Filters
Technology
Platform
GSE93986
Homo sapiens
86 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Combination of Ibrutinib and ABT-199 in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma.
Sample Metadata Fields
Disease stage
View Samples- Homo sapiens
- 84 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Brutons tyrosine kinase (BTK)mediated B-cell receptor (BCR) signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance. Ibrutinib-resistant TMD8 cells had higher BCL2 gene expression and increased sensitivity to ABT-199, a BCL-2 inhibitor. Consistently, clinical samples from ABC-DLBCL patients who experienced poorer response to ibrutinib had higher BCL2 gene expression. We further demonstrated synergistic growth suppression by ibrutinib and ABT-199 in multiple ABC-DLBCL, GCB-DLBCL, and FL lymphoma cell lines. The combination of both drugs also reduced colony formation, increased apoptosis, and inhibited tumor growth in a TMD8 xenograft model. A synergistic combination effect was also found in ibrutinib-resistant cells generated by either genetic mutation or drug treatment. Together, these findings suggest a potential clinical benefit from ibrutinib and ABT-199 combination therapy.
Publication Title
Combination of Ibrutinib and ABT-199 in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma.
Sample Metadata Fields
Disease stage
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Brutons tyrosine kinase (BTK)mediated B-cell receptor (BCR) signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance. Ibrutinib-resistant TMD8 cells had higher BCL2 gene expression and increased sensitivity to ABT-199, a BCL-2 inhibitor. Consistently, clinical samples from ABC-DLBCL patients who experienced poorer response to ibrutinib had higher BCL2 gene expression. We further demonstrated synergistic growth suppression by ibrutinib and ABT-199 in multiple ABC-DLBCL, GCB-DLBCL, and FL lymphoma cell lines. The combination of both drugs also reduced colony formation, increased apoptosis, and inhibited tumor growth in a TMD8 xenograft model. A synergistic combination effect was also found in ibrutinib-resistant cells generated by either genetic mutation or drug treatment. Together, these findings suggest a potential clinical benefit from ibrutinib and ABT-199 combination therapy.
Publication Title
Combination of Ibrutinib and ABT-199 in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Treatment of prostate cancer by hormone suppression leads to the appearance of aggressive variants with variable or no dependence on the androgen receptor. Here we show that the developmental transcription factor, ONECUT2, is a master regulator of the AR network that is highly active in castration-resistant prostate cancer (CRPC).
Publication Title
ONECUT2 is a targetable master regulator of lethal prostate cancer that suppresses the androgen axis.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To evaluate the specificity for inhibition of expression of OC2 target genes we generated microarray data of 22Rv1 cells treated for 4, 6 and 16 hours with the small molecule inhibitor.
Publication Title
ONECUT2 is a targetable master regulator of lethal prostate cancer that suppresses the androgen axis.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Human disease caused by highly pathogenic avian influenza (HPAI) H5N1 can lead to a rapidly progressive viral pneumonia leading to acute respiratory distress syndrome. There is increasing evidence suggests a role for virus-induced cytokine dysregulation in contributing to the pathogenesis of human H5N1 disease. The key target cells for the virus in the lung are the alveolar epithelium and alveolar macrophages, and previous data has shown that compared to seasonal human influenza viruses, equivalent infecting doses of H5N1 viruses markedly up-regulate pro-inflammatory cytokines in both primary cell types in vitro. The dysregulation of H5N1-induced host responses is therefore important for understanding the viral pathogenesis.
Publication Title
Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The majority of the human genome is transcribed, yielding a rich repository of non-coding transcripts that are involved in a myriad of biological processes including cancer. However, how non-coding transcripts such as Long Non-coding RNAs (lncRNAs) function in prostate cancer is still unclear. In this study, we have identified a novel set of clinically relevant androgen-regulated lncRNAs in prostate cancer. Among this group, we found LINC00844 is a direct androgen regulated target that is actively transcribed in AR-dependent prostate cancer cells. In clinical analysis, the expression of LINC00844 is higher in normal prostate compared to malignant and metastatic prostate cancer samples and patients with low expression demonstrate poor prognosis and significantly increased biochemical recurrence suggesting LINC00844 may function in suppressing tumor progression and metastasis. From in-vitroloss-of-function studies, we showed LINC00844 prevents prostate cancer cell migration and invasion. Moreover, in gene expression studies we demonstrate LINC00844 functions in trans, affecting global androgen-regulated gene transcription. Mechanistically, we provide evidence to show LINC00844 is important in facilitating AR binding to the chromatin. Finally, we showed LINC00844 mediates its phenotypic effects in part by activating the expression of NDRG1, a crucial cancer metastasis suppressor. Collectively, our findings indicate LINC00844 is a novel coregulator of AR that plays an important role in the androgen transcriptional network and the development and progression of prostate cancer.
Publication Title
Novel lncRNA <i>LINC00844</i> Regulates Prostate Cancer Cell Migration and Invasion through AR Signaling.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Epigenetic and genetic regulations are sometimes considered as separate mechanisms that influence gene expression and phenotypes. However, there are DNA sequence variants in epigenetic regulators that could affect gene regulation. The histone demethylase, KDM4C, promotes transcriptional activation by removing the repressive histone mark, tri-methylation of lysine 9 of histone H3 (H3K9me3), from its target genes. In this study, we uncovered cis-acting DNA sequence variants in KDM4C that contribute to individual differences in its expression. Utilizing this natural variation, we performed genetic analyses in B-cells in order to identify target genes that are regulated by KDM4C.
Publication Title
Natural variation in the histone demethylase, KDM4C, influences expression levels of specific genes including those that affect cell growth.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Murine Genome U74A Array (mgu74a)
Description
Inhibition of proteasome degradation pathway has been implicated in neuronal cell death leading to neurodegenerative diseases such as Parkinsons disease and Alzheimers disease. Pharmacological proteasomal inhibitors such as lactacystin can induce apoptosis in cultured mouse cortical neurons through the activation of caspase-3. Furthermore, proteasomal inhibitors are also reported to mediate deleterious alterations in cell cycle regulation, inflammatory processes and protein aggregation and trigger the cell death pathway.
Publication Title
Up-regulation of endoplasmic reticulum stress-related genes during the early phase of treatment of cultured cortical neurons by the proteasomal inhibitor lactacystin.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 128 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We carried out a high throughput analysis of insulin-induced kinase signaling pathways in primary fibroblasts from 35 unrelated individuals. We found that extensive individual variation exists in induction of various signaling pathways. ERK signaling displayed the greatest variation, which led to extensive variation in expression of downstream target genes.
Publication Title
Genetic variation in insulin-induced kinase signaling.
Sample Metadata Fields
Specimen part, Subject
View Samples