A5067721540- Glioma Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- MicroRNA in disease regulation
- RNA Research and Splicing
- RNA modifications and cancer
- Cell Adhesion Molecules Research
- Histone Deacetylase Inhibitors Research
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Molecular Biology Techniques and Applications
- Cancer-related molecular mechanisms research
- Circular RNAs in diseases
- Cancer Genomics and Diagnostics
- RNA Interference and Gene Delivery
- Diet and metabolism studies
- Genomics and Chromatin Dynamics
- Retinoids in leukemia and cellular processes
- Ubiquitin and proteasome pathways
- Advanced biosensing and bioanalysis techniques
- Cytokine Signaling Pathways and Interactions
- Cellular Mechanics and Interactions
- Congenital heart defects research
- Platelet Disorders and Treatments
- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
Luxembourg Institute of Health
2015-2023
University of Luxembourg
2010-2016
Laboratoire National de Santé
2001-2016
Genomics (United Kingdom)
2014-2015
Centre de Médecine Préventive
2012
Centre National de la Recherche Scientifique
1999-2002
Centre Hospitalier de Luxembourg
2001
University of Cologne
2000
Centre de Gestion Scientifique
1999
Inserm
1992-1996
Abstract Chemotherapy-resistant human acute myeloid leukemia (AML) cells are thought to be enriched in quiescent immature leukemic stem (LSC). To validate this hypothesis vivo, we developed a clinically relevant chemotherapeutic approach treating patient-derived xenografts (PDX) with cytarabine (AraC). AraC residual AML neither immature, nor LSCs. Strikingly, AraC-resistant preexisting and persisting displayed high levels of reactive oxygen species, showed increased mitochondrial mass,...
Systemic inflammatory reactions have been postulated to exacerbate neurodegenerative diseases via microglial activation. We now demonstrate <i>in vivo</i> that repeated systemic challenge of mice over four consecutive days with bacterial LPS maintained an elevated phenotype and induced loss dopaminergic neurons in the substantia nigra. The same total cumulative dose given within a single application did not induce neurodegeneration. Whole-genome transcriptome analysis brain demonstrated...
Small noncoding microRNAs (miRNA) regulate the expression of target mRNAs by repressing their translation or orchestrating sequence-specific degradation. In this study, we investigated miRNA and gene patterns in melanoma to identify candidate biomarkers for early progressive disease. Because data presently available on are inconsistent thus far, applied several different detection profiling techniques a panel 10 cell lines 20 patient samples representing nevi primary metastatic melanoma....
MicroRNAs (miRNAs) are ubiquitously expressed small non-coding RNAs that, in most cases, negatively regulate gene expression at the post-transcriptional level. miRNAs involved fine-tuning fundamental cellular processes such as proliferation, cell death and cycle control believed to confer robustness biological responses. Here, we investigated simultaneously transcriptional changes of miRNA mRNA levels over time after activation Janus kinase/Signal transducer activator transcription...
Major efforts have been put in anti-angiogenic treatment for glioblastoma (GBM), an aggressive and highly vascularized brain tumor with dismal prognosis. However clinical outcome agents has disappointing tumors quickly develop escape mechanisms. In preclinical GBM models we recently shown that bevacizumab, a blocking antibody against vascular endothelial growth factor, induces hypoxia treated tumors, which is accompanied by increased glycolytic activity invasiveness. Genome-wide...
Glioblastoma (GBM) is known to be a heterogeneous disease; however, the genetic composition of cells within given tumour only poorly explored. In advent personalised medicine understanding intra-tumoural heterogeneity at cellular and level mandatory improve treatment clinical outcome. By combining ploidy-based flow sorting with array-comparative genomic hybridization we show that primary GBMs present as either mono- or polygenomic tumours (64 versus 36 %, respectively). Monogenomic were...
Hypoxia is negatively associated with glioblastoma (GBM) patient survival and contributes to tumour resistance. Anti-angiogenic therapy in GBM further increases hypoxia activates pathways. The aim of this study was determine the role hypoxia-induced autophagy GBM.Pharmacological inhibition applied combination bevacizumab patient-derived xenografts (PDXs). Sensitivity towards inhibitors tested vitro under normoxia hypoxia, followed by transcriptomic analysis. Genetic interference done using...
Actin-related proteins (ARPs) are key players in cytoskeleton activities and nuclear functions. Two complexes, ARP2/3 ARP1/11, also known as dynactin, implicated actin dynamics microtubule-based trafficking, respectively. ARP4 to ARP9 components of many chromatin-modulating complexes. Conventional actins ARPs codefine a large family homologous proteins, the superfamily, with tertiary structure fold. Because share high sequence conservation, clear definition requires distinct features easily...
