, plasma-activated medium (PAM) has been widely studied in various types of cancer such as brain, lung, breast, gastric and ovarian cancer, due to its antitumor effect by inducing </span>apoptosis and DNA damage. [1] We previously demonstrated that PAM showed selective cytotoxicity towards </span>cancer cells, whereas normal cells remained unaffected. Moreover, PAM was shown to exert antitumor effects in acquired/natively chemo-resistant ovarian cancer cells. </span></span><em>In vivo</em><span><span> study, we also demonstrated the antitumor effects of PAM in a subcutaneous tumor formation xenograft<span> mouse model. [2] In the clinic, peritoneal metastasis is quite an issue for ovarian cancer patients and it is also a big obstacle for treatment. However, this model may not reflect the pathological conditions of ovarian cancer, with numerous micrometastatic disseminations in the </span></span>peritoneal cavity.</span></p><p><span>In this study, we selected between the two ovarian cancer cell lines ES2 and SKOV3, which could stably show tumor formation </span><em>in vivo</em>, and decided to use ES2 for the following <em>in vivo</em><span><span> experiments because ES2 was more sensitive than SKOV3 to the effects of PAM. We examined whether PAM therapy affects survival in a mouse model of intraperitoneal injection. Six-week-old female BALB/c nude mice were intraperitoneally injected with ES2 cells and then the mice were treated with PAM or non-plasma-irradiated medium as a control once a day for a total of 3 days. As shown in the figure, Survival analysis was performed using the Kaplan–Meier method, indicating that the survival rates were poorer in the control group than in the PAM therapy group (P &lt; 0.01). However, body weight was not significantly different between the two groups. We also assessed intraperitoneal dissemination in a mouse model by the </span>bioluminescence<span> value from luciferase-expressing ES2 cells, the peritoneal cancer metastasis state was monitored using the IVIS 200 Imaging System. Intraperitoneal PAM injection therapy markedly inhibited intraperitoneal metastasis of ES2 cells. [3]</span></span><span><figure><span><img><ol><li><span>Download : <span>Download high-res image (81KB)</span></span></li><li><span>Download : <span>Download full-size image</span></span></li></ol></span></figure></span></p><p>Overall survival</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Pages 47-48"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86929280","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: 7
Plasma, Cancer, Immunity 血浆,癌症,免疫
Clinical Plasma Medicine Pub Date : 2018-02-01 Epub Date: 2018-04-10 DOI: 10.1016/j.cpme.2017.12.021
Sander Bekeschus , Thomas von Woedtke , Klaus-Dieter Weltmann , Hans-Robert Metelmann
{"title":"Plasma, Cancer, Immunity","authors":"Sander Bekeschus ,&nbsp;Thomas von Woedtke ,&nbsp;Klaus-Dieter Weltmann ,&nbsp;Hans-Robert Metelmann","doi":"10.1016/j.cpme.2017.12.021","DOIUrl":"https://doi.org/10.1016/j.cpme.2017.12.021","url":null,"abstract":"<div><p>Incidence and prevalence of most types of cancers are continuously rising. Oncological research progresses as well, with many new drugs<span><span> and treatment<span><span><span> modalities launched in the last years. Cold physical plasma is a promising new technology for oncology, and already applied in many cancer models successfully. First tumor patients benefited from plasma therapy in the palliative setting. While superficial tumors provide an excellent treatment target for repetitive plasma treatment, tumors within the bodies are much are harder to reach. Plasma treatment can be envisioned during radical surgery to treat wound margins often harboring </span>micrometastasis but plasma intervention may be limited to a single application in such setting. Moreover, diffuse metastatic spread throughout the entire body is unlikely to be reached with plasmas at all. A conceptual paradigm from the field of </span>immunology is that </span></span>cancer cells<span><span><span> are visible to the immune system. They are seen as “foreign” because of mutated proteins and therefore