The ability to produce cold plasma at atmospheric pressure conditions was the basis for the rapid growth of plasma-related application areas in biomedicine. Plasma comprises a multitude of active components such as charged particles, electric current, UV radiation, and reactive gas species which can act synergistically. Anti-itch, antimicrobial, anti-inflammatory, tissue-stimulating, blood flow-enhancing, and proapoptotic effects were demonstrated in in vivo and in vitro experiments, and until now, no resistance of pathogens against plasma treatment was observed. The combination of the different active agents and their broad range of positive effects on various diseases, especially easily accessible skin diseases, renders plasma quite attractive for applications in medicine. For medical applications, two different types of cold plasma appear suitable: indirect (plasma jet) and direct (dielectric barrier discharge—DBD) plasma sources. The DBD device PlasmaDerm® VU-2010 (CINOGY Technologies GmbH), the atmospheric pressure plasma jet (APPJ) kINPen® MED (INP Greifswald/neoplas tools GmbH), and the SteriPlas (Adtec Ltd., London, United Kingdom) are CE-certified as a medical product to treat chronic wounds in humans and showed efficacy and a good tolerability. Recently, the use of plasma in cancer research and oncology is of particular interest. Plasma has been shown to induce proapoptotic effects more efficiently in tumor cells compared with the benign counterparts, leads to cellular senescence, and—as shown in vivo—reduces skin tumors. To this end, a world-wide first Leibniz professorship for plasmabiotechnology in dermatology has been introduced to establish a scientific network for the investigation of the efficacy and safety of cold atmospheric plasma in dermatooncology. Hence, plasma medicine especially in dermatology holds great promise.

Recently, the potential use of cold atmospheric pressure plasma (CAP) in cancer treatment has gained increasing interest. Especially the enhanced selective killing of tumor cells compared to normal cells has prompted researchers to elucidate the molecular mechanisms for the efficacy of CAP in cancer treatment. This review summarizes the current understanding of how CAP triggers intracellular pathways that induce growth inhibition or cell death. We discuss what factors may contribute to the potential selectivity of CAP towards cancer cells compared to their non-malignant counterparts. Furthermore, the potential of CAP to trigger an immune response is briefly discussed. Finally, this overview demonstrates how these concepts bear first fruits in clinical applications applying CAP treatment in head and neck squamous cell cancer as well as actinic keratosis. Although significant progress towards understanding the underlying mechanisms regarding the efficacy of CAP in cancer treatment has been made, much still needs to be done with respect to different treatment conditions and comparison of malignant and non-malignant cells of the same cell type and same donor. Furthermore, clinical pilot studies and the assessment of systemic effects will be of tremendous importance towards bringing this innovative technology into clinical practice.

Plasma medicine is gaining increasing attention and is moving from basic research into clinical practice. While areas of application are diverse, much research has been conducted assessing the use of cold atmospheric pressure plasma (CAP) in wound healing and cancer treatment—two applications with entirely different goals. In wound healing, a tissue-stimulating effect is intended, whereas cancer therapy aims at killing malignant cells. In this review, we provide an overview of the latest clinical and some preclinical research on the efficacy of CAP in wound healing and cancer therapy. Furthermore, we discuss the current understanding of molecular signaling mechanisms triggered by CAP that grant CAP its antiseptic and tissue regenerating or anti-proliferative and cell death-inducing properties. For the efficacy of CAP in wound healing, already substantial evidence from clinical studies is available, while evidence for therapeutic effects of CAP in oncology is mainly from in vitro and in vivo animal studies. Efforts to elucidate the mode of action of CAP suggest that different components, such as ultraviolet (UV) radiation, electromagnetic fields, and reactive species, may act synergistically, with reactive species being regarded as the major effector by modulating complex and concentration-dependent redox signaling pathways.

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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 TP53, NOTCH, EGFR, and CCND1. For example, the gene CCND1, 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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Introduction: Acute radiodermatitis is a common, though severe, side effect of radiotherapy against cancer that may lead to an interruption or even abortion of the radiotherapy. Mouse models provide an excellent tool to study pathomechanisms of a radiation-induced dermatitis as well as to test and develop novel innovative treatment strategies. Objective: The aim of this study is to provide an overview of different mouse models and irradiation devices that have been used so far and to describe the process of the induction of a radiation dermatitis in an immune proficient nude mouse model (SKH1-Hrhr) using a IBL 637 Cesium-137γ-ray machine. Methods: This process includes the construction of a radiation shielding chamber, restricting the radiation to the right hind leg of the mouse, a dosimetry and a dose finding study to identify the appropriate irradiation dose to induce a moderate radiation dermatitis. Results: A radiation shielding chamber was successfully constructed allowing selective irradiation of the right hind leg. A moderate radiodermatitis is induced with irradiation doses in the range of 60 – 70 Gy under the here described conditions. Symptoms peak about eight days after irradiation and decrease relatively quickly thereafter. Histological analyses confirmed typical signs of inflammation. Conclusion: This study describes for the first time a protocol to induce a moderate radiodermatitis in the nude mouse model SKH1-Hrhr using a IBL 637 gamma irradiator. This protocol will allow researchers to study novel treatment strategies to alleviate the burden of a radiodermatitis as a side effect of cancer treatment.

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