The effect of anthracene derivatives on the state of the extracellular matrix of the periodontal connective tissue and the oral mucosa of old rats

In the experiments on 27 old female rats, the effect of the anthracene derivative preparation on the state of the intercellular matrix of the connective tissue of the periodontal and oral mucosa in intact animals, as well as on the periodontitis model, was studied

The role of polymorphic variants of arginase genes (<i>ARG1, ARG2</i>) involved in beta-2-agonist metabolism in the development and course of asthma

Asthma is a common severe disease of the respiratory tract, it leads to a significant impairment in the quality of a patient’s life unless effectively treated. Uncontrolled asthma symptoms are a cause of disease progression and development, they lead to an increase in the patient’s disability. The sensitivity to asthma therapy largely depends on the interaction of genetic and epigenetic factors, which account for about 50–60 % of variability of therapeutic response. Beta-2-agonists are some of the major class of bronchodilators used for asthma management. According to published data, allelic variants of the arginase ARG1 and ARG2 genes are associated with a risk of asthma development, spirometry measures and efficacy of bronchodilator therapy. High arginase activity results in a low level of plasma L-arginine and in a decrease in nitric oxide, and, as a result, in an increase in airway inflammation and remodeling. Arginase genetic polymorphisms (rs2781667 of the ARG1 gene, rs17249437, rs3742879, rs7140310 of the ARG2 gene) were studied in 236 children with asthma and 194 unrelated healthy individuals of Russian, Tatar and Bashkir ethnicity from the Republic of Bashkortostan. Association analysis of the studied polymorphisms with asthma development and course, the sensitivity to therapy in patients was carried out. It was found that the rs2781667*C allele of the ARG1 gene is a marker of an increased risk of asthma in Tatars. In Russians, the association of rs17249437*TT and rs3742879*GG genotypes of the ARG2 gene with a decrease in spirometry measures (FEV1, MEF25) was established. In Russians and Tatars receiving glucocorticoid monotherapy or combination therapy, the association of the rs17249437*T allele and rs17249437*TT genotype of the ARG2 gene with a partially controlled and uncontrolled course of asthma was shown

Effect of small and radical surgical injury on the level of different populations of circulating tumor cells in the blood of breast cancer patients

Circulating tumor cells (CTCs) constitute a heterogeneous population. Some tumor cells are cancer stem cells (CSCs), while others are in the process of the epithelial-mesenchymal transition (EMT); however, most CTCs are neither stem cells nor in the EMT. This prospective study of 22 patients with nonspecific-type invasive carcinoma of the breast identified different populations of CTCs by flow cytometry in the blood of patients before biopsy, after biopsy and after surgical tumor removal without neoadjuvant chemotherapy. The results showed that minor surgical injury (biopsy) was accompanied by a significant increase in the blood levels of CTCs without signs of the EMT or stemness (Epcam+CD45-CD44-CD24-Ncadh-) and CTCs with signs of stemness and without signs of the EMT (Epcam+CD45-CD44+CD24-Ncadh-). Our results suggest that minor surgical injury to a tumor contributes to the release of CTCs into the bloodstream, including a population of stem cells

Clinicopathological features of nonspecific invasive breast cancer according to its molecular subtypes

The aim of the present study was to investigate the clinical and morphological features of nonspecific invasive breast cancer according to its molecular subtypes. Materials and Methods: 163 women with nonspecific invasive breast cancer (T1–4N0–3M0) were included in the present study. Luminal A type of breast cancer was detected in 101 women, luminal B type — in 23 women, overexpression of HER2/neu was identified in 14 women and triple-negative cancer — in 25 women. Results: The study revealed that various molecular subtypes of breast cancer differ in the morphological structure, the expression characteristics of the primary tumor and the rate of lymphogenous and hematogenous metastasis. Lymphogenous metastases were more frequently (in 71%) detected in HER2/neu overexpressing breast cancer than in luminal A (41%), luminal B (39%) and triple-negative tumors (40%). Hematogenous metastasis did not depend on the morphological structure of carcinoma infiltrative component, the state of tumor stroma as well as the proliferative activity in all the investigated groups. Conclusion: The revealed clinicopathological characteristics of different molecular subtypes of invasive breast cancer allow to predict the possible outcome of the disease and select personalized treatment strategy for patients more reasonably

