Vol 4, No 4 (2017)

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. 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.