Search results for "stone"

Molecular Signatures Associated with Treatment of Triple-Negative MDA-MB231 Breast Cancer Cells with Histone Deacetylase Inhibitors JAHA and SAHA

2017

Jay Amin Hydroxamic Acid (JAHA; N8-ferrocenylN1-hydroxy-octanediamide) is a ferrocene-containing analogue of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA). JAHA’s cytotoxic activity on MDA-MB231 triple negative breast cancer (TNBC) cells at 72 h has been previously demonstrated with an IC50 of 8.45 M. JAHA’s lethal effect was found linked to perturbations of cell cycle, mitochondrial activity, signal transduction and autophagy mechanisms. In order to glean novel insights on how MDA-MB231 breast cancer cells respond to the cytotoxic effect induced by JAHA, and to compare the biological effect with the related compound SAHA, we have employed a combination of…

Inhibition of cell migration and induction of apoptosis by a novel class II histone deacetylase inhibitor, MCC2344.

2020

Epigenetic modifiers provide a new target for the development of anti-cancer drugs. The eraser histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase that targets various non-histone proteins such as transcription factors, nuclear receptors, cytoskeletal proteins, DNA repair proteins, and molecular chaperones. Therefore, it became an attractive target for cancer treatment. In this study, virtual screening was applied to the MicroCombiChem database with 1162 drug-like compounds to identify new HDAC6 inhibitors. Five compounds were tested in silico and in vitro as HDAC6 inhibitors. Both analyses revealed 1-cyclohexene-1-carboxamide, 2-hydroxy-4,4-dimethyl-N-1-naphthalenyl-6-oxo- (MC…

Tumor-derived immuno-modulators induce overlapping pro-tolerogenic gene expression signatures in human dendritic cells.

2016

Immature dendritic cells (iDCs) and tolerogenic DCs are essential for the induction and maintenance of peripheral tolerance. Tumors produce immuno-modulatory factors which imprint a pro-tolerogenic, maturation-resistant state in DCs. Here we asked for common markers of differentially tolerized human monocyte-derived DC populations. For this, PBMC-derived monocytes were differentiated to DCs in the presence of established immuno-modulators as released by tumors (IL-6, IL-10, TGF-β, glucocorticoid [GC], prostaglandin E2 [PGE2]). Most unstimulated pro-tolerogenic DC populations commonly over-expressed some tolerance-associated markers (ILT-4, IL-10, HO-1) as compared with iDCs. These markers m…

2020

ObjectiveThe HBV HBx regulatory protein is required for transcription from the covalently closed circular DNA (cccDNA) minichromosome and affects the epigenetic control of both viral and host cellular chromatin.DesignWe explored, in relevant cellular models of HBV replication, the functional consequences of HBx interaction with DLEU2, a long non-coding RNA (lncRNA) expressed in the liver and increased in human hepatocellular carcinoma (HCC), in the regulation of host target genes and the HBV cccDNA.ResultsWe show that HBx binds the promoter region, enhances the transcription and induces the accumulation of DLEU2 in infected hepatocytes. We found that nuclear DLEU2 directly binds HBx and the…

Great Britain and Differentiated Integration in Europe

2018

The United Kingdom has always been a special case in the European integration project. The British exceptionalism manifested in various forms and ways over the history. June 23rd 2016 delivered another culmination point in the story of the stubborn European’s relations with its continental partners. The so-called Brexit referendum, which brought about victory for the supporters of the UK leaving the European Union, marks an important milestone in these relations. It has never been an easy marriage and many times threatened by the divorce. Instead of becoming ever closer, the European Union becomes ever loser and the UK is ever closer to leaving. Brexit is not only vital for the British, it …

Urology practice during the COVID-19 vaccination campaign

2021

Introduction: The current scenario of the COVID-19 pandemic is significantly different from that of the first, emergency phase. Several countries in the world are experiencing a second, or even a third, wave of contagion, while awaiting the effects of mass vaccination campaigns. The aim of this report was to provide an update of previously released recommendations on prioritization and restructuring of urological activities. Methods: A large group of Italian urologists directly involved in the reorganization of their urological wards during the first and second phase of the pandemic agreed on a set of updated recommendations for current urology practice. Results: The updated recommendations…

Palaeomagnetic investigations in the Hercynian mountain belt of central Europe (Dataset)

1983

Exploration of the Activation Mechanism of the Epigenetic Regulator MLL3: A QM/MM Study

2021

The mixed lineage leukemia 3 or MLL3 is the enzyme in charge of the writing of an epigenetic mark through the methylation of lysine 4 from the N-terminal domain of histone 3 and its deregulation has been related to several cancer lines. An interesting feature of this enzyme comes from its regulation mechanism, which involves its binding to an activating dimer before it can be catalytically functional. Once the trimer is formed, the reaction mechanism proceeds through the deprotonation of the lysine followed by the methyl-transfer reaction. Here we present a detailed exploration of the activation mechanism through a QM/MM approach focusing on both steps of the reaction, aiming to provide new…

Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the a…

2015

Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of his…

Blastic plasmacytoid dendritic cell neoplasm: genomics mark epigenetic dysregulation as a primary therapeutic target

2018

Blastic Plasmacytoid Dendritic Cell Neoplasm is a rare and aggressive hematological malignancy currently lacking an effective therapy. To possibly identify genetic alterations useful for a new treatment design, we analyzed by whole-exome sequencing fourteen Blastic Plasmacytoid Dendritic Cell Neoplasm patients and the patient-derived CAL-1 cell line. The functional enrichment analysis of mutational data reported the epigenetic regulatory program as the most significantly undermined (P<.0001). In particular, twenty-five epigenetic-modifiers were found mutated (e.g., ASXL1, TET2, SUZ12, ARID1A, PHF2, CHD8); ASXL1 was the most frequently affected (28.6% of cases). To evaluate the impact of …