The tumor growth was assessed by measuring bi-dimensional diameters twice a week with calipers. As shown in Fig. 3B, the tumors treated by Ad.hTERT-E1A-TK alone or Ad.hTERT-E1A-TK plus GCV started to grow slowly on the 8th day after treatment when compared with that treated with Ad.null or PBS plus GCV. On 16th day, the differences became more significant. At the end of observation, the average tumor CX-5461 purchase sizes were 2440.00 mm3, 2287.00 mm3, 1274.50 mm3 and 435.01 mm3 in group of Ad.null, PBS plus GCV, Ad.hTERT-E1A-TK alone, and Ad.hTERT-E1A-TK plus GCV,

respectively. Since Ad.null and PBS plus GCV showed no difference in tumor growth or tumor size (p > 0.05), we took both Ad.null and PBS plus GCV together as control. The tumor growth curve and tumor size between control and Ad.hTERT-E1A-TK

or Ad.hTERT-E1A-TK plus GCV was significantly different (p = 0.025 or p = 0.008) and by 54.39% and 74.34% reduction in tumor weight in Ad.hTERT-E1A-TK or Ad.hTERT-E1A-TK plus GCV treated groups compared with controls. More importantly, the tumor growth curve and tumor size between Ad.hTERT-E1A-TK and Ad.hTERT-E1A-TK plus GCV GSK872 mouse also showed different (p = 0.040), it was about 43.75% reduction in tumor size in Ad.hTERT-E1A-TK plus GCV treated group (Fig. 3C). It is necessary to mention that the timing for prodrug giving was on the 3rd day in this study. The reason was mainly dependent on our previous study in which the transgene expression reached the Neratinib price peak on the 3rd day after intratumoral injection of either replication-competent or replication-deficient adenoviral vectors. In that study the transgene (red fluorescent protein, RFP) expression was visualized by in vivo imaging (data not shown), it reached the peak

on the 3rd day which might reflect full replication and distribution of adenoviral vectors in tumor tissue. Whether the advanced administration of GCV would result in the suppression on adenoviral replication in tumor tissues or interferer with therapeutic efficacy of Ad.hTERT-E1A-TK has not been investigated in this study. The tumor sections from different groups also showed differential histopathologic features. The most obvious difference was the numbers of apoptotic cells and the range of necrosis area. As shown in Fig. 4, tumors treated with Ad.hTERT-E1A-TK plus GCV showed wider necrosis and more dark-stained and condensed nuclei. Figure 4 Histological examinations of NCIH460 tumors treated by different conditions. The hematoxylin-eosin stain of NCIH460 tumors treated by different CB-839 cell line conditions, PBS plus GCV treated (A); Ad.null treated (B); Ad.hTERT-E1A-TK alone treated (C). Ad.hTERT-E1A-TK plus GCV treated (D). The necrosis is barely seen in control groups (A and B), while there are obvious necrotic areas and numerous apoptotic bodies in the tumor tissues treated by Ad.hTERT-E1A-TK alone or Ad.hTERT-E1A-TK plus GCV treated (C and D).