Pheochromocytoma (PHEO) currently is considered to be malignant due to metastatic potential. One of the most common familial forms of PHEO is multiple endocrine neoplasia syndrome (MEN) type 2. The penetrance of PHEO in MEN2 syndrome is up to 50% of cases. It may be one- or two-sided, but metastases occur extremely rare. The fact that in majority of cases of MEN2 syndrome the source of distant metastases is medullary thyroid carcinoma (MTC) complicates differential diagnosis in case of PHEO metastasis.Isolated cases of PHEO with metastases to the lymph nodes, lungs, liver, bones, brain in MEN2 patients were described. In the available literature, we have found a description of 31 cases of metastatic PHEO in MEN2 syndrome. The available data of those cases is presented as a table in the article.We present a description of a 40-year-old woman with MEN2A syndrome (mutation of the RET proto-oncogene p.Cys634Tyr), with a history of twice-performed surgical treatment of MTC, with daily crises of arterial hypertension accompanied by vegetative symptoms, with a giant bilateral PHEO (up to 200 m on the right and up to 150 mm on the left) with synchronous large metastasis (up to 50 mm) into the pubic bone with the destruction. The patient underwent several surgeries: bilateral adrenalectomy, then a bilateral revision of the neck, removal of the right upper and right lower parathyroid glands, residual thyroid tissue, then resection of the right pubic bone with a tumor.

Oncolytic viruses represent a promising class of immunotherapeutic agents for the treatment of malignant tumors. The proposed mechanism of action of various oncolytic viruses has initially been explained by the ability of such viruses to selectively lyse tumor cells without damaging healthy ones. Recently, there have emerged more studies determining the effect of the antiviral immunostimulating mechanisms on the effectiveness of treatment in cancer patients. Stimulation of innate immune cells by an oncolytic virus can initiate an adaptive antitumor immune response, yet at the same time, the antiviral mechanisms of the immune system can limit the spread of the virus, thereby reducing its effectiveness. Thus, the success of the clinical application of the oncolytic viruses directly depends on the three key components: tumor immunosuppression, antiviral responses, and antitumor immune responses. The review presents current data on the influence of pattern recognition receptors on the effectiveness of oncolytic viruses.

The purpose of this review was to analyze the most perspective methods for risk stratification of malignant transformation of pancreatic intraductal papillary mucinous neoplasms (IPMN). Advisability of humoral predictors (tumor markers, inflammatory markers, circulating leptin and branched-chain amino acids, etc.) is in identifying prognostic signs suitable for risk stratification of IPMN malignant transformation and, therefore, determining treatment strategy for a particular patient. According to data screening, the most advisable predictors of malignant transformation of neoplasms are carbohydrate antigen 19-9, carcinoembryonic antigen, neutrophil-to-lymphocyte ratio and high-grade dysplasia. At the same time, DNA sequencing, analysis of miRNA and telomere expression, as well as liquid biopsy have a high potential and require further research for routine clinical practice.

Ovarian cancer (OC) develops asymptomatically and escapes diagnosis until advanced stages, the feature contributing to a higher mortality rate. New prospects of OC diagnosis and treatment have been opened in studies of the gene regulation mechanisms that involve long noncoding RNAs (lncRNAs) and identification of the lncRNA genes that are inhibited via methylation of the promoter region. A set of 122 samples of primary OC tumors was examined by methylation specific real-time PCR to assess the methylation level of the lncRNA genes PLUT, SNHG1, SNHG6, SNHG12, and TINCR. A significant increase in their methylation levels was observed in OC (p < 0.001 by the nonparametric Mann-Whitney test). The methylation levels of SNHG6, SNHG12, and TINCR were found to correlate significantly (p < 0.05) with the stage of the tumor process, the histological grade, and metastasis. Downregulation of SNHG6, SNHG12, and TINCR was detected by real-time RT-qPCR, and a significant correlation between methylation and expression was demonstrated for SNHG6 and TINCR (rs < -0.5, p < 0.001). The respective lncRNA genes were assumed to provide potential epigenetic markers of OC.