While the autophagic process is mainly regulated at post-translational level, a growing body of evidence suggests that autophagy might also be transcriptional level. The identification transcription factors involved in regulation genes has provided compelling for such regulation. In this context, powerful high throughput analysis tool to simultaneously monitor expression level urgently needed. Here we describe setting up first comprehensive human database (HADb, available www.autophagy.lu)...
Chemotherapeutic drugs used in the treatment of acute myeloid leukemias (AMLs) are thought to induce cancer cell death through generation DNA double-strand breaks. Here, we report that one their early effects is loss conjugation ubiquitin-like protein SUMO from its targets via reactive oxygen species (ROS)-dependent inhibition SUMO-conjugating enzymes. Desumoylation regulates expression specific genes, such as proapoptotic gene DDIT3, and helps apoptosis chemosensitive AMLs. In contrast,...
The identification and significance of cancer stem-like cells in malignant gliomas remains controversial. It has been proposed that display increased drug resistance, through the expression ATP-binding cassette transporters detoxify by effluxing exogenous compounds. Here, we investigated 'side population' phenotype based on efflux properties freshly isolated human glioblastoma samples intracranial xenografts derived thereof. Using fluorescence situ hybridization analysis sorted obtained from...
Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions. Its function has been recently described: it codes for immune-responsive protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalysing production itaconic from cis-aconitic acid, a tricarboxylic (TCA) cycle intermediate. Itaconic possesses specific antimicrobial properties inhibiting isocitrate lyase, first glyoxylate shunt, anaplerotic pathway that bypasses TCA and...
The histopathological and molecular heterogeneity of glioblastomas represents a major obstacle for effective therapies. Glioblastomas do not develop autonomously, but evolve in unique environment that adapts to the growing tumour mass contributes malignancy these neoplasms. Here, we show patient-derived glioblastoma xenografts generated mouse brain from organotypic spheroids reproducibly give rise three different histological phenotypes: (i) highly invasive phenotype with an apparent normal...
RNA sequencing (RNA-seq) and microarrays are two transcriptomics techniques aimed at the quantification of transcribed genes their isoforms. Here we compare latest Affymetrix HTA 2.0 microarray with Illumina 2000 RNA-seq for analysis patient samples - normal lung epithelium tissue squamous cell carcinoma tumours. Protein coding mRNAs long non-coding RNAs (lncRNAs) were included in study. Both platforms performed equally well protein-coding RNAs, however stochastic variability was higher data...
Acute myeloid leukemia (AML) is characterized by the accumulation of malignant blasts with impaired differentiation programs caused recurrent mutations, such as isocitrate dehydrogenase (IDH) mutations found in 15% AML patients. These result production oncometabolite (R)-2-hydroxyglutarate (2-HG), leading to a hypermethylation phenotype that dysregulates hematopoietic differentiation. In this study, we identified mutant R132H IDH1-specific gene signatures regulated key transcription factors,...
Invasion and angiogenesis are major hallmarks of glioblastoma (GBM) growth. While invasive tumor cells grow adjacent to blood vessels in normal brain tissue, within neovascularized regions exhibit hypoxic stress promote angiogenesis. The distinct microenvironments likely differentially affect metabolic processes the cells.In present study, we analyzed gene expression changes a human GBM xenograft model that displayed angiogenic phenotypes. In addition, used glioma patient biopsies confirm...
Calreticulin was recently identified as a hookworm Necator americanus allergen, implying secretion, and contact with cells of the immune system, or significant worm attrition in tissues host. As human calreticulin has been shown to bind neutralize haemolytic activity complement component C1q, be putatively involved integrin‐mediated intracellular signalling events platelets, it interest determine whether from successful nematode parasite humans, known modulatory antihaemostatic properties,...
Chronic lymphocytic leukemia (CLL) cells are often affected by genomic aberrations targeting key regulatory genes. Although fludarabine is the standard first line therapy to treat CLL, only few data available about resistance of B this purine nucleoside analog in vivo. Here we sought increase our understanding action and describe mechanisms leading We performed an analysis aberrations, gene expression profiles, microRNAs CLL blood lymphocytes isolated during course patients' treatment with...
We have previously shown that 2 human melanoma cell lines, the metastatic HT-144 and non-metastatic SK-Mel-2 cells, exhibit marked in vitro heterogeneity with respect to integrin expression, migration invasion potential. Here, we provide evidence but not undergo a reversible transition fibroblastoid morphology following treatment either their own serum-free acidified conditioned medium or biologically active exogenous TGF-β1, thus identifying TGF-β as an autocrine regulator of spindle shape...
Background Increasing number of evidence shows that soluble factors and extracellular matrix (ECM) components provide an optimal microenvironment controlling human bone marrow mesenchymal stem cell (MSC) functions. Successful in vivo administration cells lies their ability to migrate through ECM barriers differentiate along tissue-specific lineages, including endothelium. Lumican, a protein the small leucine-rich proteoglycan (SLRP) family, was shown impede migration angiogenesis. The aim...