The article presents the results of sociological survey of women of the Republic of Tatarstan (Russia) concerning establishment of level of awareness about risks of development of oncologic diseases, need for application of genetic tests determining predisposition to breast and ovary cancer and also motives of acceptance or nonacceptance of existing modes of diagnostic and prevention of oncologic diseases. The breast and ovary cancer are among the most prevalent causes of female mortality in Russia. It is established that females with gene mutations BRCA1 and BRCA2 have a higher risk of development of breast and ovary cancer. Therefore, to determine character of genes BRCA in human genome is actual for prevention of oncologic diseases. The early diagnostic of oncologic diseases can significantly increase effectiveness of struggle with similar illnesses. The obtained data shows superficial awareness of Russian females about problem of breast and ovary cancer. The majority knows about existence of gene predisposition to disease but are not aware of characteristics of diagnostic, prevention and treatment of of these types of oncologic diseases. The female respondents in most cases are favorable to pass genetic diagnostic. However, they demonstrate nonacceptance of such radical mode of problem solution as preventive surgery of ablation of potentially dangerous organ. The most of female respondents prefer strategies of traditional monitoring for early detection of disease. The main causes of refusal of early gene diagnostic and preventive surgery are related, besides psychological and personal phobias, to such factors as distrust to health care system and uncertainty in qualification and accessibility of medical care.

The study presents clinical and genetic analysis of a case of unilateral multifocal uveal choroidal melanoma in a patient of 67 years. Results of ophthalmoscopy, echography, fluorescent angiography, optical coherence tomography are described. Molecular genetic testing of peripheral blood samples was performed, including detection of the occurrences of CC genotype in C3435T polymorphism of the gene ABCB1/MDR1 associated with unfavorable vital prognosis. Analysis of the genes GNAQ and GNA11 revealed two mutually exclusive mutations in the genes GNAQG183A and GNAQA209C showing genetic heterogeneity of the two tumor lesions. Organ preservation treatment of unilateral multifocal uveal melanoma was proven possible with brachytherapy method. Uveal melanoma with multicentric growth is of interest to ophthalmologists because it requires differential diagnostics from a variety of diseases including metastases in the choroid, such as metastases of uveal melanoma and skin melanoma, as well as other intraocular neoplasms.

Increasing evidence has suggested that microRNAs (miRNAs) may function as positive regulators at the post-transcriptional level. A search for associations between miRNAs and diseases is crucial for understanding the pathogenesis. Various publicly available databases have been constructed to store meaningful information on a large number of miRNA molecules. In this study, to resolve the limitation that individual sources of miRNA target data tend to be incomplete and noisy, we propose a network-based computational method called self-weighting for integrating multiple data sources. A bipartite phenotype-miRNA network (BPMN) incorporates known disease-miRNA interactions as well as the similarities between disease phenotypes and functional similarities of miRNAs. Random walk with restart algorithm was deployed on the bipartite network to predict novel disease-miRNA associations. In leave-one-out cross-validation experiments, our technique achieves an AUC of 0.801 when evaluating against known disease-related miRNAs from HMDD. Systematic prioritization of miRNAs for 11 common diseases obtained an average AUC of 0.765. Additionally, a case study on colon cancer uncovered a number of potential miRNA candidates as biomarkers of this disease.

E-cadherin is a member of the cadherin family that plays a key role in the formation of cell-cell adhesion among epithelial tissues. Point mutations are one of the structural abnormalities of E-cadherin in human carcinomas. Such abnormalities can alter mechanical properties of proteins that play an important role in their biological activities. To determine the impact of point mutations on protein mechanical properties, the second fragment of extracellular domain of E-cadherin was modeled using steered molecular dynamics simulations. The molecular dynamics modeling included application of tensile forces in both constant velocity and constant force modes to examine the effects of Met282 to He and Asn315 to Ser mutations on mechanical behavior of protein structure. The stabilities of the wild type and mutant structures were also obtained by the protein design foldX algorithm. Results confirmed the lower stability of the mutant domains compared to the wild type. The mutated proteins displayed softer behavior than the reference protein and their stiffness decreased by up to 34%. Our findings suggest that local changes in molecular structure due to mutations may lead to noticeable alterations in mechanical properties within the entire domain. Since the function of protein is related to its structure, these changes may influence the function of the protein.

