A5059410255- Gut microbiota and health
- Cancer-related Molecular Pathways
- Acute Myeloid Leukemia Research
- Cytokine Signaling Pathways and Interactions
- Dietary Effects on Health
- Lung Cancer Research Studies
- Diet and metabolism studies
- Cell death mechanisms and regulation
- Cancer Genomics and Diagnostics
- Lymphoma Diagnosis and Treatment
- Advanced Breast Cancer Therapies
- Biochemical and Molecular Research
- Chronic Lymphocytic Leukemia Research
- RNA regulation and disease
- RNA Research and Splicing
- ATP Synthase and ATPases Research
- Histone Deacetylase Inhibitors Research
- Genetic factors in colorectal cancer
- RNA Interference and Gene Delivery
- Genomics and Chromatin Dynamics
The Maria Sklodowska-Curie National Research Institute of Oncology
2016-2021
Inhibition of oncogenic transcriptional programs is a promising therapeutic strategy. A substituted tricyclic benzimidazole, SEL120-34A, novel inhibitor Cyclin-dependent kinase 8 (CDK8), which regulates transcription by associating with the Mediator complex. X-ray crystallography has shown SEL120-34A to be type I forming halogen bonds protein's hinge region and hydrophobic complementarities within its front pocket. inhibits phosphorylation STAT1 S727 STAT5 S726 in cancer cells vitro....
Transplanting a fecal sample from lean, healthy donors to obese recipients has been shown improve metabolic syndrome symptoms. We therefore examined the gut microbiota in mice after administering long-term, high-fat diet (HFD) supplemented with feces lean through fecal-oral route. C57BL6/W were allowed adapt non-specific pathogen free (SFP) environment for 2 weeks before being divided into three groups of 16 animals. Animals fed 28 normal (ND), HFD or ND-fed (HFDS). The composition...
Genome-wide mechanisms that coordinate expression of subsets functionally related genes are largely unknown. Recent studies show receptor tyrosine kinases and components signal transduction cascades including the extracellular signal-regulated protein kinase (ERK), once thought to act predominantly in vicinity plasma membrane cytoplasm, can be recruited chromatin encompassing transcribed genes. distribution these transducers their relationship transcribing RNA polymerase II (Pol2) could...
Several studies employed the genome-wide association (GWA) analysis of single-nucleotide polymorphisms (SNPs) to identify susceptibility regions in colorectal cancer (CRC). However, functional exploring role associating SNPs with biology are limited. Herein, using chromatin immunoprecipitation assay (ChIP), reporter and chromosome conformation capture sequencing (3C-Seq) augmented publically available genomic epigenomic databases we aimed define function rs6702619/1p21.2 region associated...
TNF-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein capable of selectively inducing apoptosis in cancer cells by binding to its cognate receptors. Here, we examined the anticancer efficacy recently developed chimeric AD-O51.4 protein, TRAIL fused VEGFA-originating peptide. We tested activity against human colorectal (CRC) models and investigated resistance mechanism non-responsive CRC models. The quantitative comparison apoptotic between native nine cell lines...
Abstract Cyclin-dependent kinase 8 inhibitors (CDK8i) have anti-cancer activity in human acute myeloid leukaemia (AML) cell lines both vitro and vivo. Activity of CDK8i often involves deregulation super-enhancer-associated genes AML lines. Previous studies established SEL120 as a specific CDK8 inhibitor active cells with increased STAT1/5 signalling pathways. Differential gene expression analysis demonstrated high enrichment stem (LSC) signatures responding cells, linked to resistance...
Rarefraction curves from all samples on family level drawn with MEGAN5 software. (PDF 4369Â kb)
Abstract Despite heterogeneity deregulated transcription is one of the universal features leukemia cells. This has paved way for development active compounds targeting epigenetic and transcriptional factors. A substituted tricyclic benzimidazole, SEL120-34A, a novel inhibitor Cyclin-dependent kinase 8 (CDK8), which regulates by associating with Mediator complex. In many cancer cells SEL120-34A expression STAT1- dependent genes as major effect. AML regulation NUP98-HOXA9 - other programs...
Cyclin-dependent kinase 8 inhibitors (CDK8i) have anti-cancer activity in human acute myeloid leukaemia (AML) cell lines both vitro and vivo. Activity of CDK8i often involves deregulation super-enhancer-associated genes AML lines. Previous studies established SEL120 as a specific CDK8 inhibitor active cells with increased STAT1/5 signalling pathways. Differential gene expression analysis demonstrated high enrichment stem (LSC) signatures responding cells, linked to resistance standard...