To study the incidence and risk factors of regional lymph node metastases in patients with early primary operable prognostically unfavorable breast cancer.

Type 1 neurofibromatosis is a rare hereditary monogenic disease with an autosomal dominant inheritance associated with a mutation in the NF1 gene on chromosome 17, which encodes neurofibromin, a protein with tumor-suppressive activity. A large genomic deletion of the NF1 gene is detected in only 5-10% of patients with type 1 neurofibromatosis. A clinical case of type 1 neurofibromatosis associated with a rare extensive deletion of the NF1 gene involving the whole studied gene (exons 1 to 57) in a patient who was observed from early childhood to 17 years of age is presented. The phenotype included early clinical onset with typical skin manifestations, multisystem lesions, sequential progression of diffuse multifocal lesions in the brain and peripheral nervous system, and visual disorders associated with optic glioma.

MicroRNAs in tissues and biological fluids represent a promising class of biomarkers for the molecular diagnostics and therapy of numerous diseases, including oncological diseases. Biomarkers based on easily accessible biological fluids, primarily blood-based biomarkers, are of particular value for diagnostic and prognostic purposes. To explore the potential of microRNAs as prognostic cancer markers and targets for molecular therapy, global microRNA profiling is required, which is provided by next-generation sequencing (NGS). NGS offers high sensitivity, single nucleotide resolution, and the possibility of profiling a large number of samples in parallel. Despite the promising potential of microRNAs as biomarkers and the growing number of works in this area, the literature does not address in sufficient detail the problems associated with sample preparation methods, the specifics of library preparation for microRNA sequencing, and the difficulties of quantitative analysis. Protocols for creating libraries for microRNA sequencing present specific challenges and require selecting conditions for each type of biological sample. Here, we present in detail the preparation of libraries for microRNA sequencing from pituitary adenoma tumor tissue and blood plasma of patients with acromegaly on the Illumina platform. We discuss the difficulties and limitations of the methods and evaluate the effectiveness of sequencing plasma and brain samples. This work can serve as a guide for researchers studying the mechanisms of microRNA regulation in endocrine diseases of the pituitary gland and will also allow for the adaptation of technical procedures for various biological samples in relation to other pathologies.

Breast cancer (BC) is a multifactorial disease that is characterized by various genetic and epigenetic changes that occur due to the effect of various factors including that of environmental etiological agents. The obtained scientific data speak volumes for epigenetic dysregulation in BC pathogenesis. Out of all epigenetic markers, various microRNA regulating a wide spectrum of biological processes in a cell could be viewed as one of the predictors of potential risk. Understanding the functional role of these molecules will provide valuable information about the complex molecular mechanisms underlying the appearance and development of BC. This review summarizes currently existing publicly available data on aberrant expression of miR-125b, miR-181a, and miR-16 in case of various cancer localizations; analyzes their role in BC pathogenesis; presents an annotation of the target-genes; and evaluates the repression potential of microRNA and their diagnostic significance in case of BC. An analysis of changes in miRNA expression during radiation exposure was conducted. Interest in examining specific miRNAs is due to the results of long-term monitoring of the health of people living in radioactively contaminated areas of the Southern Urals, as well as data on the expression profiles of miR-125b, miR-181a, and miR-16 over the long term in exposed people.