It is known that microRNAs (miRNAs) are able to dynamically regulate gene expression. At the same time, methylation can reduce expression of miRNA encoding genes and, therefore, reduce their inhibitory effects on mRNAs of target genes, including those of oncogenes, that promoting the development of tumors of different localization. The role of miRNA hypermethylation in the pathogenesis of ovarian cancer is not completely understood; so we conducted a search for new hypermethylated and potentially suppressor miRNA genes in ovarian tumors. Four new miRNA genes (MIR-107, MIR-130b, MIR-203a, MIR-1258) commonly hypermethylated (28-52%) in tumor tissues vs 4-7% in paired histologically normal tissues, p < 0.01, were identified in a representative set of 54 ovarian cancer samples using methylation-specific PCR. It was shown that hypermethylation of MIR-130b, MIR-203a, and MIR-1258 genes is significantly (p < 0.05) associated with metastasis of ovarian cancer. These results suggest the involvement of four miRNAs (miR-107, miR-130b, miR-203a, and miR-1258) and hypermethylation of their encoding genes in the pathogenesis of ovarian cancer.

Li-Fraumeni syndrome (LFS) is a clinically and genetically heterogeneous hereditary syndrome with predominantly oncological manifestations, which is associated with mutations in the TP53, MDM2, and CHEK2 genes. The most common variant is a TP53 mutation.

The concept of essential genes, whose loss of functionality leads to cell death, is one of the fundamental concepts of genetics and is important for fundamental and applied research. This field is particularly promising in relation to oncology, since the search for genetic vulnerabilities of cancer cells allows us to identify new potential targets for antitumor therapy. The modern biotechnology capacities allow carrying out large-scale projects for sequencing somatic mutations in tumors, as well as directly interfering the genetic apparatus of cancer cells. They provided accumulation of a considerable body of knowledge about genetic variants and corresponding phenotypic manifestations in tumors. In the near future this knowledge will find application in clinical practice. This review describes the main experimental and computational approaches to the search for essential genes, concentrating on the application of these methods in the field of molecular oncology.

Drug bioavailability studies commonly employ in vitro barrier tissue models consisting of epithelial and endothelial cells. These experiments require that the cell barrier quality be assessed regularly, which is usually performed using various labeled substrates and/or evaluation of transepithelial (transendothelial) electrical resistance (TEER). This technique provides information on the integrity of the monolayer, but not on differentiation-induced changes in the cell morphology. The present work shows that impedance spectroscopy can be applied to monitor both the integrity of the monolayer and the morphological changes of Caco-2 cells. The growth kinetics of the apical membrane was determined by calculating the electrical capacitance of the cell monolayer. In the course of differentiation, the most pronounced changes in the expression levels were observed for the mRNAs that encode SLC30A10 and SLC23A3 transporters. Their increase correlated with an increase in the apical membrane area, indicating that SLC30A10 and SLC23A3 mRNA levels assessed by qRT-PCR may be employed as cell differentiation biomarkers in Caco-2 models.

Parathyroid carcinoma (PTC) is a rare malignant tumor with the clinical manifestation of hyperparathyroidism, reliable morphological signs of invasive growth, and poor clinical prognosis. The differential diagnosis of PTC due to the rarity of this pathology, not always explicit morphological criteria, and the lack of a certain immunohistochemical panel is complex and needs further clarification. The paper summarizes an update on the clinical and morphological characteristics of PTC.

Erythroderma is a skin lesion characterized by redness, swelling, infiltration, and desquamation of greater than 90% of the skin. The etiology of erythroderma is not completely clear and the lesion can be manifestations of various chronic dermatoses, including atopic dermatitis, psoriasis, eczema, and toxicodermia, and be represented by erythrodermic mycosis fungoides. The pathogenesis of erythroderma especially at the genetic level remains little studied. Thus, one disease (erythroderma) can be a manifestation of different dermatoses and have similar clinical and histological signs. This paper gives a review of modern literature on the study of erythroderma in terms of morphology and genetic aspects.

