Cold atmospheric plasma use in clinical studies is mainly limited to the treatment of chronic wounds, but its application in a wide range of medical fields is now the goal of many analyses. It is therefore likely that its application spectrum will be expanded in the future. Cold atmospheric plasma has been shown to reduce microbial load without any known significant negative effects on healthy tissues, and this should enhance its possible application to any microbial infection site. It has also been shown to have anti-tumour effects. In addition, it acts proliferatively on stem cells and other cultivated cells, and the highly increased nitric oxide levels have a very important effect on this proliferation. Cold atmospheric plasma use may also have a beneficial effect on immunotherapy in cancer patients. Finally, it is possible that the use of plasma devices will not remain limited to surface structures, because current endeavours to develop sufficiently miniature microplasma devices could very likely lead to its application in subcutaneous and internal structures. This study summarises the available literature on cold plasma action mechanisms and analyses of its current in vivo and in vitro use, primarily in the fields of regenerative and dental medicine and oncology.

Cold atmospheric plasma has great potential for use in modern medicine. It has been used in the clinical treatment of skin diseases and chronic wounds, and in laboratory settings it has shown effects on selective decrease in tumour-cell viability, reduced tumour mass in animal models and stem-cell proliferation. Many researchers are currently focusing on its application to internal structures and the use of plasma-activated liquids in tolerated and effective human treatment. There has also been analysis of plasma’s beneficial synergy with standard pharmaceuticals to enhance their effect. Cold atmospheric plasma triggers various responses in tumour cells, and this can result in epigenetic changes in both DNA methylation levels and histone modification. The expression and activity of non-coding RNAs with their many important cell regulatory functions can also be altered by cold atmospheric plasma action. Finally, there is ongoing debate whether plasma-produced radicals can directly affect DNA damage in the nucleus or only initiate apoptosis or other forms of cell death. This article therefore summarises accepted knowledge of cold atmospheric plasma’s influence on epigenetic changes, the expression and activity of non-coding RNAs, and DNA damage and its effect in synergistic treatment with routinely used pharmaceuticals.

Rho guanosine triphospatases (GTPases) resemble a conserved family of GTP-binding proteins regulating actin cytoskeleton dynamics and several signaling pathways central for the cell. Rho GTPases create a so-called Ras-superfamily of GTPases subdivided into subgroups comprising at least 20 members. Rho GTPases play a key regulatory role in gene expression, cell cycle control and proliferation, epithelial cell polarity, cell migration, survival, and apoptosis, among others. They also have tissue-related functions including angiogenesis being involved in inflammatory and wound healing processes. Contextually, any abnormality in the Rho GTPase function may result in severe consequences at molecular, cellular, and tissue levels. Rho GTPases also play a key role in tumorigenesis and metastatic disease. Corresponding mechanisms include a number of targets such as kinases and scaffold/adaptor-like proteins initiating GTPases-related signaling cascades. The accumulated evidence demonstrates the oncogenic relevance of Rho GTPases for several solid malignancies including breast, liver, bladder, melanoma, testicular, lung, central nervous system (CNS), head and neck, cervical, and ovarian cancers. Furthermore, Rho GTPases play a crucial role in the development of radio- and chemoresistance e.g. under cisplatin-based cancer treatment. This article provides an in-depth overview on the role of Rho GTPases in gynecological cancers, highlights relevant signaling pathways and pathomechanisms, and sheds light on their involvement in tumor progression, metastatic spread, and radio/chemo resistance. In addition, insights into a spectrum of novel biomarkers and innovative approaches based on the paradigm shift from reactive to predictive, preventive, and personalized medicine are provided.

Breast cancer is very heterogenous and the most common gynaecological cancer, with various factors affecting its development. While its impact on human lives and national health budgets is still rising in almost all global areas, many molecular mechanisms affecting its onset and development remain unclear. Conventional treatments still prove inadequate in some aspects, and appropriate molecular therapeutic targets are required for improved outcomes. Recent scientific interest has therefore focused on the non-coding RNAs roles in tumour development and their potential as therapeutic targets. These RNAs comprise the majority of the human transcript and their broad action mechanisms range from gene silencing to chromatin remodelling. Many non-coding RNAs also have altered expression in breast cancer cell lines and tissues, and this is often connected with increased proliferation, a degraded extracellular environment, and higher endothelial to mesenchymal transition. Herein, we summarise the known abnormalities in the function and expression of long non-coding RNAs, Piwi interacting RNAs, small nucleolar RNAs and small nuclear RNAs in breast cancer, and how these abnormalities affect the development of this deadly disease. Finally, the use of RNA interference to suppress breast cancer growth is summarised.

Utilization of liquid biopsy in the management of cancerous diseases is becoming more attractive. This method can overcome typical limitations of tissue biopsies, especially invasiveness, no repeatability, and the inability to monitor responses to medication during treatment as well as condition during follow-up. Liquid biopsy also provides greater possibility of early prediction of cancer presence. Corpus uteri mesenchymal tumors are comprised of benign variants, which are mostly leiomyomas, but also a heterogenous group of malignant sarcomas. Pre-surgical differentiation between these tumors is very difficult and the final description of tumor characteristics usually requires excision and histological examination. The leiomyomas and malignant leiomyosarcomas are especially difficult to distinguish and can, therefore, be easily misdiagnosed. Because of the very aggressive character of sarcomas, liquid biopsy based on early diagnosis and differentiation of these tumors would be extremely helpful. Moreover, after excision of the tumor, liquid biopsy can contribute to an increased knowledge of sarcoma behavior at the molecular level, especially on the formation of metastases which is still not well understood. In this review, we summarize the most important knowledge of mesenchymal uterine tumors, the possibilities and benefits of liquid biopsy utilization, the types of molecules and cells that can be analyzed with this approach, and the possibility of their isolation and capture. Finally, we review the typical abnormalities of leiomyomas and sarcomas that can be searched and analyzed in liquid biopsy samples with the final aim to pre-surgically differentiate between benign and malignant mesenchymal tumors.

Ovarian cancer is a highly heterogeneous disease and its formation is affected by many epidemiological factors. It has typical lack of early signs and symptoms, and almost 70% of ovarian cancers are diagnosed in advanced stages. Robust, early and non-invasive ovarian cancer diagnosis will certainly be beneficial. Herein we analysed the regulatory sequence methylation profiles of the RASSF1, PTEN, CDH1 and PAX1 tumour suppressor genes by pyrosequencing in healthy, benign and malignant ovarian tissues, and corresponding plasma samples. We recorded statistically significant higher methylation levels (p < 0.05) in the CDH1 and PAX1 genes in malignant tissues than in controls (39.06 ± 18.78 versus 24.22 ± 6.93; 13.55 ± 10.65 versus 5.73 ± 2.19). Higher values in the CDH1 gene were also found in plasma samples (22.25 ± 14.13 versus 46.42 ± 20.91). A similar methylation pattern with positive correlation between plasma and benign lesions was noted in the CDH1 gene (r = 0.886, p = 0.019) and malignant lesions in the PAX1 gene (r = 0.771, p < 0.001). The random forest algorithm combining methylation indices of all four genes and age determined 0.932 AUC (area under the receiver operating characteristic (ROC) curve) prediction power in the model classifying malignant lesions and controls. Our study results indicate the effects of methylation changes in ovarian cancer development and suggest that the CDH1 gene is a potential candidate for non-invasive diagnosis of ovarian cancer.