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Introduction. Currently, there are conflicting data regarding the effect of the c.470T> C germline mutation in the CHEK2 gene on increasing the risk of breast cancer (BC), so it is necessary to conduct research on large samples of patients, including in the Russian population, in order to analyze the contribution of this mutation to the risk of cancer developing.The aim of the study was to determine the frequency of occurrence of the genetic variant c.470Т>С in the CHEK2 gene in the Russian population in patients with BC and patients with benign breast diseases (BBD) to assess the possible effect of this deoxyribonucleic acid damage on the likelihood of cancer occurrence.Materials and methods. The study included 2,787 patients with BC and 1,004 patients with BBD who underwent examination and treatment at the Russian Scientific Center of Roentgenoradiology of the Ministry of the Russian Federation from 2010 to 2018. Molecular genetic study was carried out by real-time polymerase chain reaction to determine the characteristic of the Russian population hereditary genetic variant c.470Т>С in the CHEK2 gene using a diagnostic panel that allows to determine three germline mutations: c.1100delC, c.444+1G>A and c.470Т>С in the CHEK2 gene.Results. In patients with BC the frequency of the mutation c.470T>C in the CHEK2 gene was 3.8 %, in patients with BBD this mutation was detected in 4.7 % of cases. The frequency of the genetic variant c.470T>C in high-risk groups was: 5.1 % – for BC patients with clinical signs of hereditary disease and 4.9 % – for patients with BBD with a family history of cancer. There were no statistically significant differences between the frequency of the mutation c.470T>C in the general groups of BC patients and patients with BBD and the corresponding frequency in the high-risk groups, as well as in the groups of BC patients and patients with BBD (p >0.05).Conclusion. The results of this study indicate the probable absence of a relationship between the presence of the mutation c.470Т>С in the CHEK2 gene and an increased risk of BC.

Background. The search for molecular markers of colon diseases allowing highly specific and sensitive identification and differentiation of pathological processes is a clinically important problem. Expression levels of genes responsible for proliferation can reflect the changes in the affected tissues. The study objective is to perform comparative analysis of molecular and genetic markers of proliferative activity in benign and malignant neoplasms of the colon. Materials and methods. Analysis of the changes in proliferation markers (CCND1, с-MYC, Ki-67, HER2neu, TERT) in adenocarcinoma of the colon (n = 259), resection margin (about 15–20 cm from the tumor lesion) (n = 251), unchanged colon mucosa from healthy donors (n = 247), polyps (n = 28), unchanged colon mucosa intestinal polyposis (10–15 cm from the polyp) (n = 75) was performed using RT-PCR. Results and conclusion. It was shown that morphologically unchanged tissue of intestinal mucosa in malignant tumors has significant differences from normal tissue of healthy donors. Significant differences in the level of expression of genes responsible for the processes of proliferation, с-MYC, CCND1, TERT were found in benign hyperproliferative diseases (polyps). Moreover, these changes were specific to the type of pathological process, which allows us to consider these genes as the most promising candidates in the development of a differential method for diagnosing colon diseases.

Introduction. Adjuvant systemic therapy remains one of the main options for treating breast cancer. Results of standard immunohistochemical studies are not always a criterion for selecting systemic therapy. Nowadays, multigene expression analysis is actively used to predict the response to chemotherapy in patients with earlystage breast cancer. We studied a 24-gene multi-gene panel for typing breast cancer.Material and Methods. A prospective analysis of 199 breast cancer patients (T1–3N0–3M0) was carried out. Surgical specimens were studied using the standard immunohistochemistry (IHC) and RT-PCR for detecting expression of 24 genes.Results. According to the IHC results, breast cancer was divided into 5 molecular subtypes: luminal A was detected in 59 (30 %) patients; luminal B (HER2-negative) in 52 (26 %); luminal B (HER2-positive) in 19 (9 %); triple-negative in 28 (14 %); HER2-positive 41 (21 %). RT-PCR showed that ST K15, MYC, MYBL2, BIRCC 5, BCL2, TERT, ESRP1, PGR, HER2, GBR7, MGB1 and MMP11 were the most significant genes in subtype distribution. The total percentage of matches between the two studies was 61.7 %.Conclusion. Studies have shown the need to add additional typing methods for breast cancer to a standard IHC study, which will undoubtedly increase the information content of diagnostic measures and will improve the effectiveness of the treatment.

Adoptive immunotherapy that makes use of genetically modified autologous T cells carrying a chimeric antigen receptor (CAR) with desired specificity is a promising approach to the treatment of advanced or relapsed solid tumors. However, there are a number of challenges facing the CAR T-cell therapy, including the ability of the tumor to silence the expression of target antigens in response to the selective pressure exerted by therapy and the dampening of the functional activity of CAR T cells by the immunosuppressive tumor microenvironment. This review discusses the existing gene-engineering approaches to the modification of CAR T-cell design for 1) creating universal “switchable” synthetic receptors capable of attacking a variety of target antigens; 2) enhancing the functional activity of CAR T cells in the immunosuppressive microenvironment of the tumor by silencing the expression of inhibiting receptors or by stimulating production of cytokines.

