Publications by authors named "Sander Bekeschus"

86 Publications

A case of giant retroperitoneal lymphangioma and IgG4-positive fibrosis: Causality or coincidence?

SAGE Open Med Case Rep 2021 20;9:2050313X211016993. Epub 2021 May 20.

Department of General, Visceral, Thoracic and Vascular Surgery, Greifswald University Medical Centre, Greifswald, Germany.

Several chronic inflammatory diseases have been found to be a subtype of IgG4-related disease, all of which have a typical clinical and histological change, which is based in particular on an overexpression of IgG4 and subsequent fibrosis. At least a part of the retroperitoneal fibrosis, which was originally classified as idiopathic, seems to be assigned to IgG4-related disease. Lymphangiomas are benign, cystic tumors that rarely occur in adults. However, there is no firm association with IgG4-related disease described in the literature to date. This report is about a patient suffering from acute renal failure due to a giant retroperitoneal cyst. Surgical resection remains incomplete in the iliac vessel area due to severe fibrosis and histology revealed features of both lymphangioma and IgG4 fibrosis. The case description is followed by a brief overview of IgG4-related disease and a consideration of whether lymphangiomas might be assigned to this topic.
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http://dx.doi.org/10.1177/2050313X211016993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141978PMC
May 2021

ROS Cocktails as an Adjuvant for Personalized Antitumor Vaccination?

Vaccines (Basel) 2021 May 19;9(5). Epub 2021 May 19.

ZIK, Leibniz Institute for Plasma Science and Technology (INP), Felix Hausdorff Str. 2, 17489 Greifswald, Germany.

Cancer is the second leading cause of death worldwide. Today, the critical role of the immune system in tumor control is undisputed. Checkpoint antibody immunotherapy augments existing antitumor T cell activity with durable clinical responses in many tumor entities. Despite the presence of tumor-associated antigens and neoantigens, many patients have an insufficient repertoires of antitumor T cells. Autologous tumor vaccinations aim at alleviating this defect, but clinical success is modest. Loading tumor material into autologous dendritic cells followed by their laboratory expansion and therapeutic vaccination is promising, both conceptually and clinically. However, this process is laborious, time-consuming, costly, and hence less likely to solve the global cancer crisis. Therefore, it is proposed to re-focus on personalized anticancer vaccinations to enhance the immunogenicity of autologous therapeutic tumor vaccines. Recent work re-established the idea of using the alarming agents of the immune system, oxidative modifications, as an intrinsic adjuvant to broaden the antitumor T cell receptor repertoire in cancer patients. The key novelty is the use of gas plasma, a multi-reactive oxygen and nitrogen species-generating technology, for diversifying oxidative protein modifications in a, so far, unparalleled manner. This significant innovation has been successfully used in proof-of-concept studies and awaits broader recognition and implementation to explore its chances and limitations of providing affordable personalized anticancer vaccines in the future. Such multidisciplinary advance is timely, as the current COVID-19 crisis is inexorably reflecting the utmost importance of innovative and effective vaccinations in modern times.
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http://dx.doi.org/10.3390/vaccines9050527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161309PMC
May 2021

Multimodal Imaging Techniques to Evaluate the Anticancer Effect of Cold Atmospheric Pressure Plasma.

Cancers (Basel) 2021 May 19;13(10). Epub 2021 May 19.

Rudolf-Zenker-Institute of Experimental Surgery, Rostock University Medical Center, 18057 Rostock, Germany.

Background: Skin cancer is the most frequent cancer worldwide and is divided into non-melanoma skin cancer, including basal cell carcinoma, as well as squamous cell carcinoma (SCC) and malignant melanoma (MM).

Methods: This study evaluates the effects of cold atmospheric pressure plasma (CAP) on SCC and MM in vivo, employing a comprehensive approach using multimodal imaging techniques. Longitudinal MR and PET/CT imaging were performed to determine the anatomic and metabolic tumour volume over three-weeks in vivo. Additionally, the formation of reactive species after CAP treatment was assessed by non-invasive chemiluminescence imaging of L-012. Histological analysis and immunohistochemical staining for Ki-67, ApopTag, F4/80, CAE, and CD31, as well as protein expression of PCNA, caspase-3 and cleaved-caspase-3, were performed to study proliferation, apoptosis, inflammation, and angiogenesis in CAP-treated tumours.

Results: As the main result, multimodal in vivo imaging revealed a substantial reduction in tumour growth and an increase in reactive species after CAP treatment, in comparison to untreated tumours. In contrast, neither the markers for apoptosis, nor the metabolic activity of both tumour entities was affected by CAP.

Conclusions: These findings propose CAP as a potential adjuvant therapy option to established standard therapies of skin cancer.
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http://dx.doi.org/10.3390/cancers13102483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161248PMC
May 2021

Murine Macrophages Modulate Their Inflammatory Profile in Response to Gas Plasma-Inactivated Pancreatic Cancer Cells.

Cancers (Basel) 2021 May 21;13(11). Epub 2021 May 21.

ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP Greifswald), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany.

