Special Issue "Plasma in Cancer Treatment"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 November 2019).

Special Issue Editors

Prof. Dr. Annemie Bogaerts
E-Mail Website
Guest Editor
Research group PLASMANT, Department of Chemistry, University of Antwerp Campus Drie Eiken, Universiteitsplein 1, BE-2610 Wilrijk-Antwerp, Belgium
Tel. +32-3-265.23.77; Fax: +32-3-265.23.43
Interests: plasma; plasma chemistry; plasma oncology; plasma medicine; plasma catalysis; computer modeling; plasma cancer immunotherapy
Special Issues and Collections in MDPI journals
Dr. Angela Privat-Maldonado
E-Mail Website
Guest Editor
Research group PLASMANT, Department of Chemistry, University of Antwerp Campus Drie Eiken, Universiteitsplein 1, BE-2610 Wilrijk-Antwerp, Belgium
Tel. +32-3-265.92.64; Fax: +32-3-265.23.43
Interests: plasma; plasma oncology; plasma medicine; 3-dimensional in vitro models; cell biology, oxidative stress

Special Issue Information

Dear colleagues,

In the last decade, research on cold atmospheric plasma (CAP) has significantly advanced our understanding of the effect of CAP on cancer cells and their potential for cancer treatment. One of the most important findings is the realization that CAP can modulate and activate multiple signaling pathways in cancer cells that contribute to their elimination. This regulatory effect is mainly mediated by the rich cocktail of reactive oxygen and nitrogen species (RONS) created by plasma. This has been demonstrated for different cancer cell lines and enabled the realization of the first clinical trials with promising results. In addition, plasma could be combined with other treatments -such as immunotherapy- to boost its anticancer activity. The addition of new research tools to study the response of cancer cells to CAP -such as 3-dimensional in vitro, in ovo and in vivo models and in silico approaches- as well as the use of -OMICS technologies which facilitate the high-throughput study of the genome, proteome, transcriptome and metabolome could aid to unravel the underlying mechanisms of CAP in cancer treatment.

In order to progress towards a widespread clinical application of CAP, an integrated study of the multidimensional effect of CAP in cancer treatment is essential. In this Special Issue, we will publish reviews and original research papers that provide new insights into the mechanisms of cold atmospheric plasma in cancer treatment, based on in vitro and in vivo experiments, clinical studies, as well as by computer modeling.

Prof. Dr. Annemie Bogaerts
Dr. Angela Privat-Maldonado
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Mechanistic studies of plasma effects on cancer cells
  • Selectivity studies (cancer vs normal cells)
  • In vitro (2D and 3D cell cultures), in ovo, in vivo studies
  • Combination with immunotherapy or other therapies
  • Cell signaling pathways
  • Role of RONS in cancer treatment
  • Clinical trials
  • Tumor microenvironment

Published Papers (5 papers)

