Cancer-associated fibroblasts (CAFs) often form a major component of the tumor microenvironment (TMA), providing conditions for cancer cells to thrive. CAFs may contribute to tumor growth, invasion, metastasis, and resistance to therapy. However, clinical trials of treatment strategies targeting CAFs have largely failed. Moreover, there is evidence that CAFs are capable of inhibiting tumor development. The review considers the current data on the functional heterogeneity of CAFs and their bimodality in tumor development and progression. Understanding the tumor-promoting and tumor-inhibiting activities of CAFs can help to develop new diagnostic and therapeutic approaches.

Peutz-Jeghers Syndrome (Peutz-Jeghers Syndrome, PJS) refers to syndromes of hereditary tumor predisposition and is caused by pathological variants of the STK11 gene, leading to a defect in the synthesis of serine/threonine kinase 11 protein, which acts as a tumor suppressor.Clinical symptoms of the syndrome are combination of hamartomatous polyposis of the gastrointestinal tract and specific skin-mucosal hyperpigmentation. Also, this disease is characterized by a high risk of developing gastrointestinal and extra-intestinal tumors, including benign or malignant tumors of the reproductive system.One of the first signs of the disease in male patients may be prepubertal gynecomastia associated with large-cell calcifying Sertoli cells tumors expressing aromatase. In contrast to from pubertal gynecomastia, prepubertal is extremely rare, and it is often based on pathological causes. Early diagnosis of patients with pre-pubertal gynecomastia, including Peitz-Jaegers syndrome, defines the tactics of gynecomastia management and protocols for monitoring the development of other components of the disease in the future.This article describes two patients with pre-pubertal gynecomastia and Peitz-Jaegers syndrome with different molecular genetic defects: in one case associated with duplication of the STK11 gene site, in the other - with microdeletion of the short arm of chromosome 19 containing this gene.

Meningioma is the most common primary tumor of the central nervous system. Traditional classification is based on histological properties of tumors and distinguishes different grades of meningioma malignancy. However, knowledge about different molecular mechanisms of tumor provided new data on genetic features of meningiomas. The authors analyze current available data on the main driver mutations, new classifications based on molecular genetic characteristics and potential targets for therapy.

The article summarizes the literature data on the results of clinical, histological and molecular genetic studies of polymorphic adenocarcinoma. It is shown that the diagnosis of polymorphic adenocarcinoma presents difficulties due to the variety of morphological structure of its various components, which may correspond to the characteristics of other tumors of the salivary glands, such as pleomorphic adenoma and adenoid cystic carcinoma. Immunohistochemical markers characteristic of this pathology of the salivary glands are described. The article presents a rare clinical case of a male patient with polymorphic adenocarcinoma. Histological examination revealed perineural invasion and a characteristic immunohistochemical profile of tumor cells: low cell proliferative activity for the Ki-67 protein, a positive reaction to antigens: S100, SOX10, P63 and reverse transcriptase TERT. A study conducted by the FISH method revealed the amplification of the TERC gene, which indicates the malignant nature of this neoplasm. Conducting molecular genetic studies is of paramount importance for the diagnosis of polymorphic adenocarcinoma.

This review is dedicated to E-cadherin, a calcium-dependent cell-cell adhesion molecule with pivotal roles in epithelial cell behavior, tissue formation, and carcinogenesis. We summarize the structure of the E-cadherin, its role in the development of the body and in the carcinogenesis. The structure of the E-cadherin/β-catenin/αE-catenin complex and its relationship with the actin cytoskeleton are described in detail. The role of E-cadherin in the development of some infectious diseases, the function of E-cadherin as both a tumor suppressor and a promoter of tumor dissemination, its influence on signal transduction pathways in cells are highlighted. Particular attention is paid to the expression of E-cadherin in Helicobacter pylori infection and in tumor tissue in gastric cancer.

The article describes a rare case of small cell neuroendocrine carcinoma of the endometrium in a 67-year-old woman. According to the literature, only about 90 such observations have been described worldwide. Histological examination revealed three necessary features: the small-cell nature of the tumor, the presence of epithelial and neuroendocrine markers. An IHC study revealed a positive expression of Syn, Chrom A, CD56, CK AE1/AE3 markers; the proliferative activity index was 70%.

