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result(s) for
"Karrer, Sigrid"
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In Vivo Immune Cell Responses and Long-Term Effects of Cold Atmospheric Plasma in the Upper Respiratory Tract
2025
Cold atmospheric plasma (CAP) devices produce reactive oxygen and reactive nitrogen species, which have antimicrobial and antiviral effects, while also affecting the molecular and cellular processes in eukaryotic cells. This study investigates the effects of CAP treatment on immune responses and long-term organism health in the upper respiratory tract (URT). Using a surface-microdischarge-based plasma intensive care (PIC) device from terraplasma medical GmbH, 129Sv/Ev wildtype mice were exposed to short (single 10 min session), long (five 10 min sessions), and recovery-phase treatments (five 10 min sessions; 7 days of recovery). Bronchoalveolar lavage fluid was examined by cytospin, fluorescence-activated cell sorting, and mRNA expression analysis. Lung tissue was analyzed for morphological changes (H&E), DNA damage (γH2AX), apoptosis (TUNEL), immune cell marker alterations (CD45, Ly-6G, CD68, CD3, MCC), and fibrosis (NE). Results showed that PIC treatment increased the number of apoptotic cells and activated immune markers, such as IFN-γ, IL-6, and TNF-α, in the lungs, especially after multiple treatments. These effects largely reversed after a 7-day regeneration period. Importantly, no DNA damage or morphological lung alterations were observed across groups. The findings suggest that PIC treatment in the URT induces transient immune activation without causing tissue damage, but caution is advised for patients with cytokine release syndrome or macrophage activation syndrome due to potential cytokine surges.
Journal Article
Cold Atmospheric Plasma Improves the Therapeutic Success of Photodynamic Therapy on UV-B-Induced Squamous Cell Carcinoma in Hairless Mice
by
Unger, Petra
,
Bäumler, Wolfgang
,
Karrer, Sigrid
in
5-aminolaevulinic acid (ALA)
,
actinic keratosis (AK)
,
Animals
2025
Background/Objectives: Actinic keratosis (AK) occurs on sun-damaged skin and is considered a precursor to squamous cell carcinoma (SCC). Photodynamic therapy (PDT), using 5-aminolevulinic acid (ALA) and red light, is a common treatment for AK. However, its clinical efficacy for invasive tumors such as SCC is limited by the poor penetration and distribution of the photosensitizer. Cold atmospheric plasma (CAP), a partially ionized gas, increases skin permeability and exhibits anti-cancer properties through the generation of reactive oxygen species (ROS). In a previous study, CAP showed promising synergistic effects when combined with ALA-PDT for the treatment of SCC cells in vitro. The present study investigated the effects of combining CAP with ALA-PDT on cutaneous AK and SCC induced by ultraviolet B (UV-B) irradiation in SKH1 hairless mice. Methods: We compared various application sequences (CAP-ALA–red light, ALA–red light–CAP, and ALA-CAP–red light) against conventional ALA-PDT using visual, histological, and molecular assessments of the affected skin. Results: The results demonstrated that combined treatments strongly inhibited the growth of UV-B-induced skin lesions. TUNEL staining revealed increased apoptosis following both single and combined therapies, while Ki-67 staining indicated reduced keratinocyte proliferation and diminished DNA damage in treated areas. mRNA expression analysis showed the upregulation of apoptosis-related genes (p16INK4a, p21CIP1) alongside enhanced anti-tumor immune responses (IL-6, IL-8) in the affected tissue samples. Notably, the combined treatment enhances the therapeutic effect, whereas the sequence of application does not seem to be relevant for therapeutic efficacy in vivo. Conclusions: Overall, these results suggest that CAP may enhance the anti-tumor effect of conventional ALA-PDT, supporting previous findings on SCC cells.
Journal Article
Cold Atmospheric Plasma (CAP) Changes Gene Expression of Key Molecules of the Wound Healing Machinery and Improves Wound Healing In Vitro and In Vivo
by
Bosserhoff, Anja-Katrin
,
Morfill, Gregor E.