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Research

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Open AccessArticle
Cold Atmospheric Plasma Restores Paclitaxel Sensitivity to Paclitaxel-Resistant Breast Cancer Cells by Reversing Expression of Resistance-Related Genes
Cancers 2019, 11(12), 2011; https://doi.org/10.3390/cancers11122011 (registering DOI) - 13 Dec 2019
Abstract
Paclitaxel (Tx) is a widely used therapeutic chemical for breast cancer treatment; however, cancer recurrence remains an obstacle for improved prognosis of cancer patients. In this study, cold atmospheric plasma (CAP) was tested for its potential to overcome the drug resistance. After developing [...] Read more.
Paclitaxel (Tx) is a widely used therapeutic chemical for breast cancer treatment; however, cancer recurrence remains an obstacle for improved prognosis of cancer patients. In this study, cold atmospheric plasma (CAP) was tested for its potential to overcome the drug resistance. After developing Tx-resistant MCF-7 (MCF-7/TxR) breast cancer cells, CAP was applied to the cells, and its effect on the recovery of drug sensitivity was assessed in both cellular and molecular aspects. Sensitivity to Tx in the MCF-7/TxR cells was restored up to 73% by CAP. A comparison of genome-wide expression profiles between the TxR cells and the CAP-treated cells identified 49 genes that commonly appeared with significant changes. Notably, 20 genes, such as KIF13B, GOLM1, and TLE4, showed opposite expression profiles. The protein expression levels of selected genes, DAGLA and CEACAM1, were recovered to those of their parental cells by CAP. Taken together, CAP inhibited the growth of MCF-7/TxR cancer cells and recovered Tx sensitivity by resetting the expression of multiple drug resistance–related genes. These findings may contribute to extending the application of CAP to the treatment of TxR cancer. Full article
(This article belongs to the Special Issue Plasma in Cancer Treatment)
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Open AccessArticle
Cold Atmospheric Plasma-Treated PBS Eliminates Immunosuppressive Pancreatic Stellate Cells and Induces Immunogenic Cell Death of Pancreatic Cancer Cells
Cancers 2019, 11(10), 1597; https://doi.org/10.3390/cancers11101597 - 19 Oct 2019
Cited by 1
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with a low response to treatment and a five-year survival rate below 5%. The ineffectiveness of treatment is partly because of an immunosuppressive tumor microenvironment, which comprises tumor-supportive pancreatic stellate cells (PSCs). [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with a low response to treatment and a five-year survival rate below 5%. The ineffectiveness of treatment is partly because of an immunosuppressive tumor microenvironment, which comprises tumor-supportive pancreatic stellate cells (PSCs). Therefore, new therapeutic strategies are needed to tackle both the immunosuppressive PSC and pancreatic cancer cells (PCCs). Recently, physical cold atmospheric plasma consisting of reactive oxygen and nitrogen species has emerged as a novel treatment option for cancer. In this study, we investigated the cytotoxicity of plasma-treated phosphate-buffered saline (pPBS) using three PSC lines and four PCC lines and examined the immunogenicity of the induced cell death. We observed a decrease in the viability of PSC and PCC after pPBS treatment, with a higher efficacy in the latter. Two PCC lines expressed and released damage-associated molecular patterns characteristic of the induction of immunogenic cell death (ICD). In addition, pPBS-treated PCC were highly phagocytosed by dendritic cells (DCs), resulting in the maturation of DC. This indicates the high potential of pPBS to trigger ICD. In contrast, pPBS induced no ICD in PSC. In general, pPBS treatment of PCCs and PSCs created a more immunostimulatory secretion profile (higher TNF-α and IFN-γ, lower TGF-β) in coculture with DC. Altogether, these data show that plasma treatment via pPBS has the potential to induce ICD in PCCs and to reduce the immunosuppressive tumor microenvironment created by PSCs. Therefore, these data provide a strong experimental basis for further in vivo validation, which might potentially open the way for more successful combination strategies with immunotherapy for PDAC. Full article
(This article belongs to the Special Issue Plasma in Cancer Treatment)
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Open AccessArticle
The Influence of Cell Type and Culture Medium on Determining Cancer Selectivity of Cold Atmospheric Plasma Treatment
Cancers 2019, 11(9), 1287; https://doi.org/10.3390/cancers11091287 - 01 Sep 2019
Cited by 1
Abstract
Increasing the selectivity of cancer treatments is attractive, as it has the potential to reduce side-effects of therapy. Cold atmospheric plasma (CAP) is a novel cancer treatment that disrupts the intracellular oxidative balance. Several reports claim CAP treatment to be selective, but retrospective [...] Read more.
Increasing the selectivity of cancer treatments is attractive, as it has the potential to reduce side-effects of therapy. Cold atmospheric plasma (CAP) is a novel cancer treatment that disrupts the intracellular oxidative balance. Several reports claim CAP treatment to be selective, but retrospective analysis of these studies revealed discrepancies in several biological factors and culturing methods. Before CAP can be conclusively stated as a selective cancer treatment, the importance of these factors must be investigated. In this study, we evaluated the influence of the cell type, cancer type, and cell culture medium on direct and indirect CAP treatment. Comparison of cancerous cells with their non-cancerous counterparts was performed under standardized conditions to determine selectivity of treatment. Analysis of seven human cell lines (cancerous: A549, U87, A375, and Malme-3M; non-cancerous: BEAS-2B, HA, and HEMa) and five different cell culture media (DMEM, RPMI1640, AM, BEGM, and DCBM) revealed that the tested parameters strongly influence indirect CAP treatment, while direct treatment was less affected. Taken together, the results of our study demonstrate that cell type, cancer type, and culturing medium must be taken into account before selectivity of CAP treatment can be claimed and overlooking these parameters can easily result in inaccurate conclusions of selectivity. Full article
(This article belongs to the Special Issue Plasma in Cancer Treatment)
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Open AccessFeature PaperArticle
Risk Assessment of kINPen Plasma Treatment of Four Human Pancreatic Cancer Cell Lines with Respect to Metastasis
Cancers 2019, 11(9), 1237; https://doi.org/10.3390/cancers11091237 - 23 Aug 2019
Cited by 1
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Plasma in Cancer Treatment)
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Review

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Open AccessReview
Modifying the Tumour Microenvironment: Challenges and Future Perspectives for Anticancer Plasma Treatments
Cancers 2019, 11(12), 1920; https://doi.org/10.3390/cancers11121920 - 02 Dec 2019
Abstract
Tumours are complex systems formed by cellular (malignant, immune, and endothelial cells, fibroblasts) and acellular components (extracellular matrix (ECM) constituents and secreted factors). A close interplay between these factors, collectively called the tumour microenvironment, is required to respond appropriately to external cues and [...] Read more.
Tumours are complex systems formed by cellular (malignant, immune, and endothelial cells, fibroblasts) and acellular components (extracellular matrix (ECM) constituents and secreted factors). A close interplay between these factors, collectively called the tumour microenvironment, is required to respond appropriately to external cues and to determine the treatment outcome. Cold plasma (here referred as ‘plasma’) is an emerging anticancer technology that generates a unique cocktail of reactive oxygen and nitrogen species to eliminate cancerous cells via multiple mechanisms of action. While plasma is currently regarded as a local therapy, it can also modulate the mechanisms of cell-to-cell and cell-to-ECM communication, which could facilitate the propagation of its effect in tissue and distant sites. However, it is still largely unknown how the physical interactions occurring between cells and/or the ECM in the tumour microenvironment affect the plasma therapy outcome. In this review, we discuss the effect of plasma on cell-to-cell and cell-to-ECM communication in the context of the tumour microenvironment and suggest new avenues of research to advance our knowledge in the field. Furthermore, we revise the relevant state-of-the-art in three-dimensional in vitro models that could be used to analyse cell-to-cell and cell-to-ECM communication and further strengthen our understanding of the effect of plasma in solid tumours. Full article
(This article belongs to the Special Issue Plasma in Cancer Treatment)
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