The role of plant-derived natural substances as immunomodulatory agents in carcinogenesis.

The role of immune system in carcinogenesis represents fundamental events associated with cancer eradication; however, tumor evolution is connected with various mechanisms of tumor evasion and progression of cancer. Based on recent evidence, phytochemicals are directly associated with immunomodulation of the innate and adaptive immunity via different mechanisms of action including stimulation and amplification of immune cells, humoral compartments, and associated molecules. This comprehensive study focuses on immunomodulating potential of phytochemicals (mixture in plants or separately such as individual phytochemical) and their impact on regulation of immune response during cancer development, immune tolerance, and immune escape. Clinical application of phytochemicals as modulators of host immunity against cancer may represent perspective approach in anticancer therapy.

Cold Atmospheric Pressure Plasma (CAP) as a New Tool for the Management of Vulva Cancer and Vulvar Premalignant Lesions in Gynaecological Oncology.

Vulvar cancer (VC) is a specific form of malignancy accounting for 5-6% of all gynaecologic malignancies. Although VC occurs most commonly in women after 60 years of age, disease incidence has risen progressively in premenopausal women in recent decades. VC demonstrates particular features requiring well-adapted therapeutic approaches to avoid potential treatment-related complications. Significant improvements in disease-free survival and overall survival rates for patients diagnosed with post-stage I disease have been achieved by implementing a combination therapy consisting of radical surgical resection, systemic chemotherapy and/or radiotherapy. Achieving local control remains challenging. However, mostly due to specific anatomical conditions, the need for comprehensive surgical reconstruction and frequent post-operative healing complications. Novel therapeutic tools better adapted to VC particularities are essential for improving individual outcomes. To this end, cold atmospheric plasma (CAP) treatment is a promising option for VC, and is particularly appropriate for the local treatment of dysplastic lesions, early intraepithelial cancer, and invasive tumours. In addition, CAP also helps reduce inflammatory complications and improve wound healing. The application of CAP may realise either directly or indirectly utilising nanoparticle technologies. CAP has demonstrated remarkable treatment benefits for several malignant conditions, and has created new medical fields, such as "plasma medicine" and "plasma oncology". This article highlights the benefits of CAP for the treatment of VC, VC pre-stages, and postsurgical wound complications. There has not yet been a published report of CAP on vulvar cancer cells, and so this review summarises the progress made in gynaecological oncology and in other cancers, and promotes an important, understudied area for future research. The paradigm shift from reactive to predictive, preventive and personalised medical approaches in overall VC management is also considered.

Mechanical Testing of Composite Steel and Reactive Powder Concrete Structural Element.

Reactive powder concrete (RPC), typically with higher compressive strength, is particularly attractive to structural engineers to apply them in infrastructures for enhancing their resistance under severe environments and loads. The main objective of the initial study presented in the paper was to investigate the behavior of two types of these new cementitious materials differing in the nature of microfibers. The RPC mixes were reinforced with steel and then with basalt microfibers. To evaluate the structural performance of developed unconventional materials, properties were investigated experimentally and compared with the control normal concrete mix. Mechanical tests indicated that dispersing fine fibers for making RPC, a mean compressive strength of 198.3 MPa and flexural strength 52.6 MPa or 23.2 MPa, respectively, were developed after 28 days of standard curing at ambient temperatures. In composite structures consisting of steel girders and a concrete slab, it is necessary to prevent the relative slip at the steel and concrete interface using shear connectors. The very high RPC strength enabled a material saving, weight-reduced application of precast construction, and particularly effective joint to steel beams. The investigation of such shear connection efficiency, in the case of the higher strength concrete deck, using standard push-out test specimens was executed. Finite element numerical models were developed. The outputs of the studies are presented in the paper.

Rho GTPases in Gynecologic Cancers: In-Depth Analysis toward the Paradigm Change from Reactive to Predictive, Preventive, and Personalized Medical Approach Benefiting the Patient and Healthcare.

