American Society of Hematology

Figure 7

$Figure 7. In vivo effects of the combination of nilotinib (20 mg/kg) and imatinib (75 mg/kg) on BCR-ABL–expressing cells in a murine leukemia model. Influence of preirradiation on mouse responsivity to nilotinib. (A) Effects of vehicle, nilotinib alone (20 mg/kg), imatinib alone (75 mg/kg), or a combination of nilotinib and imatinib on growth of 32D.p210-luc+ cells in NCR nude mice. Mice were sublethally irradiated with a single fraction of 3 Gy followed by tail-vein injection of 800 000 cells/mouse. Images were taken on day 2, day 4, day 5, and day 7 after intravenous injection. On day 7 after intravenous injection, mice had received a total of 5 days of treatment with vehicle or drug. Mice were killed, weighed, and preserved for histopathologic analysis approximately 9 days after the last imaging day. Photo images show bioluminescence as seen on the last imaging day for representative mice. (B) Bioluminescence values plotted as percent of baseline for mice treated with vehicle, nilotinib alone (20 mg/kg), imatinib alone (75 mg/kg), or a combination of nilotinib and imatinib. Vehicle (n = 6), nilotinib alone (n = 4), imatinib alone (n = 6), nilotinib + imatinib (n = 5). (C) Percent spleen weights for 32D.p210-luciferase–injected NCR nude mice treated with nilotinib alone (20 mg/kg), imatinib alone (75 mg/kg), or a combination of nilotinib and imatinib. (D) Investigation of effects of gamma irradiation prior to intravenous injection of 32D.p210-luc+ cells on leukemia growth and nilotinib responsiveness. Mice were divided into 2 groups of 4: One group was sublethally irradiated with a single fraction of 3 Gy prior to being intravenously injected with 600 000 32D.p210-luc+ cells. The other group was not irradiated prior to cell injection. Both groups were then treated for a total of 6 days with either vehicle or nilotinib (20 mg/kg); final images were performed on postinjection day 7. Photo images show bioluminescence as seen on the last imaging day. (E) Bioluminescence values plotted as percent of baseline for mice treated with vehicle or nilotinib alone (20 mg/kg). Vehicle (n = 4), nilotinib alone (n = 4). (F) Raw bioluminescence values. Error bars indicate SEM.$

In vivo effects of the combination of nilotinib (20 mg/kg) and imatinib (75 mg/kg) on BCR-ABL–expressing cells in a murine leukemia model. Influence of preirradiation on mouse responsivity to nilotinib. (A) Effects of vehicle, nilotinib alone (20 mg/kg), imatinib alone (75 mg/kg), or a combination of nilotinib and imatinib on growth of 32D.p210-luc⁺ cells in NCR nude mice. Mice were sublethally irradiated with a single fraction of 3 Gy followed by tail-vein injection of 800 000 cells/mouse. Images were taken on day 2, day 4, day 5, and day 7 after intravenous injection. On day 7 after intravenous injection, mice had received a total of 5 days of treatment with vehicle or drug. Mice were killed, weighed, and preserved for histopathologic analysis approximately 9 days after the last imaging day. Photo images show bioluminescence as seen on the last imaging day for representative mice. (B) Bioluminescence values plotted as percent of baseline for mice treated with vehicle, nilotinib alone (20 mg/kg), imatinib alone (75 mg/kg), or a combination of nilotinib and imatinib. Vehicle (n = 6), nilotinib alone (n = 4), imatinib alone (n = 6), nilotinib + imatinib (n = 5). (C) Percent spleen weights for 32D.p210-luciferase–injected NCR nude mice treated with nilotinib alone (20 mg/kg), imatinib alone (75 mg/kg), or a combination of nilotinib and imatinib. (D) Investigation of effects of gamma irradiation prior to intravenous injection of 32D.p210-luc⁺ cells on leukemia growth and nilotinib responsiveness. Mice were divided into 2 groups of 4: One group was sublethally irradiated with a single fraction of 3 Gy prior to being intravenously injected with 600 000 32D.p210-luc⁺ cells. The other group was not irradiated prior to cell injection. Both groups were then treated for a total of 6 days with either vehicle or nilotinib (20 mg/kg); final images were performed on postinjection day 7. Photo images show bioluminescence as seen on the last imaging day. (E) Bioluminescence values plotted as percent of baseline for mice treated with vehicle or nilotinib alone (20 mg/kg). Vehicle (n = 4), nilotinib alone (n = 4). (F) Raw bioluminescence values. Error bars indicate SEM.

This Feature Is Available To Subscribers Only