Fig. 2.

GBM xenografts show elevated sensitivity to TMZ in the morning, compared to evening. a) Experimental paradigm testing TMZ chronotherapy in GBM orthotopic xenograft models. b) LN229-Ef1α implants grew less following five daily doses (arrows) of 100mg/kg TMZ in the morning (ZT4, mean ± SEM) compared to those treated with TMZ in the evening (ZT11) or vehicle (****p < 0.0001 AM vs. PM at 20 days post-implantation, DPI). We quantified tumor size as total bioluminescence at each 11am measurement. c) Mice bearing LN229-P2L xenografts also showed less tumor growth when treated in the morning compared to vehicle or evening TMZ (TMZ PM, *p < 0.05 AM vs. PM at 17 DPI). d) Similarly, GL261-Ef1α xenografts grew less when treated in the morning compared to vehicle or evening TMZ (*p < 0.05 AM vs. PM at 16DPI). e-g) Mice bearing LN229 or GL261implants treated with TMZ in the morning lost less weight from start to the end of TMZ treatment compared to those treated in the evening or with vehicle (mean ± SEM; *p < 0.05)