About 5-10% of all ovarian cancer cases show familial clustering, and some 15-25% of familial ovarian cancer cases are mediated by high-penetrance mutations in the BRCA1 and BRCA2 genes. Only few ...other genes have been identified for familial ovarian cancer.We conducted targeted next-generation sequencing of the protein coding region of 21 candidate genes, including UTR regions, in genomic DNA samples of 48 patients with familial ovarian cancer from the Republic of Bashkortostan. We identified deleterious variants in BRCA1, BRCA2, CHEK2, MSH6 and NBN in a total of 16 patients (33%). The NBN truncating variant, p.W143X, had not previously been reported. Seven patients (15%) were carriers of the c.5266dupC variant in BRCA1, supporting a Russian origin of this founder allele. An additional 15 variants of uncertain clinical significance were observed. We conclude that our gene panel explains about one-third of familial ovarian cancer risk in the Republic of Bashkortostan.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The use of mare's milk in mass nutrition is due to its medicinal and dietary properties. The ice cream recipe created as a result of research has included mare's milk, sugar, vanillin, pasteurized ...chicken yolks, and polysaccharides. The test samples have contained polysaccharides from 0.1 to 1.0 %: guarana; locust bean gum; gum arabic; xanthan gum; apple pectin; bamboo fibers; apple fibers. Based on the organoleptic evaluation, the best samples of ice cream with xanthan gum at the concentration of 0.1 % and bamboo fibers at the concentration of 0.4 % have been selected. In the course of studying the physicochemical and microbiological parameters of a new dairy product, it has been found that ice cream with the addition of polysaccharides in terms of the content of toxic elements, pesticides and radionuclides meets the food safety standards. The developed ice cream can be recommended to all segments of the population as a source of calcium, phosphorus and iron. The results of the analysis of physicochemical and microbiological parameters contribute to the formation of a theoretical basis for studying the properties of polysaccharides – xanthan gum and bamboo fibers. The use of these polysaccharides in mare's milk ice cream opens up prospects for their further use in the food industry.
The formation of a modern generation of engineers capable to drive changes that meet the requirements of the future necessitates a new approach in pedagogical training of engineering teachers. The ...international ENTER (
E
ngineeri
N
g educa
T
ors p
E
dagogical t
R
aining) project is being developed as part of EU Erasmus program focused on addressing the actual education needs from the standpoint of human and social capitals development both in Europe and in other countries. The ENTER project is aimed at the creation and development of an international platform for multilevel vocational training/retraining of technical universities teachers on the basis of the Eurasian interaction network. Surveys among employers, teachers, and engineering university students, as well as scientific periodicals analysis allowed us to determine the complex of universal and specific engineering and pedagogical competencies that educators should master not only for today, but also for the future needs. Based on the competency analysis, a three-level modular teacher training/retraining program (iPET program) has been developed and its international accreditation is planned.
Introduction.
Much attention in ccRCC development is paid to VHL-HIF1α pathway genes. Numerous genes involved in the pathogenesis of ccRCC are targets for miRNA. Alteration in the nature of ...interaction with miRNA binding site as a result of a single nucleotide substitution may promote change the expression of target genes involved in the genesis and development of tumors.
Purpose of research.
Analysis of the role of polymorphic variants in the miRNA binding sites of the VHL-HIF1α gene pathways in ccRCC development.
Materials and methods.
We used 225 DNA samples isolated from the venous blood of ccRCC patients who are hospitalized to the Clinic of the Bashkir State Medical University, and 298 healthy individuals. The genotyping of miRNA binding site polymorphisms in VHL-HIFα-dependent pathway genes (rs10982724 of the DEC1 gene, rs406271 of the TFRC gene, rs10491534 of the TSC1 gene, rs1642742 of the VHL gene, rs3025033 of the VEGFA gene) was performed using Taq-man assays.
Results.
The frequency distribution of alleles and genotypes of rs1642742 of the VHL gene showed that rs1642742 *GG is a marker of the increased risk for ccRCC. In addition, rs10491534 * C allele was found to be the marker for severe ccRCC (p = 0.044; OR = 1.72 (CI = 1.012-2.911)), and rs10491534 * TT genotype (p = 0.044; OR = 0.55; (95% CI = 0.31–0.98)) of the TSC1 gene was shown to be a protective marker for ccRCC of severe duration.
Conclusions.
The study indicated the association of miRNA binding sites polymorphisms with the risk of ccRCC development and severity of disease. However, further studies of the genes are needed to establish their functional significance and role in the pathogenesis of ccRCC.
