Two live, attenuated rotavirus A (RVA) vaccines, Rotarix and RotaTeq, have been successfully introduced into national immunization programs worldwide. The parent strains of both vaccines were obtained more than 30 years ago. Nonetheless, only very limited data are available on the molecular similarity of the vaccine strains and their genetic relationships to the wild-type strains circulating within the territory of Russian Federation. In this study, we have determined the nucleotide sequences of the genes encoding the viral proteins VP7 and VP4 (the globular domain VP8*) of vaccine strains and natural isolates of rotaviruses in Nizhny Novgorod, Russia. The VP7 and VP4 proteins contain antigenic sites that are the main targets of neutralizing antibodies. Phylogenetic analysis based on VP4 and VP7 showed that the majority of the natural RVA isolates from Nizhny Novgorod and the vaccine strains belong to different clusters. Four amino acids within the VP7 antigenic sites were common in both the wild-type and vaccine strains. The largest number of amino acid differences was found between the vaccine strain Rotarix and the Nizhny Novgorod G2 strains (19 residues out of 29). From 3 to 5 amino acid differences per strain were identified in the antigenic sites of VP4 (domain VP8*) between wild-type strains and the vaccine RotaTeq, and 6-8 substitutions were found when they were compared with the vaccine strain Rotarix. For the first time, immunodominant T-cell epitopes of VP7 were analyzed, and differences in the sequences between the vaccine and the wild-type strains were found. The accumulation of amino acid substitutions in the VP7 and VP4 antigenic sites may potentially reduce the immune protection of vaccinated children from wild-type strains of rotavirus.

Single-nucleotide polymorphism rs5498 E469K (A/G) in ICAM-1 gene modulates functional activity of this protein and is associated with the risk of some diseases. Tumor cell rs5498 E469K (A/G) genotypes were compared with genotypes of patients with colorectal and breast cancer, residents of the Nizhniy Novgorod region. Specimens of peripheral blood and tumor foci from patients with colorectal and breast cancer and peripheral blood specimens from normal subjects were analyzed. The frequency of genotypes of single-nucleotide rs5498 E469K (A/G) sequence in the Nizhny Novgorod population coincide with the frequency of genotypes characteristic of residents of Germany. Comparison of genotypes of peripheral blood and tumor cells from patients with colorectal and breast cancer showed loss of cancer cell heterozygosity. The frequency of heterozygosity loss increases with colorectal cancer progress from one stage to another.

.

The purpose of this study is to evaluate mRNA levels of genes encoding CD16A (FCGR3A) and CD16B (FCGR3B) in peripheral blood and tumors of colorectal cancer patients (CRC).Materials and methods. The study included 66 CRC patients from Nizhny Novgorod Regional Clinical Oncology Center and 111 people without cancer as a comparison group from Nizhny Novgorod Regional Blood Center named after N.Ya. Klimova. The mRNA relative levels in peripheral blood and tumor was detected by reverse transcription real-time polymerase chain reaction. The mRNA levels correlation and association with CRC clinical characteristics were assessed by statistic methods.Results. The study suggests that in the peripheral blood of CRC patients the levels of mRNA FCGR3A and FCGR3B were statistically significantly lower than in healthy individuals. The mRNA levels remained low at 7–10 days after surgery. The FCGR3A mRNA normalized level in the blood and tumors of CRC patients, as well as in the blood of healthy individuals, was several times higher than the FCGR3B mRNA level. At the II stage of tumor development in CRC patients, the FCGR3A and FCGR3B mRNA levels were statistically significantly decreased, but as the tumor progressed is normalized. Moderate degree of tumor differentiation was also characterized by a drop in mRNA levels of the tested genes. Reduced FCGR3A and FCGR3B mRNA levels in the blood of patients were observed in the absence of metastases. In tumor samples, FCGR3A mRNA was tested in 95.5% of cases, FCGR3B mRNA in 68.2% of cases. Progression of CRC was accompanied by an increase in FCGR3A mRNA level in tumors, the FCGR3B mRNA level did not change. Positive correlation of FCGR3A mRNA level with TNF and FOXP3 mRNA levels was found, which indicates the possible involvement of FCGR3A in the regulation of chronic inflammation in tumors of CRC patients.Conclusion. Changes in mRNA levels of genes encoding CD16A (FCGR3A) and CD16B (FCGR3A) molecules were detected in blood and tumor samples. The results indicate the potential for their use as monitoring immunological markers in CRC.