Viruses manipulate cell biology to utilize monocytes/macrophages as vessels for dissemination, long-term persistence within tissues and virus replication. Viruses enter cells through endocytosis, phagocytosis, macropinocytosis or membrane fusion. These processes play important roles in the mechanisms contributing to the pathogenesis of these agents and in establishing viral genome persistence and latency. Upon viral infection, monocytes respond with an elevated expression of proinflammatory signalling molecules and antiviral responses, as is shown in the case of the influenza, Chikungunya, human herpes and Zika viruses. Human immunodeficiency virus initiates acute inflammation on site during the early stages of infection but there is a shift of M1 to M2 at the later stages of infection. Cytomegalovirus creates a balance between pro- and anti-inflammatory processes by inducing a specific phenotype within the M1/M2 continuum. Despite facilitating inflammation, infected macrophages generally display abolished apoptosis and restricted cytopathic effect, which sustains the virus production. The majority of viruses discussed in this review employ monocytes/macrophages as a repository but certain viruses use these cells for productive replication. This review focuses on viral adaptations to enter monocytes/macrophages, immune escape, reprogramming of infected cells and the response of the host cells.

Despite significant progress in cancer diagnostics and development of novel therapeutic regimens, successful treatment of advanced forms of cancer is still a challenge and may require personalized therapeutic approaches. In this review, we analyzed major mechanisms responsible for tumor cells chemoresistance and emphasized that intratumor heterogeneity is a critical factor that limits efficiency of cancer treatment. Intratumor heterogeneity is caused by genomic instability in cancer cells, resulting in the selection of resistant clones. Moreover, cancer cells in solid tumors are surrounded by cellular and molecular microenvironment that actively influences tumor cell behavior. Local tumor microenvironment (TME) consisting of immune cells with diverse phenotypes and functions strongly contributes to intratumor heterogeneity and modulates responses to treatment. Thus, targeting specific components of TME is a novel treatment strategy that can improve the outcome of conventional anti-cancer therapy. Here, we discuss modern immunotherapeutic approaches based on targeting tumorinfiltrating immune cells including neutrophils, dendritic cells, NK cells, T cells, B cells and macrophages. Among those, tumor-associated macrophages (TAM) that display a pronounced heterogeneity and phenotypic plasticity appear to be a major component in the TME of solid tumors, and emerge as perspective targets for cancer immunotherapy. TAM intratumor heterogeneity and the possible existence of patient-specific phenotype signature generate the basis for the development of individualized TAM-based therapeutic approaches.

In this work, the micro-arc oxidation method is used to fabricate surface-modified complex-structured titanium implant coatings to improve biocompatibility. Depending on the utilized electrolyte solution and micro-arc oxidation process parameters, three different types of coatings (one of them—oxide, another two—calcium phosphates) were obtained, differing in their coating thickness, crystallite phase composition and, thus, with a significantly different biocompatibility. An analytical approach based on X-ray computed tomography utilizing software-aided coating recognition is employed in this work to reveal their structural uniformity. Electrochemical studies prove that the coatings exhibit varying levels of corrosion protection. In vitro and in vivo experiments of the three different micro-arc oxidation coatings prove high biocompatibility towards adult stem cells (investigation of cell adhesion, proliferation and osteogenic differentiation), as well as in vivo biocompatibility (including histological analysis). These results demonstrate superior biological properties compared to unmodified titanium surfaces. The ratio of calcium and phosphorus in coatings, as well as their phase composition, have a great influence on the biological response of the coatings.

: Gastric cancer (GC) is biologically and genetically heterogeneous with complex carcinogenesis at the molecular level. Despite the application of multiple approaches in the GC treatment, its 5-year survival is poor. A major limitation of anti-cancer drugs application is intrinsic or acquired resistance, especially to chemotherapeutical agents. It is known that the effectiveness of chemotherapy remains debatable and varies according to the molecular type of GC. Chemotherapy has an established role in the management of GC. Perioperative chemotherapy or postoperative chemotherapy is applied for localized ones. Most of the advanced GC patients have a poor response to treatment and unfavorable outcomes with standard therapies. : Resistance substantially limits the depth and duration of clinical responses to targeted anticancer therapies. Through the use of complementary experimental approaches, investigators have revealed that cancer cells can achieve resistance through adaptation or selection driven by specific genetic, epigenetic, or microenvironmental alterations. Ultimately, these diverse alterations often lead to the activation of MAPK, AKT/mTOR, and Wnt/β-catenin signaling pathways that, when co-opted, enable cancer cells to survive drug treatments. We have summarized the mechanisms of resistance development to cisplatin, 5-fluorouracil, and multidrug resistance in the GC management. The complexity of molecular targets and components of signaling cascades altered in the resistance development results in the absence of significant benefits in GC treatment, and its efficacy remains low. The universal process responsible for the failure in the multimodal approach in GC treatment is autophagy. Its dual role in oncogenesis is the most unexplored issue. We have discussed the possible mechanism of autophagy regulation upon the action of endogenous factors and drugs. The experimental data obtained in the cultured GC cells need further verification. To overcome the cancer resistance and to prevent autophagy as the main reason of ineffective treatment, it is suggested the concept of the direct influence of autophagy molecular markers followed by the standard chemotherapy. Dozen of studies have focused on finding the rationale for the benefits of such complex therapy. The perspectives in the molecular-based management of GC are associated with the development of molecular markers predicting the protective autophagy initiation and search for novel targets of effective anticancer therapy.

The biological properties of circulating tumor cells (CTCs), and their dynamics during neoadjuvant chemotherapy are important, both for disease progression prediction and therapeutic target determination, with the aim of preventing disease progression. The aim of our study was to estimate of different CTC subsets in breast cancer during the NACT (neoadjuvant chemotherapy). The prospective study includes 27 patients with invasive breast cancer, T2-4N0-3M0, aged 32 to 60 years. Venous heparinized blood samples, taken before and after biopsy, after each courses of chemotherapy (on days 3–7), and before surgical intervention, served as the material for this study. Different subsets of circulating tumor cells were determined on the basis of the expression of EpCAM, CD45, CD44, CD24, and N-Cadherin using flow cytometry. As the result of this study, it has been observed that significant changes in the quantity of the different subsets of circulating tumor cells in patients’ blood were observed after carrying out the 3rd course of NACT. NACT causes significant changes in the quantity of six CTC subsets, with various combinations of stemness and epithelial-mesenchymal transition (EMT) properties.