peptide sequences<span> presented on major histocompatibility complexes on the cell surface presented to </span></span>T cells, which in turn aid in killing cancer cells. However, tumor cells evolve to hide their immunogenic potential. This can be retrieved by immunogenic cancer cell death (ICD) induced with, e.g., </span>anthracyclines<span> treatment. A number of physical therapies are ICD inducers as well (radiation, photodynamic therapy), and cold plasma was suggested to be added to this list. The vision of using plasmas as immune modulators is elegant because it would provide cancer patients with an endogenous weapon (the immune system) to battle cancer not only locally but systemically. This may also work in a vaccination approach together with autologous dendritic cells, as there have been many efforts with tumor cell vaccination already in cancer immunotherapy already. This talk will focus on recent advances in plasma oncology and drafts key challenges and research strategies crucial for plasmas as adjuvant oncotherapy in future.</span></span></span></p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Pages 13-14"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137433281","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
Comparison of AC plasma jets between dielectric barrier discharge and surface barrier discharge 介质阻挡放电与表面阻挡放电的交流等离子体射流比较
Clinical Plasma Medicine Pub Date : 2018-02-01 Epub Date: 2018-04-10 DOI: 10.1016/j.cpme.2017.12.010
Insun Park , Sang-You Kim , Inje Kang , Min-keun Bae , Yoonje Lee , Yeongtak Song , Tae Ho Lim , Kyu-Sun Chung *
{"title":"Comparison of AC plasma jets between dielectric barrier discharge and surface barrier discharge","authors":"Insun Park ,&nbsp;Sang-You Kim ,&nbsp;Inje Kang ,&nbsp;Min-keun Bae ,&nbsp;Yoonje Lee ,&nbsp;Yeongtak Song ,&nbsp;Tae Ho Lim ,&nbsp;Kyu-Sun Chung *","doi":"10.1016/j.cpme.2017.12.010","DOIUrl":"10.1016/j.cpme.2017.12.010","url":null,"abstract":"<div><p><span>For plasma to be applied to practical medical tools, the length of plasma column and plasma density should be well controlled in non-thermal atmospheric pressure plasma jets, although active radicals are the real ones to react with the human surfaces. AC plasma jets from two different discharge modes (dielectric barrier discharge and surface barrier discharge) have been compared in terms of plasma and neural parameters. With different AC frequency and different gas composition (He, Ar, He/O</span><sub>2</sub>, or Ar/O<sub>2</sub>) of the source, the characteristics of plasmas and neutrals of two different jets are comparatively investigated by taking discharge images and emission spectra in terms of the length of plasma column, plasma density, and electron temperature, and rotational temperatures. Electrostatic method has also been introduced, although atmospheric plasma tends to generate arc or short-circuit with electric probe tip, in order to deduce the spatially averaged plasma or floating potentials of two jets by a capacitive couple method with condition of collisional sheath according to various discharge conditions[1].</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Page 7"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79987008","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
Plasma Cancer Therapy In Dermatology 皮肤病学中的血浆癌治疗
Clinical Plasma Medicine Pub Date : 2018-02-01 Epub Date: 2018-04-10 DOI: 10.1016/j.cpme.2017.12.029
Georg Daeschlein , Claudia Sicher , Sebastian von Podewils , Rico Rutkowski , Michael Jünger
{"title":"Plasma Cancer Therapy In Dermatology","authors":"Georg Daeschlein ,&nbsp;Claudia Sicher ,&nbsp;Sebastian von Podewils ,&nbsp;Rico Rutkowski ,&nbsp;Michael Jünger","doi":"10.1016/j.cpme.2017.12.029","DOIUrl":"10.1016/j.cpme.2017.12.029","url":null,"abstract":"&lt;div&gt;&lt;p&gt;&lt;span&gt;&lt;span&gt;&lt;span&gt;Main topics in cancer treatment in dermatology are &lt;/span&gt;melanoma (MM), &lt;/span&gt;basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and &lt;/span&gt;metastatic skin tumors&lt;span&gt;&lt;span&gt;&lt;span&gt;&lt;span&gt;&lt;span&gt;. Thereof stage IV MM because of fatal outcome is uf