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Platform
GSE11550
Homo sapiens
10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to detail gene expression changes in Hs 294T human melanoma cells after treatment with elesclomol alone, or in combination with paclitaxel, to aide in identifing the mechnism of action of elesclomol.
Publication Title
Elesclomol induces cancer cell apoptosis through oxidative stress.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to detail gene expression changes in Hs 294T human melanoma cells after treatment with elesclomol alone, or in combination with NAC, to aide in identifing the mechnism of action of elesclomol.
Publication Title
Elesclomol induces cancer cell apoptosis through oxidative stress.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
The current standard-of-care for advanced liver cancer is limited. Therefore, there is an urgent need for development of novel molecular targeted therapy. Increase of WEE1 kinase activity through an epigenetic regulation plays an important role in the development of hepatocellular carcinoma (HCC). Here we demonstrated that WEE1 siRNA silencing caused inhibition of HCC cell growth through blockade of cell cycle progression and induction of apoptosis. The anti-proliferative effects were driven by a subset of molecular alterations including the upregulation of cdk inhibitor p21 and the downregulation of AKT1, CDK2, cyclin B1 (CCNB1), PARP1 and GPAM which are functionally involved in control of cell cycle, apoptosis and lipid metabolism. Systemic delivery of a modified WEE1 siRNA encapsulated in lipid nanoparticles significantly inhibited human HCC growth in murine xenograft models, and increased mice survival. Wee1 silencing in tumor cells also resulted in a strong inhibition of lipogenesis (SREBP1C, FAS) and caused a marked decrease in fat accumulation. Of importance, knockdown of WEE1 dramatically reduced the portion of liver cancer stem cells (CSCs) population through co-downregulation of cancer stemness genes and weakened the capacity of sphere formation and the ability of cancer cell migration. Our findings suggest that the epigenetic modifier WEE1 functionally involve to HCC lipid metabolism and CSC-like phenotype maintenance and that molecular targeting of WEE1 may be an effective systemic therapy for prevention of tumor recurrence via elimination of CSCs in liver tumor microenvironment.
Publication Title
No associated publication
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Chlorella has been reported to have various physiological activities, including antiarteriosclerotic, cholesterol-lowering, anti-inflammatory, and immunoregulatory effects. However, there has been no report on the long-term effects of chlorella ingestion on immunity. In the present study, 4- to 10-week-old (young) and 4- to 50-week-old (old) female BALB/c mice were sensitized or not with ovalbumin (OVA), and given basic diet containing chlorella powder at 2% or basic diet alone. The effects of chlorella ingestion on immunity were investigated by measurement of splenic cytokines and immunoglobulin (Ig), analysis of T- and B-cells in the spleen and small intestine by flow cytometry, and analysis of the liver by DNA microarray. Results were compared between the young and old, OVA-sensitized and -nonsensitized, and chlorella and non-chlorella ingestion groups. Production of interferon- (IFN-) was maintained in the nonsensitized old groups, and ratios of T-helper type 1 (Th1) to T-helper type 2 (Th2) cells were similar in the young and old groups. In addition, overproduction of OVA-specific Igs due to OVA sensitization was strongly suppressed, and significant immunotolerance was exhibited irrespective of age. In addition, suppression of T-cell decreases in the spleen due to aging and suppression of changes in T- and B-cells due to OVA sensitization in the small intestinal lymph were demonstrated on flow cytometric analyses. On DNA microarray analysis, immune-related terms including IL11 and major histocompatibility complex (MHC) class 1 were detected, and expression of genes was shown, which were related to IL1-linked genes and complex involving macrophages from the pathways of cytokines and inflammatory response. In addition, suppressions of declined lipid metabolism and energy production were also suggested. Although how the ingredients in chlorella were involved in these changes is unclear, our findings suggest that prevention of decrease in acquired immunity by aging and induction of strong immunotolerance occurred following chlorella ingestion.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 264 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The 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.
Publication Title
Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 172 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Glatiramer 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.
Publication Title
Gene expression studies of a human monocyte cell line identify dissimilarities between differently manufactured glatiramoids.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus
- 103 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
We 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.
Publication Title
Accurate and precise transcriptional profiles from 50 pg of total RNA or 100 flow-sorted primary lymphocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 50 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Proliferating 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.
Publication Title
Small molecule activation of PKM2 in cancer cells induces serine auxotrophy.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptional analysis of the superior temporal cortex (BA22) in schizophrenia: Pathway insight into disease pathology and drug development
Publication Title
Transcription and pathway analysis of the superior temporal cortex and anterior prefrontal cortex in schizophrenia.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples