The incidence of somatic mutagenesis of p53 oncosuppressor protein in malignant tumors of the stomach and genetic polymorphism of p53 were studied in patients with stomach cancer on DNA samples isolated from tumor tissues obtained during surgery. The incidence of Pro/Pro genotype increased in the patients, while the percentage of Arg/Pro heterozygotes was markedly lower compared to long-living persons without cancer. The incidence of p53 somatic mutations in exons 5, 7, 8 was 70.8%; multiple mutations were detected in half of the examined patients. The relationship between the intensity of p53 mutagenesis and histological structure of the tumor was detected. The contribution of p53 genetic status to the risk of stomach cancer can be more effectively evaluated on DNA samples isolated from not only tumor cells, but also from normal tissues. The effects of epigenetic factors determining the intensity of somatic mutagenesis of p53 in tumors should be taken into account.
To date peptide phage display is one of the most common combinatorial methods used for identifying specific peptide ligands. Phage display peptide libraries containing billions different clones successfully used for selection of ligands with high affinity and selectivity toward wide range of targets including individual proteins, bacteria, viruses, spores, different kind of cancer cells and variety of nonorganic targets (metals, alloys, semiconductors etc.) Success of using filamentous phage in phage display technologies relays on the robustness of phage particles and a possibility to genetically modify its DNA to construct new phage variants with novel properties. In this review we are discussing characteristics of the most known non-commercial peptide phage display libraries of different formats (landscape libraries in particular) and their successful applications in several fields of biotechnology and biomedicine: discovery of peptides with diagnostic values against different pathogens, discovery and using of peptides recognizing cancer cells, trends in using of phage display technologies in human interactome studies, application of phage display technologies in construction of novel nano materials.
Vaccination forms active immunity and represents an effective way of preventing tick-borne encephalitis (TBE). However, excessive vaccination is unjustified in terms of economics and medical ethics. One of the individualized approaches to vaccines is the selection of vaccine doses depending on the expected levels of immune response. Therefore, there is a need for new methods for assessing potential human immune responses prior to vaccination. The aim of this study was to determine possible association between single nucleotide polymorphisms (SNPs) located within OAS2 and OAS3 genes, which have been previously associated with the development of severe forms of TBE, and the formation of antibodies and cytokines upon vaccination against TBE. The study involved 97 volunteers of both sexes who had not previously been vaccinated against TBE and had no contact with ticks. Venous blood samples were collected one month after vaccination against TBE using the EnceVir vaccine. Levels of specific IgG antibodies against tick-borne encephalitis virus and interleukin 4 (IL-4) were analyzed. Genomic DNA samples were genotyped for the SNPs rs2285932, rs2072136, rs1293762, rs15895 and rs1732778 in genes encoding 2’-5’-oligoadenylate synthetases OAS2 and OAS3. Antibody production in response to vaccine administration was significantly associated with SNP rs1732778 in the regulatory region of the OAS2 gene. This indicator was significantly higher in people with heterozygous genotypes G/A as compared to people with homozygous genotypes G/G and A/A. Carriers of the A allele (G/A or A/A genotypes) of the same SNP had reduced IL-4 levels as compared to the homozygous G/G individuals. Thus, the data obtained indicate that SNP rs1732778 in the regulatory region of the OAS2 gene correlates with the formation of antiviral IgG antibodies and changes in IL-4 levels upon vaccination. Evidently, the genetic polymorphism in OAS2 gene should be considered when performing individualized TBE vaccinations.
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