A search for efficient biomarkers of ovarian cancer is one of the current trends in gynecologic oncology. Metabolic profiling by ultra high-performance liquid chromatography and mass spectrometry (UHPLC-MS) yields information about the total set of low-molecular-weight metabolites of a patient's biological fluid sample. The metabolites may provide potential disease markers, and their combination with microRNA level data significantly increases the diagnostic value. To identify the potential noninvasive diagnostic markers of serous ovarian adenocarcinoma, the metabolomic profile and microRNA transcript levels were studied in urine samples of patients. The study included 60 patients diagnosed with serous ovarian adenocarcinoma and 20 women without a cancer history. Chromatographic separation of metabolites was performed on a Vanquish Flex UHPLC system coupled to an Orbitrap Exploris 480 mass spectrometer. A search for gene regulators of metabolites and microRNA regulators of genes was carried out using the Random forest machine learning method. The microRNA transcript levels in the urine were determined by real-time PCR (qPCR). LASSO-penalized logistic regression was used to build predictive models. In total, 26 compounds showed abnormal concentrations in the ovarian cancer (OC) patients compared with the control group, the set including kynurenine, phenylalanyl-valine, lysophosphatidylcholines (18:3, 18:2, 20:4, and 14:0), alanylleucine, L-phenylalanine, phosphatidylinositol (34:l), 5-methoxytryptophan, 2-hydroxymyristic acid, 3-oxocholic acid, indoleacrylic acid, lysophosphatidylserine (20:4), L-β-aspartyl-L-phenylalanine, myristic acid, decanoylcarnitine, aspartyl-glycine, malonylcarnitine, 3-hydroxybutyrylcarnitine, 3-methylxanthine, 2,6-dimethylheptanoylcarnitine, 3-oxododecanoic acid, N-acetylproline, L-octanoylcarnitine, and capryloylglycine. Metabolite-gene regulator (47 genes) and metabolite-microRNA regulator (613 unique microRNAs) relationships were established by the Random forest method. Levels of 85 microRNAs were validated by qPCR. Changes in transcript levels in the OC patients compared with the controls were observed for miR-382-5p, miR-593-3p, miR-29a-5p, miR-2110, miR-30c-5p, miR-181a-5p, let-7b-5p, miR-27a-3p, miR-370-3p, miR-6529-5p, miR-653-5p, miR-4742-5p, miR-2467-3p, miR-1909-5p, miR-6743-5p, miR-875-3p, miR-19a-3p, miR-208a-5p, miR-330-5p, miR-1207-5p, miR-4668-3p, miR-3193, miR-23a-3p, miR-12132, miR-765, miR-181b-5p, miR-4529-3p, miR-33b-5p, miR-17-5p, miR-6866-3p, miR-4753-5p, miR-103a-3p, miR-423-5p, miR-491-5p, miR-196b-5p, miR-6843-3p, miR-423-5p and miR-3184-5p. Thus, significant metabolomic imbalance in the urine was observed in the OC patients and was associated with changes in the levels of microRNAs that regulate the signaling pathways of the metabolites. The 26 compounds with abnormal concentrations and the levels of the microRNAs miR-33b-5p, miR-423-5p, miR-6843-3p, miR-4668-3p, miR-30c-5p, miR-6743-5p, miR-4742-5p, miR-1207-5p, and miR-17-5p in the urine were considered to be suitable as noninvasive diagnostic markers of OC.

Breast cancer (BC) with triple-negative molecular profile is characterized by special and rather serious problems in terms of clinical management of patients compared to other types. On the one hand this is due to the fact that tumors with such a status often do not respond to routine targeted therapy and only a minimal number of drugs are currently available for their treatment. On the other hand, cases of triple-negative BC (TNBC) are often diagnosed against the background of an extensive metastatic process, in which confirmation of the metastases histogenesis to breast tissue is a difficult task due to the low sensitivity of such carcinomas to specific organ markers. It is known that about 40-50% of all TNBC cases are characterized by the achievement of complete pathomorphological regression of the primary tumor as a result of neoadjuvant chemotherapy courses, which determines a favorable prognosis of the disease. In other cases (also up to 50%), TNBC do not respond to chemotherapy and exhibit persistent drug resistance, such tumors are more aggressive, have the highest relapse rate and a high risk of metastasis. For this group of patients, the issue of finding predictive markers and new therapeutic methods remains unresolved. The presented literature review reflects the data of the analysis of publicly available results of scientific studies devoted to potentially promising molecular markers, including IDO1, DCLK1 and FOXC1, their significance in BC, including TNBC is described. Based on the analysis of literary data, it can be argued that IDO1, DCLK1 and FOXC1 are promising objects for further research in the context of TNBC. Each marker has unique characteristics that make them important both for disease prognosis and for the development of new therapeutic approaches.

Solitary fibrous tumor is a rare mesenchymal neoplasm, the most common localization of which is the pleural cavity, but the tumor can also affect other organs. This neoplasm with localisation in the kidney was first described only in 1996. Solitary fibrous tumor accounts for 0.2% of all kidney neoplasms and is an exceptional phenomenon. Currently, there is no generally accepted theory explaining the etiology and pathogenesis, probably, its development is a multifactorial process including a combination of genetic, epigenetic and external factors. Despite the lack of unambiguous opinion on the nature of the neoplasm, the spectrum of molecular abnormalities in this tumor has been sufficiently studied. The literature presents a limited number of publications devoted to this pathology, in this regard it should be noted that in routine practice, the morphological picture may not always be so unambiguous and require the pathologist to conduct differential diagnostics with a fairly wide range of tumors. Given the rarity of this disease, we would like to share a description of our own clinical observation demonstrating the possible difficulties of morphology diagnostics.

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor. SFT was first described by Klemperer and Rabin in 1931. They described a fibrous tumor of the pleura. Currently, isolated cases of SFT of the gallbladder and common bile duct have been described in the world. SFT is characterized by nuclear expression of STAT6 and the formation of chimeric genes NAB2-STAT6. A case report of a rare SFT of the common bile duct in a 66-year-old patient is presented. The description contains data from radiation and ultrasound diagnostic methods, macro- and microscopic characteristics of the tumor and immunohistochemical characteristics.

This study explores the immunohistochemical and prognostic characteristics of gastric cancer (GC).

Squamous cell carcinomas of the vulva are divided into human papillomavirus (HPV)-associated and HPV-independent. There is a need to determine the most effective methods for determining the HPV status of a tumor. Differences in the morphological structure of carcinomas have been shown, but the histological type of tumor does not fully reflect the differences in cell size for understanding the mechanisms of carcinogenesis.

To evaluate the MMR system proteins and the MSI status of regenerative (indefinite for dysplasia) and pronounced (epithelial dysplasia) gastric mucosa precancerous lesions in the comparison with cancer to determine their possible potential as a diagnostic markers of gastric mucosa dysplasia.

The article presents an overview of the intermediate results of treatment for maxillary sinus melanoma in a 66-year-old patient. The importance of timely diagnosis and active surgical tactics for achieving the best survival results up to 5 years is noted. After further examination, the diagnosis was confirmed, the patient underwent genomic sequencing of the tumor tissue biopsy, which revealed a BRAF mutation. In this regard, adjuvant therapy was prescribed according to the dabrafenib+trametinib regimen. It was noted that this rare pathology requires careful study, monitoring of clinical outcomes and features of surgical tactics, considering the multifocal nature of the tumor and its high aggressiveness in comparison with the cutaneous form. In the future, the possibility of surgical intervention is discussed, extensive resection is considered, the expected volume, which can reach the removal of both soft tissue and bone structures up to resection of a part of the lower wall of the orbit.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by autonomous secretion of parathyroid hormone by altered parathyroid glands. In most cases PHPT is a sporadic disease, 5-10% of observations are genetically determined syndromal and non-syndromal forms. Studies of families with hereditary forms of PHPT have led to the discovery of key oncosuppressor genes and proto-oncogenes whose somatic mutations underlie the development of many sporadic parathyroid tumors. Another interest in the pathogenesis of primary hyperparathyroidism is studying mechanisms of epigenetic regulation in tumor tissue. In the first part of this review, we will discuss the classification, morphology, and etiology of PHPT. In the second part, we will present a summary of the most important studies using genetic analysis, classified according to the method used.

Gastric cancer remains the fifth most common malignant neoplasm in the world and ranks fifth among the causes associated with cancer. The TNM system remains the gold standard for predictive stratification of patients with gastric cancer, but the search for new sensitive, specific and reproducible biomarkers to develop a personalized approach to the management of patients with gastric cancer does not lose its relevance. The phenomenon of tumor budding is a well-established independent prognostic factor in colorectal cancer. In 2017, the first guideline on the method of calculating tumor budding for colorectal cancer was published. Despite the promising potential of using tumor budding in gastric cancer this parameter is still not evaluated in everyday practice. This lection provides data on various methods of counting tumor budding in gastric carcinomas, describes the molecular mechanisms of interaction between tumor cells and the immune microenvironment, and summarizes the available data on the relationship of clinical and morphological characteristics of gastric cancer with the degree of tumor budding. The relationship between the degree of tumor budding and the prognostic characteristics of gastric cancer and the prospects for its use is also described.