Macrophages and immuno-modulation play a dominant role in the pathology of pancreatic cancer. Gas plasma is a technology recently suggested to demonstrate anticancer efficacy. To this end, two murine cell lines were employed to analyze the inflammatory consequences of plasma-treated pancreatic cancer cells (PDA) on macrophages using the kINPen plasma jet. Plasma treatment decreased the metabolic activity, viability, and migratory activity in an ROS- and treatment time-dependent manner in PDA cells in vitro. These results were confirmed in pancreatic tumors grown on chicken embryos in the TUM-CAM model (in ovo). PDA cells promote tumor-supporting M2 macrophage polarization and cluster formation. Plasma treatment of PDA cells abrogated this cluster formation with a mixed M1/M2 phenotype observed in such co-cultured macrophages. Multiplex chemokine and cytokine quantification showed a marked decrease of the neutrophil chemoattractant CXCL1, IL6, and the tumor growth supporting TGFβ and VEGF in plasma-treated compared to untreated co-culture settings. At the same time, macrophage-attractant CCL4 and MCP1 release were profoundly enhanced. These cellular and secretome data suggest that the plasma-inactivated PDA6606 cells modulate the inflammatory profile of murine RAW 264.7 macrophages favorably, which may support plasma cancer therapy.
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http://dx.doi.org/10.3390/cancers13112525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196763PMC
May 2021

Gas Plasma Technology Augments Ovalbumin Immunogenicity and OT-II T Cell Activation Conferring Tumor Protection in Mice.

Adv Sci (Weinh) 2021 05 8;8(10):2003395. Epub 2021 Mar 8.

ZIK plasmatis Leibniz Institute for Plasma Science and Technology (INP) Felix-Hausdorff-Str. 2 Greifswald 17489 Germany.

Reactive oxygen species (ROS/RNS) are produced during inflammation and elicit protein modifications, but the immunological consequences are largely unknown. Gas plasma technology capable of generating an unmatched variety of ROS/RNS is deployed to mimic inflammation and study the significance of ROS/RNS modifications using the model protein chicken ovalbumin (Ova vs oxOva). Dynamic light scattering and circular dichroism spectroscopy reveal structural modifications in oxOva compared to Ova. T cells from Ova-specific OT-II but not from C57BL/6 or SKH-1 wild type mice presents enhanced activation after Ova addition. OxOva exacerbates this activation when administered ex vivo or in vivo, along with an increased interferon-gamma production, a known anti-melanoma agent. OxOva vaccination of wild type mice followed by inoculation of syngeneic B16F10 Ova-expressing melanoma cells shows enhanced T cell number and activation, decreased tumor burden, and elevated numbers of antigen-presenting cells when compared to their Ova-vaccinated counterparts. Analysis of oxOva using mass spectrometry identifies three hot spots regions rich in oxidative modifications that are associated with the increased T cell activation. Using Ova as a model protein, the findings suggest an immunomodulating role of multi-ROS/RNS modifications that may spur novel research lines in inflammation research and for vaccination strategies in oncology.
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http://dx.doi.org/10.1002/advs.202003395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132054PMC
May 2021

Plasma-Treated Water Affects Vitality and Biofilm Structure.

Front Microbiol 2021 28;12:652481. Epub 2021 Apr 28.

Leibniz Institute for Plasma Science and Technology (INP), Greifswald, Germany.

Plasma-generated compounds (PGCs) such as plasma-processed air (PPA) or plasma-treated water (PTW) offer an increasingly important alternative for the control of microorganisms in hard-to-reach areas found in several industrial applications including the food industry. To this end, we studied the antimicrobial capacity of PTW on the vitality and biofilm formation of , a common foodborne pathogen. Using a microwave plasma (MidiPLexc), 10 ml of deionized water was treated for 100, 300, and 900 s (pre-treatment time), after which the bacterial biofilm was exposed to the PTW for 1, 3, and 5 min (post-treatment time) for each pre-treatment time, separately. Colony-forming units (CFU) were significantly reduced by 4.7 log ± 0.29 log, as well as the metabolic activity decreased by 47.9 ± 9.47% and the cell vitality by 69.5 ± 2.1%, compared to the control biofilms. LIVE/DEAD staining and fluorescence microscopy showed a positive correlation between treatment and incubation times, as well as reduction in vitality. Atomic force microscopy (AFM) indicated changes in the structure quality of the bacterial biofilm. These results indicate a promising antimicrobial impact of plasma-treated water on , which may lead to more targeted applications of plasma decontamination in the food industry in the future.
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http://dx.doi.org/10.3389/fmicb.2021.652481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113633PMC
April 2021

Argon Plasma Exposure Augments Costimulatory Ligands and Cytokine Release in Human Monocyte-Derived Dendritic Cells.

Int J Mol Sci 2021 Apr 6;22(7). Epub 2021 Apr 6.

The Centre for Innovation Competence (ZIK) Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), 17489 Greifswald, Germany.

Cold physical plasma is a partially ionized gas expelling many reactive oxygen and nitrogen species (ROS/RNS). Several plasma devices have been licensed for medical use in dermatology, and recent experimental studies suggest their putative role in cancer treatment. In cancer therapies with an immunological dimension, successful antigen presentation and inflammation modulation is a key hallmark to elicit antitumor immunity. Dendritic cells (DCs) are critical for this task. However, the inflammatory consequences of DCs following plasma exposure are unknown. To this end, human monocyte-derived DCs (moDCs) were expanded from isolated human primary monocytes; exposed to plasma; and their metabolic activity, surface marker expression, and cytokine profiles were analyzed. As controls, hydrogen peroxide, hypochlorous acid, and peroxynitrite were used. Among all types of ROS/RNS-mediated treatments, plasma exposure exerted the most notable increase of activation markers at 24 h such as CD25, CD40, and CD83 known to be crucial for T cell costimulation. Moreover, the treatments increased interleukin (IL)-1α, IL-6, and IL-23. Altogether, this study suggests plasma treatment augmenting costimulatory ligand and cytokine expression in human moDCs, which might exert beneficial effects in the tumor microenvironment.
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http://dx.doi.org/10.3390/ijms22073790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038845PMC
April 2021

Plasma-Treated Solutions (PTS) in Cancer Therapy.

