D then administered orally at of 80 mg/kg once daily for

D then administered orally at of 80 mg/kg once daily for 15 days. In all groups, the dosing volume of 10 mL/kg (0.2 mL/20 g mouse) was scaled to the weight of each individual animal.where TTE is expressed in days, endpoint volume is expressed in mm3, b is the intercept, and m is the slope of the line obtained by linear regression of a log-transformed tumor growth data set. The data set is comprised of the first observation that exceeded the endpoint volume used in analysis and the three consecutive observations that immediately preceded the attainment of this endpoint volume. Any Staurosporine animal that did not reach endpoint was euthanized at the end of the study and assigned a TTE value equal to the last day of the study. Any animal determined to have died from treatment-related (TR) causes was to be assigned a TTE value equal to the day of death. Any animal that died from non-treatment-related (NTR) causes was excluded from the analysis. Treatment efficacy was determined from tumor growth delay (TGD), which is defined as the increase in the median TTE for a treatment group compared to the control group:TGD = T - C,expressed in days, or as a percentage of the median TTE of the control group:TGD =T-C ?100 Cwhere T is the median TTE for a treatment group, C is the median TTE for control Group 1.ToxicityTest animals were observed frequently for any overt signs of adverse, treatment-related side effects, and clinical signs of toxicity were recorded. Test animals were also weighed twice weekly and any animal that exceeded the limits for acceptable body weight (BW) loss was euthanized. Dosing was suspended in any group that exceeded the limits for acceptable mean BW loss. If mean BW recovered, then dosing may be resumed in that group, but at a lower dosage or less frequent dosing schedule. Acceptable toxicity for the maximum tolerated dose (MTD) was defined as group mean BW loss of less than 20 during the test, and no more than 10 TR mortality. A death was classified as TR if it was attributable to treatment side effects as evidenced by clinical signs and/ or necropsy, or due to unknown causes during the dosingHall et al. J Transl Med (2016) 14:Page 4 ofperiod or within 14 days of the last dose. A death was classified as NTR if there is no evidence that the death was related to treatment side effects.Statistical analysis and graphical presentationsPrism (GraphPad) for Windows 6.02 was used for all statistical analysis and graphical presentations. The logrank test was employed to assess the significance of the difference between the overall survival experiences of two groups. The logrank test analyzed the individual TTEs for all animals in a group, except those lost to the study due to NTR deaths. The two-tailed statistical analysis was conducted at P = 0.05. Prism reports results as non-significant (ns) at P > 0.05, significant (symbolized by "*") at 0.01 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/17139194 context of this report. When an animal exited the study due to tumor size or TR death, the final tumor volume recorded for the animal was included with the data used to calculate the median volume at subsequent time points. Tumor growth curves were truncated when the tumors in.