utmost importance. Despite some substantial therapeutic progress now in this entity by immunologic treatments alternatives are warranted when disease is progressing under therapy or the tumor basically appears refractory. National guidelines currently recommend ipilumumab, &lt;/span&gt;vemurafenib&lt;span&gt;&lt;span&gt;, dabrafenib, and high-dose IL-2 as first line agents for Stage IV melanoma but no data exists to guide management of cutaneous and subcutaneous &lt;/span&gt;metastases&lt;span&gt; which are very common. Therapeutic options include intralesional electrochemotherapy&lt;span&gt; and Bacillus Calmette-Guérin, isolated limb perfusion/infusion, interferon-α, topical imiquimod&lt;span&gt;, cryotherapy, radiation, &lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;interferon&lt;span&gt;&lt;span&gt;&lt;span&gt; therapy, and intratumoral interleukin-2 injections. Recent developments include anti-programmed cell death 1 receptor agents (PD-1, nivolumab and pembrolizumab), anti-programmed death-ligand 1 agents, and oncolytic vaccines (talimogene laherparepevec), adoptive &lt;/span&gt;T cell therapy and &lt;/span&gt;dendritic cell vaccines&lt;span&gt;. Regarding BCC and SCC mainly the aggressive variants are of interest for new therapies. A third entity are metastatic tumors of different origin exposing single to field canzerization. Since Cold Plasma (CAP) reacts by different and substantially more complex modes compared to classic drug&lt;span&gt;&lt;span&gt; chemotherapy and also modern antimetabolite&lt;span&gt; and immune therapies&lt;span&gt; like hitherto conventional treatment suffers from limited dosage options to avoid stronger toxicity, combined treatment with CAP offers better efficacy with less adverse effects. By this way substantial add on effects can be shown in vitro for fotemustin, dacarbacin, &lt;/span&gt;&lt;/span&gt;&lt;/span&gt;paclitaxel, and &lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;bleomycin&lt;span&gt;. Similar potentiation can be achieved when electrochemotherapy is applied together with CAP in the presence of bleomycin (systemic) and with the squamous cell carcinoma and the actinic keratosis&lt;span&gt; for the first time CAP was also shown to exert effective anticancer efficacy in humans. In metastatic tumors CAP was shown to decelerate tumor growth, defeat microbial superinfection&lt;span&gt;, support pain relief and therewith increasing quality of life. Additionally for some patients CAP proved significantly better outcome together with better tolerability compared with standard treatment. The combination of conventional and physically supported chemotherapy with CAP appears highly beneficial in therapy of human cancer like melanoma and squamous cell carcinoma by enhanced tumor reduction and less &lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;drug toxicity of chemotherapeutics thus improving markedly quality of life.&lt;/sp","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Pages 18-19"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77741397","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
Intracellular Rons Increase Induced By Helium Plasma Triggers Apoptosis In Cancer Cells 氦等离子体诱导的细胞内ron增加触发癌细胞凋亡
Clinical Plasma Medicine Pub Date : 2018-02-01 Epub Date: 2018-04-10 DOI: 10.1016/j.cpme.2017.12.045
Emilio Martines , Paola Brun , Riccardo Artico , Paola Brun , Roberto Cavazzana , Luigi Cordaro , Daniele Fischetto , Andrea Zuin , Matteo Zuin
{"title":"Intracellular Rons Increase Induced By Helium Plasma Triggers Apoptosis In Cancer Cells","authors":"Emilio Martines ,&nbsp;Paola Brun ,&nbsp;Riccardo Artico ,&nbsp;Paola Brun ,&nbsp;Roberto Cavazzana ,&nbsp;Luigi Cordaro ,&nbsp;Daniele Fischetto ,&nbsp;Andrea Zuin ,&nbsp;Matteo Zuin","doi":"10.1016/j.cpme.2017.12.045","DOIUrl":"10.1016/j.cpme.2017.12.045","url":null,"abstract":"<div><p><span>We describe an in-vitro study aimed at elucidating the role or Reactive Oxygen and Nitrogen Species (RONS) in promoting a selective killing of cancer cells<span>, and the possibility of emphasizing the selectivity towards cancer cells by combining the plasma treatment<span> with