Adenocarcinoma and adenosquamous carcinoma of the cervix together account for up to 20% of all cervical cancers. These histologic subtypes are characterized by a worse prognosis compared with squamous cell cancer of the same grade and have specific epidemiologic, morphologic and molecular features. Despite fundamental differences, therapeutic approaches for cervical cancer are similar regardless of tumor histology. This article discusses promising companion diagnostic markers for cervical cancer treatment, including MSI, PD-L1 and TIL's, that may find application in the therapy of prognostically unfavorable subtypes of cervical cancer. The literature review revealed that despite the low frequency of immunotherapy markers among adenocarcinomas and adenosquamous carcinomas of the cervix, analyzing them will allow us to identify a group of patients who will benefit most from immunotherapy, a key step towards improving treatment outcomes.

Germ cell tumors are rare testicular neoplasms that occur in young men, and their proportion is 2%. Pathological changes in the immune landscape of seminoma - the interaction of mast cells, T-, B-lymphocytes and macrophages with atypical spermatogenic cells, possibly impart a certain uniqueness to seminoma, and their number determines the stage of tumor growth. At the same time, the question of the participation of mast cells in the progression of seminoma remains debatable.

Lung adenocarcinoma (LAC) is one of the leading causes of cancer mortality, which is most likely due to the presence of cancer stem cells (CSC) in the tumor, which form a heterogeneous hierarchy and are responsible for the occurrence and progression of carcinoma, as well as its unfavorable prognosis. The ability of CSC to form heterogeneous tumor populations in lung cancer has not been sufficiently studied.

One of the main prognostic factors for meningioma recurrence is histological diagnosis with an assessment of tumor grade. Despite this, there are no clear microscopic criteria for recurrence prognosis in benign forms, and there is no common understanding of meningioma recurrence and continued growth clinical management.

To study the microenvironment features of MMR-proficient (pMMR) and MMR-deficient (dMMR) endometrial cancer.

Thyroid transcription factor 1 (TTF1) is the most common and reliable marker for immunohistochemical diagnostics of various thyroid tumors and lung adenocarcinoma. At the same time, some of scientific studies have been published that describe aberrant expression of TTF1 by cells of various tumors, including lymphomas. Researchers reported the possibility of TTF1 expression in diffuse large B-cell lymphoma, angioimmunoblastic T-cell lymphoma, and T-cell leukemia. However, there were no reports of this marker expression in anaplastic large cell lymphoma, which, due to its morphological characteristics, may resemble a metastatic process.

To test the possibility of creating a non-invasive system for differential diagnosis and molecular-genetic characterization of tumor lesions of the CNS based on the determination of mutations of promoter of telomerase (TERTp) C228T and C250T catalyst subunit through the example of glioblastoma.

Reactive oxygen and nitrogen species accumulate in cells during oxidative stress and cause oxidative damage to various cell components, including DNA, proteins, and lipids, thus leading to a number of severe diseases, such as atherosclerosis. Protein C3 is a central component of the complement cascade and a key player in the immune system. Proinflammatory activity of C3 can also contribute to the development of metabolic syndrome. Although hepatocytes are the main source of C3 circulating in the blood, the regulation of C3 gene expression in hepatocytes under oxidative stress remains unexplored. Suppression of C3 gene transcription and C3 protein secretion were observed during hydrogen peroxide-induced oxidative stress in HepG2 human hepatoma cells. The transcription factor FOXO1 promoted C3 expression, and C3 repression by oxidative stress was mediated through the regulation of FOXO1/HNF4α complex binding to the C3 promoter. A novel cluster of FOXO1 binding sites was identified in the distal region of the C3 promoter and found to be essential for the regulation of C3 expression by the FOXO1/HNF4α complex. Activation of the main MAP kinase cascades (ERK1/2, p38, and JNK), AMP kinase, and the transcription factor NF-κB were necessary for C3 suppression in oxidative stress. Thus, the molecular mechanisms and transcription factors that mediate suppression of C3 production in HepG2 cells during oxidative stress were identified.

The development of resistance to trastuzumab in HER2-positive breast cancer is a serious clinical problem that limits the effectiveness of targeted therapy. In a significant proportion of patients, the mechanisms in the development of resistance remain poorly understood. The BT-474 cell line was selected as an optimal model for study because it represents a HER2-positive luminal B subtype breast cancer cell line. To identify the molecular mechanisms of resistance, a comprehensive transcriptomic analysis based on RNA-seq data comparison of three independent datasets including both sensitive and trastuzumab-resistant variants was applied. The methodological approach included multistep bioinformatics analysis followed by identification of regulatory interactions. The study identified genes with increased expression (FUCA2, HSPE1, SHLD1, NMD3) and genes with decreased expression (GPC5, FSTL1, ATG16L2, POLD2) in resistant cells. Key transcription factors (E2F1, MYC, YBX1, HEY1, NFIC, TFAP2A, AP-1/JUN, NCOA1) regulating the expression of the detected genes during the development of resistance were identified. The changes identified indicate a complex reprogramming of transcriptional activity affecting cell cycle processes, DNA repair, metabolism, and the epithelial-mesenchymal transition. The findings expand our understanding of the molecular mechanisms of trastuzumab resistance and open prospects for the development of novel therapeutic strategies to overcome drug resistance in HER2-positive breast cancer.

