Search

CD4 T cells orchestrate the immune response by differentiating into T helper (Th) or regulatory (Treg) cell subsets that secrete distinct sets of cytokines. They also play a critical role in the pathogenesis of autoimmunity, asthma, allergy and, likely, cancer. The mechanisms involved in the regulation of CD4 T cell homeostasis by galectin-1 remain poorly characterized. To investigate whether galectin-1 modulates the differentiation of CD4 T cells, the effects of galectin-1 on the mRNA expression levels of TBX21, GATA- 3, FOXP3 and RORC in activated peripheral blood mononuclear cells were examined. The expression levels of GATA- 3 and FOXP3 mRNA were up-regulated after treatment with 1.0 μg/ml galectin-1 and were unchanged (for GATA- 3) or slightly elevated (for FOXP3) compared with untreated cells when 2.0 μg/ml galectin-1 was added. At the same time, at both concentrations of galectin-1, we observed reduced TBX21 and RORC mRNA expression levels. These findings support the concept that galectin-1 skews the differentiation of CD4 T cells towards Th2 and Treg cells. [ABSTRACT FROM AUTHOR]

Several groups of CD4 + T lymphocytes, known as Th1, Th2, Treg, and Th17, have currently been identified and well studied. Methods based on targeted regulation of differentiation of Th lymphocytes, which perform the immune response polarization, attract attention of scientists dealing with correction of immunemediated diseases. In the present study, endogenous β-galactoside-binding protein of the lectin family, galectin-3, was investigated as a regulator of T-cell homeostasis. Galectin-3 is known to be actively produced by tumor cells in malignant transformation and able to influence the processes of signal transduction, cell-cell cooperation, and the implementation of programmed cell death. As cell differentiation processes are directly connected with the regulation of gene expression, we investigated the effect of recombinant galectin-3 on expression of mRNA of transcription factors that guide differentiation of CD4 + lymphocytes. The study was performed using mononuclear cells from the peripheral blood of healthy individuals. The levels of gene expression were evaluated by real-time PCR. In the in vitro experiments, recombinant galectin-3 (0.5 mg/mL) upregulated mRNA expression of transcription factors Gala-3 and Rorc and down-regulated mRNA expression of transcription factors T-bet and FoxP3. Up to a concentration of 1 μg/mL, recombinant galectin-3 stimulated Th-cell in a dose-dependent manner, whereas at higher concentrations, the stimulating effect weakened and inhibitory effect started prevailing. Thus, one can suppose that, through the regulation of lymphocyte differentiation, galectin-3 promotes the development of allergic, autoimmune, and neoplastic diseases, which allows us to consider galectin-3 as a potential target for therapy of these diseases. [ABSTRACT FROM AUTHOR]

Genomic profiling, or molecular profiling of the tumor, is becoming a key component of therapeutic decision making in clinical oncology, and is typically carried out via next generation sequencing. However, the interpretation of the results and evaluation of rationale for targeting the uncovered alterations is challenging and requires a deep understanding of cancer biology, genetics, genomics and oncology. Multidisciplinary molecular tumor boards represent a promising strategy in the facilitation of molecularly-informed therapeutic decisions, and usually consist of specialists with various fields of expertise. To effectively communicate the biological and clinical significance of genomic findings, as well as to make molecular tumor board discussions more productive, we developed and implemented evidence blocks into case discussions in our center. We found that this approach facilitated clinicians' understanding of the results of genomic profiling, and resulted in shorter yet more efficient case discussions within the molecular tumor board. Here, we discuss our experience with evidence blocks and how their implementation influenced the molecular tumor board practice., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Alexandra Lebedeva reports a relationship with OncoAtlas LLC that includes: employment. Olesya Kuznetsova reports a relationship with OncoAtlas LLC that includes: employment. Maxim Ivanov reports a relationship with OncoAtlas LLC that includes: employment. Alexandra Kavun reports a relationship with OncoAtlas LLC that includes: employment. Egor Veselovsky reports a relationship with OncoAtlas LLC that includes: employment. Ekaterina Belova reports a relationship with OncoAtlas LLC that includes: employment. Vladislav Mileyko reports a relationship with OncoAtlas LLC that includes: employment and equity or stocks. Valentina Yakushina reports a relationship with OncoAtlas LLC that includes: employment., (© 2024 The Authors. Published by Elsevier Ltd.)