the effect of a molecule known to enhance intracellular ROS production. Lung carcinoma cell lines and cultured primary cells isolated from surgical samples of laryngeal and lung cancers as well as healthy tissue counterparts were treated with an indirect plasma source, which uses a RF voltage to ionize a helium flow mixed with ambient air in the region between two brass grids [1]. The helium enriched with active chemical species is then sent to the substrate to be treated. It has already been reported that this kind of treatment induces an increase in the level of endogenous </span></span></span>Reactive Oxygen Species<span> (ROS) in eukaryotic human cells [2]. In the present study, ROS generation was confirmed, but the increase was markedly higher in cancer cells than in healthy ones. The same effect was observed for intracellular nitric oxide<span><span> (NO). Furthermore, incubating the cells with antimycin A (AMA), a molecule known to increase ROS production [3], the effect could be amplified, both for ROS and NO. The selective increase in endogenous RONS was associated to increased expression of hypoxia-inducible factor (HIF)-α, an oxygen-sensitive </span>transcriptional activator<span>, and to a higher apoptosis in cancer cells than of their healthy counterparts. Again, these effects were emphasized by incubating with AMA. Overall, these results point to confirm the important role played by RONS in plasma-based cancer treatment, and to the possible combination with chemotherapeutic drugs to better tailor the selective effect induced by the plasma treatment.</span></span></span></p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Pages 28-29"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73457376","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
Sensitivity Of Murine Melanoma Cells B16 To Plasma Needle Treatment 小鼠黑色素瘤细胞B16对血浆针治疗的敏感性
Clinical Plasma Medicine Pub Date : 2018-02-01 Epub Date: 2018-04-10 DOI: 10.1016/j.cpme.2017.12.037
Jorge Humberto Serment Guerrero * , Karina Giron Romero , Régulo López-Callejas , Rosendo Peña-Eguiluz
{"title":"Sensitivity Of Murine Melanoma Cells B16 To Plasma Needle Treatment","authors":"Jorge Humberto Serment Guerrero * ,&nbsp;Karina Giron Romero ,&nbsp;Régulo López-Callejas ,&nbsp;Rosendo Peña-Eguiluz","doi":"10.1016/j.cpme.2017.12.037","DOIUrl":"10.1016/j.cpme.2017.12.037","url":null,"abstract":"&lt;div&gt;&lt;p&gt;&lt;span&gt;&lt;span&gt;Melanoma&lt;span&gt; is the most dangerous form of skin cancer originated from the pigment-producing melanocytes in the &lt;/span&gt;&lt;/span&gt;basal layer&lt;span&gt; of the epidermis. Its capability to produce metastasis, along with the development of quimio or &lt;/span&gt;&lt;/span&gt;radioresistance&lt;span&gt;&lt;span&gt; makes this kind of cancer very dangerous and hard to heal, so is important an early detection as well as the search of new treatments. B16 murine cell line has been used extensively as a model for the study of this type of cancer. Non thermal plasma needle has been effectively used in the inactivation of microorganisms, in the disinfection of several types of tissues and to accelerate the wound healing processes. It also has been tested as an inductor of &lt;/span&gt;apoptosis&lt;span&gt; in HepG2 cancer cell line&lt;span&gt;. The observed effects of plasma upon cells has been attributed to the generation of reactive oxygen/nitrogen species (RONS), which can disrupt the plasmatic membrane and react with several biomolecules including DNA. The aim of the present work is to evaluate the sensitivity of the murine melanoma cell line B16 to a helium-generated plasma needle exposure.&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;B16 cells were grown at 37°C and 5% CO2 atmosphere, in minimal essential medium with 10% FBS.