The bony fish Danio rerio (zebrafish) has become one of the important vertebrate model organisms in biomedical cancer research and is used, among other things, for the development of anticancer drugs using xenotransplantation approaches. The ex utero development of zebrafish, optically transparent tissues in the first month of growth, and the immature adaptive immune system during this period greatly facilitate the manipulation of embryos. For highly aggressive cancers where patient survival may be expected to be only a few months, a zebrafish xenograft assay may be the only appropriate method as it requires only four to seven days. Thousands of embryos can be implanted with biopsy tissue from a patient to produce zebrafish xenografts and to use them to screen a large number of drugs and compounds automatically to develop an effective treatment regimen for a specific patient. This review examines the advantages and disadvantages of the zebrafish model in oncology research. The main focus is on the use of zebrafish xenografts to study metastasis and to create avatars in personalized medicine.

Today a global problem for humanity is represented by cancer, in particular gastric cancer, which is characterized by high mortality and aggressive course. In this regard, there is a search for new approaches to the diagnosis and therapy of gastric cancer, one of these areas is the study of the expression level of the intercellular adhesion molecule claudin-18.2 in tumor tissue and its use as a target molecule. In the case of various pathological processes, including tumors, the expression profile of claudin-18.2 changes, which indicates its possible role in the initiation and progression of cancer. The aim of this review is to systematize the data on claudin-18.2, its role in normal cell physiology and embryology, as well as in the development of pathological processes in the stomach, its relation to the clinical and morphological characteristics of gastric cancer and importance in biological therapy.

The molecular classification of endometrial cancer developed by The Cancer Genome Atlas project (TCGA, 2013) is currently actively used in gynecological oncology. According to it, endometrial carcinoma is divided into four molecular subtypes: POLE-mutated, MMR deficient (dMMR), TP53-aberrant and unspecified. Endometrial cancer samples belonging to the dMMR and POLE-mutant types are characterized by specific genetic profiles reflecting the hyper- and ultramutant phenotypes of the tumor. At the same time POLE-mutated endometrial carcinomas recur rarely and exhibit the excellent prognosis. Here we report the rare case of 65 y.o. female patient with endometrioid carcinoma sharing immunohistochemical and molecular features of TP53-aberrant, MMR deficient and POLE-mutated subtypes.

To study the features of protein expression of gene NDRG1 in primary breast cancer (BC) and to identify its relationship with regional metastasis.

Rhabdomyosarcomas (RMS) are one of the most common types of sarcomas in children and adolescents. The alveolar RMS subgroup is of particular interest because in some cases, the translocation of the PAX3 and FOXO1 genes is combined with an amplification of the corresponding hybrid gene. According to literature data, the frequency of the PAX3::FOXO1 translocation is 70-90% and the PAX7::FOXO1 translocation 10-30%.

Glial cell line-derived neurotrophic factor (GDNF) is essential in maintaining the viability, function and differentiation of neuronal cells. In addition to its function in healthy nervous tissue, GDNF is involved in pathological processes, such as glioma growth. GDNF is represented by 2 main isoforms: pre-α-pro-GDNF (αGDNF) and pre-β-pro-GDNF (βGDNF). αGDNF maintains cell viability, and βGDNF has neurotrophic properties. The relationship between GDNF expression and human glioma malignancy grade, as well as migratory properties of tumor cells remains poorly understood.

