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OBJECTIVES Patients with SLE are at risk for premature atherosclerosis and metabolic syndrome. Cytokines produced by adipocytes, adipokines, are important in glucose/lipid metabolism and the development of atherosclerosis. The objectives of this study were to evaluate leptin, adiponectin and ghrelin concentrations in paediatric SLE (pSLE) and to correlate(More)
Aminopeptidase inhibitors are receiving attention as combination chemotherapeutic agents for the treatment of refractory acute myeloid leukemia. However, the factors determining therapeutic efficacy remain elusive. Here we identified the molecular basis of acquired resistance to CHR2863, an orally available hydrophobic aminopeptidase inhibitor prodrug with(More)
Bortezomib (BTZ), a registered proteasome inhibitor (PI) for multiple myeloma, has also been proposed as a potential antirheumatic agent. Its reported side effects, however, make it unappealing for long-term administration, and resistance may also develop. To overcome this, second-generation PIs became available. Here, we investigated whether a novel class(More)
UNLABELLED BACKGROUND In clinical and experimental settings, antibody-based anti-CD20/rituximab and small molecule proteasome inhibitor (PI) bortezomib (BTZ) treatment proved effective modalities for B cell depletion in lymphoproliferative disorders as well as autoimmune diseases. However, the chronic nature of these diseases requires either prolonged or(More)
Submitted 5 Inactivating PSMB5 mutations and P-glyco-protein (MDR1/ ABCB1) mediate resistance to proteasome inhibitors: ex vivo efficacy of (immuno) proteasome inhibitors in mononuclear blood cells from rheumatoid arthritis patients 106 Abstract Bortezomib (BTZ), a registered proteasome inhibitor (PI) for multiple myeloma, has also been proposed as a(More)
Bortezomib (BTZ) is a reversible proteasome inhibitor. It affects NF-κB activity and has shown clinical efficacy in multiple myeloma. However, the same mechanisms through which it curtails malignant growth may compromise antitumor immunity. As dendritic cells (DC) play a vital role in the elicitation and maintenance of antitumor immunity, we studied the(More)
High systemic levels of type-I Interferons (IFN) support autoimmunity, in part through the induction of inflammatory dendritic cells (DC). The purpose of this study was to compare ONX 0914, a next-generation selective immunoprotea-some inhibitor, to Bortezomib (BTZ), the first registered general proteasome inhibitor, in its ability to block differentiation(More)
Autoantibodies, including rheumatoid factor (RF), are an important characteristic of rheumatoid arthritis (RA). Interestingly, several studies reported a correlation between the presence of IgA autoantibodies and worse disease course. We demonstrated previously that triggering the IgA Fc receptor (FcαRI) on neutrophils results in neutrophil recruitment and(More)
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