Project description:To date, the significant anti-cancer capacity of cold atmospheric plasma (CAP) on dozens of cancer cell lines has been demonstrated in vitro and in mice models. Conventionally, CAP was directly applied to irradiate cancer cells or tumor tissue. Over past three years, the CAP irradiated media was also found to kill cancer cells as effectively as the direct CAP treatment. As a novel strategy, using the CAP stimulated (CAPs) media has become a promising anti-cancer tool. In this study, we demonstrated several principles to optimize the anti-cancer capacity of the CAPs media on glioblastoma cells and breast cancer cells. Specifically, using larger wells on a multi-well plate, smaller gaps between the plasma source and the media, and smaller media volume enabled us to obtain a stronger anti-cancer CAPs media composition without increasing the treatment time. Furthermore, cysteine was the main target of effective reactive species in the CAPs media. Glioblastoma cells were more resistant to the CAPs media than breast cancer cells. Glioblastoma cells consumed the effective reactive species faster than breast cancer cells did. In contrast to nitric oxide, hydrogen peroxide was more likely to be the effective reactive species.
Project description:Cold atmospheric plasma generates free radicals through the ionization of air at room temperature. Its effect and safety profile as a treatment modality for atopic dermatitis lesions have not been evaluated prospectively enough. We aimed to investigate the effect and safety of cold atmospheric plasma in patients with atopic dermatitis with a prospective pilot study. Cold atmospheric plasma treatment or sham control treatment were applied respectively in randomly assigned and symmetric skin lesions. Three treatment sessions were performed at weeks 0, 1, and 2. Clinical severity indices were assessed at weeks 0, 1, 2, and 4 after treatment. Additionally, the microbial characteristics of the lesions before and after treatments were analyzed. We included 22 patients with mild to moderate atopic dermatitis presented with symmetric lesions. We found that cold atmospheric plasma can alleviate the clinical severity of atopic dermatitis. Modified atopic dermatitis antecubital severity and eczema area and severity index score were significantly decreased in the treated group. Furthermore, scoring of atopic dermatitis score and pruritic visual analog scales significantly improved. Microbiome analysis revealed significantly reduced proportion of Staphylococcus aureus in the treated group. Cold atmospheric plasma can significantly improve mild and moderate atopic dermatitis without safety issues.
Project description:Cold Atmospheric Plasma (CAP) is an ionized gas with a near room temperature. CAP is a controllable source for reactive species, neutral particles, electromagnetic field and UV radiation. CAP showed the promising application in cancer treatment through the demonstration in vitro and in vivo. In this study, we first demonstrate the existence of an activation state on the CAP-treated cancer cells, which drastically decreases the threshold of cell vulnerability to the cytotoxicity of the CAP-originated reactive species such as H2O2 and NO2-. The cytotoxicity of CAP treatment is still dependent on the CAP-originated reactive species. The activation state of cancer cells will not cause noticeable cytotoxicity. This activation is an instantaneous process, started even just 2?s after the CAP treatment begins. The noticeable activation on the cancer cells starts 10-20?s during the CAP treatment. In contrast, the de-sensitization of activation takes 5 hours after the CAP treatment. The CAP-based cell activation explains the mechanism by which direct CAP treatment causes a much stronger cytotoxicity over the cancer cells compared with an indirect CAP treatment do, which is a key to understand what the effect of CAP on cancer cells.
Project description: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.
Project description:Multiple myeloma (MM) is a fatal and incurable hematological malignancy thus new therapy need to be developed. Cold atmospheric plasma, a new technology that could generate various active species, could efficiently induce various tumor cells apoptosis. More details about the interaction of plasma and tumor cells need to be addressed before the application of gas plasma in clinical cancer treatment. In this study, we demonstrate that He+O2 plasma could efficiently induce myeloma cell apoptosis through the activation of CD95 and downstream caspase cascades. Extracellular and intracellular reactive oxygen species (ROS) accumulation is essential for CD95-mediated cell apoptosis in response to plasma treatment. Furthermore, p53 is shown to be a key transcription factor in activating CD95 and caspase cascades. More importantly, we demonstrate that CD95 expression is higher in tumor cells than in normal cells in both MM cell lines and MM clinical samples, which suggests that CD95 could be a favorable target for plasma treatment as it could selectively inactivate myeloma tumor cells. Our results illustrate the molecular details of plasma induced myeloma cell apoptosis and it shows that gas plasma could be a potential tool for myeloma therapy in the future.
