Plasma Oncology

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 6 December 2024 | Viewed by 12318

Special Issue Editors


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Department of Chemistry, University of Antwerp, Campus Drie Eiken – Room B2.09, Universiteitsplein 1, Wilrijk, BE-2610 Antwerp, Belgium
Interests: plasma and plasma–surface interactions by means of computer modeling and experiments, for various applications, with a major focus on green chemistry; plasma catalysis
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Research Group PLASMANT and Center for Oncological Research (CORE), Department of Chemistry, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, BE-2610 Wilrijk-Antwerp, Belgium
Interests: plasma oncology; plasma medicine; 3D in vitro cancer models; cell biology; oxidative stress; tumor microenvironment
Special Issues, Collections and Topics in MDPI journals

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Collection Editor
Department of Chemistry, Antwarp University, Antwerpen, Belgium
Interests: plasma medicine; cancer biology; immune-modulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

To date, effective cancer treatments are still limited by a lack of specificity, which can cause varying degrees of systemic adverse side effects. Cold atmospheric plasma (CAP), also called nonthermal plasma (NTP), is a partially ionized gas that is being investigated as a localized cancer therapy. It is created by applying electricity to a gas at atmospheric pressure and near room temperature and consists of neutral gas molecules, electrons, ions, radicals, and excited species. This chemical cocktail can rapidly react with cancerous tissue and induce therapeutic effects, thus opening the new field of plasma oncology. The main effectors in plasma for oncology are the reactive oxygen and nitrogen species (RONS) created by plasma. They can modulate and activate multiple signaling pathways in cancer cells, leading to cell death and stimulation of anticancer immunity. Many different cancer cell lines have been studied in vitro, mainly using two-dimensional (2D) cell cultures. However, in recent years, much progress has been made in studying more realistic cancer models, such as a 3D spheroid model (in vitro) and the chicken chorioallantoic membrane (CAM) model (in ovo). Furthermore, in vivo experiments are increasingly providing evidence of the anticancer effects of plasma, and the first clinical trials have been carried out with promising results. In addition, much research has been performed to investigate the combination of plasma with other treatments, such as chemotherapy or immunotherapy, to boost anticancer activity. Finally, computer modeling (in silico approaches) is being used to obtain a better understanding of the underlying plasma–cell interactions.

This Topic Collection on Plasma Oncology aims to publish papers on all of the abovementioned research topics. We believe an integrated study of the multidimensional effects of plasma in cancer treatment is essential. All papers that provide new insights into the mechanisms of plasma oncology based on in vitro, in ovo, and in vivo experiments, clinical studies, as well as by computer modeling, are welcome.

Prof. Dr. Annemie Bogaerts
Dr. Angela Privat-Maldonado
Dr. Abraham Lin
Collection Editors

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Keywords

  • mechanistic studies of plasma effects on cancer cells
  • selectivity studies (cancer vs normal cells)
  • role of RONS in cancer treatment
  • role of the tumor microenvironment
  • cell signaling pathways
  • in vitro (2D and 3D cell cultures), in ovo, in vivo studies
  • combination with chemotherapy, immunotherapy or other therapies
  • clinical trials
  • safety analysis
  • immunological response

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Published Papers (4 papers)

