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- ItemTargeting malignant melanoma with physical plasmas(Amsterdam [u.a.] : Elsevier, 2018) Pasqual-Melo, Gabriella; Gandhirajan, Rajesh Kumar; Stoffels, Ingo; Bekeschus, SanderMelanoma is the deadliest form of cutaneous neoplasia. With a five-year survival rate of only 5–19%, metastatic melanoma presents severe challenges in clinical therapies. In addition, palliation is often problematic due to large numbers of fast growing metastasis. This calls for new therapeutic avenues targeting highly aggressive melanoma in palliative patients. One recently suggested innovative approach for eradication of topical tumor lesions is the application of cold physical plasma. This partially ionized gas emits a cocktail of reactive oxygen and nitrogen species (ROS/RNS). ROS/RNS have been shown to be a double-edged sword in fueling cancer growth at low doses but abrogating it at higher doses. The ROS/RNS output of plasma devices is tunable, and many studies have successfully decreased cancer cell growth in vitro and tumor burden in vivo. In general, increasing numbers of clinical trials suggest combination therapies to outperform monotherapies with regard to prognosis in patients. This review describes current challenges in melanoma treatment and highlights the concept of plasma therapy in experimental studies performed in melanoma research. Future perspectives are given that combine the usage of physical plasma with e.g. chemotherapy, immunotherapy, and ionizing radiation in melanoma medical oncology.
- ItemMultimodal imaging techniques to evaluate the anticancer effect of cold atmospheric pressure plasma(Basel : MDPI, 2021) Kordt, Marcel; Trautmann, Isabell; Schlie, Christin; Lindner, Tobias; Stenzel, Jan; Schildt, Anna; Boeckmann, Lars; Bekeschus, Sander; Kurth, Jens; Krause, Bernd J.; Vollmar, Brigitte; Grambow, EberhardBackground: 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 multi-modal 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 tu-mours. 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.
- ItemPatient-derived human basal and cutaneous squamous cell carcinoma tissues display apoptosis and immunomodulation following gas plasma exposure with a certified argon jet(Basel : Molecular Diversity Preservation International, 2021) Saadati, Fariba; Moritz, Juliane; Berner, Julia; Freund, Eric; Miebach, Lea; Helfrich, Iris; Stoffels, Ingo; Emmert, Steffen; Bekeschus, SanderReactive oxygen species (ROS) have been subject of increasing interest in the pathophysiology and therapy of cancers in recent years. In skin cancer, ROS are involved in UV-induced tumorigenesis and its targeted treatment via, e.g., photodynamic therapy. Another recent technology for topical ROS generation is cold physical plasma, a partially ionized gas expelling dozens of reactive species onto its treatment target. Gas plasma technology is accredited for its wound-healing abilities in Europe, and current clinical evidence suggests that it may have beneficial effects against actinic keratosis. Since the concept of hormesis dictates that low ROS levels perform signaling functions, while high ROS levels cause damage, we investigated herein the antitumor activity of gas plasma in non-melanoma skin cancer. In vitro, gas plasma exposure diminished the metabolic activity, preferentially in squamous cell carcinoma cell (SCC) lines compared to non-malignant HaCaT cells. In patient-derived basal cell carcinoma (BCC) and SCC samples treated with gas plasma ex vivo, increased apoptosis was found in both cancer types. Moreover, the immunomodulatory actions of gas plasma treatment were found affecting, e.g., the expression of CD86 and the number of regulatory T-cells. The supernatants of these ex vivo cultured tumors were quantitatively screened for cytokines, chemokines, and growth factors, identifying CCL5 and GM-CSF, molecules associated with skin cancer metastasis, to be markedly decreased. These findings suggest gas plasma treatment to be an interesting future technology for non-melanoma skin cancer topical therapy.
- ItemEx Vivo Exposure of Human Melanoma Tissue to Cold Physical Plasma Elicits Apoptosis and Modulates Inflammation(Basel : MDPI, 2020) Bekeschus, Sander; Moritz, Juliane; Helfrich, Iris; Boeckmann, Lars; Weltmann, Klaus-Dieter; Emmert, Steffen; Metelmann, Hans-Robert; Stoffels, Ingo; von Woedtke, ThomasCutaneous melanoma is the most aggressive type of skin cancer with a not-sufficient clinical outcome. High tumor mutation rates often hamper a remedial treatment, creating the need for palliative care in many patients. To reduce pain and burden, local palliation often includes cryo-ablation, immunotherapy via injection of IL2, or electrochemotherapy. Yet, a fraction of patients and lesions do not respond to those therapies. To reach even these resistances in a redox-mediated way, we treated skin biopsies from human melanoma ex vivo with cold physical plasma (kINPen MED plasma jet). This partially ionized gas generates a potent mixture of reactive oxygen species (ROS). Physical plasmas have been shown to be potent antitumor agents in preclinical melanoma and clinical head and neck cancer research. The innovation of this technology lies in its ease-of-use without anesthesia, as the “cold” plasma temperature of the kINPen MED does not exceed 37 °C. In metastatic melanoma skin biopsies from six patients, we identified a marked increase of apoptosis with plasma treatment ex vivo. This had an impact on the chemokine/cytokine profile of the cultured biopsies, e.g., three of six patient-derived biopsy supernatants showed an apparent decrease in VEGF compared to non-plasma treated specimens. Moreover, the baseline release levels of 24 chemokines/cytokines investigated may serve as a useful tool for future research on melanoma skin biopsy treatments. Our findings suggest a clinically useful role of cold physical plasma therapy in palliation of cutaneous melanoma lesions, possibly in a combinatory setting with other immune therapies.