Comparison of stomach and colon in normal mice.
No associated publication
Sex, Age, Specimen part
View SamplesDegraded RNA - RNA with low RIN. U-251 MG brain gliablastoma cell line.
No associated publication
Specimen part
View SamplesTo adapt a non-strandaed library preparation protocol into a strand specific one in an automated fashion. Use the data to emphasize the advantages of strand specific data.
No associated publication
No sample metadata fields
View SamplesThe aims of this study were to assess the feasibility of prospective pharmacogenomics research in multicenter international clinical trials of bortezomib in multiple myeloma and to develop predictive classifiers of response and survival with bortezomib. Patients with relapsed myeloma enrolled in phase 2 and phase 3 clinical trials of bortezomib and consented to genomic analyses of pretreatment tumor samples. Bone marrow aspirates were subject to a negative-selection procedure to enrich for tumor cells, and these samples were used for gene expression profiling using DNA microarrays. Data quality and correlations with trial outcomes were assessed by multiple groups. Gene expression in this dataset was consistent with data published from a single-center study of newly diagnosed multiple myeloma. Response and survival classifiers were developed and shown to be significantly associated with outcome via testing on independent data. The survival classifier improved on the risk stratification provided by the International Staging System. Predictive models and biologic correlates of response show some specificity for bortezomib rather than dexamethasone. Informative gene expression data and genomic classifiers that predict clinical outcome can be derived from prospective clinical trials of new anticancer agents.
Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib.
No sample metadata fields
View SamplesGlatiramer Acetate (GA) has provided safe and effective treatment for multiple sclerosis (MS) patients for two decades. It acts as an antigen, yet the precise mechanism of action remains to be fully elucidated, and no validated pharmacokinetic or pharmacodynamic biomarkers exist. In order to better characterize GAs biological impact, genome-wide expression studies were conducted with a human monocyte (THP-1) cell line. Consistent with previous literature, branded GA upregulated antiinflammatory markers (e.g. IL10), and modulated multiple immune-related pathways. Despite some similarities, significant differences were observed between expression profiles induced by branded GA and Probioglat, a differently-manufactured glatiramoid purported to be a generic GA.
Gene expression studies of a human monocyte cell line identify dissimilarities between differently manufactured glatiramoids.
Cell line, Treatment, Time
View SamplesWe have developed a total RNA amplification and labeling strategy for use with Affymetrix GeneChips. Our protocol, which we denote BIIB, employs two rounds of linear T7 amplification followed by Klenow labeling to generate a biotinylated cDNA. In benchmarking studies using a titration of mouse universal total RNA, BIIB outperformed commercially available kits in terms of sensitivity, accuracy, and amplified target length, while providing equivalent results for technical reproducibility. BIIB maintained 50 and 44% present calls from 100 and 50 pg of total RNA, respectively. Inter- and intrasample precision studies indicated that BIIB produces an unbiased and complete expression profile within a range of 5 ng to 50 pg of starting total RNA. From a panel of spiked exogenous transcripts, we established the BIIB linear detection limit to be 20 absolute copies. Additionally, we demonstrate that BIIB is sensitive enough to detect the stochastic events inherent in a highly diluted sample. Using RNA isolated from whole tissues, we further validated BIIB accuracy and precision by comparison of 224 expression ratios generated by quantitative real-time PCR. The utility of our method is ultimately illustrated by the detection of biologically expected trends in a T cell/B cell titration of 100 primary cells flow sorted from a healthy mouse spleen.
Accurate and precise transcriptional profiles from 50 pg of total RNA or 100 flow-sorted primary lymphocytes.
No sample metadata fields
View SamplesProliferating tumor cells use aerobic glycolysis to support their high metabolic demands. Paradoxically, increased glycolysis is often accompanied by expression of the lower activity PKM isoform, effectively constraining lower glycolysis. Here, we report the discovery of novel PKM activators with a unique allosteric binding mode. Characterization of how these compounds impact cancer cells revealed an unanticipated link between glucose and amino acid metabolism. PKM activation resulted in a metabolic rewiring of cancer cells manifested by a profound dependency on the non-essential amino acid serine for continued cell proliferation. Induction of serine auxotrophy by PKM activation was accompanied by reduced carbon flow into the serine biosynthetic pathway and increased expression of high affinity serine transporters. These data support the hypothesis that PKM expression confers metabolic flexibility to cancer cells that allows adaptation to nutrient stress.
Small molecule activation of PKM2 in cancer cells induces serine auxotrophy.
Cell line, Treatment, Time
View SamplesRNA expression analysis was performed to compare patterns to sensitivity to BCL2 inhibitors (ABT-263).
ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor.
No sample metadata fields
View SamplesTranscriptional analysis of the superior temporal cortex (BA22) in schizophrenia: Pathway insight into disease pathology and drug development
Transcription and pathway analysis of the superior temporal cortex and anterior prefrontal cortex in schizophrenia.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesRSPO is a WNT pathway activator and functions as a potent regulator of stem cell growth in colon. RSPO family members were produced by several human tumors representing multiple tumor types including ovarian, pancreatic, colon, breast and lung cancer. Specific monoclonal antibody antagonists of RSPO family members were developed. In human patient-derived tumor xenograft models, anti-RSPO treatment markedly inhibited tumor growth either as single agents or in combination with chemotherapy. Furthermore, blockade of RSPO signaling reduced the tumorigenicity of cancer cells based on serial transplantation studies.
Therapeutic Targeting of Tumor-Derived R-Spondin Attenuates β-Catenin Signaling and Tumorigenesis in Multiple Cancer Types.
Specimen part
View Samples