1.An Armed Oncolytic Adenovirus System, ZD55-Gene, Demonstrating Potent Antitumoral Efficacy 2.Resveratrol Induces Autophagy In BEL7404 Human Hepatoma Cells By Upregulation Of Beclin 1

ONYX-015 is an attractive therapeutic adenovirus for cancer because it can selectively replicate in tumor cells and kill them. To date, clinical trials of this adenovirus have demonstrated marked safety but not potent enough when it was used alone. In this paper, we put forward a novel concept of Targeting Gene-ViroTherapy strategy and in this way, we constructed an armed therapeutic oncolytic adenovirus system, ZD55-Gene, which is not only deleted of E1B-55kD gene similar to ONYX-015, but also armed with foreign antitumor gene. ZD55-Gene exhibited similar cytopathic effects and replication kinetics to that of ONYX-015 in vitro. Importantly, the carried gene is expressed and the expression level can be increased with the replication of virus. Consequently, a significant antitumoral efficacy was observed when ZD55-CD/5-FU was used as an example in nude mice with subcutaneous human SW620 colon cancer. Our data demonstrated that ZD55-Gene, which utilizing the targeting gene-virus therapy strategy, is more efficacious than each individual component in vivo. Considering that angiogenesis has a central role in tumor growth, we chose an antiangiogenic gene, sflt-1(1-3) (the first three extracellular domain of soluble hVEGF receptor-1) into an E1B-55kD deleted oncolytic adenovirus ZD55 to construct ZD55-sflt-1. The secretion of sFlt-1 from ZD55-sflt-1 was much higher...