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.

Why the Gold Standard Approach by Mammography Demands Extension by Multiomics? Application of Liquid Biopsy miRNA Profiles to Breast Cancer Disease Management.

In the global context, the epidemic of breast cancer (BC) is evident for the early 21st century. Evidence shows that national mammography screening programs have sufficiently reduced BC related mortality. Therefore, the great utility of the mammography-based screening is not an issue. However, both false positive and false negative BC diagnosis, excessive biopsies, and irradiation linked to mammography application, as well as sub-optimal mammography-based screening, such as in the case of high-dense breast tissue in young females, altogether increase awareness among the experts regarding the limitations of mammography-based screening. Severe concerns regarding the mammography as the "golden standard" approach demanding complementary tools to cover the evident deficits led the authors to present innovative strategies, which would sufficiently improve the quality of the BC management and services to the patient. Contextually, this article provides insights into mammography deficits and current clinical data demonstrating the great potential of non-invasive diagnostic tools utilizing circulating miRNA profiles as an adjunct to conventional mammography for the population screening and personalization of BC management.

Current approaches in the clinical management of pregnancy-associated breast cancer-pros and cons.

Malignancies are one of the leading causes of mortality in women during their reproductive life. Treatment of gynecological malignant tumors during pregnancy is possible but not simple, since it creates a conflict between care of the mother and the fetus. BC is the most prevalent malignancy diagnosed in pregnancy, ranking up to 21% of all pregnancy-related malignancies. Due to its stets increasing prevalence, aggressive cancer subtype, and severe ethical and psychological aspects linked to the disease, experts raise an alarm for an acute necessity to improve the overall management of the PABC-the issue which has strongly motivated our current paper. Comprehensive research data and clinical experience accumulated in recent years have advanced our understanding of the disease complexity. PABC treatment must be individualized with an emphasis on optimal care of the mother, while observing standard treatment protocols with regard to safety of the fetus. Treatment protocols should be elaborated based on the individualized patient profile, bearing in mind the acute danger to the mother, maximizing the therapy efficacy and minimizing harmful effects to the fetus. Complex consulting on treatment options, their impacts on pregnancy and potential teratogenic effects requires tight "doctor-patient" collaboration. Complications that may arise due to the treatment of breast cancer in pregnancy require a multiprofessional expertise including oncologists, neonatologists, perinatologists, obstetricians, teratologists, and toxicologists, and an extensive psychological support throughout the pregnancy and after giving birth. Thereby, specifically psychological aspects of PABC diagnosis and follow-up are frequently neglected, being not yet adequately explored in the entire disease management approach. Herewith, we update the status quo regarding the currently available diagnostic modalities, complex treatment algorithms, and novel clinical approaches which altogether argue for an urgent necessity of a paradigm shift moving away from reactive to predictive, preventive, and personalized medical approach in the overall management of PABC meeting the needs of young populations, persons at high risk, affected patients, and families as the society at large.

miRNA in a multiomic context for diagnosis, treatment monitoring and personalized management of metastatic breast cancer.

Metastatic breast cancer is characterized by aggressive spreading to distant organs. Despite huge multilevel research, there are still several important challenges that have to be clarified in the management of this disease. Therefore, recent investigations have implemented a modern, multiomic approach with the aim of identifying specific biomarkers for not only early detection but also to predict treatment responses and metastatic spread. Specific attention is paid to short miRNAs, which regulate gene expression at the post-transcriptional level. Aberrant miRNA expression could initiate cancer development, cell proliferation, invasion, migration, metastatic spread or drug resistance. An miRNA signature is, therefore, believed to be a promising biomarker and prediction tool that could be utilized in all phases of carcinogenesis. This article offers comprehensive information about miRNA profiles useful for diagnostic and treatment purposes that may sufficiently advance breast cancer management and improve individual outcomes in the near future.