Neuroblastoma (NB) is a malignant neoplasm originating from the primary cells of the sympathetic nervous system. Patients with NB are risk-stratified using a number of features including age at diagnosis, disease stage, tumor histology and genetic profile (status of NMYC, ALK genes, regions 1p and 11q). The interpretation of the results of genetic studies can become a source of problems because neuroblastoma has a heterogeneous histological pattern. The article describes 2 cases with classical for NB chromosomal aberrations in the stromal component of the tumor.

In 2022, the 5th edition of the of the WHO Classification of Tumours of Endocrine Organs was published, which outlines the current understanding of adrenocortical cancer (ACC), resulting from interdisciplinary research over the past decade. This article highlights the new provisions of the WHO classification for the morphological diagnosis of ACC.

The paper discusses changes in the structure of the classification, criteria for the diagnosis of lymphoid neoplasms in the 5th edition of the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues (2022). Changes are presented regarding new nosological units, renaming and abolition of some previously existing ones. The importance of molecular genetic studies in the isolation of many lymphomas and the need to apply these studies in everyday clinical practice are emphasized. Lymphoid precancerous processes and lymphoid proliferations introduced into the Classification for the first time are considered.

Currently, PD-L1 expression in patients with tumors of various localizations is being actively studied. Studies on the expression of PD-L1 detected by clones SP142 and SP263 in gastric cancer (for the drugs atezolizumab and durvalumab, respectively) are rare in the literature. The prognostic role of PD-L1 expression in patients who were not treated with immune checkpoint inhibitors has also not been investigated.

Mutations in the PIK3CA gene, encoding the catalytic subunit of the PI3K class IA p110α, is a common mechanism of activating of PI3K/AKT/mTOR pathway in breast cancer (BC). The detection of these mutations in patients with hormone-positive Her2-negative BC is of important clinical value, since they are the predictor of the sensitivity of the tumor to the PI3K inhibitor - alpelisib. According to the status of the Her2/neu expression, all patients with hormone-positive Her2-negative BC can be divided into two groups - with low expression of Her2/neu (IHC 1+; 2+, ISH-) and with a complete lack of expression of this protein (IHC 0).

Hepatocellular carcinoma (HCC) is the most frequently diagnosed primary liver tumor worldwide. Tumor-associated macrophages (TAMs) usually have a similar phenotype to M2-like macrophages and can participate in tumor progression by secreting cytokines to suppress the immune response and activity of tumor-infiltrating lymphocytes. We investigated the role of M2 macrophages in HCC progression and explored the effects of vascular endothelial growth factor receptor 2 inhibitor-apatinib. As a cellular model of HCC, Hepb3 cell line was used. M2 macrophages were obtained by differentiation of THP-1 cells. The Transwell chamber was used to co-culture M2 macrophages and Hepb3 cells. CCK-8 and EdU assays were conducted to measure cell viability and proliferation capacity. Transwell migration assay was performed to estimate cellular metastatic potential. Cytokine expression levels were assessed by ELISA. Western blotting was used to characterize activation of the VEGFR2/STAT3/PD-L1 axis. It has been shown that co-culture with M2 macrophages increased viability, cytokine production, promoted proliferation, invasion, and migration of Hepb3 cells. The secretion of TGF-β1, IL-6, MMP-9, and VEGF was significantly increased after co-culture. In contrast apatinib suppressed M2 macrophage-induced proliferation, cell viability, invasion, and migration of Hepb3 cells. Moreover, apatinib markedly decreased expression levels of p-VEGFR2, p-STAT3, and PD-L1 in Hepb3 cells under the co-culture conditions. In conclusion, apatinib treatment can suppress TAMs-mediated malignant behavior of HCC cells via modulation of the VEGFR2/STAT3/PD-L1 signaling pathway.

