Clinical Experience with Cold Atmospheric Pressure Plasma (CAP) in Cancer Treatment

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

Deadline for manuscript submissions: closed (20 June 2022) | Viewed by 8178

Special Issue Editors


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Guest Editor
Department of Oral and Maxillofacial Surgery/Plastic Surgery, Greifswald University Medicine, Greifswald, Germany
Interests: clinical cancer research; head and neck oncology; cancer surgery; cold plasma medicine; clinical pilot studies in plasma oncology

E-Mail Website
Guest Editor
Department of Oral and Maxillofacial Surgery/Plastic Surgery, Greifswald University Medicine, Greifswald, Germany
Interests: clinical cancer research; head and neck oncology; cancer surgery; cold plasma medicine; clinical pilot studies in plasma oncology

Special Issue Information

Dear Colleagues,

The therapeutically intended application of cold physical plasma in cancer patients is stepping upwards in the pyramid of evidence-based medicine (EBM). There is already a consensus among experts regarding the appropriate response to plasma in experimental settings such as cancer cell lines, cultivated human tumor cells, human tumor specimen freshly explanted from patients, animal model tumors, and animals with transplanted human tumor stem cells. Now, the next step and the main focus of this Special Issue of Cancers is the proof of concept through well-documented case reports and clinical pilot studies. There are already some studies on the way concerning clinical effectiveness, side effects, optimal application, and treatment period. If there is a manageable amount of tumor stem cells such as in precancerous lesions of skin and mucosa or in small tumors such as early basal cell carcinoma of the skin, plasma could become an approved clinical treatment option soon. At present, it is already used in the palliative care of patients with contaminated cancer ulcerations accessible to plasma because of its proven effectiveness against anaerobe pathogens. Patients greatly appreciate that plasma can reduce strong fetid odors and pain without the burden of serious side effects. We are sure that there is a lot more early therapeutic experience among researchers and clinicians, and this Special Issue of Cancers intends, for the very first time, to present and publish their sound protocols and data.

Prof. Dr. Hans-Robert Metelmann
Dr. Christian Seebauer
Guest Editors

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Keywords

  • cold physical plasma and cancer
  • clinical plasma medicine
  • case reports
  • clinical pilot studies
  • side effects
  • treatment period
  • curative cancer treatment
  • early cancer treatment
  • preventive treatment
  • palliative cancer treatment
  • rescue treatment of surgical site infections after cancer surgery

Published Papers (3 papers)

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Research

17 pages, 3916 KiB  
Article
Gas Plasma Exposure of Glioblastoma Is Cytotoxic and Immunomodulatory in Patient-Derived GBM Tissue
by Sander Bekeschus, Mikael Ispirjan, Eric Freund, Frederik Kinnen, Juliane Moritz, Fariba Saadati, Jacqueline Eckroth, Debora Singer, Matthias B. Stope, Kristian Wende, Christoph A. Ritter, Henry W. S. Schroeder and Sascha Marx
Cancers 2022, 14(3), 813; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14030813 - 05 Feb 2022
Cited by 7 | Viewed by 2419
Abstract
Glioblastoma multiforme (GBM) is the most common primary malignant adult brain tumor. Therapeutic options for glioblastoma are maximal surgical resection, chemotherapy, and radiotherapy. Therapy resistance and tumor recurrence demand, however, new strategies. Several experimental studies have suggested gas plasma technology, a partially ionized [...] Read more.
Glioblastoma multiforme (GBM) is the most common primary malignant adult brain tumor. Therapeutic options for glioblastoma are maximal surgical resection, chemotherapy, and radiotherapy. Therapy resistance and tumor recurrence demand, however, new strategies. Several experimental studies have suggested gas plasma technology, a partially ionized gas that generates a potent mixture of reactive oxygen species (ROS), as a future complement to the existing treatment arsenal. However, aspects such as immunomodulation, inflammatory consequences, and feasibility studies using GBM tissue have not been addressed so far. In vitro, gas plasma generated ROS that oxidized cells and led to a treatment time-dependent metabolic activity decline and G2 cell cycle arrest. In addition, peripheral blood-derived monocytes were co-cultured with glioblastoma cells, and immunomodulatory surface expression markers and cytokine release were screened. Gas plasma treatment of either cell type, for instance, decreased the expression of the M2-macrophage marker CD163 and the tolerogenic molecule SIGLEC1 (CD169). In patient-derived GBM tissue samples exposed to the plasma jet kINPen ex vivo, apoptosis was significantly increased. Quantitative chemokine/cytokine release screening revealed gas plasma exposure to significantly decrease 5 out of 11 tested chemokines and cytokines, namely IL-6, TGF-β, sTREM-2, b-NGF, and TNF-α involved in GBM apoptosis and immunomodulation. In summary, the immuno-modulatory and proapoptotic action shown in this study might be an important step forward to first clinical observational studies on the future discovery of gas plasma technology’s potential in neurosurgery and neuro-oncology especially in putative adjuvant or combinatory GBM treatment settings. Full article
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19 pages, 2292 KiB  
Communication
Murine Macrophages Modulate Their Inflammatory Profile in Response to Gas Plasma-Inactivated Pancreatic Cancer Cells
by Aydar Khabipov, Eric Freund, Kim Rouven Liedtke, Andre Käding, Janik Riese, Julia van der Linde, Stephan Kersting, Lars-Ivo Partecke and Sander Bekeschus
Cancers 2021, 13(11), 2525; https://doi.org/10.3390/cancers13112525 - 21 May 2021
Cited by 6 | Viewed by 2614
Abstract
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 [...] Read more.
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. Full article
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16 pages, 3605 KiB  
Article
Multimodal Imaging Techniques to Evaluate the Anticancer Effect of Cold Atmospheric Pressure Plasma
by Marcel Kordt, Isabell Trautmann, Christin Schlie, Tobias Lindner, Jan Stenzel, Anna Schildt, Lars Boeckmann, Sander Bekeschus, Jens Kurth, Bernd J. Krause, Brigitte Vollmar and Eberhard Grambow
Cancers 2021, 13(10), 2483; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13102483 - 19 May 2021
Cited by 9 | Viewed by 2417
Abstract
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) [...] Read more.
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. Full article
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