Matches in SemOpenAlex for { <https://semopenalex.org/work/W2047071079> ?p ?o ?g. }
Showing items 1 to 84 of
84
with 100 items per page.
- W2047071079 endingPage "i25" @default.
- W2047071079 startingPage "i25" @default.
- W2047071079 abstract "Background: Recurrent triple-negative breast cancer (TNBC) is a condition of high unmet medical need, due to its aggressive biology, fast development of drug resistance, and lack of molecular targets. Until now, chemotherapy remains the standard of care for advanced TNBC, with a poor median overall survival. Recently, pharmacological aggravation of endoplasmic reticulum stress (ERS) has become an attractive strategy not only for multiple myeloma, but also for solid malignancies. Methods: We determined the cytotoxic activity of proteasome inhibitors (bortezomib, bzb; carfilzomib, cfz) alone and in combination with the two HIV protease inhibitors nelfinavir (nel) and lopinavir (lop) in three different TNBC cell lines (BT 549, MDA-MB 231, MDA-MB 468). To assess cytotoxicity, the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTS) assay was applied. Results: Both proteasome inhibitors moderately reduced cell survival in all TNBC cell lines at clinically relevant concentrations (125 nM) when applied alone (21%–44%). At increased concentrations (1 uM), the irreversible proteasome inhibitor cfz exhibited even higher cytotoxicity (>80%) than bzb (>60%) in all tested cell lines. Importantly, combinations with HIV protease inhibitors yielded significantly enhanced cytotoxicity and mostly synergistic responses in all cell lines compared with either proteasome (table: cytotoxic effects of mono and combination experiments) or HIV protease inhibitors alone. Moreover, preliminary data using combinations with other HIV protease inhibitors showed similar cytotoxic effects. Conclusions: Drug combinations of the irreversible proteasome inhibitor carfilzomib and HIV protease inhibitors such as lopinavir or nelfinavir resulted in substantial cytotoxicity in preclinical models of TNBC. The concept of pharmacological aggravation of ERS is promising in patients with TNBC, and a respective phase1B-2 clinical study is in early planning.Tabled 1Bzb/-Bzb/NelBzb/LopCfz/-Cfz/NelCfz/LopMDA-MB 46827 +/- 890 +/- 284 +/- 121 +/- 788 +/- 284 +/- 4MDA-MB 23136 +/- 887 +/- 585 +/- 0.241 +/- 287 +/- 485 +/- 4BT54923 +/- 392 +/- 180 +/- 0.244 +/- 392 +/- 185 +/- 4(% cell death +/- SD) Open table in a new tab (% cell death +/- SD) Disclosure: All authors have declared no conflicts of interest." @default.
- W2047071079 created "2016-06-24" @default.
- W2047071079 creator A5018939058 @default.
- W2047071079 creator A5051714210 @default.
- W2047071079 creator A5052841374 @default.
- W2047071079 creator A5058128473 @default.
- W2047071079 creator A5071285842 @default.
- W2047071079 date "2014-05-01" @default.
- W2047071079 modified "2023-09-26" @default.
- W2047071079 title "Targeting ER Stress by the Combination of Proteasome Inhibitors and HIV Protease Inhibitors in Preclinical Models of Triple-Negative Breast Cancer" @default.
- W2047071079 doi "https://doi.org/10.1093/annonc/mdu071.4" @default.
- W2047071079 hasPublicationYear "2014" @default.
- W2047071079 type Work @default.
- W2047071079 sameAs 2047071079 @default.
- W2047071079 citedByCount "0" @default.
- W2047071079 crossrefType "journal-article" @default.
- W2047071079 hasAuthorship W2047071079A5018939058 @default.
- W2047071079 hasAuthorship W2047071079A5051714210 @default.
- W2047071079 hasAuthorship W2047071079A5052841374 @default.
- W2047071079 hasAuthorship W2047071079A5058128473 @default.
- W2047071079 hasAuthorship W2047071079A5071285842 @default.
- W2047071079 hasBestOaLocation W20470710791 @default.
- W2047071079 hasConcept C109316439 @default.
- W2047071079 hasConcept C121608353 @default.
- W2047071079 hasConcept C126322002 @default.
- W2047071079 hasConcept C142462285 @default.
- W2047071079 hasConcept C202751555 @default.
- W2047071079 hasConcept C203014093 @default.
- W2047071079 hasConcept C27740335 @default.
- W2047071079 hasConcept C2776364478 @default.
- W2047071079 hasConcept C2777478702 @default.
- W2047071079 hasConcept C2778367456 @default.
- W2047071079 hasConcept C2780108899 @default.
- W2047071079 hasConcept C2780110267 @default.
- W2047071079 hasConcept C2781160516 @default.
- W2047071079 hasConcept C2993143319 @default.
- W2047071079 hasConcept C3013748606 @default.
- W2047071079 hasConcept C502942594 @default.
- W2047071079 hasConcept C530470458 @default.
- W2047071079 hasConcept C55493867 @default.
- W2047071079 hasConcept C71924100 @default.
- W2047071079 hasConcept C86803240 @default.
- W2047071079 hasConcept C98274493 @default.
- W2047071079 hasConceptScore W2047071079C109316439 @default.
- W2047071079 hasConceptScore W2047071079C121608353 @default.
- W2047071079 hasConceptScore W2047071079C126322002 @default.
- W2047071079 hasConceptScore W2047071079C142462285 @default.
- W2047071079 hasConceptScore W2047071079C202751555 @default.
- W2047071079 hasConceptScore W2047071079C203014093 @default.
- W2047071079 hasConceptScore W2047071079C27740335 @default.
- W2047071079 hasConceptScore W2047071079C2776364478 @default.
- W2047071079 hasConceptScore W2047071079C2777478702 @default.
- W2047071079 hasConceptScore W2047071079C2778367456 @default.
- W2047071079 hasConceptScore W2047071079C2780108899 @default.
- W2047071079 hasConceptScore W2047071079C2780110267 @default.
- W2047071079 hasConceptScore W2047071079C2781160516 @default.
- W2047071079 hasConceptScore W2047071079C2993143319 @default.
- W2047071079 hasConceptScore W2047071079C3013748606 @default.
- W2047071079 hasConceptScore W2047071079C502942594 @default.
- W2047071079 hasConceptScore W2047071079C530470458 @default.
- W2047071079 hasConceptScore W2047071079C55493867 @default.
- W2047071079 hasConceptScore W2047071079C71924100 @default.
- W2047071079 hasConceptScore W2047071079C86803240 @default.
- W2047071079 hasConceptScore W2047071079C98274493 @default.
- W2047071079 hasLocation W20470710791 @default.
- W2047071079 hasOpenAccess W2047071079 @default.
- W2047071079 hasPrimaryLocation W20470710791 @default.
- W2047071079 hasRelatedWork W1850271161 @default.
- W2047071079 hasRelatedWork W2049013176 @default.
- W2047071079 hasRelatedWork W2063424779 @default.
- W2047071079 hasRelatedWork W2269989009 @default.
- W2047071079 hasRelatedWork W2391191862 @default.
- W2047071079 hasRelatedWork W2416961799 @default.
- W2047071079 hasRelatedWork W2417132786 @default.
- W2047071079 hasRelatedWork W3214088986 @default.
- W2047071079 hasRelatedWork W4241970211 @default.
- W2047071079 hasRelatedWork W4254421610 @default.
- W2047071079 hasVolume "25" @default.
- W2047071079 isParatext "false" @default.
- W2047071079 isRetracted "false" @default.
- W2047071079 magId "2047071079" @default.
- W2047071079 workType "article" @default.