To determine the most informative markers for assessing the functional state of endometrium during the 'window of implantation' and creating a model for assessment of the readiness of endometrium for embryo implantation. Forty-seven women with tubal infertility and a successful IVF pregnancy participated in the study. Pipelle endometrial sample was performed during the supposed 'window of implantation' in natural cycle with subsequent histological study, and transcriptional profile of genes GPX3, PAEP, DPP4, TAGLN, HABP2, IMPA2, AQP3, HLA-DOB, MSX1, POSTN determined by real-time quantitative polymerase chain reaction (qRT-PCR). Differences in the level of mRNA expression of all the studied genes in the receptive endometrium were found in comparison to the prereceptive one, which allowed us to classify two functional states of the endometrium. The results of histological examination responded to the stage of maturation of the endometrium in 78.7% of cases. Receptive endometrial status can be determined based on the integral evaluation of mRNA expression level of 4 PAEP, DPP4, MSX1, and HLA-DOB genes. The model for determining a personalized `window implantation' is offered for practical application in ART.

Matrix metalloproteinases (MMPs) responsible for the extracellular matrix remodeling, the activation of various growth factors, and angiogenesis play an important role in the colorectal cancer (CRC) development. In the present work the comparative analysis of MMP-7, -8, -9, and -11 mRNA as well mRNA of the Ki-67 proliferation marker in tissue samples obtained from CRC patients and healthy individuals. Employing the real time PCR method the expression levels of several MMPs (MMP-7, -8, -9, and -11) and cell proliferation marker, Ki-67, were simultaneously measured in 256 tissue samples obtained from 112 patients with CRC: 112 samples of the primary tumor (CRC), 112 samples of the most distant border of morphologically normal colonic mucosa (MNT), 16 samples of liver metastases) and from 16 healthy volunteers who underwent colonoscopy and biopsy. The expression of both MMPs studied and Ki-67 was found to be elevated in CRC primary tumors and liver metastases compared with the normal mucosa. CRC tumor and metastatic cells exhibited similar proliferative activity. The metastases are characterized by the highest cross-correlation of MMPs among tissue types tested. For the first time it was shown that normal mucosa from healthy individuals and CRC patients varied in the MMP-8 expression level. They also had dissimilar MMP correlation patterns thus suggesting that epithelial cells adjusted to CRC tumor differ from mucosal epithelial cells of healthy individuals.Matriksnye metalloproteinazy (matrix metalloproteinases, MMP), otvechaiushchie za remodelirovanie vnekletochnogo matriksa, aktivatsiiu razlichnykh rostovykh faktorov i angiogenez, igraiut vazhnuiu rol' v razvitii kolorektal'nogo raka (KRR). V dannoĭ rabote proveden sravnitel'nyĭ analiz urovneĭ ékspressii mRNK MMP-7, -8, -9 i -11, a takzhe markera proliferatsii Ki-67 v obraztsakh tkaneĭ, poluchennykh ot patsientov s KRR i zdorovykh donorov. S ispol'zovaniem metoda PTsR v real'nom vremeni byli issledovany urovni ékspressii ikh mRNK v 256 obraztsakh tkani, poluchennykh ot 112 patsientov s KRR: 112 obraztsov pervichnoĭ tkani opukholi (KRR), 112 obraztsov morfologicheski normal'noĭ tkani slizistoĭ stenki tolstoĭ kishki (MNT), udalennoĭ ot pervichnoĭ opukholi na 15-20 sm i 16 obraztsov metastaticheskoĭ opukholi KRR v pecheni (MP). Takzhe issledovany 16 bioptatov, poluchennykh vo vremia protsedury kolonoskopii u zdorovykh volonterov (NT). Vyiavleno, chto ékspressiia mRNK genov, kodiruiushchikh MMP i Ki-67, vozrastaet v pervichnoĭ tkani KRR i MP po sravneniiu s MNT i NT. Pri étom kletki pervichnoĭ tkani opukholi i kletki metastazov imeiut skhodnuiu proliferativnuiu aktivnost'. Sredi issledovannykh tipov tkaneĭ metastaticheskaia opukhol' kharakterizuetsia naibol'shim chislom i siloĭ pozitivnykh korreliatsiĭ mezhdu urovniami ékspressii mRNK genov, kodiruiushchikh MMR. Vpervye pokazano, chto normal'naia tkan' slizistoĭ obolochki kishki patsientov s KRR i zdorovykh donorov razlichaiutsia po urovniu ékspressii mRNK MMP-8. Krome togo, oni imeiut raznye korreliatsionnye patterny issleduemykh MMR, chto svidetel'stvuet o znachitel'nykh otlichiiakh mezhdu kletkami normal'noĭ tkani, sosedstvuiushcheĭ s opukhol'iu, i kletkami slizistoĭ obolochki kishki zdorovykh donorov.