,
Shimizu, Tetsuji
in
Actins - genetics
,
Animals
,
Apoptosis
2013
Cold atmospheric plasma (CAP) has the potential to interact with tissue or cells leading to fast, painless and efficient disinfection and furthermore has positive effects on wound healing and tissue regeneration. For clinical implementation it is necessary to examine how CAP improves wound healing and which molecular changes occur after the CAP treatment. In the present study we used the second generation MicroPlaSter ß® in analogy to the current clinical standard (2 min treatment time) in order to determine molecular changes induced by CAP using in vitro cell culture studies with human fibroblasts and an in vivo mouse skin wound healing model. Our in vitro analysis revealed that the CAP treatment induces the expression of important key genes crucial for the wound healing response like IL-6, IL-8, MCP-1, TGF-ß1, TGF-ß2, and promotes the production of collagen type I and alpha-SMA. Scratch wound healing assays showed improved cell migration, whereas cell proliferation analyzed by XTT method, and the apoptotic machinery analyzed by protein array technology, was not altered by CAP in dermal fibroblasts. An in vivo wound healing model confirmed that the CAP treatment affects above mentioned genes involved in wound healing, tissue injury and repair. Additionally, we observed that the CAP treatment improves wound healing in mice, no relevant side effects were detected. We suggest that improved wound healing might be due to the activation of a specified panel of cytokines and growth factors by CAP. In summary, our in vitro human and in vivo animal data suggest that the 2 min treatment with the MicroPlaSter ß® is an effective technique for activating wound healing relevant molecules in dermal fibroblasts leading to improved wound healing, whereas the mechanisms which contribute to these observed effects have to be further investigated.
Journal Article
Systemic therapy of necrobiotic xanthogranuloma: a systematic review
by
Steinhelfer, Lisa
,
Jägle, Herbert
,
Schreml, Stephan
in
Bias
,
Care and treatment
,
Corticosteroids
2022
Background
Even though a plethora of systemic therapies have been proposed for necrobiotic xanthogranuloma (NXG), there is no systematic review on this topic in literature.
Objective
To review all existing literature on the systemic therapy of NXG in order to identify the most effective therapies.
Methods
All reported papers in the literature were screened for systemic treatments of NXG. Papers without proper description of the therapies, papers describing topical therapy, and articles without assessment of effectiveness were excluded. Subsequently, we analyzed 79 papers and a total of 175 cases.
Results
The most effective treatments for NXG are intravenous immunoglobulins (IVIG), corticosteroids, and combination therapies including corticosteroids.
Conclusions
Corticosteroids and IVIG should therefore be considered first-line treatments in patients with NXG.
Journal Article
Treatment and Cleaning of Contact Lenses with Plasma-Activated Solutions
by
Unger, Petra
,
Karrer, Sigrid
,
Maisch, Tim
in
Antibacterial activity
,
antibacterial effects
,
Antibiotics
2026
The occurrence of contact lens complications caused by inadequate cleaning of the lenses using “All-in-One” contact lens cleaning solutions (CLCSs) represents a medically relevant problem worldwide. This study explores the potential of cold atmospheric plasma (CAP) to enhance the efficacy of CLCSs and address complications from inadequate lens hygiene. It was examined whether exposure to CAP for 1–24 h could boost the antibacterial effects of CLCSs and other solutions, including Milli-Q water (M-QW), physiological saline (NaCl), and Dulbecco’s Phosphate Buffered Saline (DPBS). Additionally, the stability of reactive oxygen and nitrogen species (RONS) and their impact on pH immediately after treatment and over 1–4 weeks was assessed. Furthermore, the cleaning efficacy of plasma-activated solutions (PASs) was tested on lipid-coated silicone hydrogel lenses. Results showed that CAP increased RONS concentrations immediately, with elevated levels persisting over time. While no significant improved antibacterial effect was observed against Escherichia coli in CLCSs, CAP treatment generated disinfectant properties in M-QW and NaCl solutions. Importantly, CAP-treated CLCSs significantly improved the cleaning performance on lipid-coated lenses, though M-QW’s cleaning ability worsened post-treatment. pH measurements indicated notable decreases in M-QW and NaCl after CAP, whereas buffered solutions like CLCSs and DPBS remained stable. Overall, CAP demonstrates promise for contact lens disinfection and surface modification; however, further research and pre-clinical trials are necessary before clinical application in ophthalmology.