Project description:Here we report on a non-linear spectroscopic method for visualization of cold atmospheric plasma (CAP)-induced changes in tissue for reaching a new quality level of CAP application in medicine via online monitoring of wound or cancer treatment. A combination of coherent anti-Stokes Raman scattering (CARS), two-photon fluorescence lifetime imaging (2P-FLIM) and second harmonic generation (SHG) microscopy has been used for non-invasive and label-free detection of CAP-induced changes on human skin and mucosa samples. By correlation with histochemical staining, the observed local increase in fluorescence could be assigned to melanin. CARS and SHG prove the integrity of the tissue structure, visualize tissue morphology and composition. The influence of plasma effects by variation of plasma parameters e.g., duration of treatment, gas composition and plasma source has been evaluated. Overall quantitative spectroscopic markers could be identified for a direct monitoring of CAP-treated tissue areas, which is very important for translating CAPs into clinical routine.
Project description:Cold atmospheric plasma (CAP), a technology based on quasi-neutral ionized gas at low temperatures, is currently being evaluated as a new highly selective alternative addition to existing cancer therapies. Here, we present a first attempt to identify the mechanism of CAP action. CAP induced a robust ~2-fold G2/M increase in two different types of cancer cells with different degrees of tumorigenicity. We hypothesize that the increased sensitivity of cancer cells to CAP treatment is caused by differences in the distribution of cancer cells and normal cells within the cell cycle. The expression of γH2A.X (pSer139), an oxidative stress reporter indicating S-phase damage, is enhanced specifically within CAP treated cells in the S phase of the cell cycle. Together with a significant decrease in EdU-incorporation after CAP, these data suggest that tumorigenic cancer cells are more susceptible to CAP treatment.
Project description: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.
Project description:Curcumin (CUR) has interesting properties to cure cancer. Cold atmospheric plasma (CAP) is also an emerging biomedical technique that has great potential for cancer treatment. Therefore, the combined effect of CAP and CUR on inducing cytotoxicity and apoptosis of melanoma cancer cells might be promising. Here, we investigated the combined effects of CAP and CUR on cytotoxicity and apoptosis in B16-F10 melanoma cancer cells compared to L929 normal cells using MTT method, acridine orange/ethidium bromide fluorescence microscopic assay, and Annexin V/PI flow cytometry. In addition, the activation of apoptosis pathways was evaluated using BCL2, BAX, and Caspase-3 (CASP3) gene expression and ratio of BAX to BCL2 (BAX/BCL2). Finally, in silico study was performed to suggest the molecular mechanism of this combination therapy on melanoma cancer. Results showed that although combination therapy with CUR and CAP has cytotoxic and apoptotic effects on cancer cells, it did not improve apoptosis rate in melanoma B16-F10 cancer cells compared to monotherapy with CAP or CUR. In addition, evaluation of gene expression in cancer cell line confirmed that CUR and CAP concomitant treatment did not enhance the expression of apoptotic genes. In silico analysis of docked model suggested that CUR blocks aquaporin- (AQP-) 1 channel and prevents penetration of CAP-induced ROS into the cells. In conclusion, combination therapy with CAP and CUR does not improve the anticancer effect of each alone.
Project description:In this study a novel method was implemented and investigated in order to destroy cancer cells inside the mouse body on a clinical level. In the case of in-vitro study, MTT assay was employed to discover an effective dose of applied plasma and distinguish the plasma effect in direct and in indirect treatments. Tumor growth was also measured in in-vivo section so that the effectiveness of direct and indirect treatments could be compared. Furthermore, an investigation was conducted to study the interferences between a conventional method (chemotherapy) and plasma treatment so as to increase the effectiveness of treatment inside the body. Hematoxylin and Eosin, Flow Cytometry, TUNEL and Western Blot assay were used to investigate any cell alteration and the impact of various treatment methods on cancer cell and amount of their apoptosis and protein levels. Radiology and CT scan images were taken to determine the final tumor volume. The results showed a significant cell death and substantial reduction in tumor growth in direct plasma treatment in comparison with indirect plasma treatment. Eventually, dramatic destruction of cancer cells was observed while using of indirect plasma-chemotherapy combination, thus introducing an effective method for deep tissue tumors can be introduced.