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GSE43112
Mus musculus
2 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Canonical Wnt signaling controls proliferation and differentiation of osteogenic progenitor cells, and tumor-derived secretion of the Wnt antagonist Dickkopf-1 (Dkk1) is correlated with osteolyses and metastasis in many bone malignancies. However, the role of Dkk1 in the oncogenesis of primary osteosarcoma (OS) remains unexplored. Here, we over-expressed Dkk1 in the OS cell line MOS-J. Contrary to expectations, Dkk1 had autocrine effects on MOSJ cells in that it increased proliferation and resistance to metabolic stress in vitro. In vivo, Dkk1 expressing MOS-J cells formed larger and more destructive tumors than controls. These effects were attributed in part to up-regulation of the stress response enzyme and cancer stem cell marker aldehyde-dehydrogenase-1 (ALDH1) through Jun-N-terminal kinase signaling. This is the first report linking Dkk1 to tumor stress resistance, further supporting the targeting of Dkk1 not only to prevent and treat osteolytic bone lesions but also to reduce numbers of stress-resistant tumor cells.
Publication Title
An unexpected role for a Wnt-inhibitor: Dickkopf-1 triggers a novel cancer survival mechanism through modulation of aldehyde-dehydrogenase-1 activity.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 66 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences in NSCLC from African Americans and European Americans.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Race, Subject
View Samples- Rattus norvegicus
- 111 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Mdr1a-, Bcrp-, and Mrp2-knockout rats are a more practical species for ADME studies than murine models and previously demonstrated expected alterations in pharmacokinetics of various probe substrates. At present, gene expression and pathology changes were systematically studied in small intestine, liver, kidney, and brain tissue from male SAGE Mdr1a-, Bcrp-, and Mrp2-knockout rats versus wild-type Sprague Dawley controls. Gene expression data supported the relevant knockout genotype. As expected, Mrp2-knockout rats were hyperbilirubinemic and exhibited upregulation of hepatic Mrp3. Overall, few alterations were observed within 137 ADME-relevant genes. The two most consequential changes were upregulation of intestinal carboxylesterase in Mdr1a-knockouts and catechol-O-methyltransferase in all tissues of Bcrp-knockout rats. Previously reported upregulation of hepatic Mdr1b P-glycoprotein in proprietary Wistar Mdr1a-knockout rats was not observed in the SAGE counterpart investigated herein. Relative liver and kidney weights were 22-53% higher in all three knockouts, with microscopic increases in hepatocyte size in Mdr1a- and Mrp2-knockout rats, and glomerular size in Bcrp- and Mrp2-knockouts. Increased relative weight of clearing organs is quantitatively consistent with reported increases in clearance of drugs that are not substrates of the knocked-out transporter. Overall, SAGE knockout rats demonstrated modest compensatory changes, which do not preclude their general application to study transporter-mediated pharmacokinetics. However until future studies elucidate the magnitude of functional change, caution is warranted in rare instances of extensive metabolism by catechol-O-methyltransferase in Bcrp-knockouts and intestinal carboxylesterase in Mdr1a-knockout rats, specifically for molecules with free catechol groups and esters subject to gut wall hydrolysis.
Publication Title
Minor compensatory changes in SAGE Mdr1a (P-gp), Bcrp, and Mrp2 knockout rats do not detract from their utility in the study of transporter-mediated pharmacokinetics.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 66 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Translational Relevance
Publication Title
Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences in NSCLC from African Americans and European Americans.
Sample Metadata Fields
Sex, Age, Race, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BCRABL1+ precursor B-cell acute lymphoblastic leukemia (BCR ABL1+ B-ALL) is an aggressive hematopoietic neoplasm characterized by a block in differentiation due in part to the somatic loss of transcription factors required for B-cell development. We hypothesized that overcoming this differentiation block by forcing cells to reprogram to the myeloid lineage would reduce the leukemogenicity of these cells. We found that primary human BCRABL1+ B-ALL cells could be induced to reprogram into macrophage-like cells by exposure to myeloid differentiation-promoting cytokines in vitro or by transient expression of the myeloid transcription factor C/EBP or PU.1. The resultant cells were clonally related to the primary leukemic blasts but resembled normal macrophages in appearance, immunophenotype, gene expression, and function. Most importantly, these macrophage-like cells were unable to establish disease in xenograft hosts, indicating that lineage reprogramming eliminates the leukemogenicity of BCRABL1+ B-ALL cells, and suggesting a previously unidentified therapeutic strategy for this disease. Finally, we determined that myeloid reprogramming may occur to some degree in human patients by identifying primary CD14+ monocytes/ macrophages in BCRABL1+ B-ALL patient samples that possess the BCRABL1+ translocation and clonally recombined VDJ regions.
Publication Title
Reprogramming of primary human Philadelphia chromosome-positive B cell acute lymphoblastic leukemia cells into nonleukemic macrophages.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
Illumina HiSeq 2000
Description
Folic acid supplements prior to and during gestation are recommended and necessary to prevent neural tube defects in developing embryos. But there are also studies suggesting possible adverse effects of high-dose folic acid supplementation. Here, we address whether maternal dietary folic acid supplementation at 40 mg/kg chow (FD), restricted to a period prior to conception, affects gene expression in the offspring generation. Overall design: Total RNA extracted from hippocampi of 6 control (CD) F1 mice and 5 FD F1 mice at the age of 14 weeks.
Publication Title
High-dose maternal folic acid supplementation before conception impairs reversal learning in offspring mice.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
HMCs were treated with CsA (4.2 M) for 0 12 and 48 hours. To exmaine global gene changes in the renal mesangium following CsA treatment in order to identify novel contributors to CsA-induced renal dysfunction
Publication Title
Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 80 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Bipolar affective disorder is a severe psychiatric disorder with a strong genetic component but unknown pathophysiology. We used microarray technology (Affymetrix HG-U133A GeneChips) to determine the expression of approximately 22 000 mRNA transcripts in post-mortem brain tissue (dorsolateral prefrontal cortex and orbitofrontal cortex) from patients with bipolar disorder and matched healthy controls.
Publication Title
Gene expression analysis of bipolar disorder reveals downregulation of the ubiquitin cycle and alterations in synaptic genes.
Sample Metadata Fields
Sex, Age, Disease
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Bipolar affective disorder is a severe psychiatric disorder with a strong genetic component but unknown pathophysiology. We used microarray technology (Affymetrix HG-U133A GeneChips) to determine the expression of approximately 22 000 mRNA transcripts in post-mortem brain tissue (dorsolateral prefrontal cortex) from patients with bipolar disorder and matched healthy controls. A cohort of 70 subjects was investigated and the final analysis included 30 bipolar and 31 control subjects. Differences between disease and control groups were identified using a rigorous statistical analysis with correction for confounding variables and multiple testing.
Publication Title
Gene expression analysis of bipolar disorder reveals downregulation of the ubiquitin cycle and alterations in synaptic genes.
Sample Metadata Fields
Sex, Age, Disease
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
NTHi bacteria or saline were inoculated into the middle ears of mice. Mice were sacrificed at various times to monitor the course of infection.
Publication Title
The transcriptome of a complete episode of acute otitis media.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples