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Olivier Grenet

Publications and source records attributed to Olivier Grenet.

5 recordsLinked to original sources
PubMed2006

Differentiation of spontaneous and induced mammary adenocarcinomas of the rat by gene expression profiling.

The differentiation of spontaneous and induced adenocarcinomas is of interest in the setting of carcinogenicity studies. In the experiment reported here, a differentiation of morphologically similar spontaneous and induced mammary adenocarcinomas of the rat is achieved by gene expression profiling. By choosing one marker gene based on the gene expression profile for each tumour type, we were able to distinguish the tumours by real-time quantitative polymerase chain reaction (RT-QPCR) as well.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2004

Contact allergens and irritants show discrete differences in the activation of human monocyte-derived dendritic cells: consequences for in vitro detection of contact allergens.

In recent years test systems have been described that may be applied routinely to discriminate between contact allergens and irritants in vitro. Using human monocyte-derived dendritic cells (MoDC), this study was designed to refine the settings of a potential routine screening protocol for contact allergens and to investigate the so far poorly defined concentration dependency of contact allergen-specific effects. MoDC were generated by 6 days of culture in the presence of IL-4 and GM-CSF and were then cultured for 24 or 48 h in medium with lipopolysaccharide (LPS), contact allergens [picrylsulphonic acid (TNBS), 1-chloro-2,4-dinitrobenzene (DNCB)] or irritants [sodium dodecyl sulphate (SDS), benzalkonium chloride (BAC)] that were free of detectable endotoxin contamination. The induction of CD86 and HLA-DR expression was quantified by flow cytometry as markers for MoDC activation. LPS activation upregulated CD86 about 20-fold and HLA-DR expression about 4-fold. Compared to LPS, contact allergens had weaker effects. TNBS and DNCB induced activation marker upregulation starting slightly below the cytotoxic concentration and increasing in a dose-dependent manner. However, at partially cytotoxic concentrations, irritants also induced CD86 and HLA-DR expression, as confirmed by flow cytometry and quantitative RT-PCR. Both SDS and BAC induced activation marker expression on surviving MoDC, when more than 50% of the MoDC population had been killed by the treatment. Consequently, routine testing of unknown substances would need to quantify activation marker expression as well as cytotoxicity in parallel. In the concentration range around the lowest cytotoxic concentration, the assay may be able to discriminate between contact allergens and irritants.

Allergens↗
PubMed2002

Transcriptional program of mouse osteoclast differentiation governed by the macrophage colony-stimulating factor and the ligand for the receptor activator of NFkappa B.

Cytokines macrophage colony stimulating factor (M-CSF) and the receptor activator of NFkappaB ligand (RANKL) induce differentiation of bone marrow hematopoietic precursor cells into bone-resorbing osteoclasts without the requirement for stromal cells of mesenchymal origin. We used this recently described mouse cell system and oligonucleotide microarrays representing about 9,400 different genes to analyze gene expression in hematopoietic cells undergoing differentiation to osteoclasts. The ability of microarrays to detect the genes of interest was validated by showing expression and expected regulation of several osteoclast marker genes. In total 750 known transcripts were up-regulated by > or =2-fold, and 91% of them at an early time in culture, suggesting that almost the whole differentiation program is defined already in pre-osteoclasts. As expected, M-CSF alone induced the receptor for RANKL (RANK), but also, unexpectedly, other RANK/NFkappaB pathway components (TRAF2A, PI3-kinase, MEKK3, RIPK1), providing a molecular explanation for the synergy of M-CSF and RANKL. Furthermore, interleukins, interferons, and their receptors (IL-1alpha, IL-18, IFN-beta, IL-11Ralpha2, IL-6/11R gp130, IFNgammaR) were induced by M-CSF. Although interleukins are thought to regulate osteoclasts via modulation of M-CSF and RANKL expression in stromal cells, we showed that a mix of IL-1, IL-6, and IL-11 directly increased the activity of osteoclasts by 8.5-fold. RANKL induced about 70 novel target genes, including chemokines and growth factors (RANTES (regulated on activation, normal T cell expressed and secreted), PDGFalpha, IGF1), histamine, and alpha1A-adrenergic receptors, and three waves of distinct receptors, transcription factors, and signaling molecules. In conclusion, M-CSF induced genes necessary for a direct response to RANKL and interleukins, while RANKL directed a three-stage differentiation program and induced genes for interaction with osteoblasts and immune and nerve cells. Thus, global gene expression suggests a more dynamic role of osteoclasts in bone physiology than previously anticipated.

Animals↗
PubMedDate not supplied

Toxicogenomics in drug development.

Toxicogenomics represents the merging of toxicology with technologies that have been developed, together with bioinformatics, to identify and quantify global gene expression changes. It represents a new paradigm in drug development and risk assessment, which promises to generate a wealth of information towards an increased understanding of the molecular mechanisms that lead to drug toxicity and efficacy, and of DNA polymorphisms responsible for individual susceptibility to toxicity. Gene expression profiling, through the use of DNA microarray and proteomic technologies will aid in establishing links between expression profiles, mode of action and traditional toxic endpoints. Such patterns of gene expression, or 'molecular fingerprints' could be used as diagnostic or predictive markers of exposure, that is characteristic of a specific mechanism of induction of that toxic or efficacious effect. It is anticipated that toxicogenomics will be increasingly integrated into all phases of the drug development process particularly in mechanistic and predictive toxicology, and biomarker discovery. This review provides an overview of the expression profiling technologies applied in toxicogenomics. and discusses the promises as well as the future challenges of applying this discipline to the drug development process.

Animals↗