(A and B) Graph showing predicted size of the stem-like resistant cell population for hyperfractionated, optimimum-1, and optimum-2 schedules, using the original model (A) or the time-dependent model (B). All values are normalized to predictions for standard therapy. Parameters in (A) and (B) are, respectively, from the Original Parameters and Second Iteration in .
(C) Representative gating strategy for eGFP+ tumor cell side-population (SP) analysis. The upper panel depicts the gate used to identify GFP-positive cells, based on a GFP-negative sample shown in the insert. The lower panel depicts the gate used to identify the SP, based on a Fumitremorgin C-verapamil-treated control shown in the insert.
(D) Representative images and quantification of SP analysis 24 hr after the conclusion of the standard, hyperfractionated, optimum-1, and optimum-2 schedules. For quantification, all values are normalized to the average SP of the standard schedule. Error bars represent the SD.
(E) Kaplan-Meier analysis comparing standard, optimum-1, and optimum-2 schedules. These mice represent an entirely independent cohort from mice in and .
(F) Hazard ratios of the optimum-1 and optimum-2, compared to standard radiation.
(G) Schematic briefly describing the optimum-1 and optimum-2 schedules. The arrow position represents the time of dose during the 8am–5pm treatment window. The size of the arrow correlates with the size of the dose. Error bars represent the 95% CI of the HR.