Cancers (Basel) 2021 Apr 6;13(7). Epub 2021 Apr 6.

Plasma Engineering and Medicine Institute, Old Dominion University, Norfolk, VA 23508, USA.

Cold physical plasma is a partially ionized gas generating various reactive oxygen and nitrogen species (ROS/RNS) simultaneously. ROS/RNS have therapeutic effects when applied to cells and tissues either directly from the plasma or via exposure to solutions that have been treated beforehand using plasma processes. This review addresses the challenges and opportunities of plasma-treated solutions (PTSs) for cancer treatment. These PTSs include plasma-treated cell culture media in experimental research as well as clinically approved solutions such as saline and Ringer's lactate, which, in principle, already qualify for testing in therapeutic settings. Several types of cancers were found to succumb to the toxic action of PTSs, suggesting a broad mechanism of action based on the tumor-toxic activity of ROS/RNS stored in these solutions. Moreover, it is indicated that the PTS has immuno-stimulatory properties. Two different routes of application are currently envisaged in the clinical setting. One is direct injection into the bulk tumor, and the other is lavage in patients suffering from peritoneal carcinomatosis adjuvant to standard chemotherapy. While many promising results have been achieved so far, several obstacles, such as the standardized generation of large volumes of sterile PTS, remain to be addressed.
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http://dx.doi.org/10.3390/cancers13071737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038720PMC
April 2021

Small Molecules in the Treatment of Squamous Cell Carcinomas: Focus on Indirubins.

Cancers (Basel) 2021 Apr 7;13(8). Epub 2021 Apr 7.

Clinic and Policlinic for Dermatology and Venereology, University Medical Center Rostock, 18057 Rostock, Germany.

Skin cancers are the most common malignancies in the world. Among the most frequent skin cancer entities, squamous cell carcinoma (SCC) ranks second (~20%) after basal cell carcinoma (~77%). In early stages, a complete surgical removal of the affected tissue is carried out as standard therapy. To treat advanced and metastatic cancers, targeted therapies with small molecule inhibitors are gaining increasing attention. Small molecules are a heterogeneous group of protein regulators, which are produced by chemical synthesis or fermentation. The majority of them belong to the group of receptor tyrosine kinase inhibitors (RTKIs), which specifically bind to certain RTKs and directly influence the respective signaling pathway. Knowledge of characteristic molecular alterations in certain cancer entities, such as SCC, can help identify tumor-specific substances for targeted therapies. Most frequently, altered genes in SCC include , , , and . For example, the gene , which codes for cyclin D1 protein, is upregulated in nearly half of SCC cases and promotes proliferation of affected cells. A treatment with the small molecule 5'-nitroindirubin-monoxime (INO) leads to inhibition of cyclin D1 and thus inhibition of proliferation. As a component of Danggui Longhui Wan, a traditional Chinese medicine, indirubins are used to treat chronic diseases and have been shown to inhibit inflammatory reactions. Indirubins are pharmacologically relevant small molecules with proapoptotic and antiproliferative activity. In this review, we discuss the current literature on indirubin-based small molecules in cancer treatment. A special focus is on the molecular biology of squamous cell carcinomas, their alterations, and how these are rendered susceptible to indirubin-based small molecule inhibitors. The potential molecular mechanisms of the efficacy of indirubins in killing SCC cells will be discussed as well.
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http://dx.doi.org/10.3390/cancers13081770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068014PMC
April 2021

Combined Toxicity of Gas Plasma Treatment and Nanoparticles Exposure in Melanoma Cells In Vitro.

Authors:
Sander Bekeschus

Nanomaterials (Basel) 2021 Mar 22;11(3). Epub 2021 Mar 22.

ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany.

Despite continuous advances in therapy, cancer remains a deadly disease. Over the past years, gas plasma technology emerged as a novel tool to target tumors, especially skin. Another promising anticancer approach are nanoparticles. Since combination therapies are becoming increasingly relevant in oncology, both gas plasma treatment and nanoparticle exposure were combined. A series of nanoparticles were investigated in parallel, namely, silica, silver, iron oxide, cerium oxide, titanium oxide, and iron-doped titanium oxide. For gas plasma treatment, the atmospheric pressure argon plasma jet kINPen was utilized. Using three melanoma cell lines, the two murine non-metastatic B16F0 and metastatic B16F10 cells and the human metastatic B-Raf mutant cell line SK-MEL-28, the combined cytotoxicity of both approaches was identified. The combined cytotoxicity of gas plasma treatment and nanoparticle exposure was consistent across all three cell lines for silica, silver, iron oxide, and cerium oxide. In contrast, for titanium oxide and iron-doped titanium oxide, significantly combined cytotoxicity was only observed in B16F10 cells.
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http://dx.doi.org/10.3390/nano11030806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004114PMC
March 2021

The amino acid metabolism is essential for evading physical plasma-induced tumour cell death.

Br J Cancer 2021 May 25;124(11):1854-1863. Epub 2021 Mar 25.

ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Greifswald, Germany.

Background: Recent studies have emphasised the important role of amino acids in cancer metabolism. Cold physical plasma is an evolving technology employed to target tumour cells by introducing reactive oxygen species (ROS). However, limited understanding is available on the role of metabolic reprogramming in tumour cells fostering or reducing plasma-induced cancer cell death.

Methods: The utilisation and impact of major metabolic substrates of fatty acid, amino acid and TCA pathways were investigated in several tumour cell lines following plasma exposure by qPCR, immunoblotting and cell death analysis.

