Dengue virus (DENV) infection is one of the most serious public health problems worldwide. A recent dengue outbreak in Paraguay (2007-2009) presented unusual manifestations such as hepatitis, encephalitis, pulmonary as well as cardiac disorders associated with 50% of deaths caused by dengue in the country. Despite the knowledge on inflammatory responses observed during the course of disease, the role of innate immune cells in the control of virus replication influencing clinical outcome is poorly defined. Using two clinical isolates of the virus, a non-fatal case of classical DF (DENV3/290) and a fatal case of DF with visceral complications (DENV3/5532), we sought to determine the profile of dengue infection in human dendritic cell, a major innate immune cell population. Compared to classical DENV3/290, the strain DENV3/5532 displayed higher replicative ability in mdDCs. In addition, DENV3/5532 was found to induce elevated production of pro-inflammatory cytokines associated with higher rates of programmed cell death. The observed phenotype was due to viral replication in mdDCs and TNF appeared to display a protective effect on virus-induced mdDCs apoptosis. These results suggest that the fatal case DENV3/5532 isolate modulates dendritic cell survival as well as inflammatory mediators synthesis.
Dengue virus type 3 isolated from a fatal case with visceral complications induces enhanced proinflammatory responses and apoptosis of human dendritic cells.
Specimen part, Time
View SamplesThe cellular origin of Ewing tumor (ET), a tumor of bone or soft tissues characterized by specific fusions between EWS and ETS genes, is highly debated. Through gene expression analysis comparing ETs with a variety of normal tissues, we show that the profiles of different EWS-FLI1-silenced Ewing cell lines converge toward that of mesenchymal stem cells (MSC). Moreover, upon EWS-FLI1 silencing, two different Ewing cell lines can differentiate along the adipogenic lineage when incubated in appropriate differentiation cocktails. In addition, Ewing cells can also differentiate along the osteogenic lineage upon long-term inhibition of EWS-FLI1. These in silico and experimental data strongly suggest that the inhibition of EWS-FLI1 may allow Ewing cells to recover the phenotype of their MSC progenitor.
Mesenchymal stem cell features of Ewing tumors.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks.
Cell line, Treatment, Time
View SamplesThe transcriptomic changes induced in the human liver cell line HepG2 by 7M of cisplatin after treatment for 12, 24 and 48h
Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks.
Cell line, Treatment, Time
View SamplesThe transcriptomic changes induced in primary mouse hepatocytes (C57BL/6 ) by 7M of cisplatin after treatment for 24 and 48h
Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks.
Cell line, Treatment, Time
View SamplesTo investigate the impact of the iNKT cells on the tumor-infiltrating leukocytes in TRAMP mouse prostate cancer.
Bimodal CD40/Fas-Dependent Crosstalk between iNKT Cells and Tumor-Associated Macrophages Impairs Prostate Cancer Progression.
Age, Specimen part
View SamplesThe lack of accurate in vitro assays for predicting in vivo toxicity of chemicals together with new legislations demanding replacement and reduction of animal testing has triggered the development of alternative methods. This study aimed at developing a transcriptomics-based in vitro prediction assay for in vivo genotoxicity. The transcriptomics changes induced in the human liver cell line HepG2 by 34 compounds after treatment for 12h, 24h and 48h were used for the selection of gene-sets that can discriminate between in vivo genotoxins (GTX) and in vivo non-genotoxins (NGTX). By combining publicly available results for these chemicals from standard in vitro genotoxicity studies with transcriptomics, we developed several prediction models. These models were validated by means of an additional set of 28 chemicals.
A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo.
Cell line, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Specimen part, Treatment
View SamplesBackground: Cancer cachexia is a life-threatening metabolic syndrome that causes significant loss of skeletal muscle mass and significantly increases mortality in cancer patients. Currently, there is an urgent need for better understanding of the molecular pathophysiology of this disease, so that effective therapies can be developed. Almost all pre-clinical studies evaluating skeletal muscle’s response to cancer have focused on one or two pre-clinical models, and almost all have focused specifically on limb muscles. In the current study, we reveal key differences in the histology and transcriptomic signatures of a limb muscle and a respiratory muscle in orthotopic pancreatic cancer patient-derived xenograft (PDX) mice. Methods: To create the four cohorts of PDX mice evaluated in this study, tumors resected from four pancreatic ductal adenocarcinoma (PDAC) patients were portioned and attached to the pancreas of immunodeficient NSG mice. Results: Body weight, muscle mass, and fat mass were significantly decreased in each PDX line. Histological assessment of cryosections taken from the tibialis anterior (TA) and diaphragm (DIA) revealed differential effects of tumor-burden on their morphology. Subsequent genome-wide microarray analysis on TA and DIA revealed key differences between their transcriptomes in response to cancer as well. Indeed, upregulated genes in the diaphragm were enriched for extracellular matrix (ECM) protein-encoding genes and genes related to the inflammatory response, and downregulated genes were enriched for mitochondria related protein-encoding genes. Conversely, the TA showed upregulation of canonical atrophy-associated pathways such as ubiquitin-mediated protein degradation and apoptosis and enrichment of downregulated genes encoding ECM proteins. Conclusions: These data suggest that distinct biological processes account for wasting in different skeletal muscles in response to the same tumor burden. Further investigation into these differences will be critical for the future development of effective clinical strategies to counter cancer cachexia.
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Specimen part, Treatment
View SamplesAt present, substantial efforts are focused on the development of in vitro assays coupled with omics technologies for the identification of carcinogenic substances as an alternative to the classical 2-year rodent carcinogenicity bioassay. A prerequisite for the eventual regulatory acceptance of such assays, however, is the in vivo relevance of the observed in vitro findings.
Comparison of hepatocarcinogen-induced gene expression profiles in conventional primary rat hepatocytes with in vivo rat liver.
Specimen part
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