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GSE13477
Homo sapiens
7 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
ARC (NSC 188491, SMA-491), 4-amino-6-hydrazino-7-beta-d-ribofuranosyl-7H-pyrrolo-(2,3-d)-pyrimidine-5-carboxamide, is a nucleoside analog with profound in vitro anti-cancer activity. First identified in a high-throughput screen for inhibitors of p21 mRNA expression, subsequent experiments showed that ARC also repressed expression of hdm2 and survivin, leading to its classification as a global inhibitor of transcription 1. The following Hu U133 plus 2.0 arrays represent single time point (24 hour) gene expression analysis of transcripts altered by ARC treatment. Arrays for the other compounds (sangivamycin and doxorubicin) are included as comparators.
Publication Title
ARC (NSC 188491) has identical activity to Sangivamycin (NSC 65346) including inhibition of both P-TEFb and PKC.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 56 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Development of LNA gapmers, antisense oligonucleotides used for efficient inhibition of target RNA expression, is limited by non-target mediated hepatotoxicity issues. In the present study, we investigated hepatic transcription profiles of mice receiving non-toxic and toxic LNA gapmers after a single and repeat administration.
Publication Title
Comparison of hepatic transcription profiles of locked ribonucleic acid antisense oligonucleotides: evidence of distinct pathways contributing to non-target mediated toxicity in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 72 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Germline BRCA1 or BRCA2 mutations (mtBRCA1 and mtBRCA2) dramatically increase risk for high-grade serous ovarian cancer (HGSOC), the most commonly diagnosed histotype. Other risk factors for this cancer, which originates primarily in the distal fallopian tube epithelium (FTE), implicate ovulation. To test whether mtBRCA1 or mtBRCA2 FTE cells respond differently to peri-ovulatory follicular fluid (FF) exposure than control patient FTE, gene expression profiles from primary FTE cultures were compared at baseline, 24h after FF exposure, and 24h after FF replacement with culture medium. Hierarchical clustering revealed both FF exposure and BRCA mutation status affect gene expression, with BRCA1 mutation having the greatest impact. Analysis revealed increased NFB and EGFR signaling at baseline, with increased interferon signaling after recovery from FF exposure in mtBRCA1 samples. Inhibition of EGFR signaling and ISGylation by increased BRCA1 expression was verified in an immortalized FTE cell line, OE-E6/E7, stably transfected with BRCA1. Suppression of ISG15 and ISGylated protein levels by BRCA1 expression was found to be mediated by decreased NFB signaling and was transiently suppressed by FF exposure. This study demonstrates increased NFB signaling associated with decreased BRCA1 expression resulting in increased ISG15 and ISGylation following FF exposure, which could represent potential targets for chemoprevention.
Publication Title
BRCA1 Mutation Status and Follicular Fluid Exposure Alters NFκB Signaling and ISGylation in Human Fallopian Tube Epithelial Cells.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 818 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Xenograft models remain a cornerstone technology in the development of anti-cancer agents. The ability of immunocompromised rodents to support the growth of human tumors provides an invaluable transition between in vitro testing and clinical trials. Therefore, approaches to improve model selection are required. In this study, cDNA microarray data was generated for a collection of xenograft models at in vivo passages 1, 4 and 10 (P1, P4 and P10) along with originating cell lines (P0). These data can be mined to determine transcript expression 1) relative to other models 2) with successive in vivo passage and 3) during the in vitro (P0) to in vivo (P1) transition.
Publication Title
Gene expression profiling of 49 human tumor xenografts from in vitro culture through multiple in vivo passages--strategies for data mining in support of therapeutic studies.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptomic studies of human tumor xenografts are complicated by the presence of murine cellular mRNA. As such, it is useful to know the extent to which mouse mRNA cross-hybridizes to any given array platform. In this study, murine cDNA samples from diverse sources were hybridized to Affymetrix Human Genome U133 Plus 2.0 Arrays. In this regard it is possible to identify specific probes that are potential targets of cross-species interference.
Publication Title
Gene expression profiling of 49 human tumor xenografts from in vitro culture through multiple in vivo passages--strategies for data mining in support of therapeutic studies.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study is to identify downstream targets of homeobox gene CDX1. The study assayed the expression of 2 pairs of stably transfected colorectal cancer cell lines: The CDX1 nonexpressing CRC cell line HCT116 was stably transfected with either CDX1 cDNA in the pRC/CMV expression vector (HCT116-CDX1) or with vector control (HCT116-Vec). The CDX1-expressing CRC cell line LS174T was similarly transfected with either a pSilencer vector containing a short sequence of CDX1 siRNA (LS174T-siRNA) , or a pSilencer vector containing a scrambled siRNA sequence as a control (LS174T-Vec).
Publication Title
Gastrointestinal differentiation marker Cytokeratin 20 is regulated by homeobox gene CDX1.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Gene expression analysis under normal culture conditions (RPMI-10%FBS) and at optimal cell densities.
Publication Title
Low-risk susceptibility alleles in 40 human breast cancer cell lines.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 404 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Post mortem human brain tissue comparison between HD patients and controls from 3 brain regions - cerebellum, frontal cortex [BA4, BA9] and caudate nucleus. Gene expression analysed using linear models from LIMMA package in Bioconductor suite.
Publication Title
Regional and cellular gene expression changes in human Huntington's disease brain.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a major role in responding to injury or infection as well as immune response, inflammation, and hematopoiesis. High levels of circulating IL-6 are observed in many tumor types and are associated with poor outcomes. We show that knockdown of IL-6 or IL-6 receptor (IL-6R) inhibits IL-6 signaling and cell viability. In contrast, over-expression of IL-6 enhances tumor growth in vitro and in vivo, thereby supporting the role of IL-6 in tumorigenesis. We developed a human monoclonal antibody against human IL-6 (MEDI5117) that bears Fc mutations (YTE) to extend its half-life. We tested this antibody in several cancer cell lines that secrete high levels of IL-6, soluble IL-6R, and express gp130. High constitutive pSTAT3 (phosphorylated signal transducer and activator of transcription 3) activation is seen in several of these cell lines, suggesting autocrine growth stimulation by IL-6. Treating these cell lines with MEDI5117 effectively blocked phosphorylation of STAT3 and inhibited IL-6-induced cell proliferation. In vivo, MEDI5117 suppressed the growth of multiple cancer xenograft models and specifically modulated IL-6 signaling and downstream gene expression. Combining MEDI5117 with chemotherapy or gefitinib demonstrated significantly enhanced anti-tumor activities in vivo. Taken together, our data suggest that IL-6 signaling contributes to tumor growth, thereby supporting the development of MEDI5117 as a therapy to treat solid tumors.
Publication Title
A Novel IL6 Antibody Sensitizes Multiple Tumor Types to Chemotherapy Including Trastuzumab-Resistant Tumors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
IlluminaHiSeq2000
Description
ETS1 and RAS/ERK regulate a common gene expression program in establishing enviroment suitable for prostate cancer cell migration. Overall design: mRNA profiles of luciferase knockdown (WT), ETS1 knockdown, and U0126 treated DU145 cells were generated using deep sequencing, in triplicate, using Illumina HiSeq. Knockdowns were stable shRNA expression from a lentiviral construct selected with puromycin.
Publication Title
Interaction with ZMYND11 mediates opposing roles of Ras-responsive transcription factors ETS1 and ETS2.
Sample Metadata Fields
No sample metadata fields
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