Combined intratumoral injection of TRAIL plasmid and survivin antisense ODN significantly supressed the growth of tumor xenografts in nude mice as compared to TRAIL plamid alone (0.31±0.05 vs 2.35 ±0.38 cm 3 , P <0.01) during a 4-week of observation. Conclusions: The findings indicate that survivin may play a role in tumor cell resistance to TRAIL-induced apoptosis, at least in part, through cell cycle regulation. Manipulation of survivin expression may sensitizes HCC to TRAIL-induced

more »

... This approach may offer a novel approach in molecular therapy against HCC for which no effective treatment is available for an advanced stage. 945. Purpose: The objective of this study was to evaluate the combined effect of adenovirus vector encoding Herpes simplex thymidine kinase plus ganciclovir (GCV) suicide gene therapy and Docetaxel (DTX) in human bladder cancer cell lines. Material & Methods: IC50 was determined for both Ad5F35TK plus ganciclovir (GCV) or DTX monotherapy at 48, 72 and 96 h after exposure to a serial log-fold dosing of Ad5F35TK or DTX in a coxsackievirus-adenovirus receptor (CAR) positive human bladder cancer cell line (5637) and a CAR negative cell line (TCC-SUP). Cell growth inhibition was then assessed at 72 h after treatment with Ad5F35TK+GCV or Ad5F35TK/GCV/DTX by MTT assay. Ad5F35 and DTX were given within 3, 6, 9, 12, and 24 hours of each other then MTT assay was performed at 72 h. The viability of control cells was set as 100%, and viability in other groups was calculated by comparing the optical density (OD) readings with the control. Results: The inhibitory concentration of docetaxel to achieve 50% cell death in 5637 cell line ranged from 0.002 to 0.008 ug/ml and from 0.002 to 0.02 in TCC-SUP cell line at 48, 72 and 96 hours. Adding docetexal chemotherapy to Ad5F35TK gene therapy resulted in 57% benefit in 5637 cell line (p<0.0001) and 39% benefit in TCC-SUP cell line (p<0.005). Conclusion: Combination of Ad5F35TK+GCV suicide gene therapy with DTX in human bladder cancer cells was considerably more active in vitro than with monotherapy. This result suggests that combination treatment of Ad5F35TK+GCV suicide gene therapy with DTX has the potential to enhance clinical activity as compared to monotherapy in human bladder cancer.