Gene expression profiles of 75 tissue samples were analyzed representing the stepwise carcinogenic process from pre-neoplastic lesions (cirrhosis and dysplasia) to HCC, including four neoplastic stages (very early HCC to metastatic tumors) from patients with HCV infection. Gene signatures that accurately reflect the pathological progression of disease at each stage were identified and potential molecular markers for early diagnosis uncovered. Pathway analysis revealed dysregulation of the Notch and Toll-like receptor pathways in cirrhosis, followed by deregulation of several components of the Jak/STAT pathway in early carcinogenesis, then up-regulation of genes involved in DNA replication and repair and cell cycle in late cancerous stages.
Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma.
No sample metadata fields
View SamplesHeterozygous mutations in the transcription factor GATA3 are identified in 10-15% of all breast cancer cases. Most of these are protein-truncating mutations, concentrated within or downstream of the second GATA-type zinc-finger domain. Here, we investigated the functional consequences of expression of two truncated GATA3 mutants, in vitro in breast cancer cell lines and in vivo in the mouse mammary gland. We found that the truncated GATA3 mutants display altered DNA binding activity caused by preferred tethering through FOXA1. In addition, expression of the truncated GATA3 mutants reduces E-cadherin expression and promotes anchorage-independent growth in vitro. However, we could not identify any effects of truncated GATA3 expression on mammary gland development or mammary tumor formation in mice. Together, our results demonstrate that both truncated GATA3 mutants promote cistromic re-programming of GATA3 in vitro, but these mutants are not sufficient to induce tumor formation in mice. Overall design: RNAseq data of T47D cells expressing HA-tagged wild-type GATA3 (HA_GATA3_wt) or one of two truncated variants (HA_GATA3_TR1 and HA_GATA3_TR2).
GATA3 Truncating Mutations Promote Cistromic Re-Programming In Vitro, but Not Mammary Tumor Formation in Mice.
Specimen part, Cell line, Subject
View SamplesGene expression profiling in glomeruli from human kidneys with diabetic nephropathy
Gene expression profiling in glomeruli from human kidneys with diabetic nephropathy.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene-expression signature of vascular invasion in hepatocellular carcinoma.
Sex, Age, Specimen part
View SamplesImatinib has become the current standard therapy for patients with chronic myelogenous leukaemia (CML). For a better understanding of the Imatinib-related molecular effects in vivo, we assessed gene expression profiles of Philadelphia Chromosome positive (Ph+) CD34+ cells from peripheral blood of 6 patients with de novo CML in chronic phase. After 7 days of treatment with Imatinib the Ph+ CD34+ cells were reassessed to look for changes in the transcriptome. The expression level of 303 genes was significantly different comparing the transcriptome of the Ph+ CD34+ cells before and after 7 days of Imatinib therapy (183 down-regulated, 120 up-regulated, lower bound 1.2-fold). For a substantial number of genes governing cell cycle and DNA replication, the level of expression significantly decreased (CDC2, RRM2, PCNA, MCM4). On the other hand, therapy with Imatinib was associated with an increase of genes related to adhesive interactions, such as L-selectin or CD44. A group of 8 genes with differential expression levels were confirmed using a gene specific quantitative real-time PCR. Thus, during the first week of treatment, Imatinib is preferentially counteracting the bcr-abl induced effects related to a disturbed cell cycle and defective adhesion of leukemic Ph+ CD34+ cells.
Early in vivo changes of the transcriptome in Philadelphia chromosome-positive CD34+ cells from patients with chronic myelogenous leukaemia following imatinib therapy.
No sample metadata fields
View SamplesTo get more insight in cause and consequences of proteinuria, we studied glomerular gene expression patterns before and after the onset of increased urinary albumin excretion in a proteinuric rat strain.
Increased dynamin expression precedes proteinuria in glomerular disease.
No sample metadata fields
View SamplesPrevious reports have shown low vitamin D serum levels and polymorphisms in the vitamin D receptor (VDR) to be associated with increased risk for TB. Given that 1,25-dihydroxyvitamin D3 has a role in lipid metabolism control, we tested whether the link between 1,25-dihydroxyvitamin D3 and tuberculosis involves macrophage lipid metabolism. Since formation of lipid droplets (LD) is a hallmark of lipid dysregulation in M. tuberculosis-infected macrophages, we measured LD content as a readout of altered lipid metabolism in infected THP-1 cells. Induction of LD, which peaked by 24 hours post-infection was prevented by addition of 1,25-dihydroxyvitamin D3 at the time of infection. To investigate the mechanism of 1,25-dihydroxyvitamin D3 modulation of LD formation, we analyzed the transcriptome of M. tuberculosis-infected THP-1 cells with and without 1,25-dihydroxyvitamin D3 treatment.
Cutting edge: Vitamin D regulates lipid metabolism in Mycobacterium tuberculosis infection.
Cell line, Treatment, Time
View SamplesHepatocellular carcinoma (HCC) is a complex and heterogeneous tumor due to activation of multiple cellular pathways and molecular alterations. Herein, we report the first molecular classification of 89 HCC based on the expression of 358 microRNAs and integrative genomic analysis. Three main subclasses of HCC were identified : two of them were associated with beta-catenin mutations or aggressive phenotype. A subset of the subclass of aggressive tumors (8/89, 9%) showed overexpression of a cluster of microRNAs located on chr19q13.41 (C19MC locus. We showed that miR 517a, representing C19MC, promoted cell proliferation, migration and invasion in vitro and induced the development of aggressive tumors in vivo suggesting its role as a novel oncogenic driver in HCC.
MicroRNA-based classification of hepatocellular carcinoma and oncogenic role of miR-517a.
Sex, Age, Specimen part
View SamplesmRNA expression profile modified by stable transfection of microRNA mir-517a (MIR517A) in a human hepatocellular carcinoma cell line Huh-7
MicroRNA-based classification of hepatocellular carcinoma and oncogenic role of miR-517a.
No sample metadata fields
View SamplesCD70TG mice are a model for sterile chronic immune activation and develop Anemia of Inflammation, which is dependent on the production of Ifng by effector CD4 and CD8 T cells.
Chronic IFN-γ production in mice induces anemia by reducing erythrocyte life span and inhibiting erythropoiesis through an IRF-1/PU.1 axis.
Specimen part
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