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GSE89766
Homo sapiens
12 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Autophagy plays important roles in malignant pathogenesis and drug resistance. We used medicinal chemistry approaches to generate a series of novel agents that inhibit autophagic degradation. ROC-325 was selected as a lead compound for further evaluation. Comprehensive in vitro and in vivo studies were conducted to evaluate the selectivity, tolerability, and efficacy of ROC-325 in preclinical models of renal cell carcinoma (RCC). ROC-325 exhibited superior in vitro anticancer effects than the existing autophagy inhibitor hydroxychloroquine in 12 different tumor models with diverse genetic backgrounds. Focused studies of the mechanism of action and efficacy of ROC-325 in RCC cells showed that drug treatment induced hallmark characteristics of autophagy inhibition including accumulation of autophagosomes with undegraded cargo, lysosomal deacidification, p62 stabilization, and disruption of autophagic flux. Subsequent experiments showed that ROC-325 antagonized RCC growth and survival in an ATG5/7-dependent manner, induced apoptosis, and exhibited favorable selectivity. Oral administration of ROC-325 to mice bearing 786-0 RCC xenografts was well tolerated, significantly more effective at inhibiting tumor progression than HCQ, and inhibited autophagy in vivo.
Publication Title
Disruption of Autophagic Degradation with ROC-325 Antagonizes Renal Cell Carcinoma Pathogenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
To define and compare the genome-wide transcriptional signatures of Notch1+ cells in intestinal tumors and in normal ISCs we performed Affymetrix analyses of these two populations.
Publication Title
Lineage tracing of Notch1-expressing cells in intestinal tumours reveals a distinct population of cancer stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens, Xenopus laevis
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Control of vertebrate multiciliogenesis by miR-449 through direct repression of the Delta/Notch pathway.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used microarrays to detail the global programme of gene expression that occurs in response to miR-449 or miR-34 overexpression in proliferating HAECs.
Publication Title
Control of vertebrate multiciliogenesis by miR-449 through direct repression of the Delta/Notch pathway.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The regeneration of the airway mucociliary epithelium involves several sequential events including migration, proliferation, polarization and final differentiation (i.e ciliogenesis).
Publication Title
Control of vertebrate multiciliogenesis by miR-449 through direct repression of the Delta/Notch pathway.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have used an agnostic approach to identify drug combinations by using combination high throughput screening (cHTS) technology and make the surprising discovery that adenosine A2A and beta-2 adrenergic receptor agonists are highly synergistic, selective and novel agents that enhance glucocorticoid activity in B-cell malignancies.
Publication Title
Adenosine A2A and beta-2 adrenergic receptor agonists: novel selective and synergistic multiple myeloma targets discovered through systematic combination screening.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Smoking represents a major risk factor for chronic obstructive pulmonary disease (COPD), but it is difficult to characterize smoke-induced injury responses under physiological breathing conditions in humans. Here we generated small airway-on-a-chip microdevices lined by living human bronchiolar epithelium from normal or COPD patients and connected them to an instrument that 'breathes' whole cigarette smoke in and out of the chips to study smoke-induced pathophysiology in vitro. We used microarrays to detail the global program of gene expression in well-differentiated epithelial cells following smoke exposure to recapitulate clinical pathologies and identify disease-specific responses.
Publication Title
Matched-Comparative Modeling of Normal and Diseased Human Airway Responses Using a Microengineered Breathing Lung Chip.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
GRBATKO_BAT_COLDEXPOSURE
Publication Title
The glucocorticoid receptor in brown adipocytes is dispensable for control of energy homeostasis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Lipid mobilization (lipolysis) in white adipose tissue (WAT) critically controls lipid turnover and adiposity in humans. While the acute regulation of lipolysis has been studied in detail, the transcriptional determinants of WAT lipolytic activity remain still largely unexplored. Here we show that the genetic inactivation of transcriptional co-factor transducin beta-like-related (TBLR) 1 blunts the lipolytic response of white adipocytes through the impairment of cAMP-dependent signal transduction. Indeed, mice lacking TBLR1 in adipocytes are defective in fasting-induced lipid mobilization and when placed on a high fat diet show aggravated adiposity, glucose intolerance and insulin resistance. TBLR1 levels are found to increase under lipolytic conditions in WAT of both human patients and mice, correlating with serum free fatty acids (FFA). As a critical regulator of WAT cAMP signaling and lipid mobilization, proper activity of TBLR1 in adipocytes may thus represent a critical molecular checkpoint for the prevention of metabolic dysfunction in subjects with obesity-related disorders.
Publication Title
Transcriptional cofactor TBLR1 controls lipid mobilization in white adipose tissue.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
RNAseq characterization of gene expression changes 72 hours after genomic excision of Cebpa in murine hematopoietic progenitors from Cebpaf/f;CreER mice transformed by Hoxa9/Meis1. In the presence of tamoxifen (4OHT), Cre-ER localizes to the nucleus of cells allowing for excision of Cebpa and loss of C/EBPa protein levels. Loss of C/EBPa leads to a decrease in cellular proliferation. Overall design: Examination of gene expression by RNAseq in two conditions in biological replicates.
Publication Title
C/EBPα is an essential collaborator in Hoxa9/Meis1-mediated leukemogenesis.
Sample Metadata Fields
No sample metadata fields
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