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SRP067129
Homo sapiens
12 Downloadable Samples
IlluminaHiSeq2500
Description
Purpose: The goals of this study were to identify quantitative gene expression differences between wild type, Musashi1 null, Msuashi2 null and Musashi1/Musashi2 null MIAPaCa2 pancreatic cancer cells Overall design: mRNA profiles of MIA PaCa-2 cancer cells were generated by deep sequencing, in triplicate, using Illumina HiSeq2500.
Publication Title
Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Pancreatic intraepithelial neoplasia (PanIN) is a premalignant lesion that can progress to pancreatic ductal adenocarcinoma, a highly lethal malignancy marked by its late stage at clinical presentationand profound drug resistance. Here we developed novel fluorescent reporter mice that show that the stem cell determinant, Musashi (Msi) is a critical element of pancreatic cancer progression.
Publication Title
Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
Pancreatic cancers (PCs) are highly metastatic with poor prognosis, mainly due to delayed detection. We hypothesized that intercellular communication is critical for metastatic progression. Here, we show that PC-derived exosomes induce liver pre-metastatic niche formation in naïve mice and consequently increase liver metastatic burden. Uptake of PC-derived exosomes by Kupffer cells caused transforming growth factor ß secretion and upregulation of fibronectin production by hepatic stellate cells. This fibrotic microenvironment enhanced recruitment of bone marrow-derived macrophages. We found that macrophage migration inhibitory factor (MIF) was highly expressed in PC-derived exosomes, and its blockade prevented liver pre-metastatic niche formation and metastasis. Compared to patients whose pancreatic tumors did not progress, MIF was markedly higher in exosomes from stage I PC patients who later developed liver metastasis. These findings suggest that exosomal MIF primes the liver for metastasis and may be a prognostic marker for the development of PC liver metastasis. Overall design: Normal pancreas and Pancreatic cancer exosomes education of human von Kupffer cells in vitro
Publication Title
Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver.
Sample Metadata Fields
No sample metadata fields
View Samples- Hordeum vulgare
- 35 Downloadable Samples
- Affymetrix Barley Genome Array (barley1)
Description
Drought tolerance is a key trait for increasing and stabilizing barley productivity in dry areas worldwide. Identification of the genes responsible for drought tolerance in barley (Hordeum vulgare L.) will facilitate understanding of the molecular mechanisms of drought tolerance, and also genetic improvement of barley through marker-assisted selection or gene transformation. To monitor the changes in gene expression at transcription levels in barley leaves during the reproductive stage under drought conditions, the 22K Affymetrix Barley 1 microarray was used to screen two drought-tolerant barley genotypes, Martin and Hordeum spontaneum 41-1 (HS41-1), and one drought-sensitive genotype Moroc9-75. Seventeen genes were expressed exclusively in the two drought-tolerant genotypes under drought stress, and their encoded proteins may play significant roles in enhancing drought tolerance through controlling stomatal closure via carbon metabolism (NADP malic enzyme (NADP-ME) and pyruvate dehydrogenase (PDH), synthesizing the osmoprotectant glycine-betaine (C-4 sterol methyl oxidase (CSMO), generating protectants against reactive-oxygen-species scavenging (aldehyde dehydrogenase (ALDH), ascorbate-dependant oxidoreductase (ADOR), and stabilizing membranes and proteins (heat-shock protein 17.8 (HSP17.8) and dehydrin 3 (DHN3). Moreover, 17 genes were abundantly expressed in Martin and HS41-1 compared with Moroc9-75 under both drought and control conditions. These genes were likely constitutively expressed in drought-tolerant genotypes. Among them, 7 known annotated genes might enhance drought tolerance through signaling (such as calcium-dependent protein kinase (CDPK) and membrane steroid binding protein (MSBP), anti-senescence (G2 pea dark accumulated protein GDA2) and detoxification (glutathione S-transferase (GST) pathways. In addition, 18 genes, including those encoding l-pyrroline-5-carboxylate synthetase (P5CS), protein phosphatase 2C-like protein (PP2C) and several chaperones, were differentially expressed in all genotypes under drought; thus, they were more likely general drought-responsive genes in barley. These results could provide new insights into further understanding of drought-tolerance mechanisms in barley.
Publication Title
Differentially expressed genes between drought-tolerant and drought-sensitive barley genotypes in response to drought stress during the reproductive stage.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Several reports have focused on the identification of biological elements involved in the development of abnormal systemic biochemical alterations in chronic kidney disease, but this abundant literature results most of the time fragmented. To better define the cellular machinery associated to this condition, we employed an innovative high-throughput approach based on a whole transcriptomic analysis and classical biomolecular methodologies. The genomic screening of peripheral blood mononuclear cells revealed that 44 genes were up-regulated in both chronic kidney disease patients in conservative treatment (CKD, n=9) and hemodialysis (HD, n=17) compared to healthy subjects (NORM) (p<0.001, FDR=1%). Functional analysis demonstrated that 11/44 genes were involved in the oxidative phosphorylation system (OXPHOS). Western blotting for COXI and COXIV, key constituents of the complex IV of OXPHOS, performed on an independent testing-group (12 NORM, 10 CKD and 14 HD) confirmed the elevated synthesis of these subunits in CKD/HD patients. However, complex IV activity was significantly reduced in CKD/HD patients compared to NORM (p<0.01). Finally, CKD/HD patients presented higher reactive oxygen species and 8-hydroxydeoxyguanosine levels compared to NORM. Taken together these results suggest, for the first time, that CKD/HD patients may have an impaired mitochondrial respiratory system and this condition may be both the consequence and the cause of an enhanced oxidative stress.
Publication Title
Mitochondrial dysregulation and oxidative stress in patients with chronic kidney disease.
Sample Metadata Fields
Disease, Treatment, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Human cytomegalovirus (hCMV) is a highly prevalent pathogen that, upon primary infection, establishes life-long persistence in all infected individuals. Acute hCMV infections cause a variety of diseases in humans with developmental or acquired immune deficits. In addition, persistent hCMV infection may contribute to various chronic disease conditions even in immunologically normal people. The pathogenesis of hCMV disease has been frequently linked to inflammatory host immune responses triggered by virus-infected cells. Moreover, hCMV infection activates numerous host genes many of which encode pro-inflammatory proteins. However, little is known about the relative contributions of individual viral gene products to these changes in cellular transcription. We systematically analyzed the effects of the hCMV 72-kDa immediate-early 1 (IE1) protein, a major transcriptional activator and antagonist of type I interferon (IFN) signaling, on the human transcriptome. Following expression under conditions closely mimicking the situation during productive infection, IE1 elicits a global type II IFN-like host cell response. This response is dominated by the selective up-regulation of immune stimulatory genes normally controlled by IFN-gamma and includes the synthesis and secretion of pro-inflammatory chemokines. IE1-mediated induction of IFN-stimulated genes strictly depends on tyrosine-phosphorylated signal transducer and activator of transcription 1 (STAT1) and correlates with the nuclear accumulation and sequence-specific binding of STAT1 to IFN-gamma-responsive promoters. However, neither synthesis nor secretion of IFN-gamma or other IFNs seems to be required for the IE1-dependent effects on cellular gene expression. Our results demonstrate that a single hCMV protein can trigger a pro-inflammatory host transcriptional response via an unexpected STAT1-dependent but IFN-independent mechanism and identify IE1 as a candidate determinant of hCMV pathogenicity.
Publication Title
Human cytomegalovirus IE1 protein elicits a type II interferon-like host cell response that depends on activated STAT1 but not interferon-γ.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2500
Description
Stephen Paget first proposed, in 1889, that organ distribution of metastases is a non-random event, yet metastatic organotropism remains one of the greatest mysteries in cancer biology. Here, we demonstrate that exosomes released by lung-, liver- and brain-tropic tumor cells fuse preferentially with resident cells at their predicted destination, such as fibroblasts and epithelial cells in the lung, Kupffer cells in the liver, and endothelial cells in the brain. We found that exosome homing to organ-specific cell types prepares the pre-metastatic niche and that treatment with exosomes derived from lung tropic models can redirect metastasis to the lung. Proteomic profiling of exosomes revealed distinct integrin expression patterns associated with each organ-specific metastasis. Whereas exosomal integrins a6ß4 and a6ß1 were associated with lung metastasis, exosomal integrins avß5 and avß3 were linked with liver and brain metastases, respectively. Targeting a6ß4 and avß5 integrins decreased exosome uptake and metastasis in the lung and liver, respectively. Importantly, we demonstrate that exosome uptake activates a cell-specific subset of S100 family genes, known to support cell migration and niche formation. Finally, our clinical data indicate that integrin-expression profiles in circulating plasma exosomes from cancer patients could be used to predict organ-specific metastasis. Overall design: Education of human von Kupffer cells in vitro with human pancreatic cancer exosomes
Publication Title
Tumour exosome integrins determine organotropic metastasis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Differential gene expression profiles of neurospheres derived from different regions of the adult brain.
Publication Title
Environmental impact on direct neuronal reprogramming in vivo in the adult brain.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
TGZ is an agonist of the nuclear receptor PPARgamma. This synthetic compound displays anticancer effects on breast cancer cells but some of them are PPARgamma independent. Delta-2-TGZ (delta-2-troglotazone) is a PPARgamma inactive TGZ derivative possessing a double bond adjoining the thiazolidinedione ring. This compound still displays anticancer efefcts. It is an interesting tool to study the PPARgamma-independent mechanisms.
Publication Title
Pro-apoptotic effect of Δ2-TGZ in "claudin-1-low" triple-negative breast cancer cells: involvement of claudin-1.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Several reports indicate that mesalazine (5-aminosalicylic acid or 5-ASA) is a promising candidate for the chemoprevention of Colo-Rectal Cancer (CRC) due to its ability to reach the purpose, yet avoiding at the same time the side effects that are usually determined by prolonged administrations of Non Steroidal Anti-Inflammatory Drugs. This activity of 5-ASA is probably the consequence of a number of effects determined on colon cancer cells and consisting of reduced proliferation, increased apoptosis and activation of cell cycle checkpoints. A recent observation has suggested that these effects could be mediated by the capacity of 5-ASA to interfere with the nuclear translocation of beta-catenin, in turn responsible for the inhibition of its transcription activity. The aim of our study was to better characterize the molecular mechanism by which 5-ASA inhibits the beta-catenin signaling pathway. To address this issue we assessed, by means of the Affymetrix microarray methodology, the transcriptome changes determined on Caco2 cells by a 96 h treatment with 20 mM mesalazine.
Publication Title
Mesalazine inhibits the beta-catenin signalling pathway acting through the upregulation of mu-protocadherin gene in colo-rectal cancer cells.
Sample Metadata Fields
No sample metadata fields
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