Figure 7
Figure 7. Aurk activity is required for maintenance of Myc-driven lymphoma in vivo. (A) Top panel: Schedule of lymphoma cell injection and AS703569 treatment (60 mg/kg body weight, once weekly per oral gavage). Bottom panels: Survival curves. p53 wild-type or p53 mutant Eμ-Myc lymphoma cells were injected intravenously into syngeneic recipients, and mice were followed for lymphoma onset. The differences between the control and Aurk inhibitor treatment groups (treated) are statistically significant. (B) FDG-PET scans were performed before and 24 hours after a single oral treatment with Aurk inhibitor (AS703569, 60 mg/kg body weight) in a mouse with manifest lymphoma. (C) Histologic assessment of Aurk inhibition in manifest lymphomas. Top row: Hematoxylin and eosin (HE) staining shows massive necrosis after Aurk inhibition in treated versus control mice (lymph node). Immunohistochemistry for the indicated markers shows a reduction of proliferating cells as assessed by Ki-67 positivity (second row) and increased apoptotic cell death assessed by staining for cleaved (p17) caspase-3 (p17Casp3; third row). Image acquisition: Zeiss Axioplan 2 microscope; 20×/0.5 NA Plan-Neofluar air objective; Zeiss Axiocam MRc 5 camera; Axiovision Rel 4.6 scanning software; original magnification ×200. Right panel: Quantification of the percentage of Ki-67 and p17Casp3-positive cells in control lymphomas or lymphomas from mice treated 24 hours with a single dose of the Aurk inhibitor AS703569. Bars represent the mean percentage ± SEM of positive cells from lymph nodes from 3 different control or AS703569-treated mice.

Aurk activity is required for maintenance of Myc-driven lymphoma in vivo. (A) Top panel: Schedule of lymphoma cell injection and AS703569 treatment (60 mg/kg body weight, once weekly per oral gavage). Bottom panels: Survival curves. p53 wild-type or p53 mutant Eμ-Myc lymphoma cells were injected intravenously into syngeneic recipients, and mice were followed for lymphoma onset. The differences between the control and Aurk inhibitor treatment groups (treated) are statistically significant. (B) FDG-PET scans were performed before and 24 hours after a single oral treatment with Aurk inhibitor (AS703569, 60 mg/kg body weight) in a mouse with manifest lymphoma. (C) Histologic assessment of Aurk inhibition in manifest lymphomas. Top row: Hematoxylin and eosin (HE) staining shows massive necrosis after Aurk inhibition in treated versus control mice (lymph node). Immunohistochemistry for the indicated markers shows a reduction of proliferating cells as assessed by Ki-67 positivity (second row) and increased apoptotic cell death assessed by staining for cleaved (p17) caspase-3 (p17Casp3; third row). Image acquisition: Zeiss Axioplan 2 microscope; 20×/0.5 NA Plan-Neofluar air objective; Zeiss Axiocam MRc 5 camera; Axiovision Rel 4.6 scanning software; original magnification ×200. Right panel: Quantification of the percentage of Ki-67 and p17Casp3-positive cells in control lymphomas or lymphomas from mice treated 24 hours with a single dose of the Aurk inhibitor AS703569. Bars represent the mean percentage ± SEM of positive cells from lymph nodes from 3 different control or AS703569-treated mice.

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