Murine C26 tumor xenografts displayed different responses to the treatments of PBS, Doxorubicin (Dox), and chimeric polypeptide (CP)-Dox conjugates. We used microarrays to globally study gene expression underlying these different responses and identified distinct classes of up-regulated or down-regulated genes upon treatment.
Self-assembling chimeric polypeptide-doxorubicin conjugate nanoparticles that abolish tumours after a single injection.
Age, Specimen part
View SamplesThe cure rate for childhood ALL has improved considerably in part because therapy is routinely tailored to the predicted risk of relapse. Various clinical and laboratory variables are used in current risk-stratification schemes, but many children who fail therapy lack adverse prognostic factors at initial diagnosis. Using gene expression analysis, we have identified genes and pathways in a NCI high-risk childhood B-precursor ALL cohort at diagnosis that may play a role in early blast regression as correlated with the Day 7 marrow status. We have also identified a 47-probeset signature (representing 41 unique genes) that was predictive of long term outcome in our dataset as well as three large independent datasets of childhood ALL treated on different protocols.
Gene expression signatures predictive of early response and outcome in high-risk childhood acute lymphoblastic leukemia: A Children's Oncology Group Study [corrected].
No sample metadata fields
View SamplesPompe disease is caused by autosomal recessive mutations in the GAA gene, which encodes acid alpha-glucosidase. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease induced pluripotent stem cells (PomD-iPSCs) and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features, and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen, abundant intracellular LAMP-1- or LC3-positive granules, and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to rhGAA reversed the major pathologic phenotypes. Further, L-carnitine and 3- methyladenine treatment reduced defective cellular respiration and buildup of phagolysosomes, respectively, in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for development of novel therapeutic strategies for Pompe disease.
Human Pompe disease-induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated molecular profiling.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA.
Treatment, Time
View SamplesAnalysis of ALR-deficient cells indicates that ALRs are not required for the IFN response to intracellular DNA. To explore whether AIM2-like receptors activated another innate signaling pathway upon
The AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA.
Treatment, Time
View SamplesGain or loss of genes and deregulation of gene expression can result in cumulative and progressive disruptions of normal cellular functions.
Identification of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated molecular profiling.
Specimen part
View SamplesPurpose: we tested the hypothesis that Hltf deletion in placenta either caused or exacerbated neonatal hypoglycemia via Hif-1a regulation of nutrient transporters. Methods: Individual samples [1 term placenta/sample x 5 biological replicates for test and control littermate female mice = 10 total samples] were flash frozen and sent to Otogenetics Corp. (Norcross, GA) for RNA-seq assays. Paired-end 100 nucleotide reads were aligned to genomic assembly mm10 and analyzed using the platform provided by DNAnexus, Inc. (Mountain View, CA). Results: There was no measureable evidence of uteroplacental dysfunction or fetal compromise. Conclusion: Our study is the first to show only the truncated Hltf isoform is expressed in E18.5 term placenta, and we identified a functional link between alternative splicing of Hltf and immunosuppression at the feto-maternal interface. Overall design: Placental mRNA profiles of E18.5 term placenta from five wild type control and five Hltf null mouse samples were generated by deep sequencing by Illumina HiSeq2000/2500.
Alternative splicing of helicase-like transcription factor (Hltf): Intron retention-dependent activation of immune tolerance at the feto-maternal interface.
Specimen part, Cell line, Subject
View SamplesAn unresolved issue in immunology is the extent to which inflammatory effects are needed for robust T cell responses. In this study, mice were immunized by iv injection using either high toxicity lipopolysaccharide (LPS) or low toxicity monophosphoryl lipid A (MPL) as adjuvant. Six hours after iv immunization, whole spleens were harvested and gene expression was measured in unfractionated splenic populations of cells. The analysis indicated that the low toxicity adjuvanticity of MPL was associated with TLR4-mediated signaling that was biased to the TRIF branch of TLR4, while LPS generated balanced MyD88 and TRIF-associated outcomes.
The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4.
No sample metadata fields
View SamplesMounting evidence points to a link between a cancer possessing stem-like properties and a worse prognosis. To understand the biology, a common approach is to integrate network biology with signal processing mechanics. That said, even with the right tools, predicting the risk for a highly susceptible target using only a handful of gene signatures remains very difficult. By compiling the expression profiles of a panel of tumor stem-like cells (TSLCs) originating in different tissues, comparing these to their parental tumor cells (PTCs) and the human embryonic stem cells (hESCs), and integrating network analysis with signaling mechanics, we propose that network topologically-weighted signaling processing measurements under tissue-specific conditions can provide scalable and predicable target identification.
Network biology of tumor stem-like cells identified a regulatory role of CBX5 in lung cancer.
Specimen part
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