Correction to: Biological Characterization of an Improved Pyrrole-Based Colchicine Site Agent Identified Through Structure-based Design

doi:10.1124/mol.115.101592err

In the above article [Rohena CC, Telang N, Da C, Risinger AL, Sikorski JA, Kellogg GE, Gupton, JT, and Mooberry SL (2016) Mol Pharmacol 89:287–296] errors were made in the in vivo results, Figure 5. The volume of one tumor in the paclitaxel-treated group was incorrect on day 14, due to a data transcription error following the tumor measurement. This changes the graphs in Fig 5A and B. The dosing of paclitaxel was more intense than was described, with 20 mg/kg doses given on days 0, 2, 4, 6, 8, and 11. Other experimental agents were evaluated in this vivo trial and therefore, a more appropriate statistical analysis is a one-way ANOVA with Dunnett’s post-hoc test. These have all been corrected and the statistical analyses rerun. Statistically significant antitumor effects were still noted for the test agent NT-7-16, but the P value changed from 0.0018 to 0.001. The corrected tumor volume for the paclitaxel-treated mice also resulted in statistically significant antitumor effects and this was corrected and the P value is 0.04. In panel C we replaced the original graph that showed gram weigh change with a graph with percent weight change, consistent with the descriptions throughout the text.

Fig. 5.

Antitumor effects of NT-7-16. (A) The effects of NT-7-16 on MDA-MB-435 tumors were evaluated in nude mice. The graph shows the average tumor volume ± SD starting on day 0. After the tumors were established, mice were treated daily by i.p. injection of 75 mg/kg NT-7-16. Paclitaxel was dosed at 20 mg/kg on days 0, 2, 4, 6, 8, and 11. (B) Individual tumor volumes on day 14 are presented; the mean is represented by the horizontal line in each panel ± 95% confidence intervals. Statistical analysis was performed using a one way ANOVA with a Dunnett’s post hoc test to compare each drug treated condition to control. Significant differences were found between the control and NT-7-16 groups (P = 0.001), and between the control and paclitaxel-treated groups (P = 0.04). (C) Average percent weight change for each treatment group over the course of the trial ± SD. Statistical analysis was performed using a one way ANOVA with a Dunnett’s post hoc test to compare each drug treatment condition to the control. A significant difference (p = 0.004) was only found between the control and paclitaxel groups.

These errors do not change the results or conclusions about the effects of NT-7-16 in any way. The corrected pertinent sentences and Figure 5 are contained herein.

The authors regret these errors and any inconvenience they may have caused.

Methods and Materials

In Vivo Studies. Mice were injected i.p. with either 20 mg/kg paclitaxel on days 0, 2, 4, 6, 8, and 11 or 75 mg/kg NT-7-16 daily for 15 days.

Statistical Studies. For the in vivo studies, statistical analysis of the final tumor volumes was performed using a one-way analysis of variance (ANOVA) with Dunnett’s post-hoc test. This analysis was the most appropriate given that other experimental agents were evaluated in this trial.

Results

The positive control, paclitaxel, was dosed i.p. at 20 mg/kg on days 0, 2, 4, 6, 8, and 11 for a total dose of 120 mg/kg. The results of this trial show that NT-7-16 had antitumor effects that were significantly different from control (P = 0.001). Paclitaxel at this dose and schedule also had statistically significant antitumor effects when compared to the control (P = 0.04) (Fig. 5, A and B). On day 14, the average tumor burden for NT-7-16 treated mice was 521 mm³ (range 195-858 mm³), whereas the average tumor volume for the control and paclitaxel groups were 1,182 mm³ (range 564-1,871 mm³), and 833 mm³ (range 237-1,417 mm³), respectively.

Daily dosing of NT-7-16 at 75 mg/kg did not lead to any evidence of overt toxicity and no notable change in the weight of the animals was measured as compared to the controls (Fig. 5C). In comparison to control tumors, significant cumulative weight loss was observed in the paclitaxel-treated group on day 14 (P = 0.004).