To define the diagnostic value of eosinophilic cells for the detection of BRAF-mutated serous borderline ovarian tumors.

Gastric cancer (GC) is a heterogeneous tumor with various molecular changes. An active search for molecular markers is crucial to determine the effectiveness of drug treatment and prognosis of the disease. Several biomarkers have the greatest clinical significance: HER2, MSI / dMMR, PD-L1 (CPS), EBV and Claudin 18.

The development of drugs with the ability to increase differentiation and reduce tumor malignancy is one of the promising directions in the treatment of breast cancer (BC). As such, Human Leukemia Differentiation Factor (HLDF), a protein consisting of 54 amino acids and contributing to an increase in the degree of differentiation of invasive ductal breast carcinoma cells, can be used. The key disadvantage of the full-size HLDF is its rapid biodegradation. In this connection, the acetylamide form of the peptide (HLDF-6) was synthesized to protect against hydrolysis.

In 2021, a new type of tumor was defined according to the new WHO classification (high-grade astrocytoma with piloid features, HGAP). Morphological and neuroimaging differences of HGAP from pilocytic astrocytoma complicate diagnosis. Now, significant detection of this tumor is possible only using molecular genetic testing, in particular, methylation profile analysis.

Human papillomavirus type 16 (HPV16) belongs to viruses of the high-risk type and is associated by overexpression of E6 and E7 oncoproteins, which determine the oncogenic properties of the virus, such as immortalization and malignant transformation of proliferating epithelial cells. The biogenesis of redox-sensitive proteins E6 and E7 at the early stages of viral infection leads to blocking of the cell antioxidant defense system and ubiquintin-dependent degradation of p53 and Rb tumor suppressors. Maintaining high rates of tumor cell proliferation contributes to an increase in the level of reactive oxygen species (ROS) and a shift in the redox balance towards oxidative processes. Reduced glutathione (GSH) provides antioxidant protection to tumor cells through S-glutathionylation of thiol groups of redox-sensitive proteins, which leads to the appearance of multidrug-resistant forms of cancer. In this regard, drugs restoring redox balance and increasing susceptibility to antitumor therapy are of particular importance. We have established that, Bacillus pumilus RNase (binase) modulates the redox-dependent regulatory mechanisms that ensure tumor cell resistance to apoptosis in HPV-16-positive SiHa cells of cervical squamous cell carcinoma. Binase in nontoxic concentrations initiates a number of pre-apoptogenic changes, i.e., decreases ROS and reduced glutathione (GSH) levels, suppresses the expression of the E6 oncoprotein, activates the expression of the p53 tumor suppressor, and reduces the mitochondrial potential of tumor cells. Binase-induced disruption of the integrity of the mitochondrial membrane is a signal for activation of the mitochondrial apoptosis pathway.

Pancreatic Ductal AdenoCarcinoma (PDAC) is characterized by a poor prognosis and is poorly amenable to modern therapies. A range of cell cultures reflecting different degrees of tumor differentiation and malignancy can serve as a model of PDAC development. Highly differentiated cells with low malignancy are characterized by increased expression of the KLF5 gene. The KLF5 protein is a vivid representative of multifunctional transcription factors, and its involvement in a variety of cellular processes, particularly in the pathology of various cancers, has been demonstrated. We investigated the spatial organization of chromatin of the regulatory regions of the KLF5 gene using highly differentiated Capan2 PDAC cells with a high level of KLF5 expression and poorly differentiated MIA PaCa2 PDAC cells with a low level of expression of this gene by circular chromosome conformation capture (4C-seq). It was shown that the number and distribution of contacts of the KLF5 regulatory region with other chromatin regions are significantly different for these types of cells; the number of contacts is significantly higher for Capan2 cells. There is a correlation between the expression level of genes close to KLF5 and the intensity of their sequence contacts with the KLF5 regulatory region, indicating that their expression is coordinated, possibly within the transcriptional factory. Capan2 is characterized by a high level of contacts of the KLF5 regulatory region with the gene-free region containing a cluster of PDAC-associated single nucleotide polymorphisms (SNP/InDel). Thus, the total number of contacts of the promoter region of the KLF5 gene and the expression level of most of the surrounding KLF5 genes decrease as the grade of cell malignancy increases.