The paper describes a case of chromophobe renal cell carcinoma growing into the muscular layer of the descending colon and with metastases in 4 lymph nodes of paranephral tissue in a 66-year-old woman. The tumor had a zonal structure with an alternation of epithelioid and sarcomatoid structural sites and with the signs of grades I, II and III according to the grading system by Paner and et al. (2010). The sarcomatoid renal component occupied about 70.0% of the tumor. There was a pronounced immunohistochemical reaction with VEGF-A (5 scores), a high Ki-67 proliferation index (70%), and a large number of tumor cells with nuclear p53 expression (85%) in the areas with minimal differentiation and sarcomatoid elements (Grade III). These signs can serve as criteria for the aggressive behavior of the tumor. A large volume of the sarcomatoid carcinoma component and a strong reaction with VEGF-A are indications for targeted therapy with anti-VEGF drugs.

Gemistocytic astrocytomas (GA) are a variant of diffuse astrocytomas GII (WHO, 2016). Like all diffuse astrocytomas, GA recur with time, which is often accompanied by malignant degeneretion into the anaplastic astrocytoma GIII or to the secondary glioblastoma GIV. However, the progression-free survival and overall survival in patients with GA is less than in patients with diffuse astrocytomas. Given that this group of patients, according to the WHO classification (2016), is classified as GII, patients with GA usually do not receive comprehensive treatment. We have conducted a thorough analysis of research on this problem for the period from 1956 to 2017. Differences in the histological pattern, immunohistochemical and molecular-genetic profiles, survival of patients with GA and diffuse astrocytomas GII are shown there. A clinical case of a patient with transformation of a diffuse astrocytoma in GA (GIII) and then into a secondary glioblastoma is presented.

To determine whether Epstein-Barr virus and human papillomavirus (HPV) types 6, 11, 16, 18, 35, and 43 DNA can be present in inverted papilloma (IP) and associated sinonasal carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common urologic malignancy. Understanding of the transcriptional regulation of oncogenes and tumor suppressor genes involved is critical for the development of the treatments for renal tumors. Using ccRCC subdivision of the TCGA dataset, we identified NR0B2 encoding orphan nuclear receptor as a tumor suppressor candidate in renal tissue. In independent cohort of primary renal tumors, quantitative PCR experiments confirmed significant suppression of NR0B2 mRNA in 86% of ccRCC samples studied. In 80% of these cases, we detected the hypermethylation of the NR0B2 pro-moter region. These results suggest that NR0B2 is a tumor suppressor gene in ccRCC, and that the hypermethylation of promoter region is the main mechanism of its downregulation.

High metastatic ability and poor clinical outcome are the most known clinical features of the triple-negative breast tumors. Given that the tumor cells undergoing epithelial-mesenchymal transition (EMT) often gain malignant and invasive features, we have investigated the possibility of EMT reversal in triple-negative breast cancer cells by targeting the epigenetic-modifying enzymatic complexes named histone deacetylases (HDACs) and examined the possible mechanism underlying the HDACs-based inversion in model MDA-MB-231 cells. Cells were treated with a maximal tolerable 200 nM concentrations of classical HDACs inhibitor Trichostatin A (TSA) for 48 h and afterwards the invasiveness and immigration of the cells were evaluated in TransWell Invasion Scratch Wound Healing assays. Then, in treated and control cells, quantitative real time-PCR reacions were performed for assessing the gene expression of EMT biomarkers E-cadherin, Vimentin and transcriptional factor Slug. After TSA treatment, the invasion and migration properties MDA-MB-231 cells significantly decreased, gene expression of E-cadherin was significantly up-regulated, while the levels of Slug and Vimentin encoding mRNAs were suppressed. We conclude that inhibition of HDACs in triple-negative breast cancer cells may lead to inversion of EMT and the decrease of invasiveness by down-regulating the gene expression of Slug. Since EMT is known as a pre-metastatic process, triple-negative breast tumors, the EMT reversal effects of HDACs inhibition may reduce tumor cell metastasis.

