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SRP105266
Homo sapiens
43 Downloadable Samples
NextSeq 500
Description
Resistance to platinum-based chemotherapy is a clinical challenge in the treatment of ovarian cancer (OC) and limits survival. Therefore, innovative drugs against platinum-resistance are urgently needed. Our therapeutic concept is based on the conjugation of two chemotherapeutic compounds to a monotherapeutic pro-drug, which is taken up by cancer cells and cleaved into active cytostatic metabolites. Here, we explore the activity of the duplex-prodrug 5-FdU-ECyd, covalently linking 2''-deoxy-5-fluorouridine (5-FdU) and 3''-C-ethynylcytidine (ECyd), on platinum-resistant OC cells. RNA-Sequencing was used for characterization of 5-FdU-ECyd treated platinum-sensitive A2780 and isogenic platinum-resistant A2780cis. Overall design: Platinum-sensitive A2780 and platinum resistant-cells A2780cis were treated with 5-FdU-Ecyd for 6h and 12h, there are also 6h and 12h untreated controls, all groups are in triplicates
Publication Title
The conjugated antimetabolite 5-FdU-ECyd and its cellular and molecular effects on platinum-sensitive vs. -resistant ovarian cancer cells <i>in vitro</i>.
Sample Metadata Fields
Cell line, Subject, Time
View Samples- Mus musculus
- 10 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Alveolar epithelial type II (ATII)-like cells can be generated from murine embryonic stem cells (ESCs), although to date, no robust protocols applying specific differentiation factors are established. We hypothesized that the keratinocyte growth factor (KGF), an important mediator of lung organogenesis and primary ATII cell maturation and proliferation, together with dexamethasone, 8-bromoadenosine-cAMP, and isobutylmethylxanthine (DCI), which induce maturation of primary fetal ATII cells, also support the alveolar differentiation of murine ESCs. Here we demonstrate that the above stimuli synergistically potentiate the alveolar differentiation of ESCs as indicated by increased expression of the surfactant proteins (SP-) C and SP-B. This effect is most profound if KGF is supplied not only in the late stage, but at least also during the intermediate stage of differentiation. Our results indicate that KGF most likely does not enhance the generation of (mes)endodermal or NK2 homeobox 1 (Nkx2.1) expressing progenitor cells but rather, supported by DCI, accelerates further differentiation/maturation of respiratory progeny in the intermediate phase and maturation/proliferation of emerging ATII cells in the late stage of differentiation. Ultrastructural analyses confirmed the presence of ATII-like cells with intracellular composite and lamellar bodies. Finally, induced pluripotent stem cells (iPSCs) were generated from transgenic mice with ATII cell-specific lacZ reporter expression. Again, KGF and DCI synergistically increased SP-C and SP-B expression in iPSC cultures, and lacZ expressing ATII-like cells developed. In conclusion, ATII cell-specific reporter expression enabled the first reliable proof for the generation of murine iPSC-derived ATII cells. In addition, we have shown KGF and DCI to synergistically support the generation of ATII-like cells from ESCs and iPSCs. Combined application of these factors will facilitate more efficient generation of stem cell-derived ATII cells for future basic research and potential therapeutic application.
Publication Title
Keratinocyte growth factor and dexamethasone plus elevated cAMP levels synergistically support pluripotent stem cell differentiation into alveolar epithelial type II cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Experiment with 6 hybridizations, using 30 samples of species [Homo sapiens], using 6 arrays of array design [Affymetrix GeneChip Human Genome HG-U133A [HG-U133A]], producing 6 raw data files and 6 transformed and/or normalized data files.
Publication Title
Hypoxia modifies the transcriptome of primary human monocytes: modulation of novel immune-related genes and identification of CC-chemokine ligand 20 as a new hypoxia-inducible gene.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Dendritic cells (DCs) are professional antigen-presenting cells whose activity is intrinsically linked to the microenvironment. Hypoxia is a condition of low oxygen tension occurring in inflammatory tissues that creates a special microenvironment conditioning cell physiology. We studied the effects of hypoxia on the differentiation of human monocytes into DCs. Immature DCs were differentiated in vitro from human monocytes under normoxic (iDCs) or hypoxic (Hi-DCs) conditions and the gene expression profile was determined. Hi-DCs expressed novel hypoxia-inducible genes and were characterized by up-regulation of pathways associated with cell movement/migration.