The article reports the discovery of pathological substrates with an atypical histopathological phenotype in the brains of patients undergoing surgery for drug-resistant structural epilepsy. A complete panel of histopathological staining and immunohistochemical analysis with a wide range of antibodies were available at pathological examination. In addition to pathomorphological verification, molecular genetic testing was performed for the presence of mutations in the BRAF genes at codon 600 and BRAF/KIAA1549. MRI was performed at 3.0 Tl tomography using a standard protocol and an epileptic scanning protocol. During pathomorphological examination, the patients showed mixed signs of ganglioglioma CNS WHO grade 1 and focal cortical dysplasia type IIb. This mixed combination of pathological processes in one substrate has not yet been described in publicly available sources and does not fit the definition of double pathology, when they can coexist next door, but have clear differentiation. On MRI, the pathological substrates were localized in the frontal and temporal lobes, did not demonstrate typical radiological criteria of a tumor, had a "transmantle" distribution from the the lateral ventricles to the cortex with local and regional smoothing of the gray-white demarcation and uneven thickening of the cortical plate in the area of interest. In one case, large calcification associated with cavitation of the white matter was found in the structure of the pathological substrate. In another case, the substrate showed decreased blood flow in the substrate structure on perfusion maps. The described epileptogenic substrates differ markedly from classical gangliogliomas with two cell pools according to pathomorphological, molecular genetic and radiological criteria. The published results may indicate a completely new subgroup of gangliogliomas with cellular atypia, or a previously unknown combination of two pathological processes, or argue in favor of a common origin of neuronal-glial tumors and FCD. These data require prospective verification on a larger cohort of patients and an in-depth study of the molecular genetic profile of the described pathological substrates in order to reliably verify their origin.

Cowden disease (Cowden syndrome) refers to PTEN-associated hamartoma tumor syndromes. It arises due to a mutation in the phosphatase and tensin homolog gene, one of the main functions of which is cell cycle regulation. The presence of a mutation in the gene leads to uncontrolled cell growth, and patients have a lifelong increased risk of neoplasms of various degrees of malignancy. This article presents a clinical case of Cowden syndrome with an early debut at the age of 7 years. The combination of macrocephaly (SDS of head circumference &gt;2) with various skin manifestations (facial trichilemmomas, acral keratosis, papillomatous papules) and the presence of benign and/or malignant neoplasms are pathognomonic for Cowden syndrome. Of the malignancies, breast and thyroid cancer, colorectal cancer, renal cell carcinoma, and endometrial cancer are the most common. Thyroid carcinoma has been shown to have an earlier age of manifestation and often occurs already in childhood. This determines the need to screen patients with a proven mutation in the PTEN gene for nodal neoplasms from an early age. If surgical treatment is necessary, thyroidectomy remains preferable due to the frequent recurrence of nodules, as well as the uncertain potential for malignancy due to the low study of thyroid nodules in patients with mutations in the PTEN gene.

Prognosis of IDH (IDHwt) wild-type gliomas is worse compared to IDH-mutant tumors regardless of histological criteria for glioblastoma. However, there is still uncertainty regarding favorable course of disease and predictors of long-term survival in IDHwt gliomas.

Multiple exogenous or endogenous factors alter gene expression patterns by different mechanisms that are poorly understood. We used RNA-Seq analysis in order to study changes in gene expression in melanoma cells that are capable of vasculogenic mimicry that is inhibited upon the action of an inhibitor of vasculogenic mimicry. Here, we show that the drug induces a strong upregulation of 50 genes that control the cell cycle and microtubule cytoskeleton coupled with a strong downregulation of 50 genes that control different cellular metabolic processes. We found that both groups of genes are simultaneously regulated by multiple sets of transcription factors. We conclude that one way for coordinated regulation of large groups of genes is regulation simultaneously by multiple transcription factors.

Oral cancer is an aggressive and rapidly progressive disease. The oral cavity is home to over 700 species of microorganisms that regulate metabolism, immune function, and health. There are three types of mechanisms by which bacteria may participate in carcinogenesis. First, bacteria cause chronic inflammation, which stimulates the production of cytokines, including interleukins, interferons, and tumor necrosis factor. Second, bacteria can interact directly with host cells by secreting toxins or by binding to membrane receptors. Finally, the production of metabolites by bacteria may also contribute to carcinogenesis. The importance of the bacteria level and composition in the transition of oral precancerous lesions to cancer has been demonstrated. The relationships of changes in microbiome composition with smoking, inflammation in healthy individuals, as well as with the development of oral cancer in patients, have been studied.

