Nude mice were treated by oral gavage with ETAR inhibitor ZD4054 (10 mg/kg/d) or vehicle control (VC) 24 hours before tail vein injection of UMUC3 and T24 cells. (A) Tumor cell burden in the lungs of mice dissected 24 and 48 hours after tail vein injection was determined as described above. (B) Photomicrographs of macrophage infiltration of the lungs at the indicated time points (total magnification, ×100). Bars represent the mean ± SEM of the number of macrophages. *P < 0.05, comparing macrophage infiltration in lungs of VC-treated mice injected with either UMUC3 or T24T cells at 48 versus 24 hours. (C–E) ET-1 levels, COX-2 activity, hIL-6, hMCP-1, mIL-6, and mMCP-1 were determined in lungs at the indicated time points. For all assays and time points, ZD4054-treated mice showed significant inhibition (P < 0.05, Student’s t test) compared with VC-treated counterparts (5 animals/group, performed in triplicate).