&lt;/p&gt;&lt;p&gt;&lt;span&gt;Cells were harvested by tripsinization, washed twice with Hanks balanced saline solution and further incubated for at least one hour in MEM at 37°C to recover. Blood samples were obtained from healthy donors by venopunction and lymphocytes were separated by using the Ficoll&lt;span&gt; Hypaque technique. Nucleated cells were collected, washed twice with HBSS, resuspended in RPMI-1640 with 10% FBS and kept at 37°C for at least one hour. Both cell types were resuspended in HBSS and then 200 µl aliquots were distributed in a microwell plate and exposed to plasma generated by a flow of 0.7 LPM of helium through a 13.56 MHz radiofrequency generator at a power of 5 W. The needle was kept at a distance of 2 mm. Cell death was evaluated by the fluorescein diacetate&lt;span&gt;&lt;span&gt;&lt;span&gt; technique. After treatments, cells were stained with a 1:1 fluorescein diacetate (80 µg/ml) and ethidium bromide (50 µg/ml) solution and observed with an epifluorescence microscope. Living cells are stained in green while dead cells are stained in red. &lt;/span&gt;Genotoxicity was assessed by means of the &lt;/span&gt;comet assay&lt;span&gt;. After treatments, cells were mixed with an equal volume of 1% low melting point agarose, poured on top of fully frosted microscope slides and immerse in cold lysis solution for an hour. Slides were then transferred to an &lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;electrophoresis cell&lt;span&gt;, covered with the electrophoresis solution (0.3M NaHO, 0.1 mM Na2EDTA) for 20 minutes to allow DNA unwinding and then a current was applied (20 V, 300 mA, 20 minutes). Slides were stained with 60 µl of a 20 µg/ml ethidium bromide solution and observed under an epifluorescence microscope. Comets were score","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Pages 23-24"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89757526","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
Treatment Of Hypoxic Tumours With Plasma Jets 等离子体射流治疗缺氧肿瘤
Clinical Plasma Medicine Pub Date : 2018-02-01 Epub Date: 2018-04-10 DOI: 10.1016/j.cpme.2017.12.012
Endre Szili , Jun-Seok Oh , Hideo Fukuhara , Keiji Inoue , Akimitsu Hatta , Rob Short
{"title":"Treatment Of Hypoxic Tumours With Plasma Jets","authors":"Endre Szili ,&nbsp;Jun-Seok Oh ,&nbsp;Hideo Fukuhara ,&nbsp;Keiji Inoue ,&nbsp;Akimitsu Hatta ,&nbsp;Rob Short","doi":"10.1016/j.cpme.2017.12.012","DOIUrl":"10.1016/j.cpme.2017.12.012","url":null,"abstract":"<div><p><span>A challenge in cancer therapy is the destruction of tumours, where there is the potential issue of cancer cells residing within hypoxic tissue. The concept of hypoxic regions within tumours dates back to 1909 and it has long been suspected that under low oxygen tension, cells are “afforded” radiation protection. It has been shown many decades ago, that raising the concentration of oxygen in tissues can significantly improve the outcomes in radiotherapy. For example, in 1953, a meta-analysis of 83 randomised trials showed a clear benefit from raising tissue oxygen tension during radiation therapy, with the clearest benefits seen in cancers of neck and head [1]. However, there are only a limited number of ways to raise oxygen tension in tissues, which include breathing pure oxygen at or above standard temperature and pressure, or hypoxic modification by the means of an administered </span>drug<span> (e.g. nimorazole) [2, 3, 4]. Recently, we (and other research groups) have shown that cold atmospheric plasma jets not only readily deliver reactive oxygen and nitrogen species (RONS) into tissue, but concomitantly raise the oxygen tension in tissue. Combined RONS and oxygen delivery, may significantly elevate oxidative stress<span> in cancer cells, resulting in destruction of these cells within hypoxic tumours. In this presentation, I will provide a brief historical overview of research on the modification of hypoxia<span> in cancers; I will then discuss results that have shown how plasma jets can be used to treat hypoxia in tumours (through delivery of RONS and oxygen into tissues). I will also discuss the potential opportunities, challenges and limitations of the plasma technology for treatment of hypoxic cancer tumours.</span></span></span></p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Pages 8-9"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85052508","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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