Figure 4
Figure 4. Drug activity in tVk*MYC mice. (A) C57BL/6 mice bearing transplanted Vk*MYC tumor (Vk4929 or -3478) were treated with panobinostat alone (4929, n = 16; 3478, n = 6; 25 mg/kg for 4 days followed by 15 mg/kg for 3 weeks) or vehicle control (4929, n = 15; 3478, n = 6; D5W, dextrose water) for a total period of 4 weeks. Serum paraprotein was assessed on day 1 and then weekly for 6 weeks and presented as mean change from levels on day 0 (mean ± SEM). *P < .05 vs Vk4929 vehicle treated. #P < .05 vs Vk3478 vehicle treated. (B) Survival of Vk4929 or -3478 mice treated with panobinostat alone or vehicle (D5W). Median survival of mice treated with panobinostat alone was 36.5 days and 64 days compared with vehicle control-treated mice of 16 days and 32.5 days in Vk4929 or -3478 mice, respectively (P < .05). (C) H&E, acetylated histone H3 and TUNEL-stained BM sections from tVk*MYC 4929 tumor after 8 hours and 12 hours treatment with panobinostat (25 mg/kg) compared with vehicle control (D5W). (D) FACS analysis of viable CD138+/B220− PCs in the BM of Vk4929 mice after 8 hours and 12 hours treatment with panobinostat (25 mg/kg) compared with vehicle control (D5W). Values are normalized to the percentage of PCs in vehicle control treated BM (100%). *P < .05. (E) Vk4929 mice were treated with panobinostat (20 mg/kg, days 1-2, reduced to 10 mg/kg onwards to reduce toxicity, n = 7), bortezomib (0.5 mg/kg, twice weekly, n = 7), the combination of both agents (n = 7) or vehicle control (D5W, n = 7) for 4 weeks. Serum paraprotein was assessed on day 1 and then weekly for 6 weeks and presented as mean change from levels on day 0 (mean ± SEM). *P < .05 vs vehicle control. (F) Survival of Vk4929 mice treated with panobinostat, bortezomib, the combination of both agents and vehicle control (D5W). Median survival of mice were as follows: panobinostat alone 32 days; bortezomib alone 24 days; the combination of both agents 36 days; vehicle control-treated mice 18 days. (G) FACS analysis of viable CD138+/B220− PCs in the BM of Vk4929 mice after 5 days of treatment with panobinostat (10 mg/kg daily), bortezomib (0.5 mg/kg, days 1 and 4), the combination of both agents or vehicle control (D5W). Values are normalized to the percentage of PCs in vehicle control treated BM (100%). *P < .05 vs vehicle control.

Drug activity in tVk*MYC mice. (A) C57BL/6 mice bearing transplanted Vk*MYC tumor (Vk4929 or -3478) were treated with panobinostat alone (4929, n = 16; 3478, n = 6; 25 mg/kg for 4 days followed by 15 mg/kg for 3 weeks) or vehicle control (4929, n = 15; 3478, n = 6; D5W, dextrose water) for a total period of 4 weeks. Serum paraprotein was assessed on day 1 and then weekly for 6 weeks and presented as mean change from levels on day 0 (mean ± SEM). *P < .05 vs Vk4929 vehicle treated. #P < .05 vs Vk3478 vehicle treated. (B) Survival of Vk4929 or -3478 mice treated with panobinostat alone or vehicle (D5W). Median survival of mice treated with panobinostat alone was 36.5 days and 64 days compared with vehicle control-treated mice of 16 days and 32.5 days in Vk4929 or -3478 mice, respectively (P < .05). (C) H&E, acetylated histone H3 and TUNEL-stained BM sections from tVk*MYC 4929 tumor after 8 hours and 12 hours treatment with panobinostat (25 mg/kg) compared with vehicle control (D5W). (D) FACS analysis of viable CD138+/B220− PCs in the BM of Vk4929 mice after 8 hours and 12 hours treatment with panobinostat (25 mg/kg) compared with vehicle control (D5W). Values are normalized to the percentage of PCs in vehicle control treated BM (100%). *P < .05. (E) Vk4929 mice were treated with panobinostat (20 mg/kg, days 1-2, reduced to 10 mg/kg onwards to reduce toxicity, n = 7), bortezomib (0.5 mg/kg, twice weekly, n = 7), the combination of both agents (n = 7) or vehicle control (D5W, n = 7) for 4 weeks. Serum paraprotein was assessed on day 1 and then weekly for 6 weeks and presented as mean change from levels on day 0 (mean ± SEM). *P < .05 vs vehicle control. (F) Survival of Vk4929 mice treated with panobinostat, bortezomib, the combination of both agents and vehicle control (D5W). Median survival of mice were as follows: panobinostat alone 32 days; bortezomib alone 24 days; the combination of both agents 36 days; vehicle control-treated mice 18 days. (G) FACS analysis of viable CD138+/B220− PCs in the BM of Vk4929 mice after 5 days of treatment with panobinostat (10 mg/kg daily), bortezomib (0.5 mg/kg, days 1 and 4), the combination of both agents or vehicle control (D5W). Values are normalized to the percentage of PCs in vehicle control treated BM (100%). *P < .05 vs vehicle control.

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