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Research

17 pages, 3240 KiB  
Article
Gas Flow Shaping via Novel Modular Nozzle System (MoNoS) Augments kINPen-Mediated Toxicity and Immunogenicity in Tumor Organoids
by Julia Berner, Lea Miebach, Luise Herold, Hans Höft, Torsten Gerling, Philipp Mattern and Sander Bekeschus
Cancers 2023, 15(4), 1254; https://doi.org/10.3390/cancers15041254 - 16 Feb 2023
Cited by 3 | Viewed by 2063
Abstract
Medical gas plasma is an experimental technology for anticancer therapy. Here, partial gas ionization yielded reactive oxygen and nitrogen species, placing the technique at the heart of applied redox biomedicine. Especially with the gas plasma jet kINPen, anti-tumor efficacy was demonstrated. This study [...] Read more.
Medical gas plasma is an experimental technology for anticancer therapy. Here, partial gas ionization yielded reactive oxygen and nitrogen species, placing the technique at the heart of applied redox biomedicine. Especially with the gas plasma jet kINPen, anti-tumor efficacy was demonstrated. This study aimed to examine the potential of using passive flow shaping to enhance the medical benefits of atmospheric plasma jets (APPJ). We used an in-house developed, proprietary Modular Nozzle System (MoNoS; patent-pending) to modify the flow properties of a kINPen. MoNoS increased the nominal plasma jet-derived reactive species deposition area and stabilized the air-plasma ratio within the active plasma zone while shielding it from external flow disturbances or gas impurities. At modest flow rates, dynamic pressure reduction (DPR) adapters did not augment reactive species deposition in liquids or tumor cell killing. However, MoNoS operated at kINPen standard argon fluxes significantly improved cancer organoid growth reduction and increased tumor immunogenicity, as seen by elevated calreticulin and heat-shock protein expression, along with a significantly spurred cytokine secretion profile. Moreover, the safe application of MoNoS gas plasma jet adapters was confirmed by their similar-to-superior safety profiles assessed in the hen’s egg chorioallantoic membrane (HET-CAM) coagulation and scar formation irritation assay. Full article
(This article belongs to the Special Issue Plasma Oncology)
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19 pages, 4717 KiB  
Article
Cold Atmospheric Plasma Triggers Apoptosis via the Unfolded Protein Response in Melanoma Cells
by Tom Zimmermann, Sebastian Staebler, R. Verena Taudte, Sumeyya Ünüvar, Sabine Grösch, Stephanie Arndt, Sigrid Karrer, Martin F. Fromm and Anja-Katrin Bosserhoff
Cancers 2023, 15(4), 1064; https://doi.org/10.3390/cancers15041064 - 7 Feb 2023
Cited by 7 | Viewed by 2664
Abstract
Cold atmospheric plasma (CAP) describes a partially ionized gas carrying large amounts of reactive oxygen (ROS) and nitrogen species (RNS). Numerous studies reported strong antitumor activity of CAP, thus rendering it a promising approach for tumor therapy. Although several cellular mechanisms of its [...] Read more.
Cold atmospheric plasma (CAP) describes a partially ionized gas carrying large amounts of reactive oxygen (ROS) and nitrogen species (RNS). Numerous studies reported strong antitumor activity of CAP, thus rendering it a promising approach for tumor therapy. Although several cellular mechanisms of its cytotoxicity were identified in recent years, the exact molecular effects and contributing signaling pathways are yet to be discovered. We discovered a strong activation of unfolded protein response (UPR) after CAP treatment with increased C/EBP homologous protein (CHOP) expression, which was mainly caused by protein misfolding and calcium loss in the endoplasmic reticulum. In addition, both ceramide level and ceramide metabolism were reduced after CAP treatment, which was then linked to the UPR activation. Pharmacological inhibition of ceramide metabolism resulted in sensitization of melanoma cells for CAP both in vitro and ex vivo. This study identified a novel mechanism of CAP-induced apoptosis in melanoma cells and thereby contributes to its potential application in tumor therapy. Full article
(This article belongs to the Special Issue Plasma Oncology)
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17 pages, 3254 KiB  
Article
Pancreatic Cancer Cells Undergo Immunogenic Cell Death upon Exposure to Gas Plasma-Oxidized Ringers Lactate
by Lea Miebach, Hager Mohamed, Kristian Wende, Vandana Miller and Sander Bekeschus
