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• W1987378323 endingPage "417" @default.
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• W1987378323 abstract "The anti-tumour in vitro activity of proteasome inhibitor bortezomib (PS-341, VELCADE) in combination with purine nucleoside analogues, cladribine (2-CdA) and fludarabine (FA) was tested in lymphocytes derived from 26 patients with B-cell chronic lymphocytic leukaemia (B-CLL).Cell viability was assessed by propidium iodide staining, and apoptosis by annexin-V and caspase activation flow cytometry assays. Additionally, expression of the apoptosis-regulating proteins Bax, Bak, Bid, Bcl-w, Bcl-2, XIAP and Mcl-1 was evaluated in B-CLL lymphocytes.Bortezomib alone induced significant, dose-dependent cytotoxicity starting from the low concentration 2.5 nm, inducing apoptosis of B-CLL cells. Combination of this agent with 2-CdA or FA resulted in an increase of cytotoxicity when compared with that mediated by single drugs. The observed increase was especially evident when 5 nm of bortezomib were combined with suboptimal doses of 2-CdA or FA. The combination index (CI) was 0.87 for bortezomib + 2-CdA and 0.82 for bortezomib + FA, indicating an evident additive effect of these combinations. Moreover, B-CLL cells were more sensitive to proteasome inhibitor used alone or combined with 2-CdA or FA comparing to CD3+ lymphocytes. Corresponding to enhanced apoptosis, the expression levels of several apoptosis-regulating proteins were altered. The most pronounced changes were down-regulation of XIAP and up-regulation of Bid proteins by the combination of bortezomib with either 2-CdA or FA.This study suggest that the in vitro cytotoxic effect through proteasome inhibition by bortezomib can be increased substantially with low doses of the purine nucleoside analogues, 2-CdA and FA, and that this effect on B-CLL cell is selectively higher than on normal, CD3-positive lymphocytes." @default.
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• W1987378323 date "2005-04-05" @default.
• W1987378323 modified "2023-10-17" @default.
• W1987378323 title "<i>In vitro</i> cytotoxic effect of proteasome inhibitor bortezomib in combination with purine nucleoside analogues on chronic lymphocytic leukaemia cells" @default.
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• W1987378323 doi "https://doi.org/10.1111/j.1600-0609.2004.00406.x" @default.
• W1987378323 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15813915" @default.
• W1987378323 hasPublicationYear "2005" @default.
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