Liver cancer is widespread neoplasm type that ranks second among the causes of cancer-related mortality worldwide. Hepatocellular carcinoma (HCC) is the main form of liver cancer generally detected at advanced stages in most patients. HCC development is a result of accumulation of various somatic molecular alterations. Different HCC etiology and chronic liver diseases cause numerous and heterogeneous genetic and epigenetic aberrations that determine diverse gene expression alterations in HCC. Molecular heterogeneity limits the efficacy of targeted therapy that is currently the essential approach for advanced stage HCC treatment.

The present review considers the main genetic and epigenetic alterations detected in HCC, results of transcriptomic investigations and systems biology analysis of the data. Up-to-date information on application of targeted drugs and immune checkpoint inhibitors in HCC therapy are discussed.

Cyclophilins belong to a large family of ancient conservative proteins with peptidyl-prolyl-cis-trans isomerase activity. The main member of this family – cyclophilin A – was discovered as an intracellular ligand for cyclosporine A. Further investigations revealed a wide range of functions of cyclophilin A. Cyclophilin A is involved in T-cell signaling, it takes part in folding, assembly and intracellular transport of proteins, as well as acts as an antioxidant. Different cell types secrete cyclophilin A under infection or oxidative stress. Cyclophilin A is one of the main factors involved in inflammation and pathogenesis of autoimmune, cardiovascular and other diseases. This protein is thought to take part in tumor progression. In this review we describe the structure of cyclophilin A and its main known functions in health and disease.

Background. Fine-needle aspiration biopsy is recognized as the “gold standard” in the preoperative diagnosis of thyroid cancer. However, this method does not always allow reliable differentiation between benign and malignant thyroid nodules. Thus, the cytological report of a “follicular neoplasm or suspicious for a follicular neoplasm” suggests surgical lobectomy. However, in most cases, this conclusion does not point to follicular cancer but to benign neoplasm, follicular adenoma, where the surgical intervention is excessive. This implies the great relevance of finding biological markers capable of enhancing the specificity of detecting malignant neoplasms. Such markers may include an increase in the level of expression of oncogenes or a change in the expression of microRNA, since it is known that the content of a number of microRNAs changes significantly during the development of thyroid tumors.

Materials and methods. The expression level of the HMGA2 gene, normally active at the embryonic stage, and oncogenic miRNA-221 microRNA was analyzed using real-time reverse transcription polymerase chain reaction in 713 cytological preparations of the thyroid gland (stained material dried on glasses) obtained by standard fine-needle aspiration biopsy. The sample included preparations corresponding to different cytological diagnoses: benign (n = 375), follicular neoplasm or suspicious for a follicular neoplasm (n = 143), medullary carcinoma (n = 7), papillary carcinoma (n = 186) and anaplastic carcinoma (n = 2).

Results. The content of messenger RNA (mRNA) HMGA2 (P = 1.6 × 10–66, area under curve ROC 0.946) and miR-221 (P = 6.3 × 10^–61, area under curve ROC 0.927) proved to be significantly elevated in papillary carcinoma compared to benign tumors. Follicular neoplasms showed significant heterogeneity in the quantity of both molecular markers. At the same time, an elevated level of miR-221 (3 times on average) was also characteristic of samples from this group with an increased level of expression of the HMGA2 gene (an average of 85 times). With regard to the quantity of these markers, the group of follicular neoplasms, in which no increase in the HMGA2 mRNA level was detected, did not differ from the group of benign nodules.

Conclusions. The obtained results show that assessing the expression of HMGA2 mRNA and oncogenic miR-221 makes it possible to differentiate the papillary thyroid carcinoma from goiter at the preoperative stage, and based on the content of the HMGA2 mRNA, the group of follicular neoplasms can be divided into subgroups presumably differing in the risk of malignancy.

The case report describes a rare case of hereditary diffuse gastric cancer, associated with a CDH1 gene mutation and reported in the Russian population for the fist time. In february 2013, after a medical genetic counseling in the laboratory of clinical oncogenetics of the Institute of Clinical Oncology of the N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia the 28 years old patient was applied to due to a family history of gastric cancer. Based on the results of the molecular genetic study, thе mutation in the CDH1 gene was found, which determines the risk of diffuse gastric cancer during life beyond 80 %. Histological examination of the material of the gastric mucosa biopsy performed during the esophagogastroduodenoscopy revealed single foci of the ring-cell cancer in the intrinsic plate of the gastric mucosa. In the department of abdominal oncology, the Research Institute of Clinical Oncology of the N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia a splash-preserving gastrectomy for Roux was performed with the formation of a small intestine tank, lymphodissection D2.

Background. It is accepted that 1,2-dimethylhydrazine  (DMH)  induced androgen-dependent hemangiosarcoma (HAS)  of fibrous renal capsule (RC) in CBA male mice. This experimental model is used to study hormone-dependent tumors. It is considered that RС (site of HAS growth) is avaskular. For clarifying the nature of such paradoxical phenomen we studied the tumour histogenesis.

Materials and methods. CBA male mice received 15 subcutaneous injections of DMH. The duration of the experiment was 50 weeks. From RC whole-mounted preparations and paraffin sections were made. Immunohistochemistry method with antibody against endothelium and stem cells CD34 were used to investigate the endothelium cell precursors.

Results. We have found single CD34 well expressive cells and capillary structures in intact RC. Nevertheless on the initial stages of HAS growth the CD34 expression was markedly weaker or completely absent compared with intact RC. In the late HAS develop the intensive CD34 expression was detected.

Conclusions. In summary, for the first time we have shown that murine fibrous RC is not completely avascular education, as it was supposed earlier. In the HAS morphogenesis process the phase alterations of CD34 antigen expression were found.

Background. Wide use of glucocorticoids therapy for neoplasms, autoimmune diseases and allergies is associated with suppression of adaptive immunity that requires profound study of their immunoregulatory properties and immunotoxicity.

Results. In this work, using our model of selective activation of mouse CD8⁺ memory cells in the mixed lymphocyte reaction (MLR) in vitro, we show for the first time that intraperitoneal injection of high dose hydrocortisone (2.5 mg per animal) allows to detect memory cells in the thymus of animals immunized with allogeneic tumor cells. Similar to memory cells from other lymphoid organs, hydrocortisone-resistant thymic lymphocytes from immune animals respond on allogeneic stimulators subjected to severe heat shock and are immunologically specific to immunizing alloantigen. Thus, cortisone-resistant thymocytes are partially or completely represented by memory cells. We also show here that memory responses of heterozygotes on TCR a-chain knock-out (genetically incapable to secondary rearrangement of TCR achains) are significantly enhanced as compared with the ones of wild type mice.

Conclusion. These findings allows to suggest the hypothesis according to which memory T cell clones proliferating in primary immune response migrate into thymus providing necessary microenvironment for reexpression of recombinases. After editing of genes encoding TCR achains, such T lymphocytes can return to peripheral repertoire maintaining its wideness.