Currently, due to the lack of clear criteria for predicting the aggressive course of pituitary adenomas (APA), the search for diagnostic markers is highly relevant. Genetic markers, among others, may serve as such markers since their identification is possible at early stages of the pathological process.

Disorders of sex development or hermaphroditism are a condition associated with a discrepancy between genetic, gonadal, and phenotypic sex. Persistent Müllerian duct syndrome (PMDS) is a rare form of male pseudohermaphroditism. Typical features are cryptorchidism and the presence of underdeveloped fallopian tubes, uterus or upper vagina in a male with karyotype 46, XY. Over the past 50 years, about 200 cases of persistent Müllerian duct syndrome have been reported. The article describes an observation of a 33-year-old patient with bilateral cryptorchidism, testicular neoplasm, and false hermaphroditism revealed during the examination of surgical material. Macroscopic and microscopic pictures are presented, including those using immunohistochemical methods. The results of a molecular genetic study of the surgical material are given. After all the examinations, the patient was diagnosed with: Typical seminoma of the right undescended testicle, pT2. False hermaphroditism.

To evaluate the impact of combined anti-PD-1 immunotherapy on the cellular composition of the tumor microenvironment in patients with gastric cancer.

To detect the presence or absence of correlations between the degree of tumor budding (TB) and pMMR/dMMR (proficient Mismatch Repair System/deficient Mismatch Repair System) and PD-L1 status in gastric cancer (GC).

Infection with tick-borne encephalitis virus (TBEV) can lead to severe neurological complications largely associated with the activation of innate immunity and inflammatory reactions in the tissues of the nervous system. In this regard, the study of factors, including viral factors, influencing these processes is underway. We analyzed the possible role of nonstructural protein 1 (NS1) of TBEV in the activation of innate immune response reactions in cells of the nervous system. SH-SY5Y neuroblastoma and DBTRG-05MG glioblastoma cells were transfected with a plasmid encoding NS1 or treated with extracellular vesicles of NS1-expressing HEK293T cells and then stimulated with polyinosinic-polycytidylic acid [poly(I:C)] to activate the innate immune response. It was found that poly(I:C) stimulation of NS1-expressing SH-SY5Y cells resulted in lower mRNA levels of the pro-inflammatory cytokines interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α), as well as the innate immune response of the cytokine interferon-1β(IFN-β) and the interferon-stimulated gene 15 product (ISG15), compared to stimulated cells without NS1 expression. In addition, transcription of the sensor gene MDA5, which is responsible for activating gene transcription of these cytokines, was reduced in these cells. In NS1-expressing DBTRG-05MG stimulated cells, only the IL-1β mRNA content was reduced. Treatment of SH-SY5Y cells with extracellular vesicles from NS1-expressing cells followed by poly(I:C) stimulation resulted in increased mRNA levels of IL-6, TNF-α, and IFN-β, compared with stimulated cells treated with vesicles from non-NS1-expressing cells. No differences were detected in DBTRG-05MG cells with similar treatment. Based on these data, we can assume that TBEV NS1 plays a dual role in the formation of neuroinflammation during the infection, and we can consider this protein as a potential therapeutic target.

The discovery of a class of long noncoding RNAs (lncRNAs), including lncRNAs of the small nucleolar RNA (snoRNA) host gene family, SNHG, has led to growing interest in the study of both snoRNAs themselves and the genes encoding them. Currently, of the 232 known snoRNA genes, only 32 have been confirmed to have lncRNAs. At the same time, a positive correlation has been shown between the expression of lncRNAs and snoRNAs encoded by a common host gene of the SNHG family. Thus, lncRNA of the SNHG1 gene correlates with snoRNAs SNORD22 and SNORD25-31, and lncRNA of the SNHG16 gene, with snoRNAs SNORD1A, SNORD1B, and SNORD1C. There is evidence that SNHG lncRNAs can participate in oncogenesis both through regulatory functions inherent to lncRNAs and by influencing ribosome biogenesis. At the same time, information has accumulated on the "extraribosomal" functions of snoRNAs. In addition to a brief excursion into the biological functions of snoRNAs and SNHG lncRNAs, we present a comprehensive review of data on the role of these two types of noncoding RNAs in the pathogenesis of ovarian cancer, the most insidious cancer of the female reproductive system. The influence of these regulatory RNAs on the main processes of ovarian oncogenesis, such as apoptosis, epithelial-mesenchymal transition, cell cycle control, and DNA methylation mechanisms in this type of cancer is considered. The prospects for clinical application of regulatory RNAs due to their influence on the level of drug resistance are also discussed.

DICER1 syndrome is a rare monogenic disease with autosomal dominant inheritance. DICER1 protein is involved in the regulation of gene expression by microRNAs. Changes in the expression of DICER1 can be associated with various cancers. A 13,8-year-old girl with a history of embryonal rhabdomyosarcoma (ERMS) of uterine cervix and vagina excised at 6 months of age is presented with a thyroid follicular nodular disease (TFND). Molecular genetic examination revealed a heterozygous pathogenic variant p.Arg1003Ter in the DICER1 gene (NM_030621.4). The presented case emphasizes the importance of molecular genetic diagnosis of DICER1 syndrome in a diagnostic algorithm in the management of patients with TFND and history of malignancy. Considering ERMS of genital tract as a probable component of DICER1 syndrome it is necessary to screen for other manifestations of the disease as well.

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.