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GSE46819
Homo sapiens
23 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Apoptosis is deregulated in most, if not all, cancers, including hematological malignancies. In this study, we wanted to test whether primary acute myeloid leukemia (AML) samples are sensitive for inhibitor of apoptosis (IAP) protein antagonist treatment in vitro, and which AML subgroup might profit most from such a novel therapeutic strategy. We treated diagnostic samples of 67 adult AML patients with either cytarabine (ara-C) or IAP antagonist BV6 and correlated sensitivity with clinical, cytogenetic and molecular markers, and expression levels of selected genes involved in apoptosis. Primary AML samples showed differential sensitivity to treatment with either ara-C (40% sensitive, 17% intermediate, 43% resistant) or BV6 (51% sensitive, 21% intermediate, 28% resistant). Notably, 69% of ara-C resistant samples showed a good to fair response to IAP inhibition. Furthermore, combination treatment of ara-C with BV6 showed additive effects in most samples. Differences in sensitivity to IAP antagonist treatment correlated with significantly elevated expression levels of TNF and lower levels of XIAP in BV6 sensitive samples, as well as with NPM1 mutations. Gene expression profiling pointed to apoptosis-related pathways, which were specifically induced by IAP inhibition in sensitive samples. Thus, our results suggest IAP inhibition as a potential novel therapeutic option in AML.
Publication Title
Targeting inhibitor of apoptosis proteins by Smac mimetic elicits cell death in poor prognostic subgroups of chronic lymphocytic leukemia.
Sample Metadata Fields
Sex, Age, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Inhibitor of apoptosis (IAP) proteins are expressed at high levels in CLL cells and may contribute to evasion of cell death leading to poor therapeutic outcome. Of note, prognostic unfavourable cases with e.g. non-mutated VH-status and TP53 mutation responded significantly better to BV6 than samples with unknown or favourable prognosis e.g. 13q deletion. The majority of cases with 17p deletion (10/12) and Fludarabine refractory cases were sensitive to BV6, indicating that BV6 acts independently of the p53 pathway. Importantly, BV6 dose-dependently induced cell death in 28 of 51 (54%) investigated patient samples while B cells from healthy donors were largely unaffected. BV6 also triggered cell death under survival conditions mimicking the microenvironment e.g. by adding CD40 ligand or in conditioned medium. Gene expression profiling identified cell death- and NF-kB-signaling among the top pathways regulated by BV6. This was confirmed by data showing that BV6 causes degradation of cIAP1 and cIAP2 and NF-kB pathway activation. BV6 induced cell death depended on production of reactive oxygen species, since addition of ROS scavengers significantly rescued BV6-triggerd cell death. In contrast, BV6 induced cell death independently of caspase activity, RIP1 activity or TNF-alpha, since zVAD.fmk, necrostatin-1 or TNF-alpha-blocking antibody Enbrel failed to protect against cell death. Of note, transcripts of ROS regulatory proteins were modulated by BV6. Thus, these data have important implications for developing new therapeutic strategies to overcome cell death resistance in CLL especially in poor prognostic subgroups.
Publication Title
Targeting inhibitor of apoptosis proteins by Smac mimetic elicits cell death in poor prognostic subgroups of chronic lymphocytic leukemia.
Sample Metadata Fields
Sex, Age, Treatment
View Samples- Zea mays
- 64 Downloadable Samples
Illumina HiSeq 2000
Description
Heterosis which is the improved vigor of F1-hybrids compared to their parents is widely exploited in maize (Zea mays L.) breeding to produce elite hybrids of superior yield. The transcriptomes of the maize inbred lines B73 and Mo17 and their reciprocal hybrid offspring were surveyed in the meristematic zone, the elongation zone, cortex and stele tissues of primary roots, prior to the developmental manifestation of heterosis. Single parent expression (SPE) is consistent with the dominance model for heterosis in that it denotes genes that are expressed in only one parent but in both reciprocal hybrids. In primary root tissues, between 1,027 (elongation zone) and 1,206 (stele) SPE patterns were observed. As a consequence, hybrids displayed in each tissue >400 active genes more than either parent. Analysis of tissue-specific SPE dynamics revealed that 1,233 of 2,233 SPE genes displayed SPE in all tissues in which they were expressed while 1,000 SPE genes displayed in at least one tissue a non-SPE pattern. In addition, 64% (17,351/ 27,164) of all expressed genes were assigned to the two subgenomes which are the result of an ancient genome duplication. By contrast, only between 18 and 25% of the SPE genes were assigned to a subgenome suggesting that a disproportionate number of SPE genes are evolutionary young and emerged after genome duplication. We hypothesize that this phenomenon is associated with human selection of favorable maize genotypes which might primarily affect younger genes rather than genes whose functions have been conserved for millions of years.
