Convection-enhanced delivery improves distribution and efficacy of tumor-selective retroviral replicating vectors in a rodent brain tumor model.
Convection-enhanced delivery improves distribution and efficacy of tumor-selective retroviral replicating vectors in a rodent brain tumor model.
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DOI：
10.1038/cgt.2013.25
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发表时间：
2013-06
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
--
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在本研究中，我们比较了CED和单纯注射表达酵母胞嘧啶脱氨酶(CD)的肿瘤选择性逆转录病毒复制载体(RRV)的治疗效果，然后全身注射前药5-氟胞嘧啶(5-FC)。与对照组相比，RRV-CD和5-FC联合治疗可显著提高U87 MG鼠脑胶质瘤模型的存活率(p<；0.01)。有趣的是，与瘤内注射RRV-CD然后全身注射5-FC相比，RRV-CD+5-FC CED进一步提高了该动物模型的存活率(p<；0.05)。未经治疗的肿瘤中Ki-67的表达水平高于经治疗的肿瘤。未经治疗的肿瘤也比经治疗的要大得多。注射CED后RRV分布良好，注射后RRV仅有部分分布。此外，在研究终点，治疗大鼠的肿瘤中也发现了RRV-CD和胞嘧啶脱氨酶。这些结果表明，RRV载体可以在恶性人脑胶质瘤中高效地转导和稳定地增殖，从而在初始给药后达到显著的原位扩增效果。我们的结论是，通过CED将RRV输送到胶质瘤中比单纯注射提供了更广泛的载体分布，这与更好的治疗结果相关。
In the present study, we compared the therapeutic effect of tumor-selective retroviral replicating vectors (RRV) expressing the yeast cytosine deaminase (CD) delivered by CED or simple injection, followed by systemic administration of the pro-drug, 5-fluorocytosine (5-FC). Treatment with RRV-CD and systemic 5-FC significantly increased survival in rodent U87MG glioma model in comparison to controls (p<0.01). Interestingly, CED of RRV-CD followed by 5-FC further enhanced survival in this animal model in comparison to intra-tumoral injection of RRV-CD followed by systemic 5-FC (p<0.05). High expression levels of Ki-67 were found in untreated tumors compared to treated. Untreated tumors were also much larger than treated. CED resulted in excellent distribution of RRV while only partial distribution of RRV was obtained after injection. Furthermore, RRV-CD and cytosine deaminase were also found in tumors from treated rats at study end-points. These results demonstrated that RRV vectors may efficiently transduce and stably propagate in malignant human glioma, thