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首页> 外文期刊>Molecular urology >Gene therapy for bladder cancer using adenoviral vector.
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Gene therapy for bladder cancer using adenoviral vector.

机译：使用腺病毒载体进行膀胱癌的基因治疗。

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BACKGROUND AND PURPOSE: Bladder cancer is common. Current treatment for patients with superficial bladder cancer involves transurethral resection followed by adjuvant bacillus Calmette-Guerin (BCG) administration. Adjuvant BCG has been reported to be effective in 38% to 68% of patients; however, more than 30% of patients do not respond. Because p53 mutations are common among superficial bladder cancers, we tested the feasibility of using p53 as a gene therapy agent for targeting superficial tumors, which are easily accessible using an intravesical approach. MATERIALS AND METHODS: Wild-type p53 was transduced into various human and murine bladder cancer cell lines (HTB9, KU-1, and MBT-2) using a recombinant adenoviral vector (Ad5CMV-p53) in vitro. Also, subcutaneous tumors were established and then treated with intratumoral injection of Ad5CMV-p53 or control viruses. RESULTS: In vitro assays revealed significant growth suppression of target cells by Ad5CMV-p53 in comparison with those receiving the control Ad5-CMV-PA vector or untreated control cells. In vivo studies using subcutaneous bladder tumor models established in syngeneic mice demonstrated that the rate of tumor growth and volume was reduced to a greater extent by 14 days of intratumoral injection of Ad5CMV-p53 rather than Ad5CMV-PA. Furthermore, the survival of host animals bearing tumors that were infected with Ad5CMV-p53 was significantly longer than that of the control group treated with Ad5CMV-PA (P < 0.01). CONCLUSION: Our data suggest that Ad5CMV-p53 is effective in suppressing bladder cancer growth and improving host survival.
机译：背景与目的：膀胱癌很常见。当前对浅表性膀胱癌患者的治疗包括经尿道切除，然后辅以卡介苗-卡林芽孢杆菌（BCG）。据报道，辅助卡介苗对38％至68％的患者有效;但是，超过30％的患者没有反应。由于p53突变在浅表性膀胱癌中很常见，因此我们测试了将p53用作靶向浅表性肿瘤的基因治疗剂的可行性，这些方法可通过膀胱内途径轻松获得。材料与方法：使用重组腺病毒载体（Ad5CMV-p53）在体外将野生型p53转导至各种人和鼠膀胱癌细胞系（HTB9，KU-1和MBT-2）。同样，建立皮下肿瘤，然后通过瘤内注射Ad5CMV-p53或对照病毒进行治疗。结果：体外试验显示，与接受对照Ad5-CMV-PA载体或未经处理的对照细胞相比，Ad5CMV-p53可以显着抑制靶细胞的生长。使用在同系小鼠中建立的皮下膀胱肿瘤模型进行的体内研究表明，瘤内注射Ad5CMV-p53而非Ad5CMV-PA 14天后，肿瘤的生长速率和体积更大程度地降低了。此外，带有Ad5CMV-p53感染的带有肿瘤的宿主动物的存活期明显长于用Ad5CMV-PA治疗的对照组的存活期（P <0.01）。结论：我们的数据表明，Ad5CMV-p53可有效抑制膀胱癌的生长并改善宿主存活率。

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