Journal Article
Decolonisation of MRSA, S. aureus and E. coli by Cold-Atmospheric Plasma Using a Porcine Skin Model In Vitro
2012
In the last twenty years new antibacterial agents approved by the U.S. FDA decreased whereas in parallel the resistance situation of multi-resistant bacteria increased. Thus, community and nosocomial acquired infections of resistant bacteria led to a decrease in the efficacy of standard therapy, prolonging treatment time and increasing healthcare costs. Therefore, the aim of this work was to demonstrate the applicability of cold atmospheric plasma for decolonisation of Gram-positive (Methicillin-resistant Staphylococcus aureus (MRSA), Methicillin-sensitive Staphylococcus aureus) and Gram-negative bacteria (E. coli) using an ex vivo pig skin model. Freshly excised skin samples were taken from six month old female pigs (breed: Pietrain). After application of pure bacteria on the surface of the explants these were treated with cold atmospheric plasma for up to 15 min. Two different plasma devices were evaluated. A decolonisation efficacy of 3 log(10) steps was achieved already after 6 min of plasma treatment. Longer plasma treatment times achieved a killing rate of 5 log(10) steps independently from the applied bacteria strains. Histological evaluations of untreated and treated skin areas upon cold atmospheric plasma treatment within 24 h showed no morphological changes as well as no significant degree of necrosis or apoptosis determined by the TUNEL-assay indicating that the porcine skin is still vital. This study demonstrates for the first time that cold atmospheric plasma is able to very efficiently kill bacteria applied to an intact skin surface using an ex vivo porcine skin model. The results emphasize the potential of cold atmospheric plasma as a new possible treatment option for decolonisation of human skin from bacteria in patients in the future without harming the surrounding tissue.
Journal Article
Cold atmospheric plasma causes a calcium influx in melanoma cells triggering CAP-induced senescence
by
Bosserhoff, Anja-Katrin
,
Gebhardt, Lisa
,
Karrer, Sigrid
in
631/67/1059
,
631/67/1813/1634
,
631/80/86
2018
Cold atmospheric plasma (CAP) is a promising approach in anti-cancer therapy, eliminating cancer cells with high selectivity. However, the molecular mechanisms of CAP action are poorly understood. In this study, we investigated CAP effects on calcium homeostasis in melanoma cells. We observed increased cytoplasmic calcium after CAP treatment, which also occurred in the absence of extracellular calcium, indicating the majority of the calcium increase originates from intracellular stores. Application of previously CAP-exposed extracellular solutions also induced cytoplasmic calcium elevations. A substantial fraction of this effect remained when the application was delayed for one hour, indicating the chemical stability of the activating agent(s). Addition of ryanodine and cyclosporin A indicate the involvement of the endoplasmatic reticulum and the mitochondria. Inhibition of the cytoplasmic calcium elevation by the intracellular chelator BAPTA blocked CAP-induced senescence. This finding helps to understand the molecular influence and the mode of action of CAP on tumor cells.
Journal Article
Cold Atmospheric Plasma Changes the Amino Acid Composition of Solutions and Influences the Anti-Tumor Effect on Melanoma Cells
by
Bosserhoff, Anja-Katrin
,
Boskovic, Marko
,
Samol, Claudia
in
Amino acids
,
Cancer
,
Cell culture
2021
Cold Atmospheric Plasma (CAP) is an ionized gas near room temperature. Its anti-tumor effect can be transmitted either by direct treatment or mediated by a plasma-treated solution (PTS), such as treated standard cell culture medium, which contains different amino acids, inorganic salts, vitamins and other substances. Despite extensive research, the active components in PTS and its molecular or cellular mechanisms are not yet fully understood. The purpose of this study was the measurement of the reactive species in PTS and their effect on tumor cells using different plasma modes and treatment durations. The PTS analysis yielded mode- and dose-dependent differences in the production of reactive oxygen and nitrogen species (RONS), and in the decomposition and modification of the amino acids Tyrosine (Tyr) and Tryptophan (Trp). The Trp metabolites Formylkynurenine (FKyn) and Kynurenine (Kyn) were produced in PTS with the 4 kHz (oxygen) mode, inducing apoptosis in Mel Im melanoma cells. Nitrated derivatives of Trp and Tyr were formed in the 8 kHz (nitrogen) mode, elevating the p16 mRNA expression and senescence-associated ß-Galactosidase staining. In conclusion, the plasma mode has a strong impact on the composition of the active components in PTS and affects its anti-tumor mechanism. These findings are of decisive importance for the development of plasma devices and the effectiveness of tumor treatment.
