BACKGROUND:The prolonged psychoemotional stress results in the individual adaptive response ensured by the coor- dinated interactions among the nervous, endocrine, and immune systems. A key role in this process is played by the interaction between stress hormones and effector cells of innate immunity, particularly macrophages (Mph), which con- stitute the first line of host defense. The aim of this study was to experimentally investigate the effects of stress hormones on the cytokine spectrum produced by Mph of the intact and tumor-bearing rats. MATERIALS AND METHODS:Wistar rats with transplanted Guerin carcinoma were used in a study. to induce experimental chronic stress, animals received dexamethasone or adrenaline (0.5 mg/kg body weight). Plasma levels of tNf-α, IL-6, and IL-10 were determined using ELISA. RESULTS:In the intact animals, prolonged exposure to stress hormones resulted in significant alterations in the macrophage cytokine profile. Adrenaline administration was accompanied by a transient increase in tNf-α (p < 0.05) along with a simultaneous decrease in IL-10 (p < 0.05); subsequently, tNf-α production was suppressed against a marked increase in IL-10 synthesis. Dexamethasone induced an increased tNf-α production at later time points. In rats bearing Guerin carcinoma, the most pronounced changes in tNf-α and IL-10 production were observed following dexamethasone administration: on day 14, tNf-α levels significantly increased, followed by a sharp decline accompa- nied by the elevated IL-10 levels, reflecting Mph polarization from the M1 to the M2 phenotype. This indicates the deve- lopment of immunosuppression and correlates with the active tumor growth. A significant increase in IL-6 production was observed on day 14 under both adrenaline and dexamethasone exposure. Subsequently, adrenaline suppressed IL-6 production, whereas dexamethasone stimulated it, which may indicate the development of glucocorticoid resistance and paradoxical enhancement of inflammation. CONCLUSION:The prolonged exposure to stress hormones may create condi- tions favorable for tumor progression through suppression of innate immune effectors and development of immunosup- pression, as well as through paradoxical enhancement of inflammatory responses.
Although highly penetrant genes such as BRCA1, BRCA2, TP53, PALB2, CHEK2, and ATM are well known in hereditary breast cancer, genes with low penetrance may also contribute to the disease risk. The CASR (Calcium-Sensing Receptor) gene, located on chromosome 3q13.3-q21, encodes a G-protein-coupled receptor that regulates calcium homeostasis and parathyroid hormone secretion. here we describe the clinical course and genetic findings in a breast cancer patient diagnosed with hER2-positive (hER2/neu +++) and ER/PR-negative infiltrating ductal carcinoma with a rare CASR mutation and explore its potential role in the hereditary breast cancer predisposition. Next-generation sequencing re- vealed a heterozygous CASR variant, c.2265G>t (p.Glu755Asp), classified as a variant of uncertain significance (VUS). No pathogenic mutations were found in BRCA1/2, CHEK2, or PALB2. The patient underwent neoadjuvant chemothera- py, right-sided mastectomy, and trastuzumab therapy, achieving complete pathological regression (pCR) with no recur- rence after ten months of follow-up. Although the CASR p.Glu755Asp variant's pathogenic role is unproven, emerging evidence links CASR overexpression with hER2-positive breast cancers, promoting tumor progression via calcium- dependent signaling pathways (PI3K/AKt, MAPK). This case highlights the potential role of CASR as a low-penetrance susceptibility gene in breast cancer and supports further functional and genomic studies to clarify its clinical impact.
Primary leiomyomas of the vascular system, particularly of the inferior vena cava (IVC), are extremely rare benign vascular tumors, which, due to their extraluminal growth, can mimic tumors of the adjacent organs. The report pre- sents the case of IVC leiomyoma in a patient with a complicated hematological history, with recently treated idiopathic thrombocytopenia, to demonstrate the complexity of the differential diagnosis of retroperitoneal neoplasms. The case clearly demonstrates the limitations in diagnosing IVC tumors, even using modern imaging techniques, in cases of their extraluminal growth. Only the use of an aggressive surgical approach (en bloc resection of the tumor with the involved vascular wall) in combination with morphological and immunohistochemical verification guarantees an accurate diag- nosis and favorable prognosis.
BACKGROUND:Chronic stress is a key determinant of public health, signifi antly impacting regulatory systems and potentially contributing to carcinogenesis. Chronic stress, through the activation of the hypothalamic-pituitary- adrenal axis and glucocorticoid signaling, can modify the epigenetic landscape of cells, including DNA meth- ylation. Th s study aimed to evaluate whether chronic glucocorticoid-induced stress modulates the methylation status of the promoter regions of the Mmp1 and Mmp8 genes in the tumor tissue of rats with Guerin carcinoma. MATERIALS AND METHODS:to simulate chronic stress, dexamethasone (DEX) was administered subcutaneously to laboratory rats with transplanted Guerin carcinoma. tumor samples were collected on days 7, 14, and 21 of tumor growth. The methylation status of the Mmp1 and Mmp8 gene promoters was analyzed using methylation-specifi PCR. The level of methylation was quantifi d as the ratio of methylated to unmethylated PCR products, expressed as a percentage. RESULTS:In the control group (Guerin carcinoma without DEX), the Mmp1 promoter was hypo- methylated (38-40% methylation) throughout the observation period. DEX administration led to a further slight decrease in Mmp1 methylation to 32%, though insignifi ant. In contrast, the Mmp8 promoter in tumor tissue showed baseline methylation levels of 55-57%. Under the influence of DEX, Mmp8 hypermethylation was ob- served as early as day 7 (61%) and signifi antly progressed by day 14 (67%) and day 21 (69%). CONCLUSION:Our study demonstrated that chronic glucocorticoid-induced stress altered the epigenetic profile of tumor cells by in- ducing differential methylation of the matrix metalloproteinase genes. Specifi ally, it promoted the maintenance of Mmp1 hypomethylation and signifi antly increased the Mmp8 promoter hypermethylation. These fi dings suggest that chronic stress may contribute to an aggressive tumor phenotype through the epigenetic regulation of extracel- lular matrix remodeling.
We describe an extremely rare clinical case of primary ovarian osteosarcoma (OS) in a 70-year-old woman, along with the diagnostic criteria for this condition. The patient underwent chemotherapy and has been under observation for 27 months. Currently, tumor progression with metastatic lesions of the peritoneum is observed. This case highlights the importance of further studies of primary ovarian OS. Ovarian OS is not included in the 2022 WhO classification of genital tumors, but such cases occur; their diagnosis is difficult, and there is no consensus on the treatment. Accumulat- ing data on the structural features of these tumors and their response to treatment will help improve the understanding of their treatment.