Ovarian cancer has a high mortality with low five-year survival rates. The role of the E3 ligase Makorin ring finger protein 2 (MKRN2) in ovarian cancer is unknown. This study investigated the impact of MKRN2 on the growth of ovarian cancer. MKRN2 expression in ovarian cancer tissue was analyzed by immunohistochemistry. Overexpression of MKRN2 was induced in two ovarian cancer cell lines (SKOV3 and CAOV3) by lentivirus transfection, and expression levels were verified by western blotting. Proliferation and growth were determined by CCK-8 and colony formation assays, while migration was examined using transwell assays and apoptosis by flow cytometry. Xenograft tumors of transfected SKOV3 cells were established in mice, and immunohistochemistry and TUNEL assays measured MKRN2 levels and apoptosis in tumor cells. Reduced levels of MKRN2 in cancerous tissue relative to non-cancerous ovarian tissues. Lentiviral-based MKRN2 overexpression in SKOV3 and CAOV3 cells reduced tumor-associated behavior while inducing apoptosis in vitro. In xenograft tumors, MKRN2 overexpression inhibited ovarian cancer growth and increased apoptosis in vivo. These findings imply the MKRN2 involvement in ovarian carcinogenesis and suggest its potential for treating the disease.

All-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL) has been the most famous differentiation induction therapy during which the expression of PU.1, a key transcription factor (TF) for myeloid lineage determination in normal hematopoiesis is restored. In our previous studies, we found a stress-inducible H3K27 demethylase, JMJD3, to directly upregulate PU.1 expression to promote myeloid commitment during normal myelopoiesis. In addition, JMJD3 acts as an oncorepressor and plays a critical regulatory role in the initiation and progression of malignant hematopoiesis. In this study, we further resolved the relationship between JMJD3 and PU.1 in APL therein JMJD3 exerts oncorepressor activity via promoting PU.1 expression.

Functioning pituitary adenomas and pheochromocytomas/paragangliomas are rare in the general population. Pituitary adenomas occur in the familial setting in approximately 5% of cases, whereas pheochromocytomas/paragangliomas can be hereditary in 30-40% of cases. Hereditary syndromes associated with pituitary adenomas include multiple endocrine neoplasia types 1 and 4, familial isolated pituitary adenomas, and Carney complex. Hereditary syndromes associated with pheochromocytomas/paragangliomas and genes, mutations in which predispose to their development, are more numerous. The first clinical descriptions of the co-occurrence of pituitary adenoma and pheochromocytoma/paraganglioma in one patient date back to the mid 20th century, however delineating such a co-occurrence into a particular syndrome («3PAs» (pituitary adenoma, pheochromocytoma, paraganglioma)) was suggested only in 2015. To date, approximately 100 cases of such a co-occurrence have been described in the literature. Mutations in genes encoding subunits of succinate dehydrogenase complex II (SDHx) are revealed in the majority of cases, much less common are mutations in MAX, MEN1 and some other genes. This review summarizes the current information on the «3PAs» syndrome.

Prolactinomas are the most common secreting adenomas of the pituitary. In 20% of cases resistance to dopamine-agonists treatment is observed. Medical therapy resistance causes progression of pathological symptoms of hyperprolactinemia and negative topographic and anatomical changes of prolactinoma. The causes of ineffectiveness of dopamine agonists therapy are not fully understood as well as approaches to managing patients require clarification. Current concepts of resistance are based on the data obtained as a result of surgery or after a period of long-term ineffective therapy. Thus, it is very important to find methods of assessing the sensitivity of prolactin-secreting adenomas to drug therapy before surgical treatment. Genetic and immunohistochemical studies find special place among these methods, making it possible to predict adenoma's response to drug therapy at early diagnostic stage. Obtained results will allow us to form personalized algorithm for managing patients.

Sporadic multiple parathyroid gland disease is ¼ cases of primary hyperparathyroidism (PHPT). However, a single tactic for diagnosing and operating volume in patients with this variant of PHPT has not yet been developed. One of the possible directions in the search for pathogenetically substantiated methods of diagnosis and treatment is the study of the molecular genetic features of the disease and associated clinical and laboratory factors.

