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GSE13046
Homo sapiens
16 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
OSM increases the antiviral effect of IFN in Huh7 cells infected with hepatitis A virus (HAV) or HCV replicon and synergizes with IFN in the induction of antiviral genes
Publication Title
Oncostatin M enhances the antiviral effects of type I interferon and activates immunostimulatory functions in liver epithelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Hepatocellular carcinoma (HCC) represents a major health problem as it afflicts an increasing number of patients worldwide. Albeit most of the risk factors for HCC are known, this is a deadly syndrome with a life expectancy at the time of diagnosis of less than 1 year. Definition of the molecular principles governing the neoplastic transformation of the liver is an urgent need to facilitate the clinical management of patients, based on innovative methods to detect the disease in its early stages and on more efficient therapies. In the present study we have combined the analysis of a murine model and human samples of HCC to identify genes differentially expressed early in the process of hepatocarcinogenesis, using a microarray based approach. Expression of 190 genes was impaired in murine HCC from which 65 were further validated by low-density array RT PCR. The expression of the best 45 genes was then investigated in human samples resulting in 18 genes which expression was significantly modified in HCC. Among them, JUN, methionine adenosyltransferase 1A and 2A, phosphoglucomutase 1, and acyl CoA dehydrogenase short branched chain indicate defective cell proliferation as well as one carbon pathway, glucose and fatty acid metabolism, both in HCC and cirrhotic liver, a well known preneoplastic condition. These alterations were further confirmed in public transcriptomic datasets from other authors. In addition, vasodilator stimulated phosphoprotein, an actin-associated protein involved in cytoskeleton remodelling, was also found to be increased in the liver and serum of cirrhotic and HCC patients. In addition to revealing the impairment of central metabolic pathways for liver homeostasis, further studies may probe the potential value of the reported genes for the early detection of HCC.
Publication Title
A signature of six genes highlights defects on cell growth and specific metabolic pathways in murine and human hepatocellular carcinoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The Wilms tumor 1 gene (WT1) encodes a transcription factor involved in cell growth and development. As we previously reported WT1 expression is hardly detectable in normal hepatic tissue but is induced in liver cirrhosis. Although WT1 has been found to be overexpressed in a number of malignancies, the role of WT1 in hepatocarcinogenesis has not been clarified. We found that WT1 is expressed in several human hepatocellular carcinoma (HCC) cell lines including PLC/PRF/5 and HepG2, and in HCC tumor tissue in 42% of patients. WT1 small interfering RNAs did not affect proliferation rate of HCC cells but abrogated their resistance to anoikis. Transcriptome analysis of PLC/PRF/5 cells after WT1 knockdown demonstrated upregulation of 251 genes and downregulation of 321. Ninety per cent of the former corresponded to metabolic genes mostly those characterizing the mature hepatocyte phenotype. On the contrary, genes that decreased upon WT1 inhibition were mainly related to defense against apoptosis, cell cycle and tumor progression. In agreement with these findings WT1 expression increased the resistance of liver tumor cells to doxorubicin, a compound used to treat HCC. Interestingly, doxorubicin strongly enhanced WT1 expression in both HCC cells and normal human hepatocytes. Among different chemotherapeutics, induction of WT1 transcription was restricted to topoisomerase 2 inhibitors. When WT1 expression was prohibited doxorubicin caused a marked increase in caspase-3 activation. In conclusion, WT1 is expressed in a substantial proportion of HCC contributing to tumor progression and resistance to chemotherapy, suggesting that WT1 may be an important target for HCC treatment.
Publication Title
Wilms' tumor 1 gene expression in hepatocellular carcinoma promotes cell dedifferentiation and resistance to chemotherapy.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
IFN alpha mediated gene expression pattern. The effect of IFN alpha on human CD8 T cells responding to antigen (signal 1) and costimulatory signals (signal 2) provided by beads coated with anti-CD3 and anti-CD28 mAbs.
Publication Title
Effects of IFN-α as a signal-3 cytokine on human naïve and antigen-experienced CD8(+) T cells.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
The equilibrium between cellular differentiation and proliferation is fundamental for tissue homeostasis. This is particularly important for the liver, a highly differentiated organ with systemic metabolic functions still endowed with unparalleled regenerative potential. Hepatocellular de-differentiation and uncontrolled proliferation are at the basis of liver carcinogenesis. We have identified SLU7, a pre-mRNA splicing regulator inhibited in hepatocarcinoma as a pivotal gene for hepatocellular homeostasis. SLU7 knockdown in human liver cells and mouse liver resulted in profound changes in pre-mRNA splicing and gene expression, leading to impaired glucose and lipid metabolism, refractoriness to key metabolic hormones, and reversion to a fetal-like gene expression pattern. Hepatocellular proliferation and a switch to a tumor-like glycolytic phenotype were also observed. Mechanistically, SLU7 governed the splicing and/or expression of essential genes for hepatocellular differentiation like SRSF3 and HNF4a, and was identified as a critical factor in cAMP-regulated gene transcription. SLU7 is therefore central for hepatocyte identity and quiescence.
