RNA interference (RNAi) has been proved to be a powerful tool for gene knockdown purpose and holds great promise for the treatment of cancer. Our previous study demonstrated that the reduction of Ki-67 expression by means of chemically synthesized siRNAs and shRNAs expressed from plasmid resulted in proliferation inhibition in human renal carcinoma cells. In this study, we constructed a novel oncolytic adenovirus-based shRNA expression system, ZD55-Ki67, and explored ZD55-Ki67-mediated RNAi for Ki-67 gene silencing. Our results showed that ZD55-Ki67 could induce silencing of the Ki-67 gene effectively, allow for efficient tumor-specific viral replication and induce the apoptosis of tumor cells effectively in vitro and in nude mice. We conclude that combining shRNA gene therapy and oncolytic virotherapy can enhance antitumor efficacy as a result of synergism between CRAd oncolysis and shRNA antitumor responses.
It has been shown that interleukin 18 (IL-18) exerts antitumor activity. In this study, we investigated whether oncolytic adenovirusmediated gene transfer of IL-18 could induce strong antitumor activity. A tumor-selective replicating adenovirus expressing IL-18 (ZD55-IL-18) was constructed by insertion of an IL-18 expression cassette into the ZD55 vector, which is based on deletion of the adenoviral E1B 55-kDa gene. It has been shown that ZD55-IL-18 exerted a strong cytopathic effect and significant apoptosis in tumor cells. ZD55-IL-18 significantly decreased vascular endothelial growth factor and CD34 expression in the melanoma cells. Treatment of established tumors with ZD55-IL-18 showed much stronger antitumor activity than that induced by ZD55-EGFP (enhanced green fluorescent protein) or Ad-IL-18. These data indicated that oncolytic adenovirus expressing IL-18 could exert potential antitumor activity through inhibition of angiogenesis and offer a novel approach to melanoma therapy.
Purpose: To assess the effect that mangiferin(1), a standard component of WIN-34B, has on chondrogenic differentiation of mesenchymal stem cells(MSCs) from rabbit subchondral bone. Methods: Histological analysis was performed by alcian blue, oil red O, and alizarin red staining to evaluate if progenitor cells from rabbit subchondral bone have chondrogenic, adipogenic, and osteogenic differentiation capacity. Changes in levels of chondrogenic markers type II
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