The main function of matrix metalloproteinases is the degradation of the extracellular matrix and participation in signal transduction. In addition, it is known that they are involved in all stages ...of the progression of the tumor process. The activity of metalloproteinases can be regulated by interactions with specific inhibitors of matrix metalloproteinases, so the latter are also able to participate in tumor growth. The genes of matrix metalloproteinases and their inhibitors, as well as many other genes, are characterized by polymorphism. We have analyzed the frequency distribution of the alleles and genotypes of the polymorphic loci rs1799750 and rs494379 of the
MMP1
gene, rs2285053 of the
MMP2
gene, rs3025058 of the
MMP3
gene, rs3918242 and rs17576 of the
MMP9
gene, rs2276109 of the
MMP12
gene, rs8179090 of the
TIMP2
gene, and rs9619311 of the
TIMP3
gene in 314 patients with gastric cancer, as well as in 339 unrelated healthy individuals from the Republic of Bashkortostan. It was shown that the markers of the increased risk of developing gastric cancer are the genotypes rs1799750*
1G
/
2G
of the
MMP1
gene and rs2276109*
A
/
A
of the
MMP12
gene for Tatars and the genotype rs9619311*
T
/
T
of the
TIMP3
gene for Russians. The association of the rs494379*
G
allele of the
MMP1
gene and increased risk of developing malignant tumors of the stomach were reported in men. Using the APSampler algorithm, we identified combinations of alleles/genotypes associated with an increased and a reduced risk of developing gastric oncopathologies. The data obtained confirm the influence of the studied polymorphic variants of the genes of matrix metalloproteinases and their tissue inhibitors on the risk of developing gastric cancer and are important for understanding the genetic structure of the studied pathology.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The high mortality rate from ovarian cancer is due to the asymptomatic nature of the course of the disease, which leads to the diagnosis of ovarian cancer in later stages. The sodium-dependent ...phosphate transporter NaPi2b encoded by SLC34A2 gene is expressed in 80–90% of epithelial ovarian cancers and used as a target for therapeutic antibodies XMT-1536, and XMT-1592, which are derived from MX35 antibodies and used in clinical trials for the treatment of ovarian and lung cancers. In this work, we aimed to evaluate NaPi2b as a molecular marker for diagnostics and predicting the course and outcome of ovarian cancer disease.
Quantitative analysis of SLC34A2 gene expression in ovarian tumor tissue was performed at the level of transcription and translation using real-time PCR, droplet digital PCR and Western blot analysis respectively. Statistical analysis was performed taking into account various clinicopathological characteristics of the ovarian cancer patients, including the stage of the disease, the tumor grade, the applying of neoadjuvant chemotherapy and the presence of ascites. In this work, we demonstrated that the expression of the human NaPi2b (hNaPi2b) transporter is downregulated in the tumors of patients receiving neoadjuvant therapy and during the development of disease. The data suggest that the level of expression of the SLC34A2 gene can serve as a potential marker for the monitoring and predicting responses to neoadjuvant and targeted therapy in patients with ovarian cancer.
•The NaPi2b targeting antibodies currently undergoing clinical developments for treatment of ovary and lung cancers.•The expression of phosphate transporter NaPi2b is downregulated in ovarian tumor cells of patients after neoadjuvant therapy.•The NaPi2b can serve as a potential marker for the monitoring of the use of neoadjuvant therapy in ovarian cancer patients.•The results should be considered in combinatorial treatments of ovarian cancer patients by therapeutic anti-NaPi2b antibodies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pro- and anti-inflammatory cytokines modulate the inflammatory response in the gastric mucosa. The analysis of associations of allelic variants of cytokine genes in the process of tumorous ...transformation of the gastric mucosa is an urgent problem. Its solution could make it possible to identify the features of production of inflammatory mediators by the immunocompetent cells during gastric carcinogenesis. The frequencies of alleles and genotypes of the
rs1143634
and
rs16944
loci of the
IL1β
gene,
rs71941886
of the
IL1RN
gene,
rs4073
of the
IL8
gene, and
rs1800872
of the
IL10
gene were analyzed in 221 patients with established diagnosis of gastric cancer, as well as in 279 unrelated healthy individuals from the Republic of Bashkortostan. We discovered an association of the allele
С
and genotype
C/C
of the
rs1143634
locus of the
IL1β
