Fig. 3
Results from the PINPRICS-PS subtrial. (A) Schematic representation of the trial design for the PINPRICS-PS study. One week prior to the start of paclitaxel therapy, the animals were transplanted with human 4T1 breast cancer cells by subcutaneous injection into the mammary fat pad (4T1 s.c.). Thereafter, weight and tumor size were closely monitored. The animals were sacrificed on day 42 by decapitation under deep isoflurane anesthesia. (B) Kaplan‒Meier plot of survival per treatment group. (C) Analysis of SNAP amplitudes of the caudal nerve normalized to center baselines at baseline (BL) and day 14 (VEH/VEH: n = 9; VEH/PTX n = 10; IL-6/PTX n = 10; Li/PTX n = 10). Owing to rapid tumor growth, there were not enough animals for analysis at later time points. The graph depicts the mean and individual values per group. (D) The 50% probability mechanical withdrawal threshold was measured with von Frey filaments and is presented at BL and day 14 normalized to the center baselines. Lower values indicate greater sensitivity to mechanical stimuli, which is indicative of mechanical allodynia. The graph depicts the mean and individual values per group (the sample size is identical to that in C). (E) Development of tumor volume over time. Each animal is represented with dots connected by a single line. Animals with tumors larger than 1500 mm3 were euthanized. The Y-axis uses a log10 scale. (F) Dose‒response curves of cultured 4T1 human breast cancer cells after 24 h and 48 h of incubation with increasing dosages of paclitaxel. The initial sample size was n = 15 per group. Abbreviations: 4T1 s.c, subcutaneous injection of 4T1 breast cancer cells; BL, baseline; Il6/IL-6mAB, monoclonal IL-6 antibody MAB406; i.p., intraperitoneal; Li(+), lithium carbonate; PTX, paclitaxel; RR, RotaRod test; SNAP, sensory nerve action potential; VEH, vehicle; Von Frey, von Frey hair test