Different morphological structures of breast tumors demonstrate individual drug resistance gene expression profiles

AIM

Antarctic polar vortex dynamics in 2019 and 2020 under the influence of the subtropical stratosphere

The trend of strengthening of the Antarctic polar vortex in late spring and early summer (November–December) has been observed in recent decades. A good example of this trend is the dynamics of the Antarctic polar vortex in 2020 when it existed until the last week of December. In 2019, conversely, on the contrary, an unusually early breakup of the polar vortex occurred, a minor sudden stratospheric warming was recorded. Strengthening (or weakening) of the Antarctic polar vortex occurs as a result of an increase (or decrease) in the stratospheric meridional temperature gradient under conditions of growth (or decline) in the temperature of the lower subtropical stratosphere. We considered the temperature variations in the lower subtropical stratosphere in the spring of 2019 and 2020 and the corresponding response of the Antarctic polar vortex. The dynamics of the Antarctic polar vortex in September–October 2019 and November 2020 was largely synchronized with the temperature changes in the lower subtropical stratosphere relative to climatological means. Using correlation analysis, we show that the Antarctic polar vortex dynamics in December is largely due to the temperature changes in the lower subtropical stratosphere that occurred in the second half of November, which manifested itself in 2020.The trend of strengthening of the Antarctic polar vortex in late spring and early summer (November–December) has been observed in recent decades. A good example of this trend is the dynamics of the Antarctic polar vortex in 2020 when it existed until the last week of December. In 2019, conversely, on the contrary, an unusually early breakup of the polar vortex occurred, a minor sudden stratospheric warming was recorded. Strengthening (or weakening) of the Antarctic polar vortex occurs as a result of an increase (or decrease) in the stratospheric meridional temperature gradient under conditions of growth (or decline) in the temperature of the lower subtropical stratosphere. We considered the temperature variations in the lower subtropical stratosphere in the spring of 2019 and 2020 and the corresponding response of the Antarctic polar vortex. The dynamics of the Antarctic polar vortex in September–October 2019 and November 2020 was largely synchronized with the temperature changes in the lower subtropical stratosphere relative to climatological means. Using correlation analysis, we show that the Antarctic polar vortex dynamics in December is largely due to the temperature changes in the lower subtropical stratosphere that occurred in the second half of November, which manifested itself in 2020

ЭКСПРЕССИЯ CXCR4 В РАЗЛИЧНЫХ ПОПУЛЯЦИЯХ ЦИРКУЛИРУЮЩИХ И ОДИНОЧНЫХ ОПУХОЛЕВЫХ КЛЕТОК РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ

The aim of this study was to assess CXCR4 expression in different subsets of CTCs and single (detached) breast cancer cells.Materials and methods. Thirty five patients with invasive breast carcinoma of no specialtype (IC NST) (T1-4N0-2M0), between 29 and 69 years of age were included in this study. Different subsets of CTCs with CXCR4 expression were evaluated by flow cytometry. A  confocal microscopy was used to assess CXCR4 expression in different subsets of single (detached) cancer cells in breast tissue.Results. The CXCR4 was expressed in CTCs without stem-like and EMT phenotype, in CTCs  with EMT but not stem markers and in stem-like CTCs without EMT features. In all blood  samples, the CXCR4 expression in CTCs with stem-like and EMT phenotype was absent. In  breast tumor the CXCR4 was expressed in the non stemlike single (detached) breast cancer  cells with EMT features, in the single (detached) breast cancer cells with stem and EMT  features. In all tumor samples the stem-like or non stem-like single (detached) breast  cancer cells without EMT features were absent.Conclusions. Different subsets of the CTCs exhibited CXCR4. The CXCR4 expression did not  depend on the presence or absence of stem or/and EMT features in tumor cells. We showed that some subsets of single (detached) breast cancer cells in the primary tumor  were characterized by the ability to express CXCR4 and may be a source of the respective CTC subsets.Целью исследования явилось определение экспрессии CXCR4 в различных популяциях циркулирующих (ЦОК) и одиночных (дискретных) опухолевых клеток рака молочной железы.Материал и методы. В исследование были включены 35 пациенток с инвазивной карциномой неспецифического типа молочной железы (T1–4N0–2M0) в возрасте от 29 до 69 лет. Экспрессию CXCR4 в  различных популяциях ЦОК оценивали методом проточной цитометрии. Для оценки экспрессии CXCR4 в  аналогичных популяциях одиночных (дискретных) опухолевых клеток в первичной опухоли использовали метод конфокальной микроскопии.Результаты. Нами было установлено, что CXCR4 экспрессировался ЦОК без признаков стволовости и  эпителиально-мезенхимального перехода (ЭМП), ЦОК с признаками ЭМП, но без маркеров стволовости, а  также ЦОК с признаками стволовости, но без признаков ЭМП. У всех пациенток в крови ЦОК с признаками  стволовости и ЭМП не экспрессировался CXCR4. В первичной опухоли молочной железы CXCR4  обнаруживался как на одиночных (дискретных) опухолевых клетках без признаков стволовости с  признаками ЭМП, так и на клетках с маркерами стволовости и ЭМП. У всех пациенток в образцах первичной  опухоли отсутствовали стволовые и нестволовые клетки без признаков ЭМП.Заключение. Таким образом, CXCR4 экспрессируются на различных популяциях ЦОК. Экспрессия CXCR4  не зависит от наличия или отсутствия признаков стволовости и/или ЭМП в опухолевых клетках. Также мы  показали, что некоторые популяции одиночных (дискретных) опухолевых клеток в первичной опухоли  характеризуются способностью презентировать на своей мембране CXCR4 и могут являться источником соответствующих популяций ЦОК

