Gleb A. Kuznetsov

Laminins are a family of high-molecular-weight heterotrimeric glycoproteins of the extracellular matrix that play a key structural role in basement membranes. Although mutations in intracellular proteins remain the primary drivers of carcinogenesis, the role of changes in the expression and spatial distribution of laminins in the development of malignant neoplasms is gaining increasing importance. Primary focus is given to the patterns of laminin alterations in carcinomas of various localizations, as well as their role in the acquisition of invasive and metastatic potential by tumor cells. Furthermore, the prognostic significance of different laminin isoforms is discussed.

Aim. To study the features of the expression of the integrin subunit β4 in primary tumor tissue depending on the clinical and morphological parameters of breast cancer. Materials and methods. We examined biopsy samples from 49 patients with T1–4N0–3M0 breast cancer; the median age was 51.0 [44.0; 60.0] years. Patients did not receive neoadjuvant therapy. Surgical intervention involved resection of the mammary gland with axillary lymph node dissection or radical mastectomy. The expression of markers of estrogen receptor, progesterone receptor, c-erB-2 (Her2/neu), Ki67, CD104 (integrin subunit β4) was assessed using immunohistochemistry. Statistical processing of the results was carried out using the Statisctica 10.0 software package. Results. In the group of patients with N3 degree, cases with positive cytoplasmic/membrane colocalization of integrin subunit β4 expression were more frequently detected (45%), compared with observations where no such expression was found (8%; p = 0.002). Conclusion. Positive cytoplasmic/membrane colocalization of integrin subunit β4 expression is associated with the prevalence of lymphatic metastasis, which corresponds to N3 degree.

Background. Breast cancer ranks first in the structure of cancer morbidity and mortality. Involvement of a large number of regional lymph nodes is considered a poor prognostic outcome. The mechanisms of development of lymphogenous metastasis in general and common in particular are not fully understood. Integrins are involved in the metastatic process by mediating tumor cell invasion and adhesion to vascular endothelium. Aim. To study the role of integrins in lymphogenous metastasis. Materials and methods. The study included 72 patients diagnosed with invasive breast carcinoma of no special type who underwent surgical treatment on the basis of the cancer research institute national research medical center. The average age reached 51.2 years. In accordance with the indications and morphological data, the patients underwent antitumor treatment. The tissue of the primary tumor obtained by trepanbiopsy. Histological and immunohistochemical examination was carried out according to the standard method. In primary tumor cells, the presence or absence of cytoplasmic or membrane/cytoplasmic colocalization of CD61 (Integrin beta 3), CD104 (Integrin beta 4), CD51 (Integrin alpha-V) expression was assessed. When statistically processing the results, Fisher's test and one-way regression analysis were used. Results. In the N3 group, the frequency of cytoplasmic expression of CD 61 was higher at the trend level (40.9 and 18%; p=0.074). In the group of patients with N3, positive cytoplasmic expression of CD104 (37.5 and 15.0%; p=0.029) and membrane and cytoplasmic colocalization (52.6 and 15.1%; p=0.004) were more often detected. In the group with N1 and N2, membrane and cytoplasmic colocalization of CD104 expression was less common (15.8 and 54.7%; p=0.006). When studying the expression frequency of CD51 integrin, no significant differences were found depending on the severity of lymphogenous metastasis. Conclusion. Expression of CD104 in primary tumor cells is strongly associated with widespread lymphogenous metastasis. Studies of the role of integrins in the development of lymphogenous metastasis are promising for predicting the prevalence of this process in the preoperative period and for searching for methods of influencing the tumor.

Integrins are cell adhesion receptors, which play a role in breast cancer invasion, angiogenesis, and metastasis. Moreover, it has been shown that exosomal integrins provide organotropic metastasis in a mouse model. In our study, we aimed to investigate the expression of integrins β3, β4, and αVβ5 on exosomes and tumor cells (circulating tumor cells and primary tumor) and their association with the localization of distant metastasis. We confirmed the association of exosomal integrin β4 with lung metastasis in breast cancer patients. However, we were unable to evaluate the role of integrin β3 in brain metastasis due to the rarity of this localization. We established no association of exosomal integrin αVβ5 with liver metastasis in our cohort of breast cancer patients. The further evaluation of β3, β4, and αVβ5 integrin expression on CTCs revealed an association of integrin β4 and αVβ5 with liver, but not the lung metastases. Integrin β4 in the primary tumor was associated with liver metastasis. Furthermore, an in-depth analysis of phenotypic characteristics of β4+ tumor cells revealed a significantly increased proportion of E-cadherin+ and CD44+CD24- cells in patients with liver metastases compared to patients with lung or no distant metastases.

В статье проведен ретроспективный анализ отечественных четырехцилиндровых бензиновых двигателей легковых автомобилей. По каждому из исследованных параметров и показателей выявлены изменения. Показано, что основной тенденцией развития двигателей является повышение их размерности, связанное с увеличением геометрических параметров, а также повышение энергетических показателей двигателей. The article presents a retrospective analysis of domestic four-cylinder gasoline engines of passenger cars. Changes were revealed for each of the studied parameters and indicators. It is shown that the main trend in the development of engines is an increase in their dimension associated with an increase in geometric parameters, as well as an increase in the energy performance of engines.

Aim. The aim of the study was to differentiate the endotypes in allergic rhinitis by key allergy markers in a mixed group of patients.Material and Methods. The study comprised a total of 48 patients, men and women, aged 18-60 years suffering from three endotypes of allergic rhinitis including the classic, local, and dual allergic rhinitis. The standard diagnostics of allergic rhinitis included taking a history of allergies, family history of allergic disease, video rhinoscopy, serum total IgE level assessment, allergy skin tests to house dust mite and pollen allergens, and study of eosinophilic inflammation parameters (eosinophil cationic protein, interleukin-5 (IL5), and eosinophil counts in blood and nasal secretion).Results. Based on total IgE level, the general group of patients was divided to two subgroups: subgroup 1 comprised patients with high IgE level (n = 22); subgroup 2 comprised patients with low IgE level (n = 26). Most of patients in these groups had contradictory results of allergy skin tests i.e. positive allergy skin test results in case of high IgE level (group 1) and vice versa. Cluster analysis-based exminations of general group allowed to categorize three subgroups of patients: patients with classic allergic rhinitis (n = 22), local allergic rhinitis (n = 22), and dual allergic rhinitis (n = 4). Besides, an increased rate of anxiety disorder was found in patients with local allergic rhinitis (p < 0.001).Conclusion. The obtained data showed promise for a new research trend in studying allergic rhinitis endotypes, namely: investigation of neuroimmune relationships in allergic tolerance disruption in the presence of this pathology.

В статье исследованы модели двухтактных двигателей с противоположно движущимися поршнями американской компании Achates Power мощностью от 65 до 484 л.с. В частности, представлены 8 моделей двигателей с количеством цилиндров от 1 до 4. Сформированы модельные ряды двухтактных двигателей для перспективных легковых и грузовых автомобилей. Приведены промышленные образцы двухтактных двигателей для этих автомобилей. Показано, что двигатели данного типа могут служить современной платформой для формирования модельных рядов мощных, экономичных и экологичных силовых установок транспортного...