This SuperSeries is composed of the SubSeries listed below.
Protein Syndesmos is a novel RNA-binding protein that regulates primary cilia formation.
Specimen part, Cell line
View SamplesWe show here that SDOS interacts with another important cancer-linked protein, the chaperone TRAP1, associates with actively translating polyribosomes and represses translation. Moreover, we demonstrate that SDOS binds directly RNA in living cells. Combining individual gene expression profiling, nucleotide cross-linking and immunoprecipitation (iCLIP), and ribosome profiling, we discover several crucial pathways regulated post-transcriptionally by SDOS.
No associated publication
Cell line
View SamplesHere we show that platinum-resistant ovarian cancer cells also show reduced cholesterol biosynthesis, and mostly rely on uptake of exogenous cholesterol for their needs. Expression of FDPS and OSC, enzymes involved in cholesterol synthesis, are decreased both in drug-resistant cells and upon TRAP1 silencing, whereas the expression of LDL receptor, the main mediator of extracellular cholesterol uptake, is increased. Strikingly, treatment with different statins to inhibit cholesterol synthesis reduces cisplatin-induced apoptosis, whereas silencing of LIPG, an enzyme involved in lipid metabolism, increases sensitivity to the drug.
Cholesterol Homeostasis Modulates Platinum Sensitivity in Human Ovarian Cancer.
Specimen part, Cell line
View SamplesWe have studied the genes activated in human liver transplantation to identify potential target genes for the prevention or treatment of related injuries.
Wide gene expression profiling of ischemia-reperfusion injury in human liver transplantation.
Sex, Age, Specimen part, Subject
View SamplesIn order to define the transcriptional network functionally regulated by Pax8 as well as infer its direct targets, we performed RNAi to knock-down Pax8 gene in FRTL-5 thyroid cells. Expression data from three independent silencing experiments were analyzed by microarray technology unraveling 2815 genes differentially expressed between silenced cells and controls. Of these, 1421 genes were down-regulated and 1394 genes were up-regulated 72hrs after Pax8 silencing.
Identification of novel Pax8 targets in FRTL-5 thyroid cells by gene silencing and expression microarray analysis.
Cell line
View SamplesBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematological. We used transcriptomic analysis to investigate LXR pathway, and cholesterol metabolism in leukemic cells. Malignancy with a poor prognosis that derives from plasmacytoid dendritic cells (PDC). No consensus for optimal treatment modalities is available today and the full characterization of this leukemia is still emerging. We identified here a BPDCN-specific transcriptomic profile when compared to those of acute myeloid leukemia (AML) and T-acute lymphoblastic leukemia (T-ALL), as well as the transcriptomic signature of primary PDC. This BPDCN gene signature identified a dysregulation of genes involved in cholesterol homeostasis, some of them being liver X receptor (LXR) target genes. LXR agonist treatment of primary BPDCN cells and BPDCN cell lines restored LXR target gene expression and increased cholesterol efflux via the upregulation of ATP Binding Cassette (ABC) transporters, ABCA1 and ABCG1. LXR agonist treatment was responsible for limiting BPDCN cell proliferation and inducing intrinsic apoptotic cell death. LXR activation in BPDCN cells was shown to interfere with three signaling pathways associated with leukemic cell survival, namely: NF-B activation, as well as Akt and STAT5 phosphorylation in response to the BPDCN growth/survival factor IL-3. These effects were increased by the stimulation of cholesterol efflux through a lipid acceptor, the apolipoprotein A1. In vivo experiments using a mouse model of BPDCN cell xenograft revealed a decrease of leukemic cell infiltration and BPDCN-induced cytopenia associated with an increased survival after LXR agonist treatment. This demonstrates that cholesterol homeostasis is modified in BPDCN and can be normalized by treatment with LXR agonists which can be proposed as a new therapeutic approach.
LXR agonist treatment of blastic plasmacytoid dendritic cell neoplasm restores cholesterol efflux and triggers apoptosis.
Specimen part, Disease, Disease stage
View SamplesTranscription profiling by array of pancreas from KrasG12D, Ela-Tgfa and KrasG12D Ela-Tgfa mice
Concomitant pancreatic activation of Kras(G12D) and Tgfa results in cystic papillary neoplasms reminiscent of human IPMN.
Age, Specimen part
View SamplesThe NfkB-pathway is activated early during acute pancreatitis. We investigated the influence on gene expression of two pancreas-specific deletions interfering with NfkB-activation. Pancreata from 8 week old mice were prepared, RNA was isolated and Affymetrix microarray expression analysis was performed.
Deletion of IkBa induces RelA to alleviate acute pancreatitis in mice through upregulation of Spi2a
Age, Specimen part, Disease, Disease stage, Time
View SamplesThe main objective of this study is to identify the list of genes differentially expressed between infected with Leishmania braziliensis and non-infected macrophage cultures based on gene expression microarray profiling
Changes in Macrophage Gene Expression Associated with Leishmania (Viannia) braziliensis Infection.
Specimen part
View SamplesA major limitation in the cancer treatment is the ability of cancer cells to become resistant to chemotherapeutic drugs, by multidrug establishment. Here, we evaluate the possibility to utilize MC70, either as ABC transporters inhibitor or as anticancer agent, in monotherapy or in combination with doxorubicin for cancer treatment. The study was carried out in MCF7/ADR and Caco-2, breast and colon cancer cells, respectively. Cell growth and apoptosis were measured by MTT assay and DNA laddering Elisa kit, respectively. Cell cycle perturbation and cellular targets modulation were analyzed by flowcytometry and western blotting, respectively. MC70 was analyzed for its interaction with ABC transporters, MDR-1, BCRP and MRP-1, and for its anticancer activity. In MCF7/ADR, MC70 slight inhibited cell proliferation and strongly enhanced doxorubicin effectiveness; conversely in Caco-2, it inhibited cell growth without affecting doxorubicin efficacy. In addition, it induced apoptosis, canceled in favor of necrosis when it was given in combination with high doses of the anthracycline. Moreover, MC70 inhibited cell migration probably through its residual activity as sigma-1 ligand. Among the hypothesized molecular and cellular mechanisms responsible for all these effects, modulations of cell cycle, of pAkt and of the three MAPKs phosphorylation were evidenced while activity at transcription level was excluded. MC70 can be considered as a potential new anticancer agent with the capability to enhance doxorubicin effectiveness and an interesting role in the treatment of chemotherapy resistant tumors.
MC70 potentiates doxorubicin efficacy in colon and breast cancer in vitro treatment.
Cell line, Treatment
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