ВОСПАЛЕНИЕ КАК ТЕРАПЕВТИЧЕСКАЯ МИШЕНЬ ПРИ КОМПЛЕКСНОМ ЛЕЧЕНИИ ЗЛОКАЧЕСТВЕННЫХ ОПУХОЛЕЙ

In this review, we analyzed the role of inflammation in carcinogenesis, tumor development, and metastasis. In addition, the mechanisms of non-steroidal anti-inflammatory drugs (NSAIDs) and the reasons of their contradictory influence on cancers were discussed. We summarized the numerous data about effectiveness of anti-inflammatory drugs for the prevention and additional therapy of tumor diseases. In particular, divergent effects of NSAIDs may be due to the peculiarities of immune-inflammatory responses that are realized in carcinogenesis and tumor development that have yet to be studied. We also discussed the selectivity of NSAID effects on different cancers and opposite effects of anticancer drugs with similar mechanisms of action. Apparently, the unsuccessful use of NSAIDs in cancer prevention and therapy are more specific for squamous cell carcinomas. Based on the literature, we provided significant clinical findings regarding the need of NSAID use in the current therapy of certain cancers and the determination of molecular predictors of the drug effect. In fact, anti-inflammatory therapy could eliminate the factors that contribute to the appearance of invasive and metastatic tumor cells, cancer and premetastatic niches and thus prevent metastasis and recurrence. At present, some non-selective (aspirin) and selective (celecoxib) NSAIDs are highly promising in the therapy of solid tumors. В обзоре анализируется роль воспаления в канцерогенезе, развитии опухоли и метастазировании. Обобщены многочисленные данные об эффективности противовоспалительных препаратов с целью профилактики и вспомогательной терапии опухолевой болезни. Обсуждены механизмы действия и причины противоречивости результатов использования нестероидных противовоспалительных препаратов (НПВП). Разнонаправленность эффектов может быть обусловлена особенностями иммуновоспалительных реакций, реализующихся в процессе канцерогенеза и развития опухолей, которые еще предстоит изучить. Обращается внимание на избирательность эффектов НПВП в отношении разных нозологических форм опухолей и противоположный характер противоопухолевых эффектов препаратов, относящихся по механизму действия к одной группе. Сделано заключение, что неудачи применения НПВП с профилактической и лечебной целью чаще возникают при карциномах, происходящих из плоского эпителия. Анализ литературы позволяет прийти к заключению, что имеются неоспоримые данные, позволяющие включать противовоспалительные препараты в существующие схемы противоопухолевого лечения при некоторых нозологических формах с определением молекулярных предикторов эффекта. Противовоспалительная терапия позволит устранить факторы, способствующие приобретению опухолевыми клетками инвазивных и метастатических свойств и формированию опухолевых и преметастатических ниш, а значит, развитию метастазов и рецидивов опухоли. Особенно перспективны при солидных опухолях определенные неселективные (аспирин) и селективные (целекоксиб) НПВП.