Breast carcinoma (BC) have been extensively profiled by high-throughput technologies for over a decade, and broadly speaking, these studies can be grouped into those that seek to identify patient subtypes (studies of heterogeneity) or those that seek to identify gene signatures with prognostic or predictive capacity. The shear number of reported signatures has led to speculation that everything is prognostic in BC. Here we show that this ubiquity is an apparition caused by a poor understanding of the inter- relatedness between subtype and the molecular determinants of prognosis. Our approach constructively shows how to avoid confounding due to a patient's subtype, clinicopathological or treatment profile. The approach identifies patients who are predicted to have good outcome at time of diagnosis by all available clinical and molecular markers, but who experience a distant metastasis within five years. These inherently difficult patients (~7% of BC) are prioritized for investigations of intra-tumoral heterogeneity.
The prognostic ease and difficulty of invasive breast carcinoma.
Age, Disease stage, Time
View Samplesconsequences of astrocytes on GSCs, gene expression profiles generated from glioblastoma stem-like cells grown alone (mono-culture) and compared to those generated 48h after the initiation of co-culture with astrocytes
Coculture with astrocytes reduces the radiosensitivity of glioblastoma stem-like cells and identifies additional targets for radiosensitization.
Specimen part, Subject
View SamplesDefining radioresponse using the translatome and the transcriptome to identify functional consequences of radiation.
Polysome Profiling Links Translational Control to the Radioresponse of Glioblastoma Stem-like Cells.
Specimen part, Cell line, Treatment, Time
View SamplesCytoplasmic RNA bound to eIF4E was pulled down from MDA-MB-231 cells to determine the influence of radiation on eIF4E mRNA binding
Translation initiation factor eIF4E is a target for tumor cell radiosensitization.
Cell line, Treatment, Time
View SamplesIn an ongoing translational research program involving microarray-based expression profiles in pediatric septic shock, we have now conducted longitudinal studies focused on the temporal expression profiles of canonical signaling pathways and gene networks. Genome-level expression profiles were generated from whole blood-derived RNA samples of children with septic shock (n = 30 individual patients) corresponding to days 1 and 3 of admission to the pediatric intensive care unit. Based on sequential statistical and expression filters, day 1 and day 3 of septic shock were characterized by differential regulation of 2,142 and 2,504 gene probes, respectively, relative to normal control patients. Venn analysis demonstrated 239 unique genes in the day 1 data set, 598 unique genes in the day 3 data set, and 1,906 genes common to both data sets. Analyses targeted toward derivation of biological function from these data sets demonstrated time-dependent, differential regulation of genes involved in multiple canonical signaling pathways and gene networks primarily related to immunity and inflammation. Notably, multiple and distinct gene networks involving T cell- and MHC antigen-related biological processes were persistently downregulated from day 1 to day 3. Further analyses demonstrated large scale and persistent downregulation of genes corresponding to functional annotations related to zinc homeostasis. These data represent the largest reported cohort of patients with septic shock, which has undergone longitudinal genome-level expression profiling. The data further advance our genome-level understanding of pediatric septic shock and support novel hypotheses that can be readily tested at both the experimental and translational levels.
Genome-level longitudinal expression of signaling pathways and gene networks in pediatric septic shock.
No sample metadata fields
View SamplesGoal of the experiment: To identify correlated genes, pathways and groups of patients with systemic inflammatory response syndrome and septic shock that is indicative of biologically important processes active in these patients.
Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome.
No sample metadata fields
View SamplesRat has been treated with different compounds with the purpose of investigating toxicological mechanisms. But toxic and non-toxic compounds has been administered. 3 toxic (ANIT, DMN, NMF) 3 non-tox (Caerulein, dinitrophenol(DNP), Rosiglitazone) in 5-plicates (30 arrays in all) and 9 untreated (control), 39 samples in all.
Integration of clinical chemistry, expression, and metabolite data leads to better toxicological class separation.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Induction of hepatocellular carcinoma by in vivo gene targeting.
Age, Specimen part
View SamplesThe distinct phenotypic and prognostic subclasses of human hepatocellular carcinoma (HCC) are difficult to reproduce in animal experiments. Here we have used in vivo gene targeting to insert an enhancer-promoter element at an imprinted chromosome 12 locus in mice, thereby converting ~1 in 20,000 normal hepatocytes into a focus of HCC with a single genetic modification. A 300 kb chromosomal domain containing multiple mRNAs, snoRNAs and microRNAs was activated surrounding the integration site. An identical domain was activated at the syntenic locus in a specific molecular subclass of spontaneous human HCCs with a similar histological phenotype, which was associated with partial loss of DNA methylation. These findings demonstrate the accuracy of in vivo gene targeting in modeling human cancer, and suggest future applications in studying various tumors in diverse animal species. In addition, similar insertion events produced by randomly integrating vectors could be a concern for liver-directed human gene therapy.
Induction of hepatocellular carcinoma by in vivo gene targeting.
Age
View SamplesWe profiled the skeletal muscle transcriptome between wild type and aB-crystallin/HspB2 knock mice exposed to normal chow and high fat diets to examine the role of aB-crystallin/HspB2 in diet induced obesity. Combined with metabolic profiling of the mice, these data reveal that aB-crystallin/HspB2 is involved in the genesis of insulin resistance on a high fat diet, and we provide extensive RNA profiling to illuminate potential mechanistic insights into the muscle-specific role of aB-crystallin/HspB2. Overall design: Hind limb muscle mRNA profiles of wild type and aB-crystallin/HspB2 knock mice exposed to either normal chow or high fat diets using RNAseq analysis
αB-crystallin and HspB2 deficiency is protective from diet-induced glucose intolerance.
No sample metadata fields
View Samples