Results: Metabolic substrates were utilised in Panc-1 and HeLa but not in OVCAR3 and SK-MEL-28 cells following plasma treatment. Among the key genes governing these pathways, ASCT2 and SLC3A2 were consistently upregulated in Panc-1, Miapaca2GR, HeLa and MeWo cells. siRNA-mediated knockdown of ASCT2, glutamine depletion and pharmacological inhibition with V9302 sensitised HeLa cells to the plasma-induced cell death. Exogenous supplementation of glutamine, valine or tyrosine led to improved metabolism and viability of tumour cells following plasma treatment.

Conclusion: These data suggest the amino acid influx driving metabolic reprogramming in tumour cells exposed to physical plasma, governing the extent of cell death. This pathway could be targeted in combination with existing anti-tumour agents.
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http://dx.doi.org/10.1038/s41416-021-01335-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144554PMC
May 2021

Hypochlorous acid selectively promotes toxicity and the expression of danger signals in human abdominal cancer cells.

Oncol Rep 2021 May 24;45(5). Epub 2021 Mar 24.

Centre for Innovation Competence (ZIK) Plasmatis, Leibniz Institute for Plasma Science and Technology (INP Greifswald), D‑17489 Greifswald, Germany.

Tumors of the abdominal cavity, such as colorectal, pancreatic and ovarian cancer, frequently metastasize into the peritoneum. Large numbers of metastatic nodules hinder curative surgical resection, necessitating lavage with hyperthermic intraperitoneal chemotherapy (HIPEC). However, HIPEC not only causes severe side effects but also has limited therapeutic efficacy in various instances. At the same time, the age of immunotherapies such as biological agents, checkpoint‑ inhibitors or immune‑cell therapies, increasingly emphasizes the critical role of anticancer immunity in targeting malignancies. The present study investigated the ability of three types of long‑lived reactive species (oxidants) to inactivate cancer cells and potentially complement current HIPEC regimens, as well as to increase tumor cell expression of danger signals that stimulate innate immunity. The human abdominal cancer cell lines HT‑29, Panc‑01 and SK‑OV‑3 were exposed to different concentrations of hydrogen peroxide (HO), hypochlorous acid (HOCl) and peroxynitrite (ONOO). Metabolic activity was measured, as well as determination of cell death and danger signal expression levels via flow cytometry and detection of intracellular oxidation via high‑content microscopy. Oxidation of tumor decreased intracellular levels of the antioxidant glutathione and induced oxidation in mitochondria, accompanied by a decrease in metabolic activity and an increase in regulated cell death. At similar concentrations, HOCl showed the most potent effects. Non‑malignant HaCaT keratinocytes were less affected, suggesting the approach to be selective to some extent. Pro‑immunogenic danger molecules were investigated by assessing the expression levels of calreticulin (CRT), and heat‑shock protein (HSP)70 and HSP90. CRT expression was greatest following HOCl and ONOO treatment, whereas HOCl and HO resulted in the greatest increase in HSP70 and HSP90 expression levels. These results suggested that HOCl may be a promising agent to complement current HIPEC regimens targeting peritoneal carcinomatosis.
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http://dx.doi.org/10.3892/or.2021.8022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020206PMC
May 2021

Expression of canonical transient receptor potential channels in U-2 OS and MNNG-HOS osteosarcoma cell lines.

Oncol Lett 2021 Apr 21;21(4):307. Epub 2021 Feb 21.

Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, D-17475 Greifswald, Germany.

In U-2 OS and MNNG-HOS osteosarcoma cells, small interfering RNA-mediated knockdown of the angiotensin-(1-7) receptor, Mas, increases cell proliferation. Whether alterations in canonical transient receptor potential channels (TRPC) expression contribute to this effect is not clear. In the present study, a basic description of TRPC subtype expression in osteosarcoma cell lines was provided. The pharmacological modulators of the angiotensin-(1-7) receptor, Mas, AVE0991 (agonist), or D-Ala-Ang-(1-7) (antagonist) were applied to elucidate a possible role of Mas in the regulation of TRPC mRNA levels. The contribution of other G-protein coupled receptors (GPCR) or receptor tyrosine kinases to TRCP expression was studied by applying the selective pharmacological blockers of either PI3 kinase or MEK/Erk1/2 signaling, Ly294002 and PD98059. AVE0991 and D-Ala-Ang-(1-7) exhibited no or marginal effects on TRPC mRNA expression. Ly294002 provoked a 9.6- and 5.9-fold increase in the amounts of TRPC5 mRNA in MNNG-HOS and U-2 OS cells, respectively. Additionally, Ly294002 increased TRPC6 mRNA levels; however, it had no effect on TRPCs 1, 3 and 4. Administration of PD98059 increased the amounts of TRPC6 and TRPC4 ~2-fold. In conclusion, the present study demonstrated that Mas-dependent alterations in osteosarcoma cell line proliferation were not mediated by any changes in TRPC subtype gene expression. The data shows in principle, and consistent with the literature, that the signaling pathways examined can regulate the expression of TRPCs at the mRNA level. Therefore, direct and signaling pathway-specific pharmacological targeting of TRPC subtypes may represent an option for improving the treatment of osteosarcoma.
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http://dx.doi.org/10.3892/ol.2021.12568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905632PMC
April 2021

Tumor cell metabolism correlates with resistance to gas plasma treatment: The evaluation of three dogmas.

Free Radic Biol Med 2021 May 9;167:12-28. Epub 2021 Mar 9.

ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489, Greifswald, Germany.

