期刊
MOLECULAR THERAPY
卷 10, 期 3, 页码 525-532出版社
CELL PRESS
DOI: 10.1016/j.ymthe.2004.05.027
关键词
enhanced adenoviral gene transfer; gene therapy; orthotopic bladder cancer model; superficial human bladder cancer; overcoming interferon protein resistance
资金
- NCI NIH HHS [CA16672, P50 CA091846] Funding Source: Medline
We have produced prolonged, high local concentrations of interferon in vivo by intravesical instillation of adenoviruses encoding interferon-alpha, (Ad-IFNalpha) together with the gene transferenhancing agent Syn3. We found sustained interferon protein levels for days, both in normal mouse urotheliurn and in human bladder cancer cells growing as superficial bladder tumors in nude mice using an orthotopic bladder model developed by us. Tumor burden in the bladder was determined utilizing cancer cells containing the green fluorescent protein. Marked tumor regression was observed following two 1-h exposures of Ad-IFNalpha/Syn3 and little or no cytotoxicity was detected in normal cells. Similar intravesical instillation of clinically relevant concentrations of IFN protein alone or Ad-IFNalpha without Syn3 was ineffective. Surprisingly, in vitro, Ad-IFNalpha also caused caspase-dependent death of bladder cancer cell lines that were resistant to high concentrations of IFNalpha protein, including the cell line used in vivo. These findings demonstrate that Ad-IFNalpha can overcome resistance to IFNalpha protein both in vitro and in vivo and support evaluation of intravesical Ad-IFNalpha/Syn3 for the treatment of superficial bladder cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据