gene with a risk of development of malignant tumors of the stomach in men. We identified statistically significant differences in between patients and the control group in the distribution of frequencies of alleles and genotypes of the polymorphic variants:
rs16944
of the
IL1β
gene and
rs1800872
of the
IL10
gene. Dependence of the associations with clinical features of the disease was also shown. Application of the APSampler algorithm revealed the combinations of alleles and genotypes associated with reduced and increased risk of the development of gastric cancer. The most significant were
IL1β
(
rs1143634
)
*T + IL1β
(
rs16944
)
*T/T
,
IL8*A + IL10*A + IL1β
(
rs1143634
)
*T + IL1β
(
rs16944
)
*T
, and
IL10*A + IL1RN*2/2
. The obtained results confirm the influence of the investigated allelic variants of cytokine genes on the risk of developing gastric cancer and play an important role in understanding the genetic structure of the studied pathology.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The acute antibody and T-cell immune response to Helicobacter pylori infection in humans has not been studied systematically. Serum from H. pylori-naive volunteers challenged with H. pylori and cured ...after 4 or 12 weeks was tested by enzyme-linked immunosorbent assays for anti-H. pylori-specific immunoglobulin M (IgM) and IgA established using bacterial lysates from homologous (the infecting strain) and heterologous H. pylori. Proteins recognized by IgM antibody were identified by mass spectrometry of immunoreactive bands separated by two-dimensional gel electrophoresis. Mucosal T-cell subsets (CD4, CD8, CD3, and CD30 cells) were assessed by immunohistochemistry. All 18 infected volunteers developed H. pylori-specific IgM responses to both homologous or heterologous H. pylori antigens. H. pylori antigens reacted with IgM antibody at 4 weeks postinfection. IgM Western blotting showed immunoreactivity of postinfection serum samples to multiple H. pylori proteins with molecular weights ranging between 9,000 (9K) to 150K with homologous strains but only a 70K band using heterologous antigens. Two-dimensional electrophoresis demonstrated that production of H. pylori-specific IgM antibodies was elicited by H. pylori flagellins A and B, urease B, ABC transporter binding protein, heat shock protein 70 (DnaK), and alkyl hydroperoxide reductase. Mucosal CD3, CD4, and CD8 T-cell numbers increased following infection. IgM antibody responses were detected to a range of homologous H. pylori antigens 2 to 4 weeks postchallenge. The majority of H. pylori proteins were those involved in motility and colonization and may represent targets for vaccine development.
Peptic ulcer disease (PUD) is a chronic disease based on recurrent gastric or duodenal ulcers. Association analysis of common polymorphisms of the cytokines genes IL1B (rs1143634), IL1RN ...(rs71941886), IL8 (rs4073), IL10 (rs1800872), and TNFA (rs1800629) was conducted in 254 patients with gastric ulcer or duodenal ulcer and in 277 unrelated healthy individuals from the Bashkortostan Republic. Associations of the rs1143634C allele and the C/C genotype of the IL1B gene with PUD in ethnic Bashkirs have been revealed. The frequency of the rs4073A/A genotype of the IL8 gene was significantly higher in the control group as compared to patients infected with H. pylori. Our results confirm the significant role of rs1143634 of the IL1B gene in PUD development.
Cisplatin is one of the commonly used antitumor drugs for the treatment of different cancers. One of the mechanisms of cisplatin cytotoxicity is associated with oxidative stress initiation. Increased ...levels of the reactive oxygen species (ROS) are detected in many types of malignancies enhance the cells’ proliferative activity, but its excessively high levels can lead to apoptosis. Thus, one of the promising therapeutic strategies for cancer treatment is the regulation of intracellular ROS levels by targeted drugs. Physcion is an inhibitor of 6PGD enzyme which catalyzes the intracellular antioxidant NADPH formation (Lin et al. in
Nature Cell Biology, 17
(11), 1484–1496,
2015
). In this study, the combined action of the cisplatin and Physcion on the ROS level and viability of human lung (H1299) and pancreatic cancer cell lines (AsPC-1) is described. It was shown that the combined action of Physcion with cisplatin caused a growth in the ROS level in H1299 and AsPC-1 cells up to 1.7 and 2.5 times, respectively, compared with cisplatin alone. Moreover, IC50 of the cisplatin in combination with Physcion decreased up to 1.6 times in the AsPC-1 cells and up to 2.2 times in Н1299 cells compared with cisplatin alone. The enhancing effect of Physcion on cisplatin cytotoxicity is supposedly associated with a ROS balance shift toward increase. Physcion could be considered as an adjunct compound for cancer treatment with DNA-damaging agents.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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