RNA polymerase III synthesizes a wide range of noncoding RNAs shorter than 400 nucleotides in length. These RNAs are involved in protein synthesis (tRNA, 5S rRNA, and 7SL RNA), maturation, and splicing of different types of RNA (RPR, MRP RNA, and U6 snRNA), regulation of transcription (7SK RNA), replication (Y RNA), and intracellular transport (vault RNA). BC200 and BC1 RNA genes are transcribed by RNA polymerase III in neurons only where these RNAs regulate protein synthesis. Mutations in the regulatory elements of the genes transcribed by RNA polymerase III as well as in transcription factors of this RNA polymerase are associated with the development of a number of diseases, primarily oncological and neurological. In this regard, the mechanisms of regulation of the expression of the genes containing various RNA polymerase III promoters were actively studied. This review describes the structural and functional classification of polymerase III promoters, as well as the factors involved in the regulation of promoters of different types. A number of examples demonstrate the role of the described factors in the pathogenesis of human diseases.

Uveal melanoma (UM) is a neuroectodermal tumor that results from malignant transformation of melanocytes in the eye uvea, including the iris, the ciliary body, and the choroid. UM accounts for 5% of all melanoma cases and is extremely aggressive with half of the UM patients developing metastases within the first 1-2 years after tumor development. Molecular mechanisms of UM carcinogenesis are poorly understood, but are known to differ from those of skin melanoma. Activating mutations of the GNAQ and GNA11 genes, which code for the large G protein subunits Gq and G11, respectively, are found in 90% of UM patients. The Gaq/PKC/MAPK signaling pathway is a main signaling cascade that leads to the transformation of melanocytes of the uveal tract, and major regulators of the cascade provide targets for the development of drugs. Metastatic UM (MUM) is most often associated with mutations of BAP1, EIF1AX, GNA11, GNAQ, and SF3B1. A combination of a commercial expression test panel of 15 genes and a mutation panel of 7 genes, supplemented with data on the size of the primary tumor, is highly efficient in predicting the risk of metastasis. The risk of metastasis determines the choice of therapy and the patient follow-up regimen. However, no systemic therapy for MUM has been developed to date. New drugs undergoing clinical trials are mostly targeted drugs designed to inhibit the protein products of mutant genes or immunotherapeutic agents designed to stimulate the immune response against specific antigens. In addition to these approaches, potential therapeutic targets of epigenetic regulation of UM development are considered in the review.

The number of somatic mutations among all tissues increases along with age. This process was well-studied in hematopoietic stem cells (HSCs). Some mutations lead to a proliferative advantage and expansion of HSCs to form a dominant clone. Clonal hematopoiesis is general in the elderly population. Clonal hematopoiesis of indeterminate potential (CHIP) is a more common phenomenon in the elderly and is defined as somatic mutations in clonal blood cells without any other hematological malignancies. The development of CHIP is an independent risk factor for hematological malignancies, cardiovascular diseases, and reduced overall survival. CHIP is frequently associated with mutations in DNMT3A and TET2 genes involved in DNA methylation. The epigenetic human body clocks have been developed based on the age-related changes in methylation, making it possible to detect epigenetic aging. The combination of epigenetic aging and CHUP is associated with adverse health outcomes. Further research will reveal the significance of clonal hematopoiesis and CHIP in aging, acquiring various diseases, and determining the feasibility of influencing the mutagenic potential of clones.

ALK-positive anaplastic large cell lymphoma is a rare T-cell lymphoma with ALK gene rearrangement that develops in children and young adults. The disease almost always affects the lymph nodes, and extranodal areas are also frequently involved. This article describes two cases of atypical localization of ALK-positive anaplastic large cell lymphoma with involvement of the paranasal sinuses.

Cancer cells can aberrantly express various markers, including transferrin receptor 1 (CD71) and β1-integrin molecules. Their role in invasion, migration and metastasis has been demonstrated. Determination of their expression in breast cancer (BC) may be an important point to characterize the clinical course of the tumor and prognosis of the disease.