Fig. 5: Genetic perturbation of the circadian clock influences chronotherapy treatment response. | npj Precision Oncology

Fig. 5: Genetic perturbation of the circadian clock influences chronotherapy treatment response.

From: Personalized chronotherapy in glioblastoma: integrating circadian profiling and PK–PD modelling to optimize temozolomide timing

Fig. 5: Genetic perturbation of the circadian clock influences chronotherapy treatment response.The alternative text for this image may have been generated using AI.

a KOs of core-clock proteins BMAL1, PER2 and NR1D1 were generated in T98G cells and proliferation was measured in untreated cells. b Circadian profiles of PER2 and BMAL1 bioluminescence reporters were recorded in T98G WT and clock KO cells and circadian parameters were calculated. c Proliferation curves for the treatment at 0 h after synchronization. d The heatmaps of treatment effects calculated as 1-AUC comparing T98G WT to the clock KOs. e The alterations of the circadian profiles under treatment at 0 h after synchronization for the clock KOs. f The Pearson correlation between amplitude under treatment normalized to DMSO derived from the bioluminescence recordings and mean treatment effects. Proliferation measurements were performed in three independent biological replicates with three technical replicates each and bioluminescence measurements were repeated at least twice with three replicates. Significance analysis was performed by one-way ANOVA, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Error bars represent standard deviation. Icons were generated in Biorender.com.

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