Differential effects of LY2157299 on the growth
of murine gliomas. Mice intracranially implanted with SMA-497, SMA-540, SMA-560, or
GL-261 cells were treated daily with LY2157299 at 150 mg/kg or control solvent from
day 7 on. Brain sections (early-stage) were analyzed. (A) Tumor volumes. (B) pSMAD2
and CD31+ capillaries. (C) Data are expressed as mean + SEM (*P
< .05, ****P < .0001, unpaired Student's
t-test, LY2157299 vs solvent). (D) Kaplan–Meier survival curves of
glioma-bearing mice (log-rank test was considered significant for P
< .05). (E, F) Gene expression heatmaps were obtained by unsupervised comparison
of genes differentially expressed in the 4 mouse glioma cell lines for the TGF-β
signaling (E) and immune response (F) pathways. The heatmaps indicate high to low
expression levels as red to blue color coding. Up- or downregulated gene clusters in
SMA-497 and GL-261 cells are encircled in red or blue. hpf, high-powered
field.