Search results for "Flow"

The NSL Chromatin-Modifying Complex Subunit KANSL2 Regulates Cancer Stem-like Properties in Glioblastoma That Contribute to Tumorigenesis.

2016

KANSL2 is an integral subunit of the nonspecific lethal (NSL) chromatin-modifying complex that contributes to epigenetic programs in embryonic stem cells. In this study, we report a role for KANSL2 in regulation of stemness in glioblastoma (GBM), which is characterized by heterogeneous tumor stem-like cells associated with therapy resistance and disease relapse. KANSL2 expression is upregulated in cancer cells, mainly at perivascular regions of tumors. RNAi-mediated silencing of KANSL2 in GBM cells impairs their tumorigenic capacity in mouse xenograft models. In clinical specimens, we found that expression levels of KANSL2 correlate with stemness markers in GBM stem-like cell populations. M…

IL4 Primes the Dynamics of Breast Cancer Progression via DUSP4 Inhibition

2017

Abstract The tumor microenvironment supplies proinflammatory cytokines favoring a permissive milieu for cancer cell growth and invasive behavior. Here we show how breast cancer progression is facilitated by IL4 secreted by adipose tissue and estrogen receptor–positive and triple-negative breast cancer cell types. Blocking autocrine and paracrine IL4 signaling with the IL4Rα antagonist IL4DM compromised breast cancer cell proliferation, invasion, and tumor growth by downregulating MAPK pathway activity. IL4DM reduced numbers of CD44+/CD24− cancer stem-like cells and elevated expression of the dual specificity phosphatase DUSP4 by inhibiting NF-κB. Enforced expression of DUSP4 drove conversio…

Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts

2021

Simple Summary Aberrant tissue factor (TF) expression by transformed myeloblasts and inflammatory monocytes contributes to coagulation activation in acute myeloid leukemia (AML). TF procoagulant activity (PCA) is regulated by protein disulfide isomerase (PDI), an oxidoreductase with chaperone activity, but its specific role in AML-associated TF biology is unclear. Here, we provide novel mechanistic insights into this interrelation. We show that bacitracin and rutin, two pan-inhibitors of the PDI family, prevent lipopolysaccharide (LPS)-induced monocyte TF production under inflammatory conditions and constitutive TF expression by THP1 cells and AML blasts, thus exerting promising anticoagula…

Imiquimod inhibits growth and induces differentiation of myeloid leukemia cell lines

2018

Background: The antitumoral effects of different Toll-like receptor (TLRs) agonists is mediated by activating immune responses to suppress tumors growth, although TLR ligands may also have a direct effect on tumoral cells. Given that TLR signaling induces hematopoietic cell differentiations this may serve as a novel differentiation therapeutic approach for AML. Methods: We investigated the effects of agonists for the ten human TLRs on the proliferation, apoptosis, cell cycle and differentiation of ten different types of myeloid leukemia cell lines (HL-60, U-937, KG-1, KG-1a, K-562, Kasumi-1, EOL-1, NB4, MOLM-13 and HEL). Proliferation was measured using the CellTiter 96 (R) Aqueous One Solu…

2021

Background Malignant melanoma is an immunogenic skin cancer with an increasing global incidence. Advanced stages of melanoma have poor prognoses. Currently, there are no reliable parameters to predict a patient's response to immune checkpoint inhibitor (ICI) therapy. Methods This study highlights the relevance of a distinct immune signature in the blood for response to ICI therapy and overall survival (OS). Therefore, the immune cell composition in the peripheral blood of 45 melanoma patients prior to ICI therapy was analyzed by flow cytometry and complete blood count. Results Responders to ICI therapy displayed an abundance of proliferating CD4+ T cells, an increased lymphocyte-to-monocyte…

Validating comprehensive next-generation sequencing results for precision oncology : The NCT/DKTK molecularly aided stratification for tumor eradicat…

2022

Purpose Rapidly evolving genomics technologies, in particular comprehensive next-generation sequencing (NGS), have led to exponential growth in the understanding of cancer biology, shifting oncology toward personalized treatment strategies. However, comprehensive NGS approaches, such as whole-exome sequencing, have limitations that are related to the technology itself as well as to the input source. Hence, clinical implementation of comprehensive NGS in a quality-controlled diagnostic workflow requires both the standardization of sequencing procedures and continuous validation of sequencing results by orthogonal methods in an ongoing program to enable the determination of key test parameter…

The genomic footprint of climate adaptation inChironomus riparius

2017

The gradual heterogeneity of climatic factors produces continuously varying selection pressures across geographic distances that leave signatures of clinal variation in the genome. Separating signatures of clinal adaptation from signatures of other evolutionary forces, such as demographic processes, genetic drift, and adaptation to specific non-clinal conditions of the immediate local environment is a major challenge. Here, we examine climate adaptation in five natural populations of the non-biting midge Chironomus riparius sampled along a climatic gradient across Europe. Our study integrates experimental data, individual genome resequencing, Pool-Seq data, and population genetic modelling.…

PTP1B phosphatase as a novel target of oleuropein activity in MCF-7 breast cancer model.

2019

Phosphatase PTP1B has become a therapeutic target for the treatment of type 2-diabetes, whereas recent studies have revealed that PTP1B plays a pivotal role in pathophysiology and development of breast cancer. Oleuropein is a natural, phenolic compound with anticancer activity. The aim of this study was to address the question whether PTP1B constitutes a target for oleuropein in breast cancer MCF-7 cells. The cellular MCF-7 breast cancer model was used in the study. The experiments were performed using cellular viability tests, Elisa assays, immunoprecipitation, flow cytometry analyses and computer modelling. Herein, we evidenced that the reduced activity of phosphatase PTP1B after treatmen…

Human Dental Pulp Stem Cells Exhibit Different Biological Behaviours in Response to Commercial Bleaching Products

2018

The purpose of this study was to evaluate the diffusion capacity and the biological effects of different bleaching products on human dental pulp stem cells (hDPSCs). The bleaching gel was applied for 90, 30 or 15 min to enamel/dentine discs that adapted in an artificial chamber. The diffusion of hydrogen peroxide (HP) was analysed by fluorometry and the diffusion products were applied to hDPSCs. Cell viability, cell migration and cell morphology assays were performed using the eluates of diffusion products. Finally, cell apoptosis and the expression of mesenchymal stem cell markers were analysed by flow cytometry. Statistical analysis was performed using analysis of variance and Kruskal&nda…

Differentiation and characterization of rat adipose tissue mesenchymal stem cells into endothelial-like cells

2018

In this study, mesenchymal stem cells were isolated from rat adipose tissue (AD-MSCs) to characterize and differentiate them into endothelial-like cells. AD-MSCs were isolated by mechanical and enzymatic treatments, and their identity was verified by colony-forming units (CFU) test and by differentiation into cells of mesodermal lineages. The endothelial differentiation was induced by plating another aliquot of cells in EGM-2 medium, enriched with specific endothelial growth factors. Five subcultures were performed. The expression of stemness genes (OCT4, SOX2 and NANOG) was investigated. The presence of CD90 and the absence of the CD45 were evaluated by flow cytometry. The endothelial-like…