Cognitive Coherence as the Element of Functional Valence in COVID-19 Terminological System

Background. The relevance of the study is predetermined by the uniqueness of the communicative and discursive field formed during COVID-19 pandemic. The manifestation of COVID-19-related nominative categories occurs spontaneously and depends on pragmatic motives of social interaction at the global international level. The atypicality of COVID-19 terminological system development sets up the research course directed at both the process of diffuse terminological conglomerate formation and its conceptualization based on the mechanisms of cognitive activity implementation viewed through the cultural specificity revealed at the level of terminological functioning and terminological systemic unity. Objective. This article presents the results of a corpus-based research of cognitive and discursive features of COVID-19 terminological system development. Methods. The research material is a sample of Russian and English media texts selected via automatized algorithms of data parsing. Media discourse reflects short-term socially significant fluctuations in global information agenda directly related to semantic shifts in COVID-19 representation that are revealed through the variety of linguistic and extralinguistic discursive means and compared within the linguo-cultural communities under study. Results. As a result of content analysis and subsequent component analysis the peculiarities of COVID-19 terminological system development appear to be predetermined by the parallel structuring and transformation of COVID-19 semantic representation formed in the temporal perspective of pandemic waves on the basis of fundamental mechanisms of cognitive activity. The functional valence of COVID-19 terminological system is explicated through the convergence of cognitive components that result in terminological coherence and gradual formation of the denotative component of meaning through cognitive compilation of occasional semic characteristics. Conclusion. Cognitive coherence as the element of COVID-19 terminological system functional valence contributes to its gradual structuring and determines the features of semantic arrangement of COVID-19 conceptual field

Bone Marrow Involvement in Melanoma. Potentials for Detection of Disseminated Tumor Cells and Characterization of Their Subsets by Flow Cytometry

Disseminated tumor cells (DTCs) are studied as a prognostic factor in many non-hematopoietic tumors. Melanoma is one of the most aggressive tumors. Forty percent of melanoma patients develop distant metastases at five or more years after curative surgery, and frequent manifestations of melanoma without an identified primary lesion may reflect the tendency of melanoma cells to spread from indolent sites such as bone marrow (BM). The purpose of this work was to evaluate the possibility of detecting melanoma DTCs in BM based on the expression of a cytoplasmatic premelanocytic glycoprotein HMB-45 using flow cytometry, to estimate the influence of DTCs’ persistence in BM on hematopoiesis, to identify the frequency of BM involvement in patients with melanoma, and to analyze DTC subset composition in melanoma. DTCs are found in 57.4% of skin melanoma cases and in as many as 28.6% of stage I cases, which confirms the aggressive course even of localized disease. Significant differences in the groups with the presence of disseminated tumor cells (DTCs+) and the lack thereof (DTC−) are noted for blast cells, the total content of granulocyte cells, and oxyphilic normoblasts of erythroid raw cells

Targeting Features of Curaxin CBL0137 on Hematological Malignancies In Vitro and In Vivo

The anticancer activity of Curaxin CBL0137, a DNA-binding small molecule with chromatin remodulating effect, has been demonstrated in different cancers. Herein, a comparative evaluation of CBL0137 activity was performed in respect to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia and multiple myeloma (MM) cultured in vitro. MTT assay showed AML and MM higher sensitivity to CBL0137’s cytostatic effect comparatively to other hematological malignancy cells. Flow cytometry cell cycle analysis revealed an increase in subG1 and G2/M populations after CBL0137 cell treatment, but the prevalent type of arrest varied. Apoptosis activation by CBL0137 measured by Annexin-V/PI dual staining was more active in AML and MM cells. RT2 PCR array showed that changes caused by CBL0137 in signaling pathways involved in cancer pathogenesis were more intensive in AML and MM cells. On the murine model of AML WEHI-3, CBL0137 showed significant anticancer effects in vivo, which were evaluated by corresponding changes in spleen and liver. Thus, more pronounced anticancer effects of CBL0137 in vitro were observed in respect to AML and MM. Experiments in vivo also indicated the perspective of CBL0137 use for AML treatment. This in accordance with the frontline treatment approach in AML using epigenetic drugs

DR5-Selective TRAIL Variant DR5-B Functionalized with Tumor-Penetrating iRGD Peptide for Enhanced Antitumor Activity against Glioblastoma

TRAIL (TNF-related apoptosis-inducing ligand) and its derivatives are potentials for anticancer therapy due to the selective induction of apoptosis in tumor cells upon binding to death receptors DR4 or DR5. Previously, we generated a DR5-selective TRAIL mutant variant DR5-B overcoming receptor-dependent resistance of tumor cells to TRAIL. In the current study, we improved the antitumor activity of DR5-B by fusion with a tumor-homing iRGD peptide, which is known to enhance the drug penetration into tumor tissues. The obtained bispecific fusion protein DR5-B-iRGD exhibited dual affinity for DR5 and integrin αvβ3 receptors. DR5-B-iRGD penetrated into U-87 tumor spheroids faster than DR5-B and demonstrated an enhanced antitumor effect in human glioblastoma cell lines T98G and U-87, as well as in primary patient-derived glioblastoma neurospheres in vitro. Additionally, DR5-B-iRGD was highly effective in a xenograft mouse model of the U-87 human glioblastoma cell line in vivo. We suggest that DR5-B-iRGD may become a promising candidate for targeted therapy for glioblastoma