Figure 6

Effect of Am580 treatment on mammary tumor development, tumor growth and metastatic dissemination in MMTV-Myc mice. Groups of 30 uniparous MMTV-Myc female mice were given 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carboxamido]benzoic acid (Am580) (0.3 mg/Kg/day) in the diet or control diet for up to 50 weeks. A) Time to palpable tumor development was recorded to determine percent of mice with tumor-free survival over time. Kaplan-Meier analysis of the data indicated that numbers of mice with extended latency were not significantly different between treated (Am580 (NR+R)) and untreated control (Myc-Ctrl) groups. However, separation of data from the treated group at week 50 on the basis of positive response (Am580 R) or nonresponse (Am580 NR) to Am580 dosing, and reanalysis indicated that the percent of Am580 R mice responding to Am580 as evidenced by the increased tumor latency, from the total Am580 (NR+R) group was significantly higher than the percent of Myc-Ctrl mice (log-rank test, P = 0.0456). B) Tumor growth was recorded by measuring the two main diameters weekly over an 8-week period beginning when tumors were palpable, and volumes were calculated as described in Methods. Analysis of individual tumor growth per mouse indicated two distinct populations in the Am580 treatment group on the basis of tumor volume, namely responders (Am580 R) and nonresponders (Am580 NR). C) Effect of Am580 on metastatic dissemination to lungs in the Myc-Ctrl, Am580 R and Am580 NR experimental groups. The number of overt metastases per mouse lung was quantified under a Nikon stereoscope and plotted. The statistical significance of the results was determined using the Mann-Whitney nonparametric test.