A5073263363- Glioma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Radiomics and Machine Learning in Medical Imaging
- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- RNA Research and Splicing
- Neuroblastoma Research and Treatments
- Cancer Research and Treatments
- Ferroptosis and cancer prognosis
- Cancer, Hypoxia, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- interferon and immune responses
- Cancer Cells and Metastasis
- MicroRNA in disease regulation
- DNA Repair Mechanisms
- Immunotherapy and Immune Responses
- Cancer therapeutics and mechanisms
- Mitochondrial Function and Pathology
- Heat shock proteins research
- PARP inhibition in cancer therapy
- Cancer Genomics and Diagnostics
- Circular RNAs in diseases
- RNA and protein synthesis mechanisms
- Hereditary Neurological Disorders
Luxembourg Institute of Health
2015-2023
Institut pour l'avancée des biosciences
2007-2021
Inserm
2005-2021
Centre National de la Recherche Scientifique
2021
Université Grenoble Alpes
2021
Institut de Biosciences et Biotechnologies
2021
Heidelberg University
2019
Institut Pasteur
2014-2017
Organogenesis (United States)
2017
Universität Greifswald
2016
Abstract The identity and unique capacity of cancer stem cells (CSC) to drive tumor growth resistance have been challenged in brain tumors. Here we report that expressing CSC-associated cell membrane markers Glioblastoma (GBM) do not represent a clonal entity defined by distinct functional properties transcriptomic profiles, but rather plastic state most can adopt. We show phenotypic heterogeneity arises from non-hierarchical, reversible transitions, instructed the microenvironment is...
A cellular defense mechanism counteracts the deleterious effects of misfolded protein accumulation by eliciting a stress response. The cytoplasmic deacetylase HDAC6 (histone 6) was previously shown to be key element in this response coordinating clearance aggregates through aggresome formation and their autophagic degradation. Here, for first time, we demonstrate that is involved another crucial cell ubiquitinated aggregates, unravel its molecular basis. Indeed, our data show senses...
Research Article20 October 2017Open Access Transparent process Altered metabolic landscape in IDH-mutant gliomas affects phospholipid, energy, and oxidative stress pathways Fred Fack NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute Health, City, Search for more papers by this author Saverio Tardito Cancer Metabolism Unit, UK, Beatson Institute, Glasgow, UK Guillaume Hochart IMABIOTECH, Loos, France Anais Oudin Liang Zheng Sabrina Fritah Anna Golebiewska Petr V...
Abstract Long non-coding RNAs play critical roles in tumour progression. Through analysis of publicly available genomic datasets, we found that MIR22HG, the host gene microRNAs miR-22-3p and miR-22-5p, is ranked among most dysregulated long glioblastoma. The main purpose this work was to determine impact MIR22HG on glioblastoma growth invasion elucidate its mechanistic function. MIR22HG/miR-22 axis highly expressed as well glioma stem-like cells compared normal neural stem cells. In...
Amplification of the epidermal growth factor receptor (EGFR) and its mutant EGFRvIII are among most common genetic alterations in glioblastoma (GBM), frequent aggressive primary brain tumor.In present work, we analyzed clonal evolution these major EGFR aberrations a small cohort GBM patients using unique surgical multisampling technique. Furthermore, overexpressed both receptors separately together 2 patient-derived stem cell lines (GSCs) to analyze their functions vivo orthotopic xenograft...
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...
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...
A major regulatory function has been evidenced here for HSF1, the key transcription factor of heat-shock response, in a large-scale remodeling cell epigenome. Indeed, upon heat shock, addition to its well-known transactivating activities, mediates genome-wide and massive histone deacetylation. Investigating underlying mechanisms, we show that HSF1 specifically associates with uses HDAC1 HDAC2 trigger this heat-shock-dependent This work therefore identifies as master regulator global...
The immune response of T lymphocytes to pathogens is initiated in draining secondary lymphoid organs, and activated cells then migrate the site infection. Thus, control naive regulatory CD4+ T-cell migration crucial; however, it poorly understood physiological pathological conditions. We found that subpopulations displayed characteristic regulator G-protein signalling (RGS) gene expression profiles. Regulatory express higher levels RGS1, RGS9 RGS16 than cells. These genes are up-regulated...