Gas plasma is a partially ionized gas increasingly recognized for targeting cancer. Several hypotheses attempt to explain the link between plasma treatment and cytotoxicity in cancer cells, all focusing on cellular membranes that are the first to be exposed to plasma-generated reactive oxygen species (ROS). One proposes high levels of aquaporins, membrane transporters of water and hydrogen peroxide, to mark tumor cell line sensitivity to plasma treatment. A second focuses on membrane-expression of redox-related enzymes such as NADPH oxidases (NOX) that may modify or amplify the effects of plasma-derived ROS, fueling plasma-induced cancer cell death. Another hypothesis is that the decreased cholesterol content of tumor cell membranes sensitizes these to plasma-mediated oxidation and subsequently, cytotoxicity. Screening 33 surface molecules in 36 tumor cell lines in correlation to their sensitivity to plasma treatment, the expression of aquaporins or NOX members could not explain the sensitivity but were rather associated with treatment resistance. Correlation with transporter or enzyme activity was not tested. Analysis of cholesterol content confirmed the proposed positive correlation with treatment resistance. Strikingly, the strongest correlation was found for baseline metabolic activity (Spearman r = 0.76). Altogether, these data suggest tumor cell metabolism as a novel testable hypothesis to explain cancer cell resistance to gas plasma treatment for further elucidating this innovative field's chances and limitations in oncology.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.02.035DOI Listing
May 2021

Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection.

PLoS One 2021 1;16(3):e0247125. Epub 2021 Mar 1.

Department of Microbiology and Immunology, Institute for Molecular Medicine & Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.

Effective control of infection by human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), requires continuous and life-long use of anti-retroviral therapy (ART) by people living with HIV-1 (PLWH). In the absence of ART, HIV-1 reemergence from latently infected cells is ineffectively suppressed due to suboptimal innate and cytotoxic T lymphocyte responses. However, ART-free control of HIV-1 infection may be possible if the inherent immunological deficiencies can be reversed or restored. Herein we present a novel approach for modulating the immune response to HIV-1 that involves the use of non-thermal plasma (NTP), which is an ionized gas containing various reactive oxygen and nitrogen species (RONS). J-Lat cells were used as a model of latent HIV-1 infection to assess the effects of NTP application on viral latency and the expression of pro-phagocytic and pro-chemotactic damage-associated molecular patterns (DAMPs). Exposure of J-Lat cells to NTP resulted in stimulation of HIV-1 gene expression, indicating a role in latency reversal, a necessary first step in inducing adaptive immune responses to viral antigens. This was accompanied by the release of pro-inflammatory cytokines and chemokines including interleukin-1β (IL-1β) and interferon-γ (IFN-γ); the display of pro-phagocytic markers calreticulin (CRT), heat shock proteins (HSP) 70 and 90; and a correlated increase in macrophage phagocytosis of NTP-exposed J-Lat cells. In addition, modulation of surface molecules that promote or inhibit antigen presentation was also observed, along with an altered array of displayed peptides on MHC I, further suggesting methods by which NTP may modify recognition and targeting of cells in latent HIV-1 infection. These studies represent early progress toward an effective NTP-based ex vivo immunotherapy to resolve the dysfunctions of the immune system that enable HIV-1 persistence in PLWH.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247125PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920340PMC
March 2021

Gas plasma irradiation of breast cancers promotes immunogenicity, tumor reduction, and an abscopal effect in vivo.

Oncoimmunology 2020 12 29;10(1):1859731. Epub 2020 Dec 29.

Center for Innovation Competence (ZIK) Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Greifswald, Germany.

While many new and emerging therapeutic concepts have appeared throughout the last decades, cancer still is fatal in many patients. At the same time, the importance of immunology in oncotherapy is increasingly recognized, not only since the advent of checkpoint therapy. Among the many types of tumors, also breast cancer has an immunological dimension that might be exploited best by increasing the immunogenicity of the tumors in the microenvironment. To this end, we tested a novel therapeutic concept, gas plasma irradiation, for its ability to promote the immunogenicity and increase the toxicity of breast cancer cells in vitro and in vivo. Mechanistically, this emerging medical technology is employing a plethora of reactive oxygen species being deposited on the target cells and tissues. Using 2D cultures and 3D tumor spheroids, we found gas plasma-irradiation to drive apoptosis and immunogenic cancer cell death (ICD) in vitro, as evidenced by an increased expression of calreticulin, heat-shock proteins 70 and 90, and MHC-I. In 4T1 breast cancer-bearing mice, the gas plasma irradiation markedly decreased tumor burden and increased survival. Interestingly, non-treated tumors injected in the opposite flank of mice exposed to our novel treatment also exhibited reduced growth, arguing for an abscopal effect. This was concomitant with an increase of apoptosis and tumor-infiltrating CD4 and CD8 T-cells as well as dendritic cells in the tissues. In summary, we found gas plasma-irradiated murine breast cancers to induce toxicity and augmented immunogenicity, leading to reduced tumor growth at a site remote to the treatment area.
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http://dx.doi.org/10.1080/2162402X.2020.1859731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781742PMC
December 2020

Tumor cytotoxicity and immunogenicity of a novel V-jet neon plasma source compared to the kINPen.

Sci Rep 2021 01 8;11(1):136. Epub 2021 Jan 8.

ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489, Greifswald, Germany.

