Treatment of NOD/SCID mice with Bay 11-7082 delays the development of EBV- and KSHV-associated lymphomas in vivo. (A) NOD/SCID mice (n = 10/group) were challenged with 40 × 106 LCL 9001 cells and subsequently received injections of vehicle or 20 mg/kg Bay 11 on days 1, 3, and 5 after tumor challenge and at weekly intervals thereafter. Tumors were measured on a weekly basis; tumor area for each mouse is shown by a dot, and average size is illustrated by the bar graph for each group. Differences evaluated by RMANOVA revealed significant differences in tumor size (P < .0352) between vehicle and Bay 11-treated mice averaged over all time points. (B) (i) Murine model of primary effusion lymphoma. The mouse on the left received injection of BC-3 cells and developed lymphomatous ascites, as evidenced by abdominal distention. The mouse on the right was a healthy control mouse. (ii) Disease-free survival curves. NOD/SCID mice (n = 19/group) were challenged with 10 × 106 BC-3 cells and then received injections of vehicle or Bay 11-7082 (5 or 20 mg/kg) on days 1, 3, and 5 after tumor injection. Disease-free survival evaluated by Kaplan-Meier and log rank test showed significant differences in tumor development in Bay 11 and vehicle-treated mice (P < .001 for 5 and 20 mg/kg groups). There was no major difference among the curves for the 5- and 20-mg/kg dose groups, so only the 5-mg/kg data are shown. The control group represents mice that did not receive injections of tumor cells. (C) Cells from ascites and solid tumors in BC-3- and LCL 9001-challenged mice were evaluated for morphology and viral antigen expression after tumor development. Cells were stained with hematoxylin and eosin (H&E); for KSHV, they were further evaluated with antibodies to LANA and vIL-6, and for EBV they were further evaluated with antibodies to LMP-1 and by in situ hybridization for EBER. Original magnification, 100 ×, except LCL H&E and LMP-1, for which original magnification was 400 ×.
