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GSE70115
Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Disseminated triple negative breast cancer (TNBC) is an incurable disease with limited therapeutic options beyond chemotherapy. Therefore, identification of druggable vulnerabilities is a mind aim. Protein kinases play a central role in cancer and particularly in TNBC. They are involved in many oncogenic functions including migration, proliferation, genetic stability or maintenance of stem-cell like properties. In this article we describe a novel multi-kinase inhibitor with antitumor activity in this cancer subtype. EC-70124 is a hybrid indolocarbazole analog obtained by combinatorial biosynthesis of Rebeccamycin and Staurosporine genes that showed antiproliferative effect and in vivo antitumoral activity. Biochemical experiments demonstrated the inhibition of the PI3K/mTOR and JAK/STAT pathways. EC-70124 mediated DNA damage leading to cell cycle arrest at the G2/M phase. Gene set enrichment analyses identified several deregulated functions including cell proliferation, migration, DNA damage, regulation of stem cell differentiation and reversion of the epithelial-mesenchymal transition (EMT) phenotype, among others. Combination studies showed a synergistic interaction of EC-70124 with docetaxel, and an enhanced activity in vivo. Furthermore, EC-70124 had a good pharmacokinetic profile. In conclusion these experiments demonstrate the antitumor activity of EC-70124 in TNBC paving the way for the future clinical development of this drug alone or in combination with chemotherapy.
Publication Title
Antitumor activity of the novel multi-kinase inhibitor EC-70124 in triple negative breast cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Caenorhabditis elegans
- 8 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Lactoferrin is a highly multifunctional protein. Indeed, it is involved in many physiological functions, including regulation of iron absorption and immune responses.
Publication Title
A nutritional supplement containing lactoferrin stimulates the immune system, extends lifespan, and reduces amyloid <i>β</i> peptide toxicity in <i>Caenorhabditis elegans</i>.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 250 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The purpose of this study was to characterize the transcriptional effects induced by subcutaneous IFN-beta-1b treatment (Betaferon, 250 g every other day) in patients with relapsing-remitting form of multiple sclerosis (MS).
Publication Title
Long-term genome-wide blood RNA expression profiles yield novel molecular response candidates for IFN-beta-1b treatment in relapsing remitting MS.
Sample Metadata Fields
Sex
View Samples- Xenopus laevis
- 3 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
We implemented a functional genomics approach as a means to undertake a large-scale analysis of the Xenopus laevis inner ear transcriptome through microarray analysis.
Publication Title
Probing the Xenopus laevis inner ear transcriptome for biological function.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
NextSeq 500
Description
Our analysis indicates that at least 37% of the transcriptome mobilized by KNAT1 is potentially dependent on this interaction, and includes genes involved in secondary cell wall modifications and phenylpropanoid biosynthesis. Overall design: Seven-day-old Arabidopsis wild-type (No-0) and 35S::KNAT1 seedlings growing in MS plates under continuous light were transferred to a liquid growing medium supplemented with 10 µM paclobutrazol (PAC) for 18 h. Seedlings were then incubated with 10 µM PAC+100 µM GA3 or maintained in 10 µM PAC for 5 h.
Publication Title
Regulation of xylem fiber differentiation by gibberellins through DELLA-KNAT1 interaction.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
The aim of this experiment is to determine Hhex targets in the presence and absence of Myc.
Publication Title
Growth-promoting and tumourigenic activity of c-Myc is suppressed by Hhex.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- (ffymetrixhumanexon1.0starray[cdf:huex10stv2,corer3,a20071112,ep)
Description
Patients with conventional mantle cell lymphoma (MCL) show an aggressive clinical behavior. However, cases fulfilling the WHO criteria for MCL, but that remain asymptomatic without treatment, have been reported. In an attempt to understand this heterogeneity, we have compared 17 typical cases of MCL with a homogeneous group of 13 asymptomatic individuals with monoclonal expansion of t(11;14)(q13;q32) cyclin D1-positive B-cells in peripheral blood (MALD1). None of these cases have received treatment (minimum follow-up of 26 months; median, 71 months).
Publication Title
Distinction between asymptomatic monoclonal B-cell lymphocytosis with cyclin D1 overexpression and mantle cell lymphoma: from molecular profiling to flow cytometry.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Hematopoietic stem cells (HSCs), which reside in bone marrow niches, are exposed to low levels of oxygen and follow an oxygen gradient throughout their differentiation. Hypoxia-inducible factors (HIFs) are the main factors regulating the cell response to oxygen variation. Recent studies using conditional knockout mouse models have unveiled a major role of HIF-1a in the maintenance of murine HSCs, however the role of HIF-2a is still unclear. Here, we show that knockdown of HIF-2a and to a much lower extent, HIF-1a impedes the long-term repopulating ability of human CD34+ umbilical cord blood derived cells. The defects observed in hematopoietic stem and progenitor cell (HSPC) function after HIF-2a knockdown was due to an increase in the production of reactive oxygen species (ROS), which increases the endoplasmic reticulum (ER) stress in HSPCs and triggers apoptosis by the activation of the unfolded-protein-response (UPR) pathway. Importantly, HIF-2a deregulation also resulted in a significant decrease of engraftment of human acute myeloid leukemia (AML) cells. Overall, our data demonstrates a key role of HIF-2a in the maintenance of human HSPCs and in the survival of primary AML cells.
Publication Title
HIF-2α protects human hematopoietic stem/progenitors and acute myeloid leukemic cells from apoptosis induced by endoplasmic reticulum stress.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 42 Downloadable Samples
Description
Background: Differences in breast cancer outcomes according to race/ethnicity have been reported. Hispanic/Latino (H/L) populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. Some studies suggest that breast cancer-specific mortality is higher in U.S. Hispanic/Latinas compared to non-Hispanic Whites (NHW) even after adjustment for socioeconomic status and education. The molecular profile of breast cancer has been widely described in NHWs but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian H/L women was Luminal B as defined by surrogate St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women. Methods: We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups. Results: We found 5 genes potentially modulated by genetic ancestry: ERBB2 (Fold Change = 2.367, padj < 0.01), GRB7 (Fold Change = 2.327, padj < 0.01), GSDMB (Fold Change = 1.723, padj < 0.01, MIEN1 (Fold Change = 2.195, padj < 0.01 and ONECUT2 (Fold Change = 2.204, padj < 0.01). In the replication set we found a statistical significant association between European ancestry fraction and the expression levels of ERBB2 (p = 0.02, B = 2.49) and ONECUT2 (p = 0.04, B = -4.87). We also observed statistical significant associations for ERBB2 expression with Indigenous American ancestry (p < 0.001, B = 3.82). This association was not biased by the distribution of HER2+ tumors among the groups analyzed. Conclusions: Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value. Overall design: RNA profile of 42 luminal breast cancer tumors (21 luminal A and 21 luminal B) from Colombian patients
Publication Title
Ancestry as a potential modifier of gene expression in breast tumors from Colombian women.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In a pilot experiment to reprogramme MEF into endoderm, we infected MEF with the Yamanakas factors (O: Oct4, K: Klf4, S: Sox2, M:Myc), FoxA2 (F) and Gata4 (G). Global gene expression of isolated clones was performed.
Publication Title
Gata4 blocks somatic cell reprogramming by directly repressing Nanog.
Sample Metadata Fields
No sample metadata fields
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