Journal Article
Acidified Nitrite Contributes to the Antitumor Effect of Cold Atmospheric Plasma on Melanoma Cells
by
Bosserhoff, Anja-Katrin
,
Zimmermann, Tom
,
Karrer, Sigrid
in
Acidification
,
Antineoplastic Agents - pharmacology
,
Apoptosis
2021
Cold atmospheric plasma (CAP) is partially ionized gas near room temperature with previously reported antitumor effects. Despite extensive research and growing interest in this technology, active components and molecular mechanisms of CAP are not fully understood to date. We used Raman spectroscopy and colorimetric assays to determine elevated nitrite and nitrate levels after treatment with a MiniFlatPlaster CAP device. Previously, we demonstrated CAP-induced acidification. Cellular effects of nitrite and strong extracellular acidification were assessed using live-cell imaging of intracellular Ca2+ levels, cell viability analysis as well as quantification of p21 and DNA damage. We further characterized these observations by analyzing established molecular effects of CAP treatment. A synergistic effect of nitrite and acidification was found, leading to strong cytotoxicity in melanoma cells. Interestingly, protein nitration and membrane damage were absent after treatment with acidified nitrite, thereby challenging their contribution to CAP-induced cytotoxicity. Further, phosphorylation of ERK1/2 was increased after treatment with both acidified nitrite and indirect CAP. This study characterizes the impact of acidified nitrite on melanoma cells and supports the importance of RNS during CAP treatment. Further, it defines and evaluates important molecular mechanisms that are involved in the cancer cell response to CAP.
Journal Article
Retrospective Single-Center Case Study of Clinical Variables and the Degree of Actinic Elastosis Associated with Rare Skin Cancers
by
Bollmann, Lara
,
Karrer, Sigrid
,
Haferkamp, Sebastian
in
Acquired immune deficiency syndrome
,
AIDS
,
atypical fibroxanthoma
2024
(1) Background: Rare skin cancers include epithelial, neuroendocrine, and hematopoietic neoplasias as well as cutaneous sarcomas. Ultraviolet (UV) radiation and sunburns are important drivers for the incidence of certain cutaneous sarcomas; however, the pathogenetic role of UV light is less clear in rare skin cancers compared to keratinocyte cancer and melanoma. In this study, we compared the degree of actinic elastosis (AE) as a surrogate for lifetime UV exposure among selected rare skin cancers (atypical fibroxanthoma [AFX], pleomorphic dermal sarcoma [PDS], dermatofibrosarcoma protuberans [DFSP], Kaposi sarcoma [KS], Merkel cell carcinoma [MCC], and leiomyosarcoma [LMS]) while taking into account relevant clinical variables (age, sex, and body site). (2) Methods: We newly established a semi-quantitative score for the degree of AE ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration) and multiplied it by the perilesional vertical extent (depth), measured histometrically (tumor-associated elastosis grade (TEG)). We matched the TEG of n = 210 rare skin cancers from 210 patients with their clinical variables. (3) Results: TEG values were correlated with age and whether tumors arose on UV-exposed body sites. TEG values were significantly higher in AFX and PDS cases compared to all other analyzed rare skin cancer types. As expected, TEG values were low in DFSP and KS, while MCC cases exhibited intermediate TEG values. (4) Conclusions: High cumulative UV exposure is more strongly associated with AFX/PDS and MCC than with other rare skin cancers. These important results expand the available data associated with rare skin cancers while also offering insight into the value of differentiating among these tumor types based on their relationship with sun exposure, potentially informing preventative, diagnostic and/or therapeutic approaches.
Journal Article