A systematic comparison of the anti-tumoural activity and toxicity of the three Adv-TKs.
A systematic comparison of the anti-tumoural activity and toxicity of the three Adv-TKs.
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三种Adv-TKs抗肿瘤活性和毒性的系统比较
DOI：
10.1371/journal.pone.0094050
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ma D
中科院分区：
文献类型：
--
作者：
Gao Q;Chen C;Ji T;Wu P;Han Z;Fang H;Li F;Liu Y;Hu W;Gong D;Zhang Z;Wang S;Zhou J;Ma D
腺病毒5载体分别被称为第一代、第二代和溶瘤腺病毒，在临床前和临床试验中得到了广泛的研究。然而，迄今为止，很少对这些腺病毒载体的疗效和毒性进行系统评估，这些评估反映了基于腺病毒的癌症基因治疗策略的纵向历史。本研究选择了公认的辅助治疗癌症的Adv-TK，并将其与新合成的编码HSV-TK基因的两种溶瘤腺病毒载体M7和M8的有效性和安全性进行了比较。结果显示，系统给药1×108 pfu M7的抗肿瘤效果与3×1010 pfu Adv-TK相似，而M8的效果更好。此外，与Adv-TK相比，M7和M8降低了转移发生率，并显著延长了人类原位胃癌转移小鼠的生存时间。然而，更令人兴奋的是，与Adv-TK相比，高剂量M7或M8在免疫功能正常的叙利亚仓鼠中获得了相似的毒性和免疫安全性结果。这里的数据全面展示了三种突变体的有效性和安全性，并为未来M7和M8病毒的临床前使用提供了证据。
Adenovirus 5 vectors, known respectively as, the first generation, second generation and oncolytic adenovirus, have been studied extensively in preclinical and clinical trials. However, hitherto few systemic evaluations of the efficacy and toxicity of these adenoviral vectors that have reflected the vertical history of adenovirus based cancer gene therapy strategies have been undertaken. This study has chosen Adv-TK, the well-established adjuvant treatment in cancer, and compared its efficacy and safety with those of the two newly synthesized oncolytic adenovirus vectors encoding the HSV-TK gene, namely M7 and M8. The results obtained showed that systemic administration of 1×108 pfu M7 had an anti-tumour efficacy similar to that of 3×1010 pfu Adv-TK whilst M8 performed even better. Furthermore, compared to Adv-TK, M7 and M8 reduced the incidence of metastases and substantially prolonged the survival time of the mice xenografted with human orthotopic gastric carcinomas with disseminated metastasis. Even more exciting, however, were the similar toxic and immune safety results obtained from the administration of high doses of M7 or M8 in comparison with Adv-TK in immunocompetent and permissive syrian hamster. The data here exhibit a comprehensive display of the efficacy and safety of the three mutants and provide evidence for the future preclinical use of the M7 and M8 viruses.
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影响因子：
4.2
作者：
Habib, NA;Sarraf, CE;Jensen, SL
通讯作者：
Jensen, SL
辅助腺病毒介导的单纯疱疹病毒胸苷激酶给药可改善晚期肝细胞癌患者肝移植的结果
影响因子：
11.5
作者：
Li, Ning;Zhou, Jianfeng;Ma, Ding
通讯作者：
Ma, Ding
影响因子：
8
作者：
Kirn, D
通讯作者：
Kirn, D
影响因子：
6.4
作者：
通讯作者：
--
影响因子：
9.8
作者：
Page, John G.;Tian, Baohong;Alvarez, Ronald D.
通讯作者：
Alvarez, Ronald D.