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accession-icon GSE70115
Antitumor activity of the novel multi-kinase inhibitor EC-70124 in triple negative breast cancer
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon 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

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accession-icon GSE33455
Expression data from docetaxel-resistant prostate cancer cell lines
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Docetaxel-based chemotherapy is the standard first-line therapy in metastatic castration-resistant prostate cancer. However, most patients eventually develop resistance to this treatment.

Publication Title

Identification of docetaxel resistance genes in castration-resistant prostate cancer.

Sample Metadata Fields

Disease, Disease stage, Cell line, Treatment

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accession-icon GSE22187
Changes in gene expression in implantation sites by absence of Cbs
  • organism-icon Mus musculus
  • sample-icon 2 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)

Description

The change in gene expression on the 8th day of gestation was investigated using DNA microarrays.

Publication Title

Cystathionine β-synthase deficiency causes infertility by impairing decidualization and gene expression networks in uterus implantation sites.

Sample Metadata Fields

Sex, Age, Specimen part

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accession-icon GSE22189
Changes in gene expression in inter-implantation sites by absence of Cbs
  • organism-icon Mus musculus
  • sample-icon 2 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)

Description

The change in gene expression on the 8th day of gestation was investigated using DNA microarrays. Uterine gene expression of interimplanted sites was analyzed in female mice.

Publication Title

Cystathionine β-synthase deficiency causes infertility by impairing decidualization and gene expression networks in uterus implantation sites.

Sample Metadata Fields

Sex, Age, Specimen part

View Samples
accession-icon GSE66370
Expression and role of Galectins 1 and 3 in the lesioned brain
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Astrocytes react to brain injury in a heterogeneous manner with only a subset resuming proliferation and acquiring in vitro neural stem cell properties. In order to identify novel regulators of this astrocyte subset, we performed a genome-wide expression analysis of reactive astrocytes isolated 5 days after stab wound injury from the adult mouse cerebral cortex. The expression pattern was compared with astrocytes from normal cortex and adult neural stem cells isolated from the sub-ependymal zone (GSE18765). These comparisons revealed a set of genes up-regulated both in neurogenic neural stem cells and reactive astrocytes, including the lectins Galectin-1 and -3. These results, as well as the pattern of Galectin expression in the lesioned brain, led us to examine the functional significance of these lectins in brains of Galectin-1/3 double-knockout mice.

Publication Title

Astrocyte reactivity after brain injury-: The role of galectins 1 and 3.

Sample Metadata Fields

Sex, Specimen part, Treatment, Time

View Samples
accession-icon GSE70921
Identification and successful negotiation of a metabolic checkpoint in direct neuronal reprogramming
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

Description

Despite the widespread interest in direct neuronal reprogramming, the mechanisms underpinning fate conversion remain largely unknown. Our study revealed a critical time point after which cells either successfully convert into neurons or succumb to cell death. Co-transduction with Bcl-2 greatly improved negotiation of this critical point by faster neuronal differentiation. Surprisingly, mutants with reduced or no affinity for Bax demonstrated that Bcl-2 exerts this effect by an apoptosis-independent mechanism. Consistent with a caspase-independent role, ferroptosis inhibitors potently increased neuronal reprogramming by inhibiting lipid peroxidation occurring during fate conversion. Genome-wide expression analysis confirmed that treatments promoting neuronal reprogramming elicit an anti-oxidative stress response. Importantly, coexpression of Bcl-2 and anti-oxidative treatments lead to an unprecedented improvement in glial-to-neuron conversion after traumatic brain injury in vivo, underscoring the relevance of these pathways in cellular reprograming irrespective of cell type, in vitro and in vivo.

Publication Title

Identification and Successful Negotiation of a Metabolic Checkpoint in Direct Neuronal Reprogramming.

Sample Metadata Fields

Sex, Specimen part

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accession-icon SRP035359
Competence for reprogramming sex
  • organism-icon Caenorhabditis elegans
  • sample-icon 77 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer IIx

Description

We used RNA-Seq to compare transcriptomes of chemical reprogramming competent worms versus worms not competent for chemical reprogramming. We also performed RNA-seq during a time course of chemical reprogramming. Overall design: Three replicates of each of two reprogramming non-competent strains and three replicates of each of two reprogramming competent strains were collected. For the time course, five time points were analyzed (1, 2, 4, 6, and 18 hours) in either DMSO or DMSO + U0126 in three genotypes (non-reprogramming competent worms, reprogramming competent, and wildtype worms).

Publication Title

Competence for chemical reprogramming of sexual fate correlates with an intersexual molecular signature in Caenorhabditis elegans.

Sample Metadata Fields

Subject

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accession-icon GSE19246
A novel method of amplification of FFPET derived-RNA enables accurate disease classification with microarrays
  • organism-icon Homo sapiens
  • sample-icon 171 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

A new method for amplification and labeling of RNA is assessed that permits gene expression microarray analysis of formalin-fixed paraffin embedded tissue (i.e. FFPET) samples.

Publication Title

A novel method of amplification of FFPET-derived RNA enables accurate disease classification with microarrays.

Sample Metadata Fields

Specimen part, Treatment

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accession-icon SRP047289
Dosage compensation can buffer copy-number variation in wild yeast
  • organism-icon Saccharomyces cerevisiae
  • sample-icon 59 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000, Illumina HiSeq 2500

Description

We show that aneuploidy is common in wild isolates of yeast, which are inherently tolerant to chromosome amplification and down-regulate expression at 40% of amplified genes.  To dissect the mechanism of this dosage response, we generated isogenic strain panels in which diploid cells carried either two, three, or four copies of the affected chromosomes.  Using a mixture of linear regression (MLR) model to classify genes, we find that expression is actively down regulated in proportion to increased gene copy at up to 30% of genes. Genes subject to dosage control are under higher expression constraint – but show elevated rates of gene amplification – in wild populations, suggesting that dosage compensation buffers copy number variation (CNV) at toxic genes Overall design: RNA-seq and transcriptome analysis of S. cerevisiae natural isolates having aneuploidy. Technical triplicate was performed for isogenic diploid strains having 2, 3 and 4 copies of a given chromosome (strain panels), while technical duplicate or singulate was performed on all other aneuploids.

Publication Title

Dosage compensation can buffer copy-number variation in wild yeast.

Sample Metadata Fields

Subject

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accession-icon SRP082529
Single cell RNA-seq data of human hESCs to evaluate SCnorm: robust normalization of single-cell rna-seq data
  • organism-icon Homo sapiens
  • sample-icon 414 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Normalization of RNA-sequencing data is essential for accurate downstream inference, but the assumptions upon which most methods are based do not hold in the single-cell setting. Consequently, applying existing normalization methods to single-cell RNA-seq data introduces artifacts that bias downstream analyses. To address this, we introduce SCnorm for accurate and efficient normalization of scRNA-seq data. Overall design: Total 183 single cells (92 H1 cells, 91 H9 cells), sequenced twice, were used to evaluate SCnorm in normalizing single cell RNA-seq experiments. Total 48 bulk H1 samples were used to compare bulk and single cell properties. For single-cell RNA-seq, the identical single-cell indexed and fragmented cDNA were pooled at 96 cells per lane or at 24 cells per lane to test the effects of sequencing depth, resulting in approximately 1 million and 4 million mapped reads per cell in the two pooling groups, respectively.

Publication Title

SCnorm: robust normalization of single-cell RNA-seq data.

Sample Metadata Fields

Specimen part, Cell line, Subject

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...

refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Developed by the Childhood Cancer Data Lab

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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