Cancers 2023, 15(1), 319; https://doi.org/10.3390/cancers15010319 - 3 Jan 2023
Cited by 8 | Viewed by 2902
Abstract
Survival rates among patients with pancreatic cancer, the most lethal gastrointestinal cancer, have not improved compared to other malignancies. Early tumor dissemination and a supportive, cancer-promoting tumor microenvironment (TME) limit therapeutic options and consequently impede tumor remission, outlining an acute need for effective [...] Read more.
Survival rates among patients with pancreatic cancer, the most lethal gastrointestinal cancer, have not improved compared to other malignancies. Early tumor dissemination and a supportive, cancer-promoting tumor microenvironment (TME) limit therapeutic options and consequently impede tumor remission, outlining an acute need for effective treatments. Gas plasma-oxidized liquid treatment showed promising preclinical results in other gastrointestinal and gynecological tumors by targeting the tumor redox state. Here, carrier solutions are enriched with reactive oxygen (ROS) and nitrogen (RNS) species that can cause oxidative distress in tumor cells, leading to a broad range of anti-tumor effects. Unfortunately, clinical relevance is often limited, as many studies have forgone the use of medical-grade solutions. This study investigated the efficacy of gas plasma-oxidized Ringer’s lactate (oxRilac), a physiological solution often used in clinical practice, on two pancreatic cancer cell lines to induce tumor toxicity and provoke immunogenicity. Tumor toxicity of the oxRilac solutions was further confirmed in three-dimensional tumor spheroids monitored over 72 h and in ovo using stereomicroscope imaging of excised GFP-expressing tumors. We demonstrated that cell death signaling was induced in a dose-dependent fashion in both cell lines and was paralleled by the increased surface expression of key markers of immunogenic cell death (ICD). Nuclear magnetic resonance (NMR) spectroscopy analysis suggested putative reaction pathways that may cause the non-ROS related effects. In summary, our study suggests gas plasma-deposited ROS in clinically relevant liquids as an additive option for treating pancreatic cancers via immune-stimulating and cytotoxic effects. Full article
(This article belongs to the Special Issue Plasma Oncology)
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20 pages, 3727 KiB  
Article
Cold Atmospheric Plasma Reduces Vessel Density and Increases Vascular Permeability and Apoptotic Cell Death in Solid Tumors
by Philipp Kugler, Sven Becker, Christian Welz, Nadine Wiesmann, Jonas Sax, Christoph R. Buhr, Markus H. Thoma, Juergen Brieger and Jonas Eckrich
Cancers 2022, 14(10), 2432; https://doi.org/10.3390/cancers14102432 - 14 May 2022
Cited by 6 | Viewed by 2972
Abstract
Cold atmospheric plasma (CAP) has demonstrated promising anti-cancer effects in numerous in vitro and in vivo studies. Despite their relevance for the treatment of solid tumors, effects of CAP on tumor vasculature and microcirculation have only rarely been investigated. Here, we report the [...] Read more.
Cold atmospheric plasma (CAP) has demonstrated promising anti-cancer effects in numerous in vitro and in vivo studies. Despite their relevance for the treatment of solid tumors, effects of CAP on tumor vasculature and microcirculation have only rarely been investigated. Here, we report the reduction of vessel density and an increase in vascular permeability and tumor cell apoptosis after CAP application. Solid tumors in the chorioallantoic membrane of chicken embryos were treated with CAP and evaluated with respect to effects of CAP on embryo survival, tumor size, and tumor morphology. Furthermore, intratumoral blood vessel density, apoptotic cell death and the tumor-associated microcirculation were investigated and compared to sham treatment. Treatment with CAP significantly reduced intratumoral vessel density while increasing the rate of intratumoral apoptosis in solid tumors. Furthermore, CAP treatment increased vascular permeability and attenuated the microcirculation by causing vessel occlusions in the tumor-associated vasculature. These effects point out the potential of CAP as a promising and yet underrated therapeutic modality for addressing the tumor vasculature in the treatment of solid tumors. Full article
(This article belongs to the Special Issue Plasma Oncology)
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