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学科主题: 临床医学
题名:
Antitumor effects of oncolytic adenovirus armed with PSA-IZ-CD40L fusion gene against prostate cancer
作者: Yang, Y-F1; Xue, S-Y1; Lu, Z-Z2; Xiao, F-J1; Yin, Y.3; Zhang, Q-W1; Wu, C-T1; Wang, H.1; Wang, L-S1
刊名: GENE THERAPY
发表日期: 2014-08-01
DOI: 10.1038/gt.2014.46
卷: 21, 期:8, 页:723-731
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental
研究领域[WOS]: Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
关键词[WOS]: DENDRITIC CELLS ; IMMUNE-SYSTEM ; IMMUNOTHERAPY ; THERAPY ; APOPTOSIS ; PSA
英文摘要:

Advanced prostate cancer (PC) still remains incurable. Novel immunogene therapy shows promise as treatment strategy that can target both localized and metastasized PC. In this study, we have developed a PC-specific oncolytic adenovirus (Ad-PL-PPT-E1A) armed with fusion gene of prostate-specific antigen and CD40 ligand, and aimed to evaluate its therapeutic effect in vitro and in vivo. After they were rescued in human embryonic kidney 293 cells, we confirmed that Ad-PL-PPT-ElA could mediate the expression of El A efficiently and produce abundant progeny viruses in PC cells in vitro. Our data showed that Ad-PL-PPT-ElA induced apoptosis and resulted in specific oncolytic toxicity in PC cells, which was detected by Annexin-V staining and crystal violet, respectively. After stimulation with lysates, immune phenotypes and cytokines expression of human dendritic cells was detected by flow cytometry and real-time polymerase chain reaction, respectively. And, the results showed that the lysate of Ad-PL-PPT-ElA infected LNCaP cells upregulated the expression of CD80, CD83, CD86 and mRNA level of interleukin-6 (IL-6), IL-12,1L-23 and tumor necrosis factor-a significantly. In established PC3M cell-xenografted mouse models, Ad-PL-PPT-ElA treatment improved the survival and suppressed the tumor growth obviously. In conclusion, Ad-PL-PPT-ElA exhibited enhanced antitumor activity is a promising approach for gene therapy of advanced PC.

语种: 英语
所属项目编号: 2012AA020807 ; 2014AA020515 ; 2012CB518205 ; 30901379
项目资助者: National High Technology Research and Development Program of China (863 Program) ; National Basic Research and Development of China (973 Program) ; National Natural Science Foundation of China
WOS记录号: WOS:000340351900002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52759
Appears in Collections:北京大学第一临床医学院_血液内科_期刊论文

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作者单位: 1.Beijing Inst Radiat Med, Dept Expt Hematol, Beijing 100850, Peoples R China
2.Chinese Ctr Dis Control & Prevent, Inst Viral Dis Control & Prevent, Beijing, Peoples R China
3.Peking Univ, Hosp 1, Dept Hematol, Beijing 100871, Peoples R China

Recommended Citation:
Yang, Y-F,Xue, S-Y,Lu, Z-Z,et al. Antitumor effects of oncolytic adenovirus armed with PSA-IZ-CD40L fusion gene against prostate cancer[J]. GENE THERAPY,2014,21(8):723-731.
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