Transcatheter arterial chemoembolization is one of the interventional treatments for hepatocellular carcinoma (HCC). This treatment is generally used for patients with intermediate to advanced hepatocellular carcinoma, and identifying the role of HCC-related genes can help improve the efficiency of transcatheter arterial chemoembolization. To investigate the role of HCC-related genes and to provide valid evidence for transcatheter arterial chemoembolization treatment, we performed a comprehensive bioinformatics analysis. Through text mining ("hepatocellular carcinoma") and microarray data analysis (GSE104580), we obtained a standard gene set, which was followed by gene ontology and Kyoto Gene and Genome Encyclopedia analysis. The significant 8 genes clustered in protein-protein interactions network were chosen to be used in the follow-up analysis. Through survival analysis low expression of the key genes were found to be strongly associated with survival in HCC patients in this study. The correlation between the expression of the key genes and tumor immune infiltration was assessed by Pearson correlation analysis. As a result, 15 drugs targeting seven of the eight genes have been identified, and therefore can be considered as potential components for transcatheter arterial chemoembolization treatment of HCC.

Cisplatin (DDP) is widely used in the chemotherapy of cervical cancer (CC), the fourth most common female malignancy worldwide. However, some patients progress to chemotherapy resistance, which leads to chemotherapy failure, tumor recurrence, and poor prognosis. Therefore, strategies to identify the regulatory mechanisms underlying CC development and increase tumor sensitivity to DDP will help improve patient survival. This research was designed to ascertain the mechanism of EBF1-dependent regulation of FBN1 which promotes chemosensitivity of CC cells. The expression of EBF1 and FBN1 was measured in CC tissues resistant or sensitive to chemotherapy and in DDP-sensitive or -resistant cells (SiHa and SiHa-DDP cells). SiHa-DDP cells were transduced with lentiviruses encoding EBF1 or FBN1 to evaluate the influence of these two proteins on cell viability, expression of MDR1 and MRP1, and cell aggressiveness. Moreover, the interaction between EBF1 and FBN1 was predicted and demonstrated. Finally, to further verify the EBF1/FB1-dependent mechanism of DDP sensitivity regulation in CC cells a xenograft mouse model of CC was established using SiHa-DDP cells transduced with lentiviruses carrying EBF1 gene and shRNA directed to FBN1 EBF1 and FBN1 showed decreased expression in CC tissues and cells, particularly in those resistant to chemotherapy. Transduction of SiHa-DDP cells with lentiviruses encoding EBF1 or FBN1 lead to decreased viability, IC50, proliferation capacity, colony formation ability, aggressiveness, and increased cell apoptosis. We have shown that EBF1 activates FBN1 transcription by binding to FBN1 promoter region. Additionally, it was revealed that FBN1 silencing reversed the promoting effect of EBF1 overexpression on chemosensitivity of CC cells in vivo. EBF1 facilitated chemosensitivity in CC cells by activating FBN1 transcription.

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of cancers that differ in pathogenesis and prognosis. The main methods of treating NHL include chemotherapy, immunochemotherapy, and radiation therapy. However, a significant proportion of these tumors are chemoresistant or rapidly recur after a short chemotherapy-induced remission. In this regard, the search for alternative cytoreductive therapeutic methods is relevant. Aberrant expression of microRNA (miRNA) is one of the mechanisms responsible for the emergence and progression of malignant lymphoid neoplasms. We analyzed the profile of miRNA expression in the biopsy material from lymph nodes affected by diffuse large B-cell lymphoma (DLBCL). The key material of the study was histological preparations of lymph nodes obtained by excisional diagnostic biopsy and treated using conventional histomorphological formalin fixation methods. The study group consisted of patients with DLBCL (n = 52); the control group consisted of patients with reactive lymphadenopathy (RL) (n = 40). It was shown that the miR-150 expression level in DLBCL was reduced by more than 12 times (</>p = 3.6 x 10^(-15)) compared with RL. Bioinformatics analysis revealed the involvement of miR-150 in the regulation of hematopoiesis and lymphopoiesis. The data we obtained allow us to consider miR-150 as a promising therapeutic target with great potential in clinical practice.