(A) Normal saline group (6.88 ± 1.40), (B) Bifutobacterium infantis with empty plasmid group (16.01 ± 3.48), and (C) Bifutobacterium infantis-PGEX-TK group (41.72 ± 4.27). There is statistically significant difference between each groups (p < 0.05). Representative samples are shown. Magnification, 100×. Caspase 3 protein expression in bladder tumor tissues We further analyzed the protein levels of caspase 3 in bladder tumor tissues by immunohistochemistry. Caspase 3 positive staining

showed brownish yellow in the cytoplasm (in some cases, on cell membranes) (Figure BAY 80-6946 clinical trial 4). The percentage of positive caspase 3 staining was 41.72 ± 4.27% for the BI-TK group, 16.01 ± 3.48% for the BI-pGEX-5X-1 group, and GF120918 order 6.88

± 1.40% for the normal saline group, respectively. The differences between each group were statistically significant (p < 0.05). Nonetheless, these findings strongly suggest that BI-TK/GCV gene therapy system may upregulate Caspase 3 expression in bladder tumors and hence promote bladder tumor cell apoptosis (Figure 4). Figure 4 Immunohistochemical staining of Caspase 3 expression in BI-TK/GCV treated rat bladder cancer. The percentage of positive caspase 3 staining was 6.88 ± 1.40% for the normal saline group(A), 16.01 ± 3.48% for the BI-pGEX-5X-1 group(B), and 41.72 ± 4.27% for the BI-TK group(C), respectively. The differences between each group were statistically significant (p < 0.05).,100×. Discussion Currently animal models of bladder tumors are mostly limited to the use of xenograft tumor models with subcutaneous or planting bladder tumor cells. Subcutaneous tumor model is most commonly used because of its easy manipulation, tumor growth consistency, and easy observation. However, the subcutaneous xenograft models ignore the anatomic and physiological characteristics of the organ. Casein kinase 1 The method of MNU induce tumor have many good quality: easy, little used, induce way agility,

it can be filling into bladder or injection by vein. Steinberg [12] evaluate the drug treatment therapeutic efficacy in MNU induced rat bladder tumor model, the result showed that the occurrence and biological behaviour is similar between MNU induced rat bladder tumor model and human TCCB, so MNU induced rat bladder tumor model can be used to research the treatment of bladder tumor. In this study, we demonstrated that MNU reperfusion – induced rat bladder tumor have a high rate of success (nearly 100%) with morphological and pathological features similar to that of human bladder cancer. At the endpoint of this study, we also examined other organs, including liver, kidney, heart and lungs, and did not found any tumor formation, which is consistent with earlier reports [7, 13–15].