Publication Title
Splicing regulator SLU7 is essential for maintaining liver homeostasis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Molecular profiling of patient-matched brain and extracranial melanoma metastases implicates the PI3K pathway as a therapeutic target.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
An improved understanding of the molecular pathogenesis of brain metastases, one of the most common and devastating complications of advanced melanoma, may identify and prioritize rational therapeutic approaches for this disease. In particular, the identification of molecular differences between brain and extracranial metastases would support the need for the development of organ-specific therapeutic approaches. Hotspot mutations, copy number variations (CNV), global mRNA expression patterns, and protein expression and activation, quantitatively analyzed by molecular inversion probe arrays, microarrays and reverse phase protein array (RPPA) were evaluated in pairs of melanoma brain metastases and extracranial metastases from patients who had undergone surgical resection for both types of tumors.
Publication Title
Molecular profiling of patient-matched brain and extracranial melanoma metastases implicates the PI3K pathway as a therapeutic target.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Deregulated intracellular Ca2+ homeostasis underlies synaptic dysfunction and is a common feature in neurodegenerative processes, including Huntington's disease (HD). DREAM/calsenilin/KChIP-3 is a multifunctional Ca2+ binding protein that controls the expression level and/or the activity of several proteins related to Ca2+ homeostasis, neuronal excitability and neuronal survival. We found that expression of endogenous DREAM (DRE antagonist modulator) is reduced in the striatum of R6 mice, in STHdh-Q111/111 knock in striatal neurons and in HD patients. DREAM down regulation in R6 striatum occurs early after birth, well before the onset of motor coordination impairment, and could be part of an endogenous mechanism of neuroprotection, since i) R6/2 mice hemizygous for the DREAM gene (R6/2xDREAM+/-) showed delayed onset of locomotor impairment and prolonged lifespan, ii) motor impairment after chronic administration of 3-NPA was reduced in DREAM knockout mice and enhanced in daDREAM transgenic mice and, iii) lentiviral-mediated DREAM expression in STHdh-Q111/111 knock in cells sensitizes them to oxidative stress. Transcriptomic analysis showed that changes in gene expression in R6/2 striatum were notably reduced in R6/2xDREAM+/- striatum. Chronic administration of repaglinide, a molecule able to bind to DREAM in vitro and to accelerate its clearance in vivo, delayed the onset of motor dysfunction, reduced striatal loss and prolonged the lifespan in R6/2 mice. Furthermore, exposure to repaglinide protected STHdh-Q111/111 knock in striatal neurons sensitized to oxidative stress by lentiviral-mediated DREAM overexpression. Thus, genetic and pharmacological evidences disclose a role for DREAM silencing in early neuroprotective mechanisms in HD.
Publication Title
Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease.
Sample Metadata Fields
Specimen part
View Samples- Oryza sativa
- 78 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Rice (Oryza sativa, ssp. Japonica, cv. Nipponbare 1) plants were grown in a Conviron PGR 15 growth chamber using precise control of temperature, light, and humidity.<br></br>Diurnal (driven) conditions included 12L:12D light cycles and 31C/20C thermocycles in three different combinations. These were: photocycles (LDHH), 12 hrs. light (L)/12 hrs. dark (D) at a constant temperature (31C; HH); photo/thermocycles (LDHC): 12 hrs. light (L) /12 hrs. dark (D) with a high day temperature (31C) and a low night temperature (20C); and thermocycles (LLHC): continuous light (LL) with 12 hrs. high/12 hrs. low temperature (31C, day; 20C, night). Light intensity and relative humidity were 1000 micromol m-2s-2 and 60%, respectively.<br></br>Three-month-old rice plants were entrained for at least one week under the respective condition prior to initiation of each experiment. Leaves and stems from individual rice plants were collected every four hours for 48 hrs in driven (diurnal) conditions followed by a two day freerun spacer under continuous light/temperature followed by two additional days of sampling under the same continuous free run condition.<br></br>
Publication Title
Global profiling of rice and poplar transcriptomes highlights key conserved circadian-controlled pathways and cis-regulatory modules.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Oryza sativa
- 37 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Rice (Oryza sativa, spp. Indica, cv. 93-11) plants were grown in a Conviron PGR 15 growth chamber using precise control of temperature, light, and humidity.<br></br>Diurnal (driven) conditions included 12L:12D light cycles and 31C/20C thermocycles in three different combinations. These were: photocycles (LDHH), 12 hrs. light (L)/12 hrs. dark (D) at a constant temperature (31C; HH); photo/thermocycles (LDHC): 12 hrs. light (L) /12 hrs. dark (D) with a high day temperature (31C) and a low night temperature (20C); and thermocycles (LLHC): continuous light (LL) with 12 hrs. high/12 hrs. low temperature (31C, day; 20C, night). Light intensity and relative humidity were 1000 micromol m-2s-2 and 60%, respectively.<br></br>Three-month-old rice plants were entrained for at least one week under the respective condition prior to initiation of each experiment. Leaves and stems from individual rice plants were collected every four hours for 48 hrs in driven (diurnal) conditions followed by a two day freerun spacer under continuous light/temperature followed by two additional days of sampling under the same continuous free run condition.
Publication Title
Global profiling of rice and poplar transcriptomes highlights key conserved circadian-controlled pathways and cis-regulatory modules.
Sample Metadata Fields
Age, Specimen part, Time
View Samples