Figure 5.
Effect of MDM2is on EBV-positive lymphoma cells derived from patients with PTLD. TRL1 and TRL595 were derived from tumors of patients with PTLD. (A) Dose response to navtemadlin and idasanutlin. Dose-response analysis was performed as described for Figure 4. The data are presented as the mean ± SD of a quadruplicate assay. (B) Protein levels were determined by western blot analysis. Controls were at basal levels; Navt samples were treated with 1 µM navtemadlin for 24 hours. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as loading control. (C) In vivo treatment response. Animals were enrolled onto the study when tumors reached 200 mm3 and were treated once per day for 21 days. Top: tumor volume changes for each mouse. Bottom: tumor volume changes at day 21 (end of treatment). P < .01 for TRL1. (D) Tumor nodules in liver of TRL595 mice. PARP, poly(ADP-ribose) polymerase.