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Author: Weltmann, Klaus-Dieter × Author: Woedtke, Thomas von × Has files: Yes × Version: publishedVersion × WGL Institute: INP ×

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Now showing 1 - 7 of 7
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    Risk 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, Sander
    The 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.
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    Oxygen atoms are critical in rendering THP-1 leukaemia cells susceptible to cold physical plasma-induced apoptosis
    ([London] : Macmillan Publishers Limited, part of Springer Nature, 2017-6-5) Bekeschus, Sander; Wende, Kristian; Hefny, Mohamed Mokhtar; Rödder, Katrin; Jablonowski, Helena; Schmidt, Anke; Woedtke, Thomas von; Weltmann, Klaus-Dieter; Benedikt, Jan
    Cold physical plasma has been suggested as a powerful new tool in oncology. However, some cancer cells such as THP-1 leukaemia cells have been shown to be resistant towards plasma-induced cell death, thereby serving as a good model for optimizing plasmas in order to foster pro-apoptotic anticancer effects. A helium/oxygen radio frequency driven atmospheric plasma profoundly induced apoptosis in THP-1 cells whereas helium, humidified helium, and humidified helium/oxygen plasmas were inefficient. Hydrogen peroxide – previously shown as central plasma-derived agent – did not participate in the killing reaction but our results suggest hypochlorous acid to be responsible for the effect observed. Proteomic analysis of THP-1 cells exposed to He/O2 plasma emphasized a prominent growth retardation, cell stress, apoptosis, and a pro-immunogenic profile. Altogether, a plasma setting that inactivates previously unresponsive leukaemia cells is presented. Crucial reactive species in the plasma and liquid environment were identified and discussed, deciphering the complexity of plasma from the gas phase into the liquid down to the cellular response mechanism. These results may help tailoring plasmas for clinical applications such as oxidation-insensitive types of cancer.
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    Plasma treatment limits cutaneous squamous cell carcinoma development in vitro and in vivo
    (Basel : MDPI AG, 2020) Pasqual-Melo, Gabriella; Nascimento, Thiago; Sanches, Larissa Juliani; Blegniski, Fernanda Paschoal; Bianchi, Julya Karen; Sagwal, Sanjeev Kumar; Berner, Julia; Schmidt, Anke; Emmert, Steffen; Weltmann, Klaus-Dieter; Woedtke, Thomas von; Gandhirajan, Rajesh Kumar; Cecchini, Alessandra Lourenço; Bekeschus, Sander
    Cutaneous squamous cell carcinoma (SCC) is the most prevalent cancer worldwide, increasing the cost of healthcare services and with a high rate of morbidity. Its etiology is linked to chronic ultraviolet (UV) exposure that leads to malignant transformation of keratinocytes. Invasive growth and metastasis are severe consequences of this process. Therapy-resistant and highly aggressive SCC is frequently fatal, exemplifying the need for novel treatment strategies. Cold physical plasma is a partially ionized gas, expelling therapeutic doses of reactive oxygen and nitrogen species that were investigated for their anticancer capacity against SCC in vitro and SCC-like lesions in vivo. Using the kINPen argon plasma jet, a selective growth-reducing action of plasma treatment was identified in two SCC cell lines in 2D and 3D cultures. In vivo, plasma treatment limited the progression of UVB-induced SSC-like skin lesions and dermal degeneration without compromising lesional or non-lesional skin. In lesional tissue, this was associated with a decrease in cell proliferation and the antioxidant transcription factor Nrf2 following plasma treatment, while catalase expression was increased. Analysis of skin adjacent to the lesions and determination of global antioxidant parameters confirmed the local but not systemic action of the plasma anticancer therapy in vivo. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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    Combination treatment with cold physical plasma and pulsed electric fields augments ros production and cytotoxicity in lymphoma
    (Basel : MDPI AG, 2020) Wolff, Christina M.; Kolb, Juergen F.; Weltmann, Klaus-Dieter; Woedtke, Thomas von; Bekeschus, Sander
    New approaches in oncotherapy rely on the combination of different treatments to enhance the efficacy of established monotherapies. Pulsed electric fields (PEFs) are an established method (electrochemotherapy) for enhancing cellular drug uptake while cold physical plasma is an emerging and promising anticancer technology. This study aimed to combine both technologies to elucidate their cytotoxic potential as well as the underlying mechanisms of the effects observed. An electric field generator (0.9–1.0 kV/cm and 100-μs pulse duration) and an atmospheric pressure argon plasma jet were employed for the treatment of lymphoma cell lines as a model system. PEF but not plasma treatment induced cell membrane permeabilization. Additive cytotoxicity was observed for the metabolic activity and viability of the cells while the sequence of treatment in the combination played only a minor role. Intriguingly, a parallel combination was more effective compared to a 15-min pause between both treatment regimens. A combination effect was also found for lipid peroxidation; however, none could be observed in the cytosolic and mitochondrial reactive oxygen species (ROS) production. The supplementation with either antioxidant, a pan-caspase-inhibitor or a ferroptosis inhibitor, all partially rescued lymphoma cells from terminal cell death, which contributes to the mechanistic understanding of this combination treatment. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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    Risk 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, André
    Cold 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.