Recent research indicated the potential of cold physical plasma in cancer therapy. The plethora of plasma-derived reactive oxygen and nitrogen species (ROS/RNS) mediate diverse antitumor effects after eliciting oxidative stress in cancer cells. We aimed at exploiting this principle using a newly designed dual-jet neon plasma source (jet) to treat colorectal cancer cells. A treatment time-dependent ROS/RNS generation induced oxidation, growth retardation, and cell death within 3D tumor spheroids were found. In TUM-CAM, a semi in vivo model, the jet markedly reduced vascularized tumors' growth, but an increase of tumor cell immunogenicity or uptake by dendritic cells was not observed. By comparison, the argon-driven single jet kINPen, known to mediate anticancer effects in vitro, in vivo, and in patients, generated less ROS/RNS and terminal cell death in spheroids. In the TUM-CAM model, however, the kINPen was equivalently effective and induced a stronger expression of immunogenic cancer cell death (ICD) markers, leading to increased phagocytosis of kINPen but not jet plasma-treated tumor cells by dendritic cells. Moreover, the jet was characterized according to the requirements of the DIN-SPEC 91315. Our results highlight the plasma device-specific action on cancer cells for evaluating optimal discharges for plasma cancer treatment.
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http://dx.doi.org/10.1038/s41598-020-80512-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794240PMC
January 2021

BK virus-induced nephritis and cystitis after matched unrelated donor stem cell transplantation: A case report.

Clin Case Rep 2020 Dec 7;8(12):2839-2842. Epub 2020 Sep 7.

Department of Urology University Medicine Greifswald Greifswald Germany.

Currently, there is no standard therapy for a BK virus infection of the urogenital tract in immunocompromised, stem cell transplanted patients, so that early diagnosis and introduction of supportive measures have the highest response rates to date.
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http://dx.doi.org/10.1002/ccr3.3246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752429PMC
December 2020

Gas plasma-spurred wound healing is accompanied by regulation of focal adhesion, matrix remodeling, and tissue oxygenation.

Redox Biol 2021 01 25;38:101809. Epub 2020 Nov 25.

ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489, Greifswald, Germany. Electronic address:

In response to injury, efficient migration of skin cells to rapidly close the wound and restore barrier function requires a range of coordinated processes in cell spreading and migration. Gas plasma technology produces therapeutic reactive species that promote skin regeneration by driving proliferation and angiogenesis. However, the underlying molecular mechanisms regulating gas plasma-aided cell adhesion and matrix remodeling essential for wound closure remain elusive. Here, we combined in vitro analyses in primary dermal fibroblasts isolated from murine skin with in vivo studies in a murine wound model to demonstrate that gas plasma treatment changed phosphorylation of signaling molecules such as focal adhesion kinase and paxillin α in adhesion-associated complexes. In addition to cell spreading and migration, gas plasma exposure affected cell surface adhesion receptors (e.g., integrinα5β1, syndecan 4), structural proteins (e.g., vinculin, talin, actin), and transcription of genes associated with differentiation markers of fibroblasts-to-myofibroblasts and epithelial-to-mesenchymal transition, cellular protrusions, fibronectin fibrillogenesis, matrix metabolism, and matrix metalloproteinase activity. Finally, we documented that gas plasma exposure increased tissue oxygenation and skin perfusion during ROS-driven wound healing. Altogether, these results provide critical insights into the molecular machinery of gas plasma-assisted wound healing mechanisms.
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http://dx.doi.org/10.1016/j.redox.2020.101809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710641PMC
January 2021

Physical Plasma-Treated Skin Cancer Cells Amplify Tumor Cytotoxicity of Human Natural Killer (NK) Cells.

Cancers (Basel) 2020 Nov 30;12(12). Epub 2020 Nov 30.

ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany.

Skin cancers have the highest prevalence of all human cancers, with the most lethal forms being squamous cell carcinoma and malignant melanoma. Besides the conventional local treatment approaches like surgery and radiotherapy, cold physical plasmas are emerging anticancer tools. Plasma technology is used as a therapeutic agent by generating reactive oxygen species (ROS). Evidence shows that inflammation and adaptive immunity are involved in cancer-reducing effects of plasma treatment, but the role of innate immune cells is still unclear. Natural killer (NK)-cells interact with target cells via activating and inhibiting surface receptors and kill in case of dominating activating signals. In this study, we investigated the effect of cold physical plasma (kINPen) on two skin cancer cell lines (A375 and A431), with non-malignant HaCaT keratinocytes as control, and identified a plasma treatment time-dependent toxicity that was more pronounced in the cancer cells. Plasma treatment also modulated the expression of activating and inhibiting receptors more profoundly in skin cancer cells compared to HaCaT cells, leading to significantly higher NK-cell killing rates in the tumor cells. Together with increased pro-inflammatory mediators such as IL-6 and IL-8, we conclude that plasma treatment spurs stress responses in skin cancer cells, eventually augmenting NK-cell activity.
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http://dx.doi.org/10.3390/cancers12123575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761052PMC
November 2020

Nonenzymatic post-translational modifications in peptides by cold plasma-derived reactive oxygen and nitrogen species.

Biointerphases 2020 11 25;15(6):061008. Epub 2020 Nov 25.

ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP Greifswald), Felix-Hausdorff-Straße 2, 17489 Greifswald, Germany.

Cold physical plasmas are emerging tools for wound care and cancer control that deliver reactive oxygen species (ROS) and nitrogen species (RNS). Alongside direct effects on cellular signaling processes, covalent modification of biomolecules may contribute to the observed physiological consequences. The potential of ROS/RNS generated by two different plasma sources (kINPen and COST-Jet) to introduce post-translational modifications (PTMs) in the peptides angiotensin and bradykinin was explored. While the peptide backbone was kept intact, a significant introduction of oxidative PTMs was observed. The modifications cluster at aromatic (tyrosine, histidine, and phenylalanine) and neutral amino acids (isoleucine and proline) with the introduction of one, two, or three oxygen atoms, ring cleavages of histidine and tryptophan, and nitration/nitrosylation predominantly observed. Alkaline and acidic amino acid (arginine and aspartic acid) residues showed a high resilience, indicating that local charges and the chemical environment at large modulate the attack of the electron-rich ROS/RNS. Previously published simulations, which include only OH radicals as ROS, do not match the experimental results in full, suggesting the contribution of other short-lived species, i.e., atomic oxygen, singlet oxygen, and peroxynitrite. The observed PTMs are relevant for the biological activity of peptides and proteins, changing polarity, folding, and function. In conclusion, it can be assumed that an introduction of covalent oxidative modifications at the amino acid chain level occurs during a plasma treatment. The introduced changes, in part, mimic naturally occurring patterns that can be interpreted by the cell, and subsequently, these PTMs allow for prolonged secondary effects on cell physiology.
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http://dx.doi.org/10.1116/6.0000529DOI Listing
November 2020

Review of Innovative Physical Therapy Methods: Introduction to the Principles of Cold Physical Plasma.

