Figure 4
Reduction of tumour volume of C33-A and A2780 xenografts after intra tumoural injection of telomerase gene therapy viruses followed by systemic administration of CB1954 (a) and (b) 107 C33a or A2780 cells per mouse were injected subcutaneously into the flanks of six groups of six female athymic nude mice and allowed to develop for 14 days until tumour diameters were approximately 5 mm. At this time (day 0), four groups of mice were injected intra tumourally with a total of 4Ă—l08 PFU for C33a xenografts (panel a) or 1Ă—109 PFU for A2780 (panel b) of Ad-hTR-NTR or Ad-hTERT-NTR per tumour (two groups for each virus). The following day (day 1), three groups (one-drug-only group and 1 each of the virus-injected groups) were intravenously injected with 80 mg/kg CB1954 and the mean tumour volumes of all groups were monitored daily for 7 days. Results given are the mean tumour volumes and standard errors at each time point derived from six mice per group by the formula volume=d3Ă—Ï€/6. A clear reduction in tumour volume over the course of the experiment is evident in the groups injected with both virus and drug, but not in any of the control groups. The differences in tumour volume between virus-only and virus/CB1954 groups were analysed using Students' t-test and found to be highly significant for both experiments (P<0.001). Filled box: hTR virus with CB1954, open box: hTERT virus with CB1954. Closed triangle: hTR virus alone, open triangle: hTERT virus alone. Closed circle: diluent alone, filled circle: CB1954 alone. (c) and (d) Photomicrographs of vector-infected frozen tissue sections at low magnification (original magnification Ă—2.5). C33a xenografts (panel c) were injected with a single dose of 4Ă—108 PFU Ad-CMV-LacZ in parallel with tumour reduction experiments. Tumours were excised and cryosections were stained for LacZ expression and counterstained with eosin, 24 h later. A2780 xenografts (panel d) were infected with Ad-hTR-NTR or Ad-hTERT-NTR at 1Ă—109 PFU. After 24 h, tumours were excised for immunohistochemical analysis of NTR expression and counterstained with haematoxylin. The figure shows a section infected with Ad-hTERT-NTR
