Review describes the phenomenon of RNA interference – the recently discovered biological mechanism of the negative regulation of gene expression. The mechanism is based on the block of the translation and/or degradation of messenger RNA under short non-coding RNA, among them: microRNA and small interfering RNA. The paper reviews the molecular processes of the formation of small RNA, the mechanism of their action and the feasibility of small RNA implementation in the anti-tumor therapy. Specially, we analyze the approaches to in vivo delivery of small RNA, in particular – the liposome and exosome constructs, and perspectives of the involvement of such constructs in the cancer treatment.

Lipid rafts are lateral assembles of cholesterol, sphingomyelin, glicosphingolipids and specific proteins within cell plasma membrane. These microdomains are involved into a number of important cellular processes including membrane rearrangement, protein internalization, signal transduction, entry of viruses into the cell. Some of lipid rafts are stabilized by special microdomain-forming proteins such as caveolins, SPFH domain containing superfamily, tetraspanins, galectins, which maintain integrity of rafts and regulate signal transduction via forming of “signalosomes”. Involvement of the different lipid rafts is necessary in many situations such as binding of growth factors with their receptors, integrin regulation, cytoskeleton and extracellular matrix rearrangements, vesicular transport, etc. However, such classes of microdomain-forming proteins are still considered separately from each other. In this review we tried to perform complex analysis of microdomain-forming proteins in regulation of cancer assotiated processes.

The recent years have seen considerable advancement in the therapy of oncology patients and hence better survival and longer lifespan. Thus, studies on the distant effects of antitumor therapy have become increasingly important. That particularly concerns the risk of development of the second primary tumors. The patients that received therapy for the first malignant neoplasm become a higher-risk group for the development of a second tumor for their entire subsequent life. The review represents the data of analytical epidemiological studies on the second leukemia and solid tumors caused by the aftereffects of antitumor therapy using alkylating agents. Data are also considered on the risk of the second tumors that developed upon transplantation of stem cells. The second tumor etiology includes other significant risk factors such as genetic predisposition, smoking, alcohol consumption, imbalanced diet, etc. In combination with the aftereffects of antitumor therapy they may influence significantly the probability of the development of the second tumors in cancer patients, which should be considered in developing preventive measures. The review data suggest the need for cooperation of specialists in various fields and the use of clinical, epidemiological and molecular approaches to study the carcinogenesis of the first and second tumors, the choice of efficient and the safest methods of antitumor therapy to reduce the risk of the development of distant aftereffects and their prevention.

Cytostatic drugs used in chemotherapy cause secondary tumors in some patients cured of the antecedent neoplasm. Thus the incidence of second neoplasia for cancer survivors compared with the general population represents a 4-fold to 6-fold increased risk.The review presents recent data on the mechanisms of malignant transformation of cells by cytostatics, on the characteristics of high- risk groups associated with congenital polymorphisms of xenobiotic metabolizing enzymes and DNA repair systems. Increased risk of drug-related cancer was observed in patients with high activity of P450 isoforms, transforming cytotoxic prodrugs into the active electrophilic metabolites and low level of detoxifying enzymes. All things being equal the risk of therapy related neoplasia is higher in patients with low activity of DNA repair enzymes. It is evaluated the possibility of experimental study of new targeted drugs carcinogenic potential in order to minimize the future risk of secondary malignancies.

Neuroendocrine tumors comprise the heterogeneous group of malignant epithelial neoplasms, the diagnosis of which is based on their histopathologic features and immunohistochemical profile. For neuroendocrine tumors of the digestive system in the World Health Organization (2010) classification were introduced main categories, the nomenclature, criterions for grading and staging. However, accumulating evidence demonstrates actual controversies in the histopathology of neuroendocrine neoplasms and unreserved problems in their classification. In this review we focus on some of the common features of neuroendocrine neoplasms, their classification, and differences in pathology, biology of the main categories, and the most important immunohistochemical markers.

Curaxins represent low molecular weight carbazole derivatives, which simultaneously activate p53-dependent apoptosis and inhibit NF-kBdependent signal transduction pathways. Antitumor activity of curaxin CBL0137 was demonstrated in vivo on the model of solid transplantable mouse colon adenocarcinoma Akatol. Significant tumor growth inhibition caused by CBL0137 treatment was observed. On the 37th day after tumor transplantation for CBL0137 oral doses 5, 10, 15 and 20 mg/kg the tumor growth inhibition indexes were 53, 50, 56 and 74 %, respectively. CBL0137 treatment extended life span of mice in all study groups receiving this test article. Maximum lifespan increase (81,7 %) was observed in the group of mice treated with 20 mg/kg dose of CBL0137. The cytotoxicity of CBL0137 was assessed on human colon cancer cells in vitro. We demonstrated that CBL0137 inhibits the expression COX2, which in its turn is known to exhibit antiapoptotic, pro-angiogenic and pro- metastatic properties. Thus, we demonstrated antitumor effect of CBL0137 against colon cancer in vitro and in vivo.

The dynamics of the production of nitric oxide (NO) metabolites: nitrites, nitrates, volatile nitrosamines and iNOS expression was studied in mice with subcutaneous transplanted, spontaneous and chemical- induced tumors. Tumor growth was accompanied by increased production of nitrites + nitrates in tumors or their release with urine that not dependent on tumor histotype. The total concentration of nitrites and nitrates in tumors reached micromolar levels characteristic of nitrosative stress. The ability of peritoneal macrophages + monocytes to generates nitrites was suppressed at the stage of intensive growth of the Lewis lung carcinoma, which may indicate a decrease in the cytotoxic properties of immune cells. The possibility of formation in the Erlich carcinoma of volative N-nitrosodimethylamine and N-nitrosodiethylamine compounds with pronounced carcinogenic properties was demonstrated. A positive expression of iNOS was revealed in some areas of lung carcinoma at all investigated time points using the immunohistochemical method. The lungs metastases were not stain or weakly stained. This may indicate selection of the cells with a low activity of iNOS migrating in the lungs.

Continuous cell line Рпоч1-КК from the сollection of N. N. Blokhin Russian Cancer Research Center refers to the kidney clear cell carcinoma subtypе. It is useful for study of carcinogenesis and molecular targets for targeted therapy.

Objective. Analysis of the genetic alterations in a stable cell culture Рпоч1-КК to characterize this model cell line.

Results. Alterations in VHL (exons 1, 2 and 3) and TP53 genes (exons 6–10) were identified by amplification of genomic DNA followed by fragment analysis polymerase chain reaction and direct Sanger sequencing. An extended deletion in exon 1 in combination with mutation in exon 7 of VHL gene and 2 polymorphisms in exon 4 of TP53 gene were reveated. Such simultaneous alterations in 2 suppressor genes maight be one of the causes of aggressive tumor growth and its resistance to standard therapy.