Publication Title
Transcriptome of hypoxic immature dendritic cells: modulation of chemokine/receptor expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques.
Publication Title
A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Clariom S Human array (clariomshuman)
Description
HIF-1 plays a crucial role in sustaining glioblastoma (GBM) cell growth and the maintenance of their undifferentiated phenotype. However, HIF-1 has been suggested to interplay with Wnt signaling components, thus activating a neuronal differentiation process in both GBM and normal brain. Here, we show that a -catenin/TCF1/HIF-1 complex directly controls the transcription of neuronal differentiation genes in hypoxia. Conversely, at higher oxygen levels, the increased expression of TCF4 exerts a transcriptional inhibitory function on the same genomic regions, thus counteracting differentiation. Moreover, we demonstrate the existence of a positive correlation between HIF-1, TCF1 and neuronal phenotype in GBM tumors, accompanied by the over-expression of several Wnt signaling components, finally impacting on patient prognosis. In conclusion, we unveil a mechanism by which TCF1 and HIF-1 induce a reminiscent neuronal differentiation of hypoxic GBM cells, which is hampered, in normoxia, by high levels of TCF4, thus de facto sustaining cell aggressiveness.
Publication Title
HIF-1α/Wnt signaling-dependent control of gene transcription regulates neuronal differentiation of glioblastoma stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Glioblastoma (GBM) is the most devastating tumour of the brain, endowed with a fatal prognosis. Indeed, the complete eradication of cancer cell disseminated outside the GBM mass still remains a crucial issue. Given the reported strong association existing between Annexin 2A (ANXA2) expression and cell dissemination in many cancers, we evaluated the effects exerted by the modulation of ANXA2 levels in GBM cells and assessed its potential in predicting patient outcome. Here, we show that expression of ANXA2 positively correlates with metastatic gene signatures and demonstrates to be prognostic by itself. Indeed, we prove that ANXA2 is involved in cell migration, invasion, cytoskeletal remodeling and proliferation in GBM cells. Moreover, we were able to construct a gene signature representative of ANXA2 inhibition, which showed a significant prognostic potential in different GBM patient cohorts.
Publication Title
Annexin 2A sustains glioblastoma cell dissemination and proliferation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
phenotypic reprogramming ability of teh zebtafish brain microenviroment on GBM derived cells controlled by the activation of endogenous Wnt pathway
Publication Title
Wnt activation promotes neuronal differentiation of glioblastoma.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
STAT3 is a transcription factor playing a crucial role in inflammation, immunity and oncogenesis, able to induce distinct subsets of target genes in different cell types or under different conditions. Identification of direct transcriptional targets however has only defined a relatively limited set of genes, not sufficient to explain its variegated functions. In order to improve our understanding of the STAT3 transcriptional network we decided to develop a computational approach for the discovery of STAT3 functional binding sites. Upon generating a Positional Weight Matrix to define STAT3 binding sites, we applied a loglikelihood ratio scoring function and were able to assign affinity scores with very high specificity (93.5%) as measured by EMSA. STAT3 binding sites scoring above a stringent threshold have been identified genome-wide in Homo sapiens and Mus musculus and selected for phylogenetic conservation by genomic sequence alignment using eight vertebrate species. Validation was carried out on a subset of predicted
Publication Title
Genome-wide discovery of functional transcription factor binding sites by comparative genomics: the case of Stat3.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 38 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Thirty-eight tumors from 17 patients treated with BRAF inhibitor (n=12) or combination BRAF/MEK inhibitors (n=5) with known PD-L1 expression were analyzed. RNA expression arrays were performed on all pre-treatment (PRE, n=17), early during treatment (EDT, n=8) and progression (PROG, n=13) biopsies. HLA-A/HLA-DPB1 expression was assessed by immunohistochemistry (IHC). Gene set enrichment analysis (GSEA) of PRE, EDT and PROG melanomas revealed that transcriptome signatures indicative of immune cell activation were strongly positively correlated with PD-L1 staining. In contrast, MAPK signaling and canonical Wnt/--catenin activity were negatively associated with PD-L1 melanoma expression. The expression of PD-L1 and immune activation signatures did not simply reflect the degree or type of immune cell infiltration, and was not sufficient for tumor response to MAPK inhibition.
Publication Title
PD-L1 Expression and Immune Escape in Melanoma Resistance to MAPK Inhibitors.
Sample Metadata Fields
Specimen part
View Samples