In Vivo 2020 Nov-Dec;34(6):3103-3107

Plasma Oncology Laboratory, Department of Urology, University Medicine Greifswald, Greifswald, Germany

The principles of physics and precision engineering have allowed many technologies to enter standard treatment regimens for a range of diseases. Recently, a new type of technology has been accredited as safe and efficient routine procedure in dermatology in Europe: cold physical plasma. Several accredited devices successfully restrain the powerful energy of plasmas to make them available for therapeutic purposes. Herein, we introduce an introduction to the concept of cold physical plasmas and highlight some fields of their medical applications.
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http://dx.doi.org/10.21873/invivo.12143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811668PMC
June 2020

Effects of cold physical plasma on oral lichen planus: An in vitro study (Effects of CAP on OLP).

Oral Dis 2020 Oct 27. Epub 2020 Oct 27.

ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Greifswald, Germany.

Objectives: In the search for more effective and safe treatment avenues, we investigated cold physical plasma as a new treatment modality for therapy of oral lichen planus (OLP).

Material And Methods: Healthy and diseased human mucosal tissue samples with a size of 3 mm in diameter obtained from OLP patients were subjected to plasma treatment ex vivo or were left untreated. Tissue sections were quantified for immune-infiltration of CD4 , CD8 , CD45RA , and CD45R0 T cells. Moreover, the tissues' inflammatory profile was assessed by analyzing 12 different cytokines in the surrounding media.

Results: A significantly increased infiltrate of CD8 and CD45-R0 T cells was detected in OLP tissue samples when compared to healthy tissue. A higher concentration of interleukin (IL) 1β, IL6, IL8, and granulocyte macrophage-colony stimulating factor (GM-CMF) was detected in OLP samples compared to healthy mucosal tissue. For all cytokines and chemokines investigated, 23 out of 24 comparisons showed a decrease in tendency (significant for IL1β, IL2, IL10, and GM-CSF) in response to plasma treatment. In ex vivo-treated tissue, a decrease of T-cell infiltrate in OLP lesions compared with healthy tissue was observed.

Conclusion: Our findings suggest cold physical plasma can be a promising therapeutic option for OLP that requires further validation in vivo.
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http://dx.doi.org/10.1111/odi.13697DOI Listing
October 2020

The molecular and physiological consequences of cold plasma treatment in murine skin and its barrier function.

Free Radic Biol Med 2020 12 1;161:32-49. Epub 2020 Oct 1.

Plasma Life Science and ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489, Greifswald, Germany. Electronic address:

Cold 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.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.09.026DOI Listing
December 2020

The progression of metastatic melanoma augments a pro-oxidative milieu locally but not systemically.

Pathol Res Pract 2020 Nov 23;216(11):153218. Epub 2020 Sep 23.

Laboratory of Molecular Pathology, State University of Londrina, Brazil; Laboratory of Pathophysiology and Free Radicals, State University of Londrina, Brazil. Electronic address:

Malignant melanoma is the most dangerous form of skin cancer. Despite new therapies for melanoma treatment, effective therapy is mainly limited by excessive metastasis. Currently, the factors determining metastasis development are not elucidated, but oxidative stress was suggested to be involved. To this end, we analyzed oxidative stress parameters during the metastatic development using the syngeneic B16F10 melanoma model. An increase in blood plasma lipid peroxidation occurred at the earliest stage of the disease, with a progressive decrease in oxidative damage and an increase in antioxidant defense. Vice versa, increased lipid peroxidation and 3-nitrotyrosine, and decreased antioxidant parameters were observed in the metastatic nodules throughout the disease. This was concomitant with a progressive increase in vascular endothelial growth factor and proliferating cell nuclear antigen. We conclude that the oxidative stress in the bloodstream decreases during the metastatic process and that nitrosative stress increases during the proliferation and growth of metastatic nodules in the tumor microenvironment. These results will help to better understand the role of oxidative stress during melanoma metastasis.
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http://dx.doi.org/10.1016/j.prp.2020.153218DOI Listing
November 2020

Inhibition of Angiogenesis by Treatment with Cold Atmospheric Plasma as a Promising Therapeutic Approach in Oncology.

Int J Mol Sci 2020 Sep 26;21(19). Epub 2020 Sep 26.

Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.

Background: Cold atmospheric plasma (CAP) is increasingly used in the field of oncology. Many of the mechanisms of action of CAP, such as inhibiting proliferation, DNA breakage, or the destruction of cell membrane integrity, have been investigated in many different types of tumors. In this regard, data are available from both in vivo and in vitro studies. Not only the direct treatment of a tumor but also the influence on its blood supply play a decisive role in the success of the therapy and the patient's further prognosis. Whether the CAP influences this process is unknown, and the first indications in this regard are addressed in this study.

