Age-specific biological differences in breast cancer (BC) shape the disease course, therapeutic sensitivity, and prognosis. The microRNAs hsa-miR-26b-5p and hsa-miR-186-5p are considered promising biomarkers of tumor aggressiveness and treatment response, yet their age-dependent expression features remain insufficiently characterized. To evaluate age-related expression patterns of hsa-miR-26b-5p and hsa-miR-186-5p in the BC tissue samples and their relation to the response to neoadjuvant 4AC chemotherapy. Expression levels of hsa-miR- 26b-5p and hsa-miR-186-5p were analyzed by qRT-PCR in formalin-fixed paraffin-embedded tissue samples of BC patients (n = 56) divided into two age groups: ≤45 and >45 years. MiRNAs expression patterns were analyzed in relation to molecular BC subtype, disease stage, T and N categories by TNM, and treatment response grades assessed by the Miller - Payne system. Patients ≤45 years exhibited significantly higher miR-26b-5p levels (1.78-fold; p = 0.0005), especially in the luminal B subtype tumors (7.26-8.45-fold). The reduced miR-26b-5p and miR-186-5p levels in younger patients were associated with a locoregionally advanced disease (stage III) and lymph-node metastasis. In patients ≥45 years, miR-186-5p levels were significantly higher in the HER2/neu-positive subtype (2.9-fold; p = 0.0278) and in the younger patients responding to 4AC NACT compared to the older responders. In BC, hsa-miR-26b-5p and hsa-miR-186-5p exhibited pronounced age-specific regulatory patterns and could be considered potential markers of BC course and efficacy of anthracycline-based therapy.

There are some data that viral respiratory infections facilitate metastasis of breast cancer (BC). However, whether the coronavirus SARS-CoV-2 is a trigger for BC progression is not yet clear, as well as the possible mechanisms of its involvement. The work aimed to study the effect of the SARS-Cov-2 spike protein (SP) on the expression profile of components of the CXCL12/CXCR4 key signaling аxis of BC, cell adhesion markers CD326, CD54, epithelial cells cytokeratin-18 and b-catenin, and migratory activity in in vitro model system. The expression profile of the studied markers was detected by flow cytometry after 48 h of incubation of MCF-7 and MDA-MB-231 cells with SP. Marker expression was assessed by the number of positive cells (%) and the level of its expression (the relative index of mean fluorescence intensity of cells, iMFI). Cell migration was analyzed by the scratch assay. After SP treatment, a significant increase in CXCR4 expression was detected in the cytoplasm of both MCF-7 and MDA-MB-231 cells. SP caused opposite effects on CXCL12 expression - an increase in the MDA-MB-231 cells and decrease in the MCF-7 cells. In addition, in MCF-7 cells, SP treatment resulted in a decrease in the number of CD54-positive cells, the iMFI of CD326, cytokeratin-18, and a slight increase in the iMFI of b-catenin, while in the MDA-MB-231 cell line, a significant decrease in the iMFI of CD54 was observed. SP accelerated the migration activity of MDA-MB-231 and MCF-7 cells, the effect being more pronounced in MDA-MB-231 cells. The immunophenotypic changes in the expression profile of several markers under the influence of SP may indicate the induction of the epithelial-mesenchymal transition in the MCF-7 cells and increased migration activity in both cell lines.

Cervical cancer (СС) continues to be the leading cancer pathology affecting women of both young and older ages. In the advanced stages of СС, the choice of treatment typically favors chemoradiotherapy. However, in a number of cases, radical surgery may be the only effective treatment. Th s issue requires further analysis. Five selected cases of the advanced СС (stages IIa-IVa) that required non-standard treatment are presented. In all presented cases, the radical surgical treatment had an undeniable immediate curative effect. On follow-up, two patients are alive without any evidence of the disease; two patients died from disease progression and one patient is still receiving treatment for bone recurrence. Despite the fact that in most cases of advanced stages of СС, chemoradiotherapy is effectively used, in some selected cases, surgery may be leading and effective if the operation is performed in a radical manner. Important in this regard are the clinical experience, high level of surgical skills, presence of a multidisciplinary team, and the technical equipment of the medical center for performing such operations.

Pancreatic cancer is an extremely aggressive malignancy with a 5-year survival rate among all stages of about 7%. Treatment options for unresectable forms are limited to fluoropyrimidine- and gemcitabine-containing regimens, and starting from the 3rd line, international guidelines do not provide clear recommendations because of the poor clinical condition of patients and the low efficacy of the consecutive lines. The arterial infusion is a promising method of treatment for locally advanced or liver-only metastatic disease, providing a higher local concentration with the same or lower systemic toxicity. The most often used intra-arterial regimens are those based on 5-fluorouracil and gemcitabine. This method was found to be superior in overall survival, response rate, and control of local symptoms compared to control groups treated with systemic chemotherapy. The approach has a good safety profile and is well tolerated. The method is promising for patients with an adequate performance status, who have run out of other potential regimens, in cases without distant metastases or liver-only metastatic disease, and for upcoming clinical trials or studies.

This prospective randomized study included 64 patients allocated in a 1:1 ratio to EA or QL block groups. 56 patients (28 per group) were included in the final analysis. The primary endpoints were the postoperative alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate levels. Secondary endpoints included protein-synthetic markers, coagulation parameters (fibrinogen, prothrombin index), and thromboelastography (TEG) variables. Both analgesic techniques provided comparable postoperative hepatic and coagulation profiles. The QL block group demonstrated a significant but clinically minimal elevation in ALT/AST on postoperative day 1. The lactate dynamics was similar between the groups without significant differences. Protein-synthetic (albumin, total protein) and coagulation markers showed no significant intergroup differences. TEG revealed transient postoperative alterations characteristic of liver resection; LMM identified consistently higher G values and platelet counts in the QL block group, although these differences lacked clinical significance. No analgesia-related complications were observed. The QL block is a safe and effective alternative to epidural analgesia following liver resection, providing a comparable profile of hepatic function, coagulation status, and hemodynamic stability. Minor statistical differences in selected parameters did not translate into clinical relevance. The QL block may be a rational option for patients with contraindications to EA or increased risk of hemodynamic instability.

We present a case of stage I chromophobe renal cell carcinoma, which initially was treated with laparoscopic partial nephrectomy, and four years later progressed to multifocal metastatic nodules in the perirenal adipose capsule without local recurrence in the kidney itself. The curative approach included the surgical complete removal of perirenal adipose tissue with adjuvant pembrolizumab. We discuss the molecular and genetic peculiarities of chromophobe renal cell carcinoma as applied to the diagnosis and a rationale for adjuvant pembrolizumab.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Despite major advances in therapy, the treatment of ALL remains a significant challenge. Therapeutic protocols are based on the use of combinations of chemotherapeutic drugs. While such combinations increase treatment efficacy, they also complicate the assessment of toxicity. It should be noted that the variability in the occurrence of toxic responses to ALL therapy in children may be determined by the presence of gene variants that influence both the pharmacokinetics and pharmacodynamics of chemotherapeutic drugs. This review summarized and analyzed the most significant and well-studied pharmacogenetic markers to date associated with the toxicity and response to chemotherapeutic agents used in the treatment of pediatric ALL. In particular, pharmacogenetic markers for the following drugs were analyzed: anthracyclines (doxorubicin, daunorubicin), vincristine, glucocorticoids (prednisone, dexamethasone), L-asparaginase, methotrexate, alkylating agents (cyclophosphamide, ifosfamide), 6-mercaptopurine, cytarabine, and etoposide. At present, only a few genes, TPMT and NUDT15, have well-established clinical utility, whereas the clinical relevance of pharmacogenetic markers for other drugs used in pediatric ALL therapy remains under investigation. The review also highlights the main knowledge gaps in current research and outlines promising directions for future studies aimed at integrating pharmacogenetic testing into clinical practice for personalized treatment of ALL.

Tumor-associated macrophages (TAMs) are among the main regulators of the immune microenvironment of breast cancer (BC). Still, their relationships with cytokine signals and the state of the extracellular matrix (ECM) remain poorly characterized. The study aimed to evaluate associations of the degree of infiltration with CD68+ and CD163+ macrophages (Mj) with the status of pro-inflammatory and immunosuppressive cytokines, as well as with the expression of the key ECM proteins in BC tissue. Postoperative material from 67 patients with stage I-II BC was studied. TAMs infiltration and the expression of SPP1, COX-2, SERPINE2, COL1A1, and COL3A1 were assessed immunohistochemically. The serum IL-6 and IL-10 levels were determined by the ELISA. IL6, IL10, and TNF mRNA expressions were assessed by qRTPCR. The high levels of IL-6 in the serum of patients (p = 0.0159) and IL10 mRNA in BC tissue (p = 0.0316) were associated with an increase in the number of CD68+ TAMs. The pronounced infiltration of CD163+ TAMs correlated with an increase in the systemic level of IL-10 (p = 0.0357), IL-6 (p = 0.0286), and local TNF expression (p = 0.001). The increased SPP1 expression was accompanied by an increase in CD163+ TAMs (p = 0.008) against the background of a decrease in the CD68+ Mj population in BC tissue (p = 0.0271). The high levels of COX-2 were also directly correlated with the degree of M2-like Mj infiltration (p = 0.0357). At the same time, COL1A1 expression was associated with increased infiltration of both TAM phenotypes, while high COL3A1 expression was associated with a decrease in CD68+ Mj in tumor tissue. The bioinformatic analysis confirmed the obtained results and also allowed us to highlight the features of the tumor microenvironment composition, which depended on the degree of TAM infiltration in BC tissue of different molecular subtypes. The results demonstrated the existence of a single regulatory axis, "TAMs - cytokines - ECM", which determined the development of the immunosuppressive and invasive BC microenvironment. The predominance of CD163+ Mj against the background of increased levels of IL-10, SPP1, and COX-2 was associated with a high degree of BC malignancy.

The microbiota has a significant impact on the host's immune system. However, the influence of the microbiome is heavily dependent on species, strain, and context. The aim of this study was to evaluate the influence of Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and Lactobacillus rhamnosus GG (LGG) supplementation on the polarization of tumor-associated macrophages (TAMs) in mice with Ehrlich carcinoma. Female Balb/c mice bearing solid Ehrlich carcinoma were administered via gavage with BB-12, LGG, or 0.9% NaCl. On days 14, 21, and 28 of tumor growth, macrophages from tumor tissue were isolated and subjected to functional analysis. The nitric oxide (NO) production was measured using the standard Griess reaction. The arginase activity was determined based on the urea measurements. The reactive oxygen species (ROS) production was checked using flow cytometry. The cytotoxic activity was estimated by an MTT assay. The application of different probiotic bacteria elicited different TAM polarization states. The TAMs in the group supplemented with LGG demonstrated M1 polarization with low arginase activity but high production of NO and ROS, as well as cytotoxic activity toward Ehrlich carcinoma cells. The TAMs of BB-12-treated mice exhibited M2 (supposedly M2b) polarization, characterized by high arginase activity alongside the preserved cytotoxic activity toward Ehrlich carcinoma cells in vitro. The results indicate that the consumption of two probiotics, BB-12 and LGG, affects the polarization of TAMs in distantly located experimental tumors.

Paracrine crosstalk between tumor cells and bone-resident cells drives osteoclastogenesis in the metastatic bone niche. miR-519d-3p has been linked to suppression of matrix metalloproteinases. To test whether osteoblastic miR-519d-3p restrains tumor-conditioned osteoclastogenesis by lowering MMP2 expression and shifting signaling toward osteoprotegerin (OPG). Mouse osteoblasts (MC3T3-E1) were transfected with miR‑519d-3p mimic, inhibitor, or corresponding negative controls. Osteoblast-conditioned medium (OB-CM) was mixed 1:1 with MDA-MB-231 tumor-conditioned medium (231-CM) and applied to bone-marrow-derived macrophages for tartrate-resistant acid phosphatase (TRAP) staining. Osteoblastic MMP2 and OPG mRNAs were quantified by RT-qPCR, and a dual-luciferase system compared the wild-type vs seed-mutant MMP2 3'UTR reporters. Relative to their controls, miR-519d-3p mimic OB-CM produced fewer TRAP-positive multinucleated osteoclasts, whereas inhibitor OB-CM produced more. In osteoblasts, the mimic decreased MMP2 mRNA, whereas the inhibitor increased it, and the changes in OPG mRNA were modest. Dual-luciferase assays did not show a reproducible wildtype-over-mutant selective repression by miR-519d-3p, indicating context-dependent or indirect regulation of MMP2. Elevating osteoblastic miR-519d-3p in vitro associated with lower MMP2 and an anti-osteoclastogenic paracrine output, suggesting a tractable microRNA-based approach to modulate the metastatic bone niche and warranting further validation in vivo.