With the growing use of comprehensive tumor molecular profiling (CTMP), the therapeutic landscape of cancer is rapidly evolving. NGS produces large amounts of genomic data requiring complex analysis and subsequent interpretation. We sought to determine the utility of publicly available knowledge bases (KB) for the interpretation of the cancer mutational profile in clinical practice. Analysis was performed across patients who previously underwent CTMP. Independent interpretation of the CTMP was performed manually, and then, the recommendations were compared to ones present in KBs (OncoKB, CIViC, CGI, CGA, VICC, MolecularMatch). A total of 222 CTMP reports from 222 patients with 932 genomic alterations (GA) were identified. For 368 targetable GA identified in 171 (77%) of the patients, 1381 therapy recommendations were compiled. Except for CGA, therapy ESCAT LOE I, II, IIIA and IIIB therapy options were equally represented in the majority of KB. Personalized treatment options with ESCAT LOE I-II were provided for 35 patients (16%); MolecularMatch/CIViC allowed to collect ESCAT I-II treatment options for 34 of them (97%), OncoKB/CGI-for 33 of them (94%). Employing VICC and CGA 6 (17%) and 20 (57%) of patients were left without ESCAT I or II treatment options. For 88 patients with ESCAT level III-B therapy recommendations: only 2 (2%), 3 (3%), 4 (5%) and 6 (7%) of patients were left without options with CIViC, MolecularMatch, CGI and OncoKB, and with VICC-12 (14%). Highest overlap ratio was observed for IIIA (0.81) biomarkers, with the comparable results for LOE I-II. Meanwhile, overlap ratio for ESCAT LOE IV was 0.22. Public KBs provide substantial information on ESCAT-I/R1 biomarkers, but the information on ESCAT II-IV and resistance biomarkers is underrepresented. Manual curation should be considered the gold standard for the CTMP interpretation., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Microsatellite instability (MSI) is one of the most important molecular characteristics of a tumor, which occurs among various tumor types. In this review article, we examine the molecular characteristics of MSI tumors, both sporadic and Lynch-associated. We also overview the risks of developing hereditary forms of cancer and potential mechanisms of tumor development in patients with Lynch syndrome. Additionally, we summarize the results of major clinical studies on the efficacy of immune checkpoint inhibitors for MSI tumors and discuss the predictive role of MSI in the context of chemotherapy and checkpoint inhibitors. Finally, we briefly discuss some of the underlying mechanisms causing therapy resistance in patients treated with immune checkpoint inhibitors.

The aim of this study was to establish the role of redox modification of proteins and redox status in the realization of apoptosis of MCF-7 breast adenocarcinoma cells du-ing cultivation with the SH-group blocker N-ethylmaleimide (NEM) and the SH-group protector 1,4-dithioerythritol (DTE). The activation of apoptosis in MCF-7 breast adenocarcinoma cells was shown to be due to the irreversible modification of redox sensitive protein molecules. The presence of DTE in the culture medium of cancer.cells caused reversible glutathionylation of protein molecules and did not change the: number of apoptotic MCF-7 cells.

The effects of the SH-group blocker N-ethylmaleimide (NEM) and thiol group protector 1,4-dithioerythritol (DTE) on the redox status of cells HBL-100 cells, oxidative modification of their proteins and the state of glutathione and thioredoxin systems have been investigated. Breast epithelial cells cultivated in the presence of NEM were characterized by decreased redox status, increased glutathione reductase activity, and increased concentrations of products of irreversible oxidative modification of protein and amino acids. Cultivation of HBL-100 cells in the presence of DTE resulted in a shift of the redox status towards reduction processes and increased reversible protein modification by glutathionylation. The proposed model of intracellular redox modulation may be used in the development of new therapeutic approaches to treat diseases accompanied by impaired redox homeostasis (e.g. oncologic, inflammatory, cardiovascular and neurodegenerative disease).