Filters
Technology
Platform
Homo sapiens
8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Protein homeostasis in the endoplasmic reticulum (ER) has recently emerged as a therapeutic target for cancer treatment. Disruption of ER homeostasis results in ER stress, which is a major cause of cell death for cells exposed to the proteasome inhibitor Bortezomib, an anti-cancer drug approved for treatment of multiple myeloma and Mantle cell lymphoma. We recently reported that the ERAD inhibitor Eeyarestatin I (EerI) also disturbs ER homeostasis and has anti-cancer activities resembling that of Bortezomib.
Publication Title
The ERAD inhibitor Eeyarestatin I is a bifunctional compound with a membrane-binding domain and a p97/VCP inhibitory group.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The ubiquitin-proteasome system (UPS) has recently emerged as a major target for drug development in cancer therapy. The proteasome inhibitor bortezomib has clinical activity in multiple myeloma and mantle cell lymphoma. Here we report that Eeyarestatin I (EerI), a chemical inhibitor that blocks ER-associated protein degradation (ERAD), has anti-tumor and biologic activities similar to bortezomib, and can synergize with bortezomib. Like bortezomib, EerI-induced cytotoxicity requires the upregulation of the BH3 only pro-apoptotic protein NOXA. We further demonstrate that both EerI and bortezomib activate NOXA via an unanticipated mechanism that requires cooperation between two processes: First, these agents elicit an integrated stress response program at the ER to activate the CREB/ATF transcription factors ATF3 and ATF4. We show that ATF3 and ATF4 form a complex capable of binding to the NOXA promoter, which is required for NOXA activation. Second, EerI and bortezomib also block ubiquitination of histone H2A to relieve its inhibition on NOXA transcription. Our results identify a class of anti-cancer agents that integrate ER stress response with an epigenetic mechanism to induce cell death.
Publication Title
ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
TBX5 is hypomethylated in Rheumatoid Arthritis synovial fibroblasts (RASF). Hypomethylation increased the TBX5 expression in RASF.
Publication Title
Epigenome analysis reveals TBX5 as a novel transcription factor involved in the activation of rheumatoid arthritis synovial fibroblasts.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Our laboratory wanted to define the transcription profile of aged skeletal muscle. For this reason, we performed a triplicate microarray study on young (3 weeks) and aged (24 months) gatrocnemius muscle from wild-type C57B16 Mice
Publication Title
Transcriptional profiling of skeletal muscle reveals factors that are necessary to maintain satellite cell integrity during ageing.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Fibrogenic processes instigate fatal chronic diseases leading to organ failure and death. Underlying biological processes involve induced massive deposition of extracellular matrix (ECM) by aberrant fibroblasts. We subjected diseased primary human lung fibroblasts to an advanced 3D phenotypic high-content assay and screened a library of FDA/EMA approved small molecules for inhibiting ECM deposition. Fibrotic Pattern Detection by Artificial Intelligence (FANTAIL) identified Tranilast as an effective inhibitor, however, by structure-activity relationship studies we found N-(2-butoxyphenyl)-3-(phenyl)acrylamides (N23Ps) as a novel and highly potent compound class. N23Ps suppressed myofibroblast transdifferentiation, ECM deposition, cellular contractility, and altered cell shapes, thus advocating a unique mode of action. Mechanistically, transcriptomics identified SMAD (de)ubiquitination/Smurf2 as a potential therapeutic target network. Antifibrotic activity of N23Ps was verified by proteomics in a human ex vivo tissue fibrosis disease model, suppressing profibrotic markers SERPINE1/PAI1 and CXCL8/IL8. Conclusively, these data suggest N23Ps as a novel class of highly potent compounds with implications for inhibiting organ fibrosis in patients.
Publication Title
Phenotypic drug screening in a human fibrosis model identified a novel class of antifibrotic therapeutics.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 96 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray gene expression (MAGE) signatures allow insights into the transcriptional processes of leukemias and may evolve as a molecular diagnostic test. Introduction of MAGE into clinical practice of leukemia diagnosis will require comprehensive assessment of variation due to the methodologies.
Publication Title
New data on robustness of gene expression signatures in leukemia: comparison of three distinct total RNA preparation procedures.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Identification of relevant subgroups in childhood MDS patients by gene expression analysis and gene involve in progression into AML
Publication Title
Gene expression signatures of pediatric myelodysplastic syndromes are associated with risk of evolution into acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Disease
View Samples
GSE4737- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Summary:
Publication Title
HCaRG increases renal cell migration by a TGF-alpha autocrine loop mechanism.
Sample Metadata Fields
No sample metadata fields
View Samples GSE2555- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Genome U133A Array (hgu133a)
Description
HEK293 cells were transfected with control plasmid (pcDNAI/Neo;Invitrogen) or with the plasmid encoding HCaRG. Stable transfectants were synchronized and grown in the presence of 10% FBS for 48 h. Total RNAs were purified with the mini RNeasy kit (Qiagen).
Publication Title
HCaRG increases renal cell migration by a TGF-alpha autocrine loop mechanism.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Diesel exhaust (DE) is the primary source of urban fine particulate matter, which has been associated with cardiovascular disease in epidemiological studies. These effects may be related to oxidative stress and systemic inflammation with resulting perturbation of vascular homeostasis. Peripheral leukocytes are involved in both inflammation and control of vascular homeostasis. Objectives: We conducted an exploratory study using microarray techniques to analyze whether global gene expression in peripheral blood mononuclear cells (PBMCs) can inform on potential mechanisms of effect of DE inhalation. Methods: In a double-blind, crossover, controlled exposure study, healthy adult volunteers were exposed in randomized order to filtered air (FA) and diluted DE in two-hour sessions. We isolated RNA (Trizol/Qiagen method) form PBMCs before, and two times after each exposure. RNA samples were arrayed using the Affymetrix platform (GeneChip Human Genome U133 Plus 2.0 Array). Results: Microarray analyses were conducted on five subjects with available RNA sample form exposures to FA and to the highest DE inhalation (200 g/m of fine particulate matter). Following data normalization and statistical analysis, a total of 1290 out of 54,675 probe sets with significant evidence for differential expression (more than 1.5-fold up or down regulated with p < 0.05) were identified. These include genes involved in inflammatory response (e.g., IL8RA, TNFAIP6, FOS), oxidative stress (e.g., HMOX1, BAX, PRDX1,), and in biochemical pathways like mitogen-activated protein kinases (MAPK) and tight junction pathways. Conclusions: These data suggest that DE may exert time-dependent changes in gene expression in PBMCs in healthy individuals. Genes that may be affected by DE inhalation are involved in inflammatory and oxidative stress processes.
Publication Title
Diesel exhaust inhalation and assessment of peripheral blood mononuclear cell gene transcription effects: an exploratory study of healthy human volunteers.
Sample Metadata Fields
No sample metadata fields
View Samples