Publication Title
Nonsyntenic genes drive highly dynamic complementation of gene expression in maize hybrids.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression profile was analyzed after knockdown of PAEP in lung cancer cell lines 2106T and H1975 as well as in skin cancer cell line MeWo.
Publication Title
Glycodelin: A New Biomarker with Immunomodulatory Functions in Non-Small Cell Lung Cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
substantial number of people at risk to develop type 2 diabetes could not improve insulin sensitivity by physical training intervention. We studied the mechanisms of this impaired exercise response in 20 middle-aged individuals who performed a controlled eight weeks cycling and walking training at 80 % individual VO2max. Participants identified as non-responders in insulin sensitivity (based on Matsuda index) did not differ in pre-intervention parameters compared to high responders. The failure to increase insulin sensitivity after training correlates with impaired up-regulation of mitochondrial fuel oxidation genes in skeletal muscle, and with the suppression of the upstream regulators PGC1 and AMPK2. The muscle transcriptome of the non-responders is further characterized by an activation of TGF and TGF target genes, which is associated with increases in inflammatory and macrophage markers. TGF1 as inhibitor of mitochondrial regulators and insulin signaling is validated in human skeletal muscle cells. Activated TGF1 signaling down-regulates the abundance of PGC1, AMPK2, mitochondrial transcription factor TFAM, and of mitochondrial enzymes. Thus, increased TGF activity in skeletal muscle can attenuate the improvement of mitochondrial fuel oxidation after training and contribute to the failure to increase insulin sensitivity.
Publication Title
TGF-β Contributes to Impaired Exercise Response by Suppression of Mitochondrial Key Regulators in Skeletal Muscle.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Investigation whether hypoxic stabilization of HIF-1alpha quantitatively or qualitatively modifies the gene expression pattern induced by poly I:C, a TLR ligand that does not induce normoxic HIF-1alpha stabilization on its own (non-HIF-1alpha-stabilizing TLR ligand).
Publication Title
Toll-like receptor activation and hypoxia use distinct signaling pathways to stabilize hypoxia-inducible factor 1α (HIF1A) and result in differential HIF1A-dependent gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 6 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
We used microarrays to detail the global gene expression changes following apical infection of porcine choroid plexus epithelial cells (PCPEC) with Streptococcus suis (S. suis)
Publication Title
In vitro transcriptome analysis of porcine choroid plexus epithelial cells in response to Streptococcus suis: release of pro-inflammatory cytokines and chemokines.
Sample Metadata Fields
Specimen part
View Samples- Zea mays
- 64 Downloadable Samples
- Illumina HiSeq 2500
Description
An atlas of RNA and protein expression maps across a diverse set of developmental tissues from Zea mays Overall design: RNA-seq collected from a variety of maize tissues
Publication Title
Integration of omic networks in a developmental atlas of maize.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study we analyzed the myeloma cell contact-mediated changes on the transcriptome of skeletal precursor cells. Therefore, human mesenchymal stem cells (MSC) and osteogenic precursor cells (OPC) were co-cultured with the representative myeloma cell line INA-6 for 24 h. Afterwards, MSC and OPC were separated from INA-6 cells by fluorescence activated cell sorting. Total RNA of MSC and OPC fractions was used for whole genome array analysis.
Publication Title
Contact of myeloma cells induces a characteristic transcriptome signature in skeletal precursor cells -Implications for myeloma bone disease.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Type II testicular germ cell cancers (GCC) are the most frequently diagnosed tumors in young men (20 - 40 years) and are classified as seminoma or non-seminoma. GCCs are commonly treated by orchiectomy and chemo- or radiotherapy. However, a subset of metastatic non-seminomas display only incomplete remission or relapse and require novel treatment options. Recent studies have shown effective application of the small-molecule inhibitor JQ1 in tumor therapy, which interferes with the function of bromodomain and extra-terminal (BET)-proteins. Here, we demonstrate that upon JQ1 doses 250 nM GCC cell lines and Sertoli cells display compromised survival and induction of cell cycle arrest. JQ1 treated GCC cell lines display upregulation of genes indicative for DNA damage and a cellular stress response. Additionally, downregulation of pluripotency factors and induction of mesodermal differentiation was detected. GCCs xenografted in vivo showed a reduction in tumor size, proliferation and angiogenesis when subjected to JQ1 treatment. The combination of JQ1 and the histone deacetylase inhibitor romidepsin further enhanced the apoptotic effect in vitro and in vivo. Thus, we propose that JQ1 alone, or in combination with romidepsin may serve as a novel therapeutic option for GCCs.
Publication Title
The bromodomain inhibitor JQ1 triggers growth arrest and apoptosis in testicular germ cell tumours in vitro and in vivo.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples