Matches in SemOpenAlex for { <https://semopenalex.org/work/W4366990191> ?p ?o ?g. }
- W4366990191 endingPage "8617" @default.
- W4366990191 startingPage "8605" @default.
- W4366990191 abstract "Ewing's sarcoma is a highly malignant childhood tumour whose outcome has hardly changed over the past two decades despite numerous attempts at chemotherapy intensification. It is therefore essential to identify new treatment options. The present study was conducted to explore the effectiveness of combined inhibition of two promising targets, ATR and ribonucleotide reductase (RNR), in Ewing's sarcoma cells.Effects of the ATR inhibitor VE821 in combination with the RNR inhibitors triapine and didox were assessed in three Ewing's sarcoma cell lines with different TP53 status (WE-68, SK-ES-1, A673) by flow cytometric analysis of cell death, mitochondrial depolarisation and cell cycle distribution as well as by caspase 3/7 activity determination, by immunoblotting and by real-time RT-PCR. Interactions between inhibitors were evaluated by combination index analysis.Single ATR or RNR inhibitor treatment produced small to moderate effects, while their combined treatment produced strong synergistic ones. ATR and RNR inhibitors elicited synergistic cell death and cooperated in inducing mitochondrial depolarisation, caspase 3/7 activity and DNA fragmentation, evidencing an apoptotic form of cell death. All effects were independent of functional p53. In addition, VE821 in combination with triapine increased p53 level and induced p53 target gene expression (CDKN1A, BBC3) in p53 wild-type Ewing's sarcoma cells.Our study reveals that combined targeting of ATR and RNR was effective against Ewing's sarcoma in vitro and thus rationalises an in vivo exploration into the potential of combining ATR and RNR inhibitors as a new strategy for the treatment of this challenging disease." @default.
- W4366990191 created "2023-04-27" @default.
- W4366990191 creator A5010988539 @default.
- W4366990191 creator A5013238387 @default.
- W4366990191 creator A5045943156 @default.
- W4366990191 creator A5055154765 @default.
- W4366990191 creator A5074401244 @default.
- W4366990191 creator A5084313307 @default.
- W4366990191 date "2023-04-25" @default.
- W4366990191 modified "2023-10-13" @default.
- W4366990191 title "Synergistic anticancer activity of combined ATR and ribonucleotide reductase inhibition in Ewing's sarcoma cells" @default.
- W4366990191 cites W1964170886 @default.
- W4366990191 cites W1973109316 @default.
- W4366990191 cites W1994568630 @default.
- W4366990191 cites W2017836748 @default.
- W4366990191 cites W2022529631 @default.
- W4366990191 cites W2062040583 @default.
- W4366990191 cites W2103562758 @default.
- W4366990191 cites W2115011722 @default.
- W4366990191 cites W2124328974 @default.
- W4366990191 cites W2141419938 @default.
- W4366990191 cites W2142393970 @default.
- W4366990191 cites W2289284908 @default.
- W4366990191 cites W2513016538 @default.
- W4366990191 cites W2514410552 @default.
- W4366990191 cites W2596553151 @default.
- W4366990191 cites W2606331566 @default.
- W4366990191 cites W2626073626 @default.
- W4366990191 cites W2729989042 @default.
- W4366990191 cites W2768260049 @default.
- W4366990191 cites W2792813139 @default.
- W4366990191 cites W2804038339 @default.
- W4366990191 cites W2808161922 @default.
- W4366990191 cites W2895030469 @default.
- W4366990191 cites W2903036851 @default.
- W4366990191 cites W2937119895 @default.
- W4366990191 cites W2954903613 @default.
- W4366990191 cites W2964569023 @default.
- W4366990191 cites W2981993825 @default.
- W4366990191 cites W2995953807 @default.
- W4366990191 cites W3025513346 @default.
- W4366990191 cites W3032665916 @default.
- W4366990191 cites W3034290849 @default.
- W4366990191 cites W3035812011 @default.
- W4366990191 cites W3048317992 @default.
- W4366990191 cites W3089853008 @default.
- W4366990191 cites W3114373975 @default.
- W4366990191 cites W3120488242 @default.
- W4366990191 cites W3152750978 @default.
- W4366990191 cites W3162151317 @default.
- W4366990191 cites W3165375248 @default.
- W4366990191 cites W3177038339 @default.
- W4366990191 cites W3183216761 @default.
- W4366990191 cites W4200402885 @default.
- W4366990191 cites W4211227438 @default.
- W4366990191 cites W4225516110 @default.
- W4366990191 cites W4280521208 @default.
- W4366990191 cites W4283012954 @default.
- W4366990191 cites W4302424483 @default.
- W4366990191 cites W4307922066 @default.
- W4366990191 cites W4309245951 @default.
- W4366990191 cites W4309409772 @default.
- W4366990191 cites W4310946789 @default.
- W4366990191 cites W571790835 @default.
- W4366990191 cites W71855758 @default.
- W4366990191 doi "https://doi.org/10.1007/s00432-023-04804-0" @default.
- W4366990191 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37097390" @default.
- W4366990191 hasPublicationYear "2023" @default.
- W4366990191 type Work @default.
- W4366990191 citedByCount "1" @default.
- W4366990191 crossrefType "journal-article" @default.
- W4366990191 hasAuthorship W4366990191A5010988539 @default.
- W4366990191 hasAuthorship W4366990191A5013238387 @default.
- W4366990191 hasAuthorship W4366990191A5045943156 @default.
- W4366990191 hasAuthorship W4366990191A5055154765 @default.
- W4366990191 hasAuthorship W4366990191A5074401244 @default.
- W4366990191 hasAuthorship W4366990191A5084313307 @default.
- W4366990191 hasBestOaLocation W43669901911 @default.
- W4366990191 hasConcept C104292427 @default.
- W4366990191 hasConcept C104317684 @default.
- W4366990191 hasConcept C12519072 @default.
- W4366990191 hasConcept C142724271 @default.
- W4366990191 hasConcept C143425029 @default.
- W4366990191 hasConcept C190283241 @default.
- W4366990191 hasConcept C207001950 @default.
- W4366990191 hasConcept C2777586341 @default.
- W4366990191 hasConcept C2778256501 @default.
- W4366990191 hasConcept C31573885 @default.
- W4366990191 hasConcept C43759708 @default.
- W4366990191 hasConcept C4710235 @default.
- W4366990191 hasConcept C502942594 @default.
- W4366990191 hasConcept C54355233 @default.
- W4366990191 hasConcept C552990157 @default.
- W4366990191 hasConcept C55493867 @default.
- W4366990191 hasConcept C71924100 @default.
- W4366990191 hasConcept C86803240 @default.
- W4366990191 hasConceptScore W4366990191C104292427 @default.
- W4366990191 hasConceptScore W4366990191C104317684 @default.