Following the discovery of circulating tumor cells (CTCs) in the peripheral blood of cancer patients, CTCs were initially postulated to hold promise as a valuable prognostic tool through liquid ...biopsy. However, a decade and a half of accumulated data have revealed significant complexities in the investigation of CTCs. A challenging aspect lies in the reduced expression or complete loss of key epithelial markers during the epithelial-mesenchymal transition (EMT). This likely hampers the identification of a pathogenetically significant subset of CTCs. Nevertheless, there is a growing body of evidence regarding the prognostic value of such molecules as CD24 expressing in the primary breast tumor. Herewith, the exact relevance of CD24 expression on CTCs remains unclear. We used two epithelial markers (EpCAM and cytokeratin 7/8) to assess the count of CTCs in 57 breast cancer patients, both with (M0
) and without metastasis (M0) during the follow-up period, as well as in M1 breast cancer patients. However, the investigation of these epithelial markers proved ineffective in identifying cell population expressing different combinations of EpCAM and cytokeratin 7/8 with prognostic significance for breast cancer metastases. Surprisingly, we found CD24+ circulating cells (CCs) in peripheral blood of breast cancer patients which have no epithelial markers (EpCAM and cytokeratin 7/8) but was strongly associated with distant metastasis. Namely, the count of CD45-EpCAM-CK7/8-CD24+ N-cadherin-CCs was elevated in both groups of patients, those with existing metastasis and those who developed metastases during the follow-up period. Simultaneously, an elevation in these cell counts beyond the established threshold of 218.3 cells per 1 mL of blood in patients prior to any treatment predicted a 12-fold risk of metastases, along with a threefold decrease in distant metastasis-free survival over a 90-month follow-up period. The origin of CD45-EpCAM-CK7/8-CD24+ N-cadherin-CCs remains unclear. In our opinion their existence can be explained by two most probable hypotheses. These cells could exhibit a terminal EMT phenotype, or it might be immature cells originating from the bone marrow. Nonetheless, if this hypothesis holds true, it's worth noting that the mentioned CCs do not align with any of the recognized stages of monocyte or neutrophil maturation, primarily due to the presence of CD45 expression in the myeloid cells. The results suggest the presence in the peripheral blood of patients with metastasis (both during the follow-up period and prior to inclusion in the study) of a cell population with a currently unspecified origin, possibly arising from both myeloid and tumor sources, as confirmed by the presence of aneuploidy.
Molecular subtype of breast cancer has a great clinical significance and used as one of the major criteria for therapeutic strategy. Recently, for anticancer therapy, the trend for oncologists is the ...predominant determination of biomarkers in the existing foci of the disease. In the case of adjuvant therapy prescribed for distant metastases prevention, CTCs could be a suitable object for investigation. CTCs as one of the factors responsible for tumor metastatic potential could be more convenient and informative for evaluation of hormone receptors, Ki-67 and HER2 expression, which are determine molecular subtype in breast cancer patient. In our study, we aimed to investigate the molecular subtype discordance between the primary tumor and CTCs in breast cancer patients. We established conversion of molecular subtype in most of the cases. Namely, conversion was detected in 90% of untreated patients and in 82% of breast cancer patients treated by neoadjuvant chemotherapy. At the same time, molecular subtype conversions in patients treated by neoadjuvant chemotherapy were more diverse. Molecular subtype conversions resulted more often in the unfavorable variants in circulating tumor cells. We stratified all patients according to the adequacy of treatment against converted CTCs molecular subtype. Our study revealed that good response to neoadjuvant chemotherapy observed in case of adequate therapy, namely, when chemotherapy scheme was sufficient against CTCs. It turned out that patients with inadequate therapy were characterized by decreased simulated 5-year metastasis-free survival compared to patients who received appropriate therapy. Thus, detection of molecular subtype conversion in circulating tumor cells could be a perspective tool for optimization of antitumor therapy.
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The paleogeographic development of the natural process in the Late Pleistocene on the East European Plain had a rhythmic pattern with repeated alternation of cold and warm climatic eras. ...Continental glaciations arising on the East European Plain, in particular, the Late Valdai (Weichselian) glaciation, were reflected in changes in topography formation. Regional paleoenvironmental conditions of the formation of modern soil cover in the area of gray forest soils in central Russia are discussed. The impact of paleocryogenesis on the features of the Holocene soils is considered by the example of Vladimir and Moscow oblasts. In Vladimir oblast, soils were studied in Suzdal district on the territory of the Kibol-5 archaeological site of the early Middle Ages. In Moscow oblast, studied were conducted at the Pushchino key site. The differentiation of soil profiles related to the specificity of parent materials formed under the impact of the Late Weichselian paleocryogenesis with the development of cryogenic microtopography was demonstrated. It was also found that the surface microtopography is predetermined by the buried paleocryogenic polygonal network of elevated blocks (microhighs) and interblock depressions (microlows). The paleocryogenic genesis of this microtopography caused by cryogenic deformation of large wedge-shaped features was confirmed. Large cryogenic wedge-shaped soil features in the study area formed about 22–14 ka ago, which is confirmed by radiocarbon data. The dependence of the Holocene loamy soils in central Russia on the characteristics of parent materials is manifested at the levels of soil profiles, soil horizons, and particular soil properties. It is argued that the presence of Late Pleistocene paleocryogenic features greatly affects the formation of the profiles of Holocene soils and enhances the action of the anthropogenic factor on soil development. As an environmental factor, Late Weichsel paleocryogenesis differentiates soils at the high taxonomic level contributing to the formation of complex soil cover patterns.
