AZD1480 Inhibits Thyroid Tumorigenesis Figure 3. AZD1480 leads to TPC-1 xenograft tumor remission. (A) TPC-1 cells (106) were injected subcutaneously in the flanks of nude mice. 3 Following tumor engraftment (,0.5 cm ), mice were distributed into four groups (n = 5/group) with similar mean tumor volumes. Groups were treated with drug vehicle (untreated), AZD6244, at 25 mg/Kg, once a day, or AZD1480, at 30 mg/Kg, bi-daily. Tumor volumes were determined bi- weekly (mean 6 SE). (B) AZD1480- and AZD6244- treated TPC-1 tumor sections were immunostained for phospho-STAT3 and phospho-ERK1/2 expression, respectively. Phospho-STAT3-positive stromal cells are outlined with a dotted-line (magnification: 400x). (C) JAK inhibitor decreases proliferation and vasculogenesis of TPC-1 xenografts. H&E staining of TPC-1 tumors treated with drug vehicle (control), AZD6244 or AZD1480. Representative tumor sections were stained for proliferation (Ki67), angiogenesis (Meca-32) and apoptosis (TUNEL) markers. Original magnification: 200x. Quantification is represented graphically. **p,0.001; ***p,0.0001. doi:10.1371/journal.pone.0046869.g003 PLOS ONE | www.plosone.org 5 October 2012 | Volume 7 | Issue 10 | e46869