1. Fig. 6. AZD6738 induces DNA damage and apoptosis and exhibits antitumor efficacy in xenograft models of high-risk medulloblastoma and neuroblastoma.
AZD6738 induces DNA damage and apoptosis and exhibits antitumor efficacy in xenograft models of high-risk medulloblastoma and neuroblastoma. (A and B) Tumor volumes over time of nude mice harboring IMR5 (A) and HD-MB03 (B) subcutaneously xenografted tumors treated with AZD6738 by oral gavage at 50 mg/kg body weight per day (red) as compared to vehicle control (blue). *P < Error bars represent SDs of 10 individual xenografted mice per group. Arrows denote start of treatment. (C) Representative photomicrographs of sections from IMR5 (top) or HD-MB03 (bottom) tumors upon completion of treatment with AZD6738 (50 mg/kg per day) or vehicle control in vivo, stained with hematoxylin and eosin (H&E) or for Ki67, ClCas3, or γH2AX, as indicated. (D to F) Quantification of the number of cells positively stained for Ki67 (D), ClCas3 (E), and γH2AX (F) in IMR5 or HD-MB03 xenograft tumors upon completion of treatment with AZD6738 (50 mg/kg per day; red) or vehicle control (blue) in vivo. *P = 3.1 × 10−5 and for Ki67 in AZD6738 versus vehicle-treated IMR5 and HD-MB03, respectively. *P = and 4.3 × 10−4 for γH2AX in AZD6738 versus vehicle-treated IMR5 and HD-MB03, respectively. *P = and 4.9 × 10−4 for ClCas3 in AZD6738 versus vehicle-treated IMR5 and HD-MB03, respectively. Error bars represent SDs of three independent fields analyzed.
Anton G. Henssen et al., Sci Transl Med 2017;9:eaam9078
Published by AAAS