Figure 8. Long-term survival and tumor presence outcomes for PDGF-BHA/shp53 glioma-bearing mice treated with Pen-d/n-ATF5-RP.

A. Survival of glioma (PDGF-B/shRNA-p53 induced)-bearing mice (verified by MRI) with or without treatment with Pen-d/n-ATF5-RP (subcutaneous delivery as described in the text). Of the nine control mice, four mice were treated with Pen-Control-RP peptide and five were untreated. The experimental endpoint was 200 days after initial tumor detection by MRI. Survival analysis achieved by Log-rank (Mantel-Cox) test showed a p-value = 0.0194. B. MRI outcomes for tumor-bearing mice before and after subcutaneous treatment with Pen-d/n-ATF5-RP as described in the text. Fisher Exact Match test showed p = 0.0002 with Positive Predictive Value 95% confidence interval of 0.6306 to 1.000. The latter times range from 176-225 days after tumor treatment (183-230 days after tumor detection). C. Brain histopathological outcomes for tumors in control and Pen-d/n-ATF5-RP treated mice. In all cases, MRI verified the presence of tumors prior to treatment. Fisher Exact Match test showed p < 0.0001 with Positive Predictive Value 95% confidence interval of 0.0 to 0.3694. The brains of animals described in A. were harvested either after death (6 controls), after the experimental endpoint (4 Pen-d/n-ATF5-RP treated animals; 2 Pen-Control or 1 non-Treated animal) or after sacrifice for non-tumor related health problems (2 Pen-d/n-ATF5-RP treated animals). For treated animals, histological analysis was carried out 260-547 days after tumor initiation (183-392 days after Pen-d/n-ATF5-RP administration and 190-397 days after initial tumor detection). Brain sections were prepared as described in Methods and were stained with H&E and immunostained for Ki67 and HA (to identify PDGF-B-HA+ tumor cells). The presence/absence of tumors was based on observations of hyperchromatic nuclei, high cellularity, elevated Ki67 staining and HA immunostaining.