PDX tumors at various passages post first implantation in nude mice
High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response.
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View SamplesRsf1p is a putative transcription factor required for efficient growth using glycerol as sole carbon source but not for growth on the alternative respiratory carbon source ethanol.
Rsf1p is required for an efficient metabolic shift from fermentative to glycerol-based respiratory growth in S. cerevisiae.
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View SamplesPurpose: The management of adrenocortical tumors (ACTs) is complex, compounded by the difficulty in discriminating benign from malignant tumors using conventional histology. The Weiss score is the current most widely used system for ACT diagnosis but it has limitations, particularly with ACTs with a score of 3. The am of this study was to identify molecular markers whose expression can discriminate adrenocortical carcinomas (ACCs) from adrenocortical adenomas (ACAs) by microarray gene expression profiling and to determine their clinical applicability by using immunohistochemistry (IHC). Experimental design: Microarray gene expression profiling was used to identify 7 molecular markers which were significantly differentially expressed between ACCs and ACAs. These results were confirmed with quantitative PCR for all 7 genes and IHC for 3 protein. Results: Microarray gene expression profiling was able to accurately categorize ACTs into ACCs and ACAs. All 7 genes were strong discriminators of ACCs from ACAs on qPCR. IHC with IGF2, MAD2L1, CCNB1 and Ki-67, but not ACADVL or ALOX15B, had high diagnostic accuracy in differentiating ACCs from ACAs. The best results however were obtained with a combination of IGF2 and Ki-67 with 96% sensitivity and 100% specificity in diagnosing ACCs. Conclusion: Microarray gene expression profiling accurately differentiates ACCs from ACAs. The combination of IGF2 and Ki-67 IHC is also highly accurate in distinguishing between the 2 groups and is particularly helpful in ACTs with Weiss score of 3.
Microarray gene expression and immunohistochemistry analyses of adrenocortical tumors identify IGF2 and Ki-67 as useful in differentiating carcinomas from adenomas.
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View SamplesCompetitive inhibitors of acetyl-lysine binding to the bromodomains of the BET (bromodomain and extra terminal) family are being developed for the treatment of solid and heme malignancies. BET family member BRD4 function at enhancers/super-enhancers has been shown to sustain signal-dependent or pathogenic gene expression programs.
HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues.
Specimen part
View SamplesTo identify genes that are modulated by BET inhibitors in blood, we determined global gene expression changes in ABBV-075-treated mouse whole blood samples
HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues.
Specimen part
View SamplesDetermination of transcriptional alterations in skin samples from ABBV-075 treated mice
HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues.
Specimen part
View SamplesTo identify genes that are modulated by BET inhibitors in blood, we determined global gene expression changes in ABBV-075-treated human PBMC samples
HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues.
Specimen part
View SamplesCompetitive inhibitors of acetyl-lysine binding to the bromodomains of the BET (bromodomain and extra terminal) family are being developed for the treatment of solid and heme malignancies. BET family member BRD4 function at enhancers/super-enhancers has been shown to sustain signal-dependent or pathogenic gene expression programs. Here we tested the hypothesis that the transcription factor drivers of castration-resistant prostate cancer (CRPC) clinical progression, including the Androgen Receptor (AR), are critically dependent on BRD4 and thus represent a sensitive solid tumor indication for the BET inhibitor ABBV-075. DHT-stimulated transcription of AR target genes was inhibited by ABBV-075 without significant effect on AR protein expression. Further, ABBV-075 disrupted DHT-stimulated recruitment of BET family member BRD4 to gene regulatory regions co-occupied by AR, including the well-established PSA and TMPRSS2 enhancers. Persistent BET inhibition disrupted the composition and function of AR occupied enhancers as measured by a reduction in AR and H3K27Ac ChIP signal and inhibition of eRNA transcription. ABBV-075 displayed potent anti-proliferative activity in multiple models of resistance to second generation anti-androgens and inhibited the activity of AR-V7 and the AR LBD gain-of-function mutations, F877L and L702H. ABBV-075 was also a potent inhibitor of MYC and the TMPRSS2-ETS fusion protein, important parallel transcription factor drivers of CRPC.
HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues.
Cell line
View SamplesBackground: The force generating mechanism of muscle is evolutionarily ancient; the fundamental structural and functional components of the sarcomere are common to motile animals throughout phylogeny. Recent evidence suggests that the transcription factors that regulate muscle development are also conserved. Thus, a comprehensive description of muscle gene expression in a simple model organism should define a basic muscle transcriptome that is also expressed in animals with more complex body plans. To this end, we have applied Micro-Array Profiling of Caenorhabditis elegans Cells (MAPCeL) to muscle cell populations extracted from developing Caenorhabditis elegans embryos. Results: Fluorescence Activated Cell Sorting (FACS) was used to isolate myo-3::GFP-positive muscle cells, and their cultured derivatives, from dissociated early Caenorhabditis elegans embryos. Microarray analysis identified 6,693 expressed genes, 1,305 of which are enriched in the myo-3::GFP positive cell population relative to the average embryonic cell. The muscle-enriched gene set was validated by comparisons to known muscle markers, independently derived expression data, and GFP reporters in transgenic strains. These results confirm the utility of MAPCeL for cell type-specific expression profiling and reveal that 60% of these transcripts have human homologs.
The embryonic muscle transcriptome of Caenorhabditis elegans.
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View SamplesBackground:
The embryonic muscle transcriptome of Caenorhabditis elegans.
No sample metadata fields
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