Methods: Two different devices, kINPen and MiniJet, were used as CAP sources. Human endothelial cell line HDMEC were treated directly and indirectly with CAP, and growth kinetics were performed. To indicate apoptotic processes, caspase-3/7 assay and TUNEL assay were used. The influence of CAP on cellular metabolism was examined using the MTT and glucose assay. After CAP exposure, tube formation assay was performed to examine the capillary tube formation abilities of HDMEC and their migration was messured in separate assays. To investigate in a possible mutagenic effect of CAP treatment, a hypoxanthine-guanine-phosphoribosyl-transferase assay with non malignant cell (CCL-93) line was performed.

Results: The direct CAP treatment of the HDMEC showed a robust growth-inhibiting effect, but the indirect one did not. The MMT assay showed an apparent reduction in cell metabolism in the first 24 h after CAP treatment, which appeared to normalize 48 h and 72 h after CAP application. These results were also confirmed by the glucose assay. The caspase 3/7 assay and TUNEL assay showed a significant increase in apoptotic processes in the HDMEC after CAP treatment. These results were independent of the CAP device. Both the migration and tube formation of HDMEC were significant inhibited after CAP-treatment. No malignant effects could be demonstrated by the CAP treatment on a non-malignant cell line.
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http://dx.doi.org/10.3390/ijms21197098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582386PMC
September 2020

Plasma Treatment Limits Human Melanoma Spheroid Growth and Metastasis Independent of the Ambient Gas Composition.

Cancers (Basel) 2020 Sep 9;12(9). Epub 2020 Sep 9.

ZIK plasmatis, Leibniz Institute for Plasma Science and Technology, Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany.

Melanoma skin cancer is still a deadly disease despite recent advances in therapy. Previous studies have suggested medical plasma technology as a promising modality for melanoma treatment. However, the efficacy of plasmas operated under different ambient air conditions and the comparison of direct and indirect plasma treatments are mostly unexplored for this tumor entity. Moreover, exactly how plasma treatment affects melanoma metastasis has still not been explained. Using 3D tumor spheroid models and high-content imaging technology, we addressed these questions by utilizing one metastatic and one non-metastatic human melanoma cell line targeted with an argon plasma jet. Plasma treatment was toxic in both cell lines. Modulating the oxygen and nitrogen ambient air composition (100/0, 75/25, 50/50, 25/75, and 0/100) gave similar toxicity and reduced the spheroid growth for all conditions. This was the case for both direct and indirect treatments, with the former showing a treatment time-dependent response while the latter resulted in cytotoxicity with the longest treatment time investigated. Live-cell imaging of in-gel cultured spheroids indicated that plasma treatment did not enhance metastasis, and flow cytometry showed a significant modulation of S100A4 but not in any of the five other metastasis-related markers (β-catenin, E-cadherin, LEF1, SLUG, and ZEB1) investigated.
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http://dx.doi.org/10.3390/cancers12092570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565798PMC
September 2020

Plasma Treatment Limits Cutaneous Squamous Cell Carcinoma Development In Vitro and In Vivo.

Cancers (Basel) 2020 Jul 21;12(7). Epub 2020 Jul 21.

ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany.

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.
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http://dx.doi.org/10.3390/cancers12071993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409328PMC
July 2020

Cold Atmospheric Plasma Is a Potent Tool to Improve Chemotherapy in Melanoma In Vitro and In Vivo.

Biomolecules 2020 07 8;10(7). Epub 2020 Jul 8.

Department of Immunology, Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari 4847191971, Iran.

Malignant melanoma is a devastating disease. Because of its aggressiveness, it also serves as a model tumor for investigating novel therapeutic avenues. In recent years, scientific evidence has shown that cold atmospheric plasma (CAP) might be a promising modality in cancer therapy. In this study, we aimed to evaluate the effect of CAP generated by an argon plasma jet alone or in combination with dacarbazine (DAC) on melanoma cells in vitro and in vivo. The effects of the CAP on inducing lipid peroxidation and nitric oxide production were higher in B16 melanoma cells in comparison to non-malignant L929 cells. Assays on cell growth, apoptosis, and expression of genes related to, e.g., autophagic processes, showed CAP to have a substantial impact in melanoma cells while there were only minoreffects in L929 cells. In vivo, both CAP monotherapy and combination with DAC significantly decreased tumor growth. These results suggest that CAP not only selectively induces cell death in melanoma but also holds promises in combination with chemotherapy that might lead to improved tumor control.
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http://dx.doi.org/10.3390/biom10071011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407977PMC
July 2020

Determination of Immediate Kinetic Growth Retardation in Physically Plasma-treated Cells by Experimental and Modelling Data.

Anticancer Res 2020 Jul;40(7):3743-3749

Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Bonn, Germany

Background/aim: The antiproliferative effects of cold atmospheric plasma (CAP) make it a promising application option in oncology. The aim of the present study was to examine whether short-term CAP treatment leads to an initial partial elimination of the treated cells or to long-term impairement and inhibition of cell growth.

Materials And Methods: Cells were treated with CAP and biostatistical modelling was used to estimate growth rates over the incubation time. Four cell lines (U2-OS and MNNG osteosarcoma cells, 3T3 fibroblasts, HaCaT keratinocytes) and three CAP sources (MiniJet-R, kINPen MED, Maxium) were used.

Results: The antiproliferative efficacy of CAP was due to a significant reduction in cell count during treatment and the long-lasting inhibition of growth rate in the remaining cells, detectable in all cell lines and after treatment using all three CAP devices.

Conclusion: Induction of cell death and inhibition of cell growth are part of a general mechanism of biological CAP efficacy. However, data contradict the hypothesis that cancer cells respond more sensitively to CAP treatment compared to non-malignant cells.
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http://dx.doi.org/10.21873/anticanres.14363DOI Listing
July 2020