The LIMCH1 protein reduces cell motility by regulating the activity of NM-IIA, which may be critical for tumor cell invasion. At present, the role of the LIMCH1 protein in cancer is not well ...understood. This work is devoted to the study of the localization of LIMCH1 protein domains in different tumor-cell compartments of patients with nonspecific invasive breast carcinoma (NSBC) and the involvement of LIMCH1 protein domains in the collective or individual migration of tumor cells. The phenomenon of tumor morphological heterogeneity was used as a model system in the work. The LIM domain of the LIMCH1 protein most often had nuclear and submembrane localization, while another domain of the LIMCH1 protein, calponin, most often had submembrane and cytoplasmic localization. The nuclear localization of the LIMCH1 protein in tumor cells suggests that the functions of the LIMCH1 protein in tumor cells are not limited to the effect on cell motility. Much more often, the LIMCH1 protein was found in the cytoplasm of single tumor cells compared to multicellular structures, which can be regarded as an indicator of the amoeboid type of movement, given the association of single tumor cells with hematogenous metastasis. It can be supposed that the main function of the LIMCH1 protein in multicellular structures is to provide intercellular adhesion.
Delineation of the features of paleocryogenic microtopography by zero-curvature morphoisographs on a test plot in the south of Moscow oblast enabled us to reveal the polygonal-blocky microrelief ...(microelevations, microdepressions, slopes, and runoff strips), forming eluvial, trans-eluvial, and trans-accumulative agrolandscapes. The soil cover pattern of eluvial agrolandscape includes elementary soil areas of noneroded, slightly eroded, moderately eroded, and aggraded soils. The agrolandscape is dominated by noneroded soils. The soil cover pattern of trans-eluvial agrolandscapes with microdepressions includes elementary soil areas of slightly, moderately, and strongly eroded soils, as well as eroded–aggraded and aggraded soils, with the dominations of slightly eroded soils. The soil cover pattern of trans-accumulative agrolandscapes also includes elementary soil areas of slightly, moderately, and strongly eroded soils; eroded–aggraded soils; and aggraded soils with the domination of strongly eroded soils. The paleocryogenic microrelief became the initial factor of the formation of elementary soil areas with different erosion rates during the long-term (200 years) agricultural use of these lands. Elementary soil areas with different erosion rates of the upper horizons are characterized by outcropping of underlying horizons of different textures. We have identified silt loam, light clay, and clay loam exposed to the surface by erosion on the studied plot. As a result, a complex soil cover pattern with differentiation of soils at the level of varieties (in Russian soil classification system, a taxonomic category based on the topsoil texture) was formed.
Priming effects initiated by the addition of
14
С glucose have been compared for humus horizons of soils existing under continuous input of fresh organic substrates and for buried soil horizons, in ...which entering of organic matter has been essentially limited. The effect of microrelief on the manifestation of priming effect in the humus horizons of gray forest soil on microhigh and in microlow has been estimated. Humus horizon in soils on microhigh, not activated by glucose, produced two times more СО
2
in comparison with soils of microlow. However, the introduction of glucose canceled the effect of microrelief on СО
2
emission. The intensity of absolute priming effect correlated with the С
org
pool, initial microbial biomass, and enzyme activity, decreasing from humus horizons to the buried ones, and did not depend on microrelief. The effect of microrelief was observed, when assessing the priming effect relative to control (soil not activated by glucose): the value of relative priming effect was 1.5 times greater in А horizon of gray forest soil in microlow in comparison with that on microhigh being the result of increasing activity of enzymes.
Living cultural strains of the green algae
‘Chlorella’ mirabilis and Muriella terrestris
have been isolated from buried soils, and their identification has been confirmed by morphological and ...molecular-genetic analysis. It has been shown that the retention of their viability could be related to their small size and the presence of sporopollenin in cell walls. The effect of methods for the reactivation of dormant microbial forms on the growth of algae in paleosols has been estimated. The total DNA content has been determined in buried and recent background soils, and relationship between DNA and the presence and age of burial has been established.
