Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA263564 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Modulation of the activity of the ubiquitin-proteasome pathway with the proteasome inhibitor (PI) is an established component of therapy for plasma cell disorders. However, resistance emerges and the mechanism is incompletely understood. We generated carfilzomib-resistant (CR) myeloma cell lines by exposing drug-naive ANBL-6, KAS-6/1, U266, and OPM-2 cells to increasing concentrations of carfilzomib and then performed gene expression profiling (GEP) to identify prominent changes compared to their vehicle-treated counterparts, followed by exploration of the mechanism(s) of proteasome inhibitor resistance.
2016-10-09 | GSE62237 | GEO
Project description:The clinical efficacy of bortezomib in multiple myeloma (MM) is limited due to secondary drug resistance driven by clonal evolution and currently available pre-clinical models are inadequate for comprehensive understanding of mechanisms underlying drug resistance. In the present study, we have established and characterized bortezomib-resistant cell lines BR1 and BR2, and identified upregulation of proteasome pathway as the potential mechanism underlying bortezomib resistance. Furthermore, both the cell lines retained sensitivity towards imatinib suggesting the lack of general resistance towards broad classes of inhibitors. Notably, BR1 and BR2 showed increased sensitivity than the parental cell line towards the next-generation proteasome inhibitor carfilzomib, suggesting its utility in treating patients who relapse upon bortezomib treatment. When compared to the wild type cell line, BR1 and BR2 displayed similar sensitivity towards sorafenib and vorinostat, but enhanced sensitivity towards geldanamycin treatment. Taken together, our study identified carfilzomib and HSP90 inhibition as promising therapeutic strategies to overcome bortezomib resistance.
2026-04-07 | GSE326599 | GEO
Project description:Ubiquitin proteasome expression in Mulitple Myeloma cell lines
| PRJNA314296 | ENA
Project description:RNA was extracted from myeloma cell lines that were either drug-naïve or resistant to bortezomib or carfilzomib and the transcriptome was characterised using RNA sequencing.
2021-12-01 | GSE144249 | GEO
Project description:Proteasome inhibitors (PIs) such as carfilzomib (Cfz) are highly efficacious for patients with Multiple myeloma (MM). However, relapses and acquired resistance to PI treatment emerges in most patients. Here, we established Cfz-resistant MM cells. RNA-seq analysis revealed significant alterations in cholesterol- and lipid-related metabolic pathways in the resistant cells.
2026-07-01 | GSE296076 | GEO
Project description:Comparison of the gene expression profiles of carfilzomib-resistant derivatives versus parental human myeloma cell lines
| PRJNA284490 | ENA
Project description:Acquired resistance to proteasome inhibitors remains a major therapeutic challenge in multiple myeloma. In this study, we investigated mechanisms underlying resistance to bortezomib and carfilzomib using comprehensive proteomic profiling of RPMI8226 and U266B1 cell lines across different stages of resistance evolution.
2026-04-24 | PXD077551 |
Project description:Transcriptomic profiling of drug-naïve or proteasome inhibitor-resistant myeloma cell lines
| PRJNA603122 | ENA
Project description:The use of proteasome inhibitors (PIs) is the backbone of multiple myeloma (MM) treatment. However, almost all MM patients who initially respond to PIs eventually develop resistance to these drugs. The discovery of a pharmacological intervention that increase the potency of PIs in order to reduce their dose and/or restore the sensitivity of MM cells to PIs is an important avenue in MM research. Insulin Degrading Enzyme (IDE) is a druggable protease known to modulate proteasome. We show here that, in two independent cohorts, a high expression of IDE in cells from MM patients is associated with shorter overall survival. Likewise, we designed specific, cell permeable, IDE inihibitors and showed that full pharmacological engagement of IDE is associated with enhanced sensitivity to PIs of MM cell lines, as well as of primary patient MM cells. Furthermore, treatment of PI-resistant MM cells with the inhibitor overcomes their resistance to PI. Finally we designed an improved IDE inhibitor suitable for in vivo pharmacology. This inhibitor which develops multiple interactions with IDE at the catalytic site and display good pharmacocinetic properties, boosts the anti-myeloma potency of bortezomib in a syngenic mouse model of MM. In vitro, it appears that IDE inhibition reduces the residual proteasome activty in PI-treated cells and increases the apoptotic potency of carfilzomib through induction of an Integrated Stress Response associated with strongly reduced IGF1 and IGF1R expressions. The pharmacological profile of this new combination appears highly desirable for the treatment of MM.
2024-09-15 | GSE184310 | GEO
Project description:Bortezomib (BTZ), Carfilzomib (CFZ) and Ixazomib (IXA) are proteasome inhibitors (PI) approved for Multiple Myeloma (MM) treatment. By design, they all target the rate-limiting proteasome beta 5 (B5) subunit. CFZ treatment increases the survival of patients with relapsed/refractory MM compared to BTZ but is associated with heart failure not commonly observed for BTZ. The molecular basis for CFZ-induced cardiotoxicity is poorly understood. We time to investigate the transcriptomic effects of acute proteasome inhibition in the murine heart.
2023-07-01 | E-MTAB-11028 | biostudies-arrayexpress