S. I. Makarova

Tyrosine protein kinase HER2 plays an important role in carcinogenesis. In breast cancer (BC), the HER2 gene is amplified in approximately 20% of cases. Trastuzumab is used to treat BC with HER2 gene amplification. Trastuzumab is not effective in treating tumors with low HER2 expression, but trastuzumab deruxtecan was recently found to significantly improve prognosis in these patients. Nonetheless, there are still difficulties with accurate diagnosis of HER2-low BC, especially at the preoperative stage. In this study, when comparing the results between core needle biopsies and resection specimens using three immunohistochemistry scores (0, 1+, and 3+) of the HER2 protein level, we observed only moderate agreement (66.2%, κ = 0.486) in patients who did not undergo neoadjuvant therapy (n = 71). Other miRNA- or protein-coding genes regulated by HER2 signaling pathways may be additional markers for the scoring of the HER2 level. We measured levels of HER2-regulated miR-378a, -205, and -21 and mRNA levels of their target genes TRPS1, ITGA2, BCL6, and PTEN in BC surgical specimens. For estrogen receptor-positive BC (n = 64), we confirmed that the expression of miR-21, miR-378a, TRPS1, PTEN, and BCL6 is associated with the HER2 protein level. Moreover, the expression profile of miR-378a, BCL6, and PTEN differed between HER2 1+ and HER2 3+ tumors. TRPS1 expression was significantly higher in HER2 3+ tumors compared with HER2 0 tumors, but there was no difference in the amount of TRPS1 mRNA between HER2 1+ and HER2 3+ tumors. Thus, an analysis of the expression of miR-21, miR-378a, TRPS1, PTEN, and BCL6 may help to distinguish between HER2-negative, HER2-positive, and HER2-low BCs.

Роль полиморфных вариантов генов CYP3A4, CYP3A5, CYP1A1 и CYP2B6 в развитии органотоксических эффектов химиотерапии у больных лимфомой Ходжкина

High prevalence of bronchial asthma among the population (about 300 million people all over the world) provides rationale for the search for candidate genes of disease. Human acidic chitinase (CHIA (AMCase)), encoded by theCHIAgene, is involved in the degradation of chitin, a component of the fungal cell wall and arthropod exoskeleton, which, if present in food or house dust, is a provoking factor for the bronchial asthma (BA) development. Functionally significant mutations in theCHIAgene may apparently increase the risk of susceptibility to BA.Aim.The aim of the study was to assess the associations of single nucleotide polymorphisms (SNPs) rs12033184 and rs3806448 in theCHIAgene with bronchial asthma in children in Novosibirsk.Material and Methods. The study was organized as case-control. A total of 537 blood samples were used. SNPs were determined by real-time PCR. The associations of polymorphic variants with the disease were assessed by the odds ratio.Results.No associations of rs12033184 and rs3806448 with BA were found.Conclusion.The role of acidic chitinase gene in the development of BA in residents of Novosibirsk was found to be less significant than in the Indian population where it was previously shown to be associated with the disease.

Atopic diseases remain one of the most common childhood diseases. At the beginning of life, atopic dermatitis (AD) occurs, and only then bronchial asthma (BA). This staged development of sensitization and transformation of clinical manifestations is called the atopic march. Are the genetic factors of predisposition to AD the same for BA? There is still no definite answer to this question. Mutations in the filaggrin gene (FLG) are known to impair skin barrier function. Filaggrin is expressed not only in the skin, but also in the respiratory organs of the nasal mucosa, lungs, and bronchi. Filaggrin defects lead not only to disruption of the skin barrier, but also to an increase in the Th2 response and increased production of IgE, typical of bronchial asthma. Therefore, mutations in the FLG gene can be a risk factor for the development of not only AD, but also BA.The aimof this study was to compare the values of the association of mutations in the FLG gene with AD and BA in the Russian sample.Material and methods.Case-control study design. We used 265 blood samples from children. 4 mutations in the filaggrin gene were identified by real-time PCR. The association of mutations with disease was assessed by odds ratio.Results.We showed a strongly pronounced association of the deletion of 4 nucleotides (2282del4) with AD, but not with BA, although for patients with atopic BA the indicator of the association of this mutation with the disease was higher than for the group with symptoms of bronchial asthma identified by the ISAAC questionnaire. These results lead to the conclusion that the role of the filaggrin gene for BA is much less significant than for AD.

NAT2^*5 allele was found in 54.8% healthy children and 35.9% children with bronchial asthma,i.e. the risk of bronchial asthma was considerably lower in individuals carryingNAT2^*5 allele.NAT2^*5 allele manifests itself in both homo- and heterozygous states.