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    Concept for improved handling ensures effective contactless plasma treatment of patients with kINPen® MED
    (Basel : MDPI, 2020) Hahn, Veronika; Grollmisch, Daniel; Bendt, Hannes; Woedtke, Thomas von; Nestler, Bodo; Weltmann, Klaus-Dieter; Gerling, Torsten
    The nursing of patients with wounds is an essential part of medical healthcare. In this context, cold atmospheric-pressure plasma sources can be applied for skin decontamination and stimulation of wound healing. One of these plasma devices is the commercially available kINPen® MED (neoplas tools GmbH), a cold atmospheric-pressure plasma jet which is approved as a medical device, class-IIa. For the plasma treatment, a sterile disposable spacer is recommended to ensure a constant and effective distance between plasma and skin. The disadvantage of this spacer is its form and size which means that the effective axis/area is not visible for the attending doctor or qualified personnel and consequently it is a more or less intuitive treatment. In addition, the suggested perpendicular treatment is not applicable for the attending specialist due to lack of space or patient/wound positioning. A concept of a sensory unit was developed to measure the treatment distance and to visualize the effective treatment area for different angles. To determine the effective area for the plasma treatment, some exemplary methods were performed. Thus, the antimicrobial (Staphylococcus aureus DSM799/ATCC6538) efficacy, reactive oxygen species (ROS) distribution and (vacuum) ultraviolet ((V)UV) irradiation were determined depending on the treatment angle. Finally, a simplified first approach to visualize the effective treatment area at an optimal distance was designed and constructed to train attending specialists for optimal wound area coverage. © 2020 by the authors.
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    Cold physical plasma-induced oxidation of cysteine yields reactive sulfur species (RSS)
    (Amsterdam [u.a.] : Elsevier, 2019) Bruno, Giuliana; Heusler, Thea; Lackmann, Jan-Wilm; Woedtke, Thomas von; Weltmann, Klaus-Dieter; Wende, Kristian
    Purpose: Studying plasma liquid chemistry can reveal insights into their biomedical effects, i.e. to understand the direct and indirect processes triggered by the treatment in a model or clinical application. Due to the reactivity of the sulfur atom, thiols are potential targets for plasma- derived reactive species. Being crucial for protein function and redox signaling pathways, their controllable modification would allow expanding the application range. Additionally, models to control and standardize CAP sources are desired tools for plasma source design. Methods: Cysteine, a ubiquitous amino acid, was used as a tracer compound to scavenge the reactive species produced by an argon plasma jet (kINPen). The resulting product pattern was identified via high-resolution mass spectrometry. The Ellman´s assay was used to screen CAP derived thiol consumption, and long-lived species deposition (hydrogen peroxide, nitrite, nitrate) was monitored in relation to the presence of cysteine. Results: The intensity of cysteine oxidation increased with treatment time and availability of oxygen in the feed gas. A range of products from cysteine was identified, in part indicative for certain treatment conditions. Several non-stable products occur transiently during the plasma treatment. Bioactive reactive sulfur species (RSS) have been found for mild treatment conditions, such as cysteine sulfoxides and cysteine-S-sulfonate. Considering the number of cysteine molecules in the boundary layer and the achieved oxidation state, short-lived species dominate in cysteine conversion. In addition, a boundary layer depletion of the tracer was observed. Conclusion: Translating these data into the in-vivo application, strong direct oxidation of protein thiol groups with subsequent changes in protein biochemistry must be considered. Plasma-derived RSS may in part contribute to the observed biomedical effects of CAP. Care must be taken to control the discharge parameter tightly as chemical dynamics at or in the liquid are subject to change easily. © 2019