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- W3136935594 endingPage "665" @default.
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- W3136935594 abstract "At present, 20–30% of children with acute leukemia still relapse from current chemotherapy protocols, underscoring the unmet need for new treatment options, such as proteasome inhibition. Ixazomib (IXA) is an orally available proteasome inhibitor, with an improved safety profile compared to Bortezomib (BTZ). The mechanism of action (proteasome subunit inhibition, apoptosis induction) and growth inhibitory potential of IXA vs. BTZ were tested in vitro in human (BTZ-resistant) leukemia cell lines. Ex vivo activity of IXA vs. BTZ was analyzed in 15 acute lymphoblastic leukemia (ALL) and 9 acute myeloid leukemia (AML) primary pediatric patient samples. BTZ demonstrated more potent inhibitory effects on constitutive β5 and immunoproteasome β5i proteasome subunit activity; however, IXA more potently inhibited β1i subunit than BTZ (70% vs. 29% at 2.5 nM). In ALL/AML cell lines, IXA conveyed 50% growth inhibition at low nanomolar concentrations, but was ~10-fold less potent than BTZ. BTZ-resistant cells (150–160 fold) displayed similar (100-fold) cross-resistance to IXA. Finally, IXA and BTZ exhibited anti-leukemic effects for primary ex vivo ALL and AML cells; mean LC50 (nM) for IXA: 24 ± 11 and 30 ± 8, respectively, and mean LC50 for BTZ: 4.5 ± 1 and 11 ± 4, respectively. IXA has overlapping mechanisms of action with BTZ and showed anti-leukemic activity in primary leukemic cells, encouraging further pre-clinical in vivo evaluation." @default.
- W3136935594 created "2021-03-29" @default.
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- W3136935594 date "2021-03-17" @default.
- W3136935594 modified "2023-10-15" @default.
- W3136935594 title "Pre-Clinical Evaluation of the Proteasome Inhibitor Ixazomib against Bortezomib-Resistant Leukemia Cells and Primary Acute Leukemia Cells" @default.
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- W3136935594 cites W1986036865 @default.
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- W3136935594 cites W2016833582 @default.
- W3136935594 cites W2017937681 @default.
- W3136935594 cites W2037132614 @default.
- W3136935594 cites W2039180923 @default.
- W3136935594 cites W2039825457 @default.
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- W3136935594 cites W2071191421 @default.
- W3136935594 cites W2077945404 @default.
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- W3136935594 cites W2137365058 @default.
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- W3136935594 cites W2398639705 @default.
- W3136935594 cites W2508476086 @default.
- W3136935594 cites W2511378889 @default.
- W3136935594 cites W2531520114 @default.
- W3136935594 cites W2536857190 @default.
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- W3136935594 cites W2887022567 @default.
- W3136935594 cites W2887703760 @default.
- W3136935594 cites W2901300056 @default.
- W3136935594 cites W2921234630 @default.
- W3136935594 cites W2929945025 @default.
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- W3136935594 doi "https://doi.org/10.3390/cells10030665" @default.
- W3136935594 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8002577" @default.
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- W3136935594 hasPublicationYear "2021" @default.
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