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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- Arabidopsis thaliana
- 21 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Virus infection and over expression of protein in cytosol induce a subset of HSP70s. We named this response the Cytosolic Protein Response (CPR) and have been investigating it in the context of a parallel mechanism in the soluble cytosol with the UPR, and as a subcomponent of the larger HS response. This experiment was carried out to study the transcriptional aspect of CPR. In this analysis, we have triggered CPR by infiltrating proline analogue, L-azetidine-2-carboxylic acid (AZC) into Arabidopsis mature leaves. Since AZC trigger unfolded protein response(UPR) in ER as well as CPR, we have included tunicamycin treatment, which is a specific inducer of UPR to subtract the effect of UPR from the AZC response. Heat shocked samples were included to identify CPR as a subcomponent of larger HS response.
Publication Title
The cytosolic protein response as a subcomponent of the wider heat shock response in Arabidopsis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Our previous study using nude rats revealed that the parental JDCaP xenografts predominantly expressed full-length androgen receptor (AR) whereas the relapsed JDCaP xenografts after castration acquired AR splice variants including AR-V7 and ARv567es. To understand molecular mechanisms underlying the acquisition of AR splice variants in the JDCaP model, we performed microarray analysis using RNA samples of the xenografts without castration (Parent), the relapsed xenografts overexpressing full-length AR and AR-V7 (ARhiV7hi), and the relapsed xenografts expressing ARv567es (ARv567es).
Publication Title
The RNA helicase DDX39B and its paralog DDX39A regulate androgen receptor splice variant AR-V7 generation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
NextSeq 500
Description
Purpose: Cortical thymic epithelial cells (cTECs) contain a unique type of proteasomes, thymoproteasomes. Indirect evidence suggests that the key role of PSMB11, a catalytic subunit of thymoproteasomes specific to cTECs, is to generate a unique repertoire of MHC I peptides. Notably, PSMB11-deficient mice display defective development of CD8 thymocytes. The objective of this study was to characterize the impact of PSMB11 on cTECs and thymocyte development. Since different types of proteasomes have non-redundant effects on gene expression, we hypothesized that thymoproteasomes should have a distinct impact on the transcriptome and thereby the function of cTECs. Results: We report that PSMB11 in cortical thymic epithelial cells has dramatic effects on cTECs on both CD4 and CD8 thymocyte populations. PSMB11 modulates the expression of 850 genes in cTECs, 582 in CD4 thymocytes and 284 in CD8 thymocytes. PSMB11-regulated cTEC genes are involved mainly in cell-cell adhesion, extracellular matric organization and thymocyte chemotaxis. PSMB11-deficient cTECs acquire features of mTECs and perturb thymocyte development. Deletion of PSMB11 causes a major cell stress in both CD4 and CD8 thymocyte populations. Of note, PSMB11-deficiency had no impact on medullary thymic epithelial cells (mTECs), which originate from progenitors that express PSMB11 early in ontogeny. Conclusion: We conclude that PSMB11 has pervasive effects on both CD4 and CD8 thymocytes via regulation of gene expression in cTECs. Overall design: We performed RNA-sequencing in triplicate on cTECs, mTECs, and SM, M1 and M2 thymocytes from the CD4 and CD8 lineages, in order to identify differential gene expression between WT and Psmb11-deficient mice.
Publication Title
PSMB11 Orchestrates the Development of CD4 and CD8 Thymocytes via Regulation of Gene Expression in Cortical Thymic Epithelial Cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Primary T cells were isolated from spleen of Parp-1-/- and wild-type mice by magnetic depletion of non-T cells using a MACS Pan-T Cell isolation kit, according to the manufacturer´s instruction (Mintenyi Biotec, Bergisch Gladbach, Germany). Purity was assessed by flow cytometry analysis using antibodies against CD3, CD4 and CD8 and all preparations were more than 98% pure of T cells. The cells were activated with plate-bound anti-mouse CD3 (clone 145-2C11) (5 microg/ml) in the absence or the presence of anti-mouse CD28 (clone 37.51) (5microg/ml) both from BD PharMingen (San Diego, CA) and culture for 3.5 h in RPMI 1640 medium (BioWhittaker) supplemented with 10% FCS, 2mM L-glutamine, 5x10-5 M 2-mercaptoethanol (Sigma), 2.5 microg/ml fungizone, 100 IU/ml penicillin, and 10 microg/ml streptomycin.
Publication Title
Transcriptional regulation by poly(ADP-ribose) polymerase-1 during T cell activation.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Microarray-based expression profiling of BRCA2 knockout and isogenic wild type HCT116 human colorectal cancer cells
Publication Title
Up-regulation of the interferon-related genes in BRCA2 knockout epithelial cells.
Sample Metadata Fields
Cell line
View Samples- Saccharomyces cerevisiae
- 10 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Quantitative analysis of protein interaction network dynamics in yeast.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 28 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Adult mammalian CNS neurons undergo a developmental switch in intrinsic axon growth ability associated with their failure to regenerate axons after injury. Krppel-like transcription factors (KLF) regulate intrinsic axon growth ability, but signaling regulation upstream and downstream is poorly understood. Here we find that suppressing expression of KLF9, an axon growth suppressor normally upregulated 250-fold in retinal ganglion cell (RGC) development, promotes long-distance optic nerve regeneration in vivo. We identify a novel binding partner, MAPK10/JNK3, critical for KLF9s axon growth suppressive activity. Additionally, by screening genes regulated by KLFs in RGCs, we identify dual-specificity phosphatase 14 (Dusp14) as key to limiting axon growth and regenerative ability downstream of KLF9, associated with its dephosphorylation of MAPKs critical to neurotrophic signaling of RGC axon elongation. These results now link intrinsic and extrinsic regulation of axon growth and suggest new therapeutic strategies to promote axon regeneration in the adult CNS.
Publication Title
The Krüppel-Like Factor Gene Target Dusp14 Regulates Axon Growth and Regeneration.
Sample Metadata Fields
Specimen part
View Samples