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- ItemRisk assessment of kINPen plasma treatment of four human pancreatic cancer cell lines with respect to metastasis(Basel : MDPI AG, 2019) Bekeschus, Sander; Freund, Eric; Spadola, Chiara; Privat-Maldonado, Angela; Hackbarth, Christine; Bogaerts, Annemie; Schmidt, Anke; Wende, Kristian; Weltmann, Klaus-Dieter; Woedtke, Thomas von; Heidecke, Claus-Dieter; Partecke, Lars-Ivo; Käding, AndréCold physical plasma has limited tumor growth in many preclinical models and is, therefore, suggested as a putative therapeutic option against cancer. Yet, studies investigating the cells’ metastatic behavior following plasma treatment are scarce, although being of prime importance to evaluate the safety of this technology. Therefore, we investigated four human pancreatic cancer cell lines for their metastatic behavior in vitro and in chicken embryos (in ovo). Pancreatic cancer was chosen as it is particularly metastatic to the peritoneum and systemically, which is most predictive for outcome. In vitro, treatment with the kINPen plasma jet reduced pancreatic cancer cell activity and viability, along with unchanged or decreased motility. Additionally, the expression of adhesion markers relevant for metastasis was down-regulated, except for increased CD49d. Analysis of 3D tumor spheroid outgrowth showed a lack of plasma-spurred metastatic behavior. Finally, analysis of tumor tissue grown on chicken embryos validated the absence of an increase of metabolically active cells physically or chemically detached with plasma treatment. We conclude that plasma treatment is a safe and promising therapeutic option and that it does not promote metastatic behavior in pancreatic cancer cells in vitro and in ovo. © 2019 by the authors.
- ItemCold argon plasma as adjuvant tumour therapy on progressive head and neck cancer: A preclinical study(Basel : MDPI, 2019) Hasse, Sybille; Seebauer, Christian; Wende, Kristian; Schmidt, Anke; Metelmann, Hans-Robert; Woedtke, Thomas von; Bekeschus, SanderInvestigating cold argon plasma (CAP) for medical applications is a rapidly growing, innovative field of research. The controllable supply of reactive oxygen and nitrogen species through CAP has the potential for utilization in tumour treatment. Maxillofacial surgery is limited if tumours grow on vital structures such as the arteria carotis. Here CAP could be considered as an option for adjuvant intraoperative tumour therapy especially in the case of squamous cell carcinoma of the head and neck. Further preclinical research is necessary to investigate the efficacy of this technology for future clinical applications in cancer treatment. Initially, a variety of in vitro assays was performed on two cell lines that served as surrogate for the squamous cell carcinoma (SCC) and healthy tissue, respectively. Cell viability, motility and the activation of apoptosis in SCC cells (HNO97) was compared with those in normal HaCaT keratinocytes. In addition, induction of apoptosis in ex vivo CAP treated human tissue biopsies of patients with tumours of the head and neck was monitored and compared to healthy control tissue of the same patient. In response to CAP treatment, normal HaCaT keratinocytes differed significantly from their malignant counterpart HNO97 cells in cell motility only whereas cell viability remained similar. Moreover, CAP treatment of tumour tissue induced more apoptotic cells than in healthy tissue that was accompanied by elevated extracellular cytochrome c levels. This study promotes a future role of CAP as an adjuvant intraoperative tumour therapy option in the treatment of head and neck cancer. Moreover, patient-derived tissue explants complement in vitro examinations in a meaningful way to reflect an antitumoral role of CAP. © 2019 by the authors.
- ItemThe molecular and physiological consequences of cold plasma treatment in murine skin and its barrier function(New York, NY [u.a.] : Elsevier, 2020) Schmidt, Anke; Liebelt, Grit; Striesow, Johanna; Freund, Eric; Woedtke, Thomas von; Wende, Kristian; Bekeschus, SanderCold plasma technology is an emerging tool facilitating the spatially controlled delivery of a multitude of reactive species (ROS) to the skin. While the therapeutic efficacy of plasma treatment has been observed in several types of diseases, the fundamental consequences of plasma-derived ROS on skin physiology remain unknown. We aimed to bridge this gap since the epidermal skin barrier and perfusion plays a vital role in health and disease by maintaining homeostasis and protecting from environmental damage. The intact skin of SKH1 mice was plasma-treated in vivo. Gene and protein expression was analyzed utilizing transcriptomics, qPCR, and Western blot. Immunofluorescence aided the analysis of percutaneous skin penetration of curcumin. Tissue oxygenation, perfusion, hemoglobin, and water index was investigated using hyperspectral imaging. Reversed-phase liquid-chromatography/mass spectrometry was performed for the identification of changes in the lipid composition and oxidation. Transcriptomic analysis of plasma-treated skin revealed modulation of genes involved in regulating the junctional network (tight, adherence, and gap junctions), which was confirmed using qPCR, Western blot, and immunofluorescence imaging. Plasma treatment increased the disaggregation of cells in the stratum corneum (SC) concomitant with increased tissue oxygenation, gap junctional intercellular communication, and penetration of the model drug curcumin into the SC preceded by altered oxidation of skin lipids and their composition in vivo. In summary, plasma-derived ROS modify the junctional network, which promoted tissue oxygenation, oxidation of SC-lipids, and restricted penetration of the model drug curcumin, implicating that plasma may provide a novel and sensitive tool of skin barrier regulation. © 2020 The Author(s)