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- ItemRisk Evaluation of EMT and Inflammation in Metastatic Pancreatic Cancer Cells Following Plasma Treatment(Lausanne : Frontiers Media, 2020) Freund, Eric; Spadola, Chiara; Schmidt, Anke; Privat-Maldonado, Angela; Bogaerts, Annemie; Woedtke, Thomas von; Weltmann, Klaus-Dieter; Heidecke, Claus-Dieter; Partecke, Lars-Ivo; Käding, André; Bekeschus, SanderThe requirements for new technologies to serve as anticancer agents go far beyond their toxicity potential. Novel applications also need to be safe on a molecular and patient level. In a broader sense, this also relates to cancer metastasis and inflammation. In a previous study, the toxicity of an atmospheric pressure argon plasma jet in four human pancreatic cancer cell lines was confirmed and plasma treatment did not promote metastasis in vitro and in ovo. Here, these results are extended by additional types of analysis and new models to validate and define on a molecular level the changes related to metastatic processes in pancreatic cancer cells following plasma treatment in vitro and in ovo. In solid tumors that were grown on the chorion-allantois membrane of fertilized chicken eggs (TUM-CAM), plasma treatment induced modest to profound apoptosis in the tissues. This, however, was not associated with a change in the expression levels of adhesion molecules, as shown using immunofluorescence of ultrathin tissue sections. Culturing of the cells detached from these solid tumors for 6d revealed a similar or smaller total growth area and expression of ZEB1, a transcription factor associated with cancer metastasis, in the plasma-treated pancreatic cancer tissues. Analysis of in vitro and in ovo supernatants of 13 different cytokines and chemokines revealed cell line-specific effects of the plasma treatment but a noticeable increase of, e.g., growth-promoting interleukin 10 was not observed. Moreover, markers of epithelial-to-mesenchymal transition (EMT), a metastasis-promoting cellular program, were investigated. Plasma-treated pancreatic cancer cells did not present an EMT-profile. Finally, a realistic 3D tumor spheroid co-culture model with pancreatic stellate cells was employed, and the invasive properties in a gel-like cellular matrix were investigated. Tumor outgrowth and spread was similar or decreased in the plasma conditions. Altogether, these results provide valuable insights into the effect of plasma treatment on metastasis-related properties of cancer cells and did not suggest EMT-promoting effects of this novel cancer therapy. © Copyright © 2020 Freund, Spadola, Schmidt, Privat-Maldonado, Bogaerts, von Woedtke, Weltmann, Heidecke, Partecke, Käding and Bekeschus.
- ItemPlasma medical oncology: Immunological interpretation of head and neck squamous cell carcinoma(Hoboken, NJ : Wiley Interscience, 2020) Witzke, Katharina; Seebauer, Christian; Jesse, Katja; Kwiatek, Elisa; Berner, Julia; Semmler, Marie‐Luise; Boeckmann, Lars; Emmert, Steffen; Weltmann, Klaus‐Dieter; Metelmann, Hans‐Robert; Bekeschus, SanderThe prognosis of patients suffering from advanced-stage head and neck squamous cell carcinoma (HNSCC) remains poor. Medical gas plasma therapy receives growing attention as a novel anticancer modality. Our recent prospective observational study on HNSCC patients suffering from contaminated tumor ulcerations without lasting remission after first-line anticancer therapy showed remarkable efficacy of gas plasma treatment, with the ulcerated tumor surface decreasing by up to 80%. However, tumor growth relapsed, and this biphasic response may be a consequence of immunological and molecular changes in the tumor microenvironment that could be caused by (a) immunosuppression, (b) tumor cell adaption, (c) loss of microbe-induced immunostimulation, and/or (d) stromal cell adaption. These considerations may be vital for the design of clinical plasma trials in the future.
- ItemOral SARS-CoV-2 reduction by local treatment: A plasma technology application?(Weinheim : Wiley-VCH, 2022) von Woedtke, Thomas; Gabriel, Gülsah; Schaible, Ulrich E.; Bekeschus, SanderThe SARS-CoV-2 pandemic reemphasized the importance of and need for efficient hygiene and disinfection measures. The coronavirus' efficient spread capitalizes on its airborne transmission routes via virus aerosol release from human oral and nasopharyngeal cavities. Besides the upper respiratory tract, efficient viral replication has been described in the epithelium of these two body cavities. To this end, the idea emerged to employ plasma technology to locally reduce mucosal viral loads as an additional measure to reduce patient infectivity. We here outline conceptual ideas of such treatment concepts within what is known in the antiviral actions of plasma treatment so far.
- ItemCombined toxicity of indirubins with cold physical plasma in skin cancer cells in vitro(Bristol : IOP Publ., 2022) Berner, Julia; Bekeschus, SanderCold physical plasma is a partially ionized gas that generates various components identified as potential anticancer compounds. Due to its topical application, cold plasmas are suitable, especially in dermatological applications. We, therefore, tested the cold plasma effects in skin cancer cells in vitro. An atmospheric pressure argon plasma jet was used as the plasma source. The plasma exposure alone reduced the metabolic activity and induced lethal effects in a treatment time-dependent fashion in both cell lines investigated. This was accompanied by executioner caspases 3 and 7, cleavage indicative of apoptosis and reduced cell migration and proliferation. Recent research also indicated roles of novel indirubin derivatives with potent anticancer effects. Three candidates were tested, and reduced metabolic activity and viability in a dose-dependent manner were found. Strikingly, one compound exerted notable synergistic toxicity when combined with plasma in skin cancer cells, which may be promising for future in vivo experiments.