Figure 4.

Suppressing tumor growth by docetaxel, LBH-589, and pralatrexate in orthotopic (top) and PDX (bottom) models. (Top) U-Hth83 (left) and K2 (right) cells carrying luciferase (5 × 10⁵) were injected into nude mice thyroid orthotopically and tumor growth was monitored by Xenogen twice a week. Treatment started on day 7 for vehicle control (12 mice for U-Hth83 and 10 mice for K2), 5 mg/kg docetaxel (13 mice for U-Hth83 and 8 mice for K2), and 20 mg/kg pralatrexate (13 mice for U-Hth83 and 10 mice for K2). Docetaxel and pralatrexate were given once every 3 days by intraperitoneal injection for total of 5 treatments. LBH-589 was given once a day for 5 days at 20 mg/kg (first cycle), rested for 2 days, and then once a day for 5 days at 10 mg/kg (second cycle) by intraperitoneal injection (12 mice for U-Hth83 and 10 mice for K2). Tumor volume (ex vivo) was calculated after mice were euthanized by caliber and graph was generated by Prism. P-values were calculated by Student’s t-test. (Bottom) PDX models of MDA-ATC1 (left) and MDA-ATC5 (right) were treated with docetaxel (10 mice for MDA-ATC1 and 9 mice for MDA-ATC5), LBH-589 (12 mice for MDA-ATC1 and 10 mice for MDA-ATC5), or pralatrexate (9 mice for MDA-ATC1 and 8 mice for MDA-ATC5). Vehicle controls were 10 mice for MDA-ATC1 and 16 mice for MDA-ATC5. The doses and treatment schedules for PDX models were the same as described for the orthotopic models. SubQ tumor was measured by caliber 2 to 3 times weekly. Percentage of tumor volume change was determined by correction with the starting tumor volume.