The discovery of B-RAF activating mutations in malignant melanoma cells has led to the development of a number of targeted drugs, which block exclusively the mutant B-RAF protein. Tumor cells often acquire resistance to B-RAF inhibitors via activation of alternative signaling pathways. One of the resistance mechanisms is activation of PDGF, VEGF, c-KIT, and certain other tyrosine kinases. The possibility of overcoming the resistance to the B-RAF inhibitor Vemurafenib by inactivating receptor tyrosine kinases (RTKs) was studied in metastatic melanoma cell lines differing in B-RAF mutations and RTK activity. It was found that RTK inactivation may help to overcome resistance to B-RAF inhibitors via inhibition of tyrosine kinase phosphorylation and a subsequent blocking of the PI3K-AKT-mTOR and MEK-ERK1/2 downstream signaling pathways. The changes eventually mitigated the cell growth and enhanced the Vemurafenib-dependent cell cycle arrest.

Clear cell renal cell carcinoma (ccRCC) is a common oncourological disease with a high mortality level. The incidence of this type of cancer is constantly increasing, while molecular mechanisms involved in the disease initiation and progression remain far from being fully understood. A problem of the search for novel markers is crucial for improvement of diagnosis and therapy of ccRCC. We have previously found that the disease is characterized by increased expression of the NETO2 gene. In the present study, we showed that isoform 1 (NM_018092.4) makes the main contribution to the upregulation of this gene. Using original CrossHub software, "The Cancer Genome Atlas" (TCGA) project data were analyzed to identify possible mechanisms of NETO2 gene activation in ccRCC. The absence of significant contribution of methylation to the increase of mRNA level of the gene was observed. At the same time, a number of genes encoding transcription factors, which could potentially regulate the expression of NETO2 in ccRCC, were identified. Three such genes (MYCBP, JMY, and SAP30) were selected for the further analysis of their mRNA levels in a set of ccRCC samples with quantitative PCR. We showed a significant increase in mRNA level of one of the examined genes, SAP30, and revealed its positive correlation with NETO2 gene expression. Thus, upregulation of NETO2 gene is first stipulated by the isoform 1 (NM_018092.4), and the probable mechanism of its activation is associated with the increased expression of SAP30 transcription factor.

Laminins are a family of extracellular heterotrimeric glycoproteins that are the main structural component of basement membranes (BMs), perform a barrier function, and are important for adhesion, differentiation, migration, and resistance to apoptosis of various cells, including cancer cells. The review summarizes the current knowledge of how laminins produced by cancer and normal cells influence the key stages of carcinogenesis. Laminin 332 (LN-332) and LN-111 enhance proliferation of certain cancer cells and increase the tumour growth. LN-111 increases resistance to apoptosis, induces differentiation, and inhibits the epithelial-mesenchymal transition (EMT) of cancer cells. LN-332 is associated with higher adhesion and higher migration potential of cancer cells. LN-411 and LN-421 significantly increase motility of cancer cells. LN-332 and LN-511 facilitate cell-cell adhesion and affect the efficacy of cell-cell interactions. The laminin chains α4 and α5 are important for the development and function of blood and lymphatic vessels. The expression ratio of the α4 and α5 laminin chains defines the BM permeability to leukocytes and, presumably, cancer cells in blood and lymphatic vessels. Interactions between LN-511 and α2-containing laminins enhance self-renewal and survival of circulating cancer stem cells. Moreover, laminins are involved in the formation of premetastatic niches and new colonies. Endogenous expression of the α4 laminin chain stimulates proliferation of individualised circulating cancer cells in vitro and in vivo and facilitates micrometastasis.

Bispecific antibodies capable of simultaneously binding two targets have been studied for many years with a view to their implementation in clinical practice. Unique biological and pharmacological properties, as well as the diversity of their formats, make it possible to consider bispecific antibodies as promising agents for use in various procedures: from visualization of intracellular processes to targeted anticancer therapy. Bispecific antibodies help to determine more precisely the therapeutic target, thereby increasing the efficiency of therapy and reducing the probability of side effects. The present review describes the main formats of bispecific antibodies, methods for their generation, and possibilities for practical application.

The somatic mutation in BRAFT1799A (BRAFV600E), the data on the prognostic role of which are contradictory, is one of the most common molecular genetic abnormalities in the cells of papillary thyroid carcinoma (PTC).