Tumor volume was measured in 2 mice at 2 weeks by sacrificing a few mice for measurements and then at the time

of sacrifice following treatment of mice for 1, 2, 3 and 4 mos. 5c. Mice were injected with tumor cells according to methods in fig. 5b and treated with either (◆) 4 ug/ml, (■) 3 ug/ml and (●) 2 ug/ml biw DNAZYM-1P. Control mice were treated with (▲) lipofectamine and (Ж) scrambled oligonucleotide. Mice were treated for 2 mos, then treatment was discontinued for up to 17 weeks. 5d–5e. H&E and RPS2 antibody immunolabeled sections of a tumor from a mouse treated with the scrambled oligonucleotide for 2 mos (see fig. 5c). Similar studies were then carried out to assess whether DNAZYM-1P delivered systemically, could block the growth of tumors disseminated to a variety of organ systems. In these experiments, mice were injected i.v. via the tail vein at day 1 and day 10 with 1 × 105 cells/ml then selleckchem treatment BKM120 ic50 started after

2 weeks by i.v. injection via the tail vein of DNAZYM-1P (▲)(n = 30), scrambled oligonucleotide (◆)(n = 30), vehicle (○)(n = 30), or buffer (Ж)(n = 30). The data in fig. 5b showed that tumors did not survive in mice treated with DNAZYM-1P (▲), whereas numerous tumors were found in the kidney, sternum, peritoneum, liver and lungs of mice treated with scrambled oligonucleotide (◆), vehicle (○) or buffer (Ж). Mouse survival studies were then carried out under the conditions described in fig. 5b, where treatment with the

different agents was discontinued after 2 mos and the mice monitored for ~4 mos. The mouse survival data showed that the mice all died by ~7–15 weeks in mice treated with lipofectamine (▲) or scrambled oligonucleotide (Ж) (fig. 5c). In mice treated with 2, 3 and 4 ug/ml DNAZYM-1P, mouse survival was either (●) 40%, (■) 90% and (◆) 100%, respectively. H&E stained sections and RPS2 antibody labeled sections of the tiny tumors present at the time treatment was initiated, showed that the PC-3ML cells normally formed solid tumor masses and the cells over expressed RPS2. In mice treated with the scrambled oligonucleotide for 2–3 mos, the cAMP tumors still consisted of a packed mass of PC-3ML cells (fig. 5d) which expressed RPS2 (fig. 5e). Residual nodules sometimes BIIB057 datasheet remained following treatment of the mice with DNAZYM-1P for 2 mos. These nodules consisted of a collagen shell, but were largely empty masses filled with debris that was not immunolabeled with RPS2 antibodies (data not shown). Overall, we found that DNAZYM-1P treatment of the mice appeared to be of low or zero toxicity to the mice since they gained weight on a regular basis, were robust and healthy in appearance and showed zero neuropathy or hair loss. Histology of the liver, kidney, spleen, brain, spine, lungs, and heart indicated normal undamaged tissue.