Erythropoietin-producing human hepatocellular receptors (EPHs) compose the largest known subfamily of receptor tyrosine kinases (RTKs). They bind and interact with the EPH family receptor interacting proteins (ephrins). EPHs/ephrins are implicated in a variety of physiological processes, as well as in cancer pathogenesis. With neoplastic disease remaining a leading cause of death world-wide, the development of novel biomarkers aiding in the field of diagnosis, prognosis, and disease monitoring is of utmost importance. A multitude of studies have proven the association between the expression of members of the EPH/ephrin system and various clinicopathological parameters, including disease stage, tumor histologic grade, and patients’ overall survival. Besides their utilization in timely disease detection and assessment of outcome, EPHs/ephrins could also represent possible novel therapeutic targets. The aim of the current review of the literature was to present the existing data regarding the association between EPH/ephrin system expression and the clinical characteristics of malignant tumors.

Endometrial cancer (EC) is one of the main causes of cancer-related death among women. In the last decade, the incidence of EC is on the rise, and the relative 5-year survival remains unchanged. This creates a dire need for new diagnostic and therapeutic approaches that can only result from a deeper understanding of the pathogenesis of the disease. In this direction, exosomes are under heavy research, with two main aims: to identify the potential diagnostic and prognostic markers and to develop technologies based on their use as therapeutic vectors targeting EC cells. Exosomes are widely available in all bodily fluids and are sources of ideal biomarkers for liquid biopsies. They are extracellular vesicles containing DNA, RNA, lipids, and proteins, which they transfer between cells, serving multiple functions and being implicated in both the physiological processes and the pathogenesis of diseases. Of all the biomolecules contained in exosomes, microRNAs (miRNAs) seem to have the most clinical utility in the diagnosis and treatment of EC. Exosomal miRNAs mediate the communication between EC cells, cancer-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs) and have a pivotal role in the tumor cells’ proliferation, epithelial to mesenchymal transition (EMT), and the formation of a tumor microenvironment. They participate in many processes that are tied to carcinogenesis and cancer progression, and they are therefore considered as attractive therapeutic targets. Here, we review the functions of exosomes in EC, focusing on potential biomarkers of diagnostic and prognostic significance or potential therapeutic use.

Ovarian cancer (OC) is the leading cause of death from gynecological malignancies. Despite great advances in treatment strategies, therapeutic resistance and the gap between preclinical data and actual clinical efficacy justify the necessity of developing novel models for investigating OC. Organoids represent revolutionary three-dimensional cell culture models, deriving from stem cells and reflecting the primary tissue’s biology and pathology. The aim of the current review is to study the current status of mouse- and patient-derived organoids, as well as their potential to model carcinogenesis and perform drug screenings for OC. Herein, we describe the role of organoids in the assessment of high-grade serous OC (HGSOC) cells-of-origin, illustrate their use as promising preclinical OC models and highlight the advantages of organoid technology in terms of disease modelling and drug sensitivity testing.

The discovery of novel biomarkers of diagnostic, prognostic, and therapeutic value is a major challenge of current cancer research. The assessment of tumour cell proliferative capacity is pivotal for grading and clinical decision-making, highlighting the importance of proliferation markers as diagnostic and prognostic tools. Currently, the immunohistochemical analysis of Ki-67 expression levels is routinely used in clinical settings to assess tumour proliferation. Inasmuch as the function of Ki-67 is not fully understood and its evaluation lacks standardization, there is interest in chromatin regulator proteins as alternative proliferation markers of clinical value. Here, we review recent evidence demonstrating that chromatin assembly factor 1 (CAF-1), a histone chaperone selectively expressed in cycling cells, is a proliferation marker of clinical value. CAF-1 expression, when evaluated by immunocytochemistry in breast cancer cytology smears and immunohistochemistry in cancer biopsies from several tissues, strongly correlates with the expression of Ki-67 and other proliferation markers. Notably, CAF-1 expression is upregulated in almost all cancers, and CAF-1 overexpression is significantly associated, in most cancer types, with high histological tumour grade, advanced stage, recurrence, metastasis, and decreased patient survival. These findings suggest that CAF-1 is a robust, reproducible, and feasible proliferation marker of prognostic importance. CAF-1 may represent an attractive alternative or complementary to Ki-67 for cancer stratification and clinical guidance.

Background: Recent advances demonstrate the role of chromatin regulators, including histone variants and histone chaperones, in cancer initiation and progression. Methods: Histone H3K4me3, histone variant centromere protein (CENP-A) and histone chaperones Holliday junction recognition protein (HJURP) as well as DAXX expression were examined immunohistochemically in 95 thymic epithelial tumor (TET) specimens. Our results were compared with the expression profile of DAXX, HJURP and CENP-A in gene expression profiling interactive analysis (GEPIA2). Results: The lymphocyte-poor B3- and C-type TETs were more frequently DAXX negative (p = 0.043). B3 and C-Type TETs showed higher cytoplasmic and nuclear CENP-A (p = 0.007 and p = 0.002) and higher cytoplasmic HJURP H-score (p < 0.001). Higher nuclear CENP-A and cytoplasmic HJURP expression was associated with advanced Masaoka–Koga stage (p = 0.048 and p < 0.001). A positive correlation between HJURP and CENP-A was also observed. The presence of cytoplasmic CENP-A expression was correlated with a favorable overall survival (p = 0.03). CENP-A overexpression in survival analysis of TCGA TETs showed similar results. H3K4me3 expression was not associated with any clinicopathological parameters. Conclusions: Our results suggest a significant interaction between CENP-A and HJURP in TETs. Moreover, we confirmed the presence of a cytoplasmic CENP-A immunolocalization, suggesting also a possible favorable prognostic value of this specific immunostaining pattern.

Introduction Despite their suboptimal long‐term patency, saphenous vein grafts are the most widely used conduits to achieve complete revascularization during coronary artery bypass grafting (CABG). Although vein storage critically impairs endothelial integrity, contradictory data concerning optimal storage solutions exist. The aim of this study is to explore any in vitro impact of cardioplegic solutions and temperature on vein grafts endothelial integrity during their storage. Materials and Methods A single‐center, prospective trial including 40 consecutive patients was conducted. Eligibility criteria included patients submitted to CABG receiving at least one vein graft. An excess segment of the graft was harvested and divided into four different parts. Each one of them was stored under different conditions; either in a conventional heparin‐enriched blood solution or in a cardioplegic solution, at room temperature (20°C‐22°C) and in the refrigerator (5°C). Endothelial integrity was evaluated via immunohistochemistry using an antibody against CD31. Results Endothelial integrity (measured in a scale from 1—worst to 5—best) was significantly better after cardioplegic solution storage (2.83 ± 0.15 and 3.10 ± 0.13 in cold and room temperature, respectively) compared with storage in conventional solutions (2.23 ± 0.16 and 2.0 ± 0.15 in cold and room temperature, respectively). A significant effect of cardioplegic storage solution, as well as of cold temperature and cardioplegic solution interaction on endothelial preservation was reported, whereas storage temperature did not prove a significant factor by its own. Conclusions Cardioplegic storage solutions result in significantly better endothelial preservation compared with conventional heparin‐enriched blood solutions. The association with superior clinical outcomes remains to be proved.