Disruption of the sumoylation/desumoylation equilibrium is associated with several disease states such as cancer and infections, however mechanisms regulating global SUMO balance remain poorly defined. Here, we show that infection by Shigella flexneri, causative agent human bacillary dysentery, switches off host sumoylation during epithelial cell in vitro vivo this effect mainly mediated a calcium/calpain-induced cleavage E1 enzyme SAE2, thus leading to inhibition. Furthermore, describe...
Abstract Replication-associated single-ended DNA double-strand breaks (seDSBs) are repaired predominantly through RAD51-mediated homologous recombination (HR). Removal of the non-homologous end-joining (NHEJ) factor Ku from resected seDSB ends is crucial for HR. The coordinated actions MRE11-CtIP nuclease activities orchestrated by ATM define one pathway eviction. Here, we identify pre-mRNA splicing protein XAB2 as a required resistance to seDSBs induced chemotherapeutic alkylator...
By generating protein diversity, alternative splicing provides an important oncogenic pathway. Isocitrate dehydrogenase (IDH) 1 and 2 mutations 1p/19q co-deletion have become crucial for the novel molecular classification of diffuse gliomas, which also incorporates DNA methylation profiling. In this study, we carried out a bioinformatics analysis to examine impact IDH mutation, as well glioma CpG island methylator phenotype (G-CIMP) status on in cohort 662 gliomas from The Cancer Genome...
Resistance to chemotherapy by temozolomide (TMZ) is a major cause of glioblastoma (GBM) recurrence. So far, attempts characterize factors that contribute TMZ sensitivity have largely focused on protein-coding genes, and failed provide effective therapeutic targets. Long noncoding RNAs (lncRNAs) are essential regulators epigenetic-driven cell diversification, yet, their contribution the transcriptional response drugs less understood. Here, we performed RNA-seq small comprehensive map...
Abstract The heat shock factor 1 (HSF1)-dependent transcriptional activation of human pericentric heterochromatin in heat-shocked cells is the most striking example heterochromatin. Until now, chromosome 9 has been identified as primary target HSF1, both normal and tumor cells. Transcriptional awakening this large genomic region results nuclear accumulation satellite III ( SATIII ) noncoding RNAs (ncRNAs) formation cis specific structures known stress bodies (nSBs). Here, we show that, four...
Targeted approaches for inhibiting epidermal growth factor receptor (EGFR) and other tyrosine kinases (RTKs) in glioblastoma (GBM) have led to therapeutic resistance little clinical benefit, raising the need development of alternative strategies. Endogenous LRIG1 (Leucine-rich Repeats ImmunoGlobulin-like domains protein 1) is an RTK inhibitory required stem cell maintenance, we previously demonstrated soluble ectodomain (sLRIG1) potently inhibit GBM vitro vivo.Here, generated a recombinant...
The 'Precision Medicine for Cancer' was the first meeting of a new series conferences organised biannually by European Association Cancer Research (EACR) and Organisation Institutes (OECI). main objective to focus on novel topics in precision medicine allowing strong interactions between participants access speakers easily. As implementations personalised are appreciated clinic, aim further educate both researchers clinicians learn more from approaches field. Similarly, interaction two...
Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor prognosis (the median survival of GBM patients 14.6 months). Current treatment, which consists surgical resection followed by radiation therapy and temozolomide (TMZ) chemotherapy, faced the development resistance. The DNA-alkylating agent TMZ exerts its cytotoxic function damaging DNA inducing cell death. However, efficient repair and/or tolerance TMZ-induced lesions can mediate resistance to chemotherapy. One such...
Abstract Genetic and signaling pathways involved in the development of glioblastoma have been relatively well characterized. Gene/protein expression profiles described that reflect stem-like phenotype tumor. However, no reliable individual markers exist up-to-date differentiate cells from neural stem cells. Glioblastoma appears to be heterogenous cellular population, but detailed origin these tumors is unknown. Using a label-free proteomic approach, we analyzed two different glioma models...