Antitumor effects of bladder cancer-specific adenovirus carrying E1A-androgen receptor in bladder cancer.
Antitumor effects of bladder cancer-specific adenovirus carrying E1A-androgen receptor in bladder cancer.
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膀胱癌的高复发率和低生存率需要探索新的治疗策略。通过腺病毒进行的基因治疗在肿瘤治疗中显示出良好的潜力。在UPII启动子和前列腺干细胞抗原增强子（PSCAE）的控制下，构建了携带e1a -雄激素受体（AR）的膀胱癌特异性腺病毒，命名为Ad/PSCAE/UPII/E1A-AR，并对其体外和体内抗肿瘤作用进行了研究。我们证明，与对照腺病毒Ad/PSCAE/UPII/Luc相比，Ad/PSCAE/UPII/E1A-AR在膀胱肿瘤细胞株（5637、BIU87、EJ和T24）中可以选择性地复制。然而，对正常人膀胱细胞系SV-HUC-1和肝癌细胞系SMMC7721没有细胞毒性的证据。AR激动剂R1881可增强Ad/PSCAE/UPII/E1A-AR对膀胱癌细胞的溶瘤作用。此外，我们还证明，裸鼠皮下人EJ肿瘤瘤内注射Ad/PSCAE/UPII/E1A-AR可显著抑制肿瘤的生长，显著延长瘤鼠的生存期；另一方面，经盐水治疗的肿瘤继续快速生长。我们的研究表明，Ad/PSCAE/UPII/E1A-AR在体外和体内均能有效治疗膀胱癌。此外，我们的研究结果为膀胱癌的治疗提供了一种有希望的治疗方式。
The high frequency of recurrence and poor survival rate of bladder cancer demand exploration of novel strategies. Gene therapy via adenovirus has shown promising potential for the treatment of tumors. We constructed a bladder cancer-specific adenovirus carrying E1A-androgen receptor (AR) under the control of UPII promoter and prostate stem cell antigen enhancer (PSCAE), designated as Ad/PSCAE/UPII/E1A-AR, and investigated its antitumor effects in vitro and in vivo. We demonstrated that Ad/PSCAE/UPII/E1A-AR could be selectively replicated in bladder tumor cell lines (5637, BIU87, EJ and T24) when compared with control adenovirus Ad/PSCAE/UPII/Luc. However, there was no evidence of cytotoxicity for normal human bladder cell line SV-HUC-1 and hepatoma cell line SMMC7721. AR agonist R1881 could strengthen the oncolytic effect of Ad/PSCAE/UPII/E1A-AR in bladder cancer cells. In addition, we demonstrated that intratumoral injection of Ad/PSCAE/UPII/E1A-AR into established subcutaneous human EJ tumors in nude mice could significantly regress the growth of tumor and markedly prolong survival for tumor-bearing mice; on the other hand, saline-treated tumors continued to grow rapidly. Our studies indicate that Ad/PSCAE/UPII/E1A-AR could effectively treat bladder cancer in vitro and in vivo. Furthermore, our findings provide a promising therapeutic modality for the treatment of bladder cancer.
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影响因子：
2.6
作者：
Liu C;Zhang Y;Liu MM;Zhou H;Chowdhury W;Lupold SE;Deweese TL;Rodriguez R
通讯作者：
Rodriguez R
影响因子：
2.1
作者：
Boorjian, S;Ugras, S;Scherr, DS
通讯作者：
Scherr, DS
影响因子：
12.4
作者：
Houti, Naseruddin;Chowdhury, Wasim;Rodriguez, Ronald
通讯作者：
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影响因子：
50.3
作者：
Andersen, Raymond J.;Mawji, Nasrin R.;Sadar, Marianne D.
通讯作者：
Sadar, Marianne D.
尿路上皮特异性重组腺病毒的构建及其对膀胱癌细胞的抑制作用
影响因子：
1.6
作者：
He, Xiang-Dong;Wang, Zhi-Ping;Rodriguez, Ronald
通讯作者：
Rodriguez, Ronald