Search results for "MerA"
showing 10 items of 3426 documents
CD36 gene is associated with intraocular pressure elevation after intravitreal application of anti-VEGF agents in patients with age-related macular d…
2017
IF 1.886; International audience; Background: The wet form of age-related macular degeneration (AMD) is characterized by pathological vascularization of the outer retinal layers. The condition responds to treatment with antibodies against vascular endothelial growth factor (VEGF), but the patients receiving such anti-VEGF therapy sometimes show undesirable acute short-term increases in the intraocular pressure (IOP). The cause of this adverse effect is unknown, and here, we are testing a hypothesis that it is related to CD36 gene polymorphisms.Materials and Methods: A group of 134 patients with AMD were given three therapeutic doses of anti-VEGF antibody (ranibizumab) at monthly intervals. …
Increased expression of interleukin-22 in patients with giant cell arteritis
2017
Objectives GCA is characterized by arterial remodelling driven by inflammation. IL-22 is an attractive cytokine which acts at the crosstalk between immune and stromal cells. We hypothesized that IL-22 might be induced in GCA and might be involved in disease pathogenesis. Methods Patients subjected to temporal artery biopsies (TABs) naive from therapy were enrolled: 27 biopsy-proven GCA, 8 biopsy-negative GCA, 21 biopsy-negative non-GCA patients. Expression of IL-22 was determined in TABs by immunohystochemistry, in plasma by ELISA, in peripheral blood mononuclear cells by real-time PCR and flow cytometry. Effects of IL-22 on viability and gene expression of primary cultures obtained from TA…
Reciprocal regulation of the Il9 locus by counteracting activities of transcription factors IRF1 and IRF4.
2017
The T helper 9 (Th9) cell transcriptional network is formed by an equilibrium of signals induced by cytokines and antigen presentation. Here we show that, within this network, two interferon regulatory factors (IRF), IRF1 and IRF4, display opposing effects on Th9 differentiation. IRF4 dose-dependently promotes, whereas IRF1 inhibits, IL-9 production. Likewise, IRF1 inhibits IL-9 production by human Th9 cells. IRF1 counteracts IRF4-driven Il9 promoter activity, and IRF1 and IRF4 have opposing function on activating histone modifications, thus modulating RNA polymerase II recruitment. IRF1 occupancy correlates with decreased IRF4 abundance, suggesting an IRF1-IRF4-binding competition at the I…
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…
Extracellular Vesicles Shed by Melanoma Cells Contain a Modified Form of H1.0 Linker Histone and H1.0 mRNA-binding Proteins
2016
Extracellular vesicles (EVs) are shed in the extracellular environment by both prokaryotes and eukaryotes. Although produced from both normal and cancer cells, malignant cells release a much higher amount of EVs, which also contain tumor-specific proteins and RNAs. We previously found that G26/24 oligodendroglioma cells shed EVs that contain the pro-apoptotic factors FasL and TRAIL1-2. Interestingly, G26/24 release, via EVs, extracellular matrix remodelling proteases3, and H1° histone protein4, and mRNA. To shed further light on the role of EVs in discarding proteins and mRNAs otherwise able to counteract proliferative signals, we studied a melanoma cell line (A375). We found that also thes…
Growth differentiation factor 15 as a radiation-induced marker in oral carcinoma increasing radiation resistance.
2015
Background Growth differentiation factor 15 (GDF15) is involved in tumor pathogenesis of oral squamous cell carcinoma (OSCC). The aim of this study was an investigation of the potential influence of GDF15 on radioresistance of OSCC cells in vitro. Methods Oral squamous cell carcinoma cell lines were irradiated with 0, 2, or 6 Gy, and GDF15 expression in the supernatant per survived cell colony was examined with ELISA. Non-irradiated and OSCC cell lines irradiated with 6 Gy were evaluated for GDF15 expression using immunofluorescent staining. For further investigation of GDF15 effects on radioresistance, a GDF15 knockdown model in a human OSCC cell line was established, and apoptotic activit…
NGS‐based liquid biopsy profiling identifies mechanisms of resistance to ALK inhibitors: a step toward personalized NSCLC treatment
2021
Despite impressive and durable responses, nonsmall cell lung cancer (NSCLC) patients treated with anaplastic lymphoma kinase (ALK) inhibitors (ALK‐Is) ultimately progress due to development of resistance. Here, we have evaluated the clinical utility of circulating tumor DNA (ctDNA) profiling by next‐generation sequencing (NGS) upon disease progression. We collected 26 plasma and two cerebrospinal fluid samples from 24 advanced ALK‐positive NSCLC patients at disease progression to an ALK‐I. These samples were analyzed by NGS and digital PCR. A tool to retrieve variants at the ALK locus was developed (VALK tool). We identified at least one resistance mutation in the ALK locus in ten (38.5%) p…
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…
Parthenolide and DMAPT exert cytotoxic effects on breast cancer stem-like cells by inducing oxidative stress, mitochondrial dysfunction and necrosis
2016
Triple-negative breast cancers (TNBCs) are aggressive forms of breast carcinoma associated with a high rate of recidivism. In this paper, we report the production of mammospheres from three lines of TNBC cells and demonstrate that both parthenolide (PN) and its soluble analog dimethylaminoparthenolide (DMAPT) suppressed this production and induced cytotoxic effects in breast cancer stem-like cells, derived from dissociation of mammospheres. In particular, the drugs exerted a remarkable inhibitory effect on viability of stem-like cells. Such an effect was suppressed by N-acetylcysteine, suggesting a role of reactive oxygen species (ROS) generation in the cytotoxic effect. Instead z-VAD, a ge…
Plastic and micro-evolutionary responses of a nematode to the host immune environment
2017
9 pages; International audience; Parasitic organisms have to cope with the defences deployed by their hosts and this can be achieved adopting immune evasion strategies or optimal life history traits according to the prevailing pattern of immune-mediated mortality. Parasites often encounter variable immune environments both within and between hosts, promoting the evolution of plastic strategies instead of fixed responses. Here, we explored the plasticity and micro-evolutionary responses of immunomodulatory mechanisms and life history traits to the immune environment provided by the host, using the parasitic nematode Heligmosomoides polygyrus. To test if the parasite responds plastically to t…