The synergistic effects of DNA-damaging drugs @entity900 and @entity2879 with a XXXX inhibitor @entity1092 in high-risk @entity521 cells.

@entity1 @entity137 @entity522 @entity3262 @entity5 @entity1092 @entity900 @entity15152 @entity2879 @entity3996 @entity2148 @entity1891 @entity521
UNASSIGNED: High-risk @entity521 remains one of the most important therapeutic challenges for pediatric oncologists. New agents or regimens are urgently needed to improve the treatment outcome of this fatal @entity5 . We examined the effect of @entity15152 ( @entity15152 ) inhibitors in a combination with other chemotherapeutics on a high-risk @entity521 UKF- @entity1 cell line. Treatment of UKF- @entity1 cells with DNA-damaging chemotherapeutics @entity900 or @entity2879 combined with the @entity15152 inhibitor @entity1092 ( @entity3262 ) resulted in the synergistic antitumor effect. This was associated with @entity522 -dependent induction of apoptosis. Another @entity15152 inhibitor @entity3996 and a derivative of @entity3262 that does not exhibit @entity15152 inhibitory activity, @entity2148 , lacked this effect. The synergism was only induced when @entity3262 was combined with cytostatics targeted to cellular DNA; @entity3262 does not potentiate the @entity137 of the anticancer drug @entity1891 that acts by a mechanism different from that of DNA damage. The @entity3262 -mediated sensitization of UKF- @entity1 cells to @entity900 or @entity2879 was dependent on the sequence of drug administration; the potentiating effect was only produced either by simultaneous treatment with these drugs or when the cells were pretreated with @entity900 or @entity2879 before their exposure to @entity3262 . The synergistic effects of @entity3262 with @entity900 or @entity2879 were associated with changes in the acetylation status of histones H3 and H4. The results of this study provide a rationale for clinical evaluation of the combination of @entity3262 and @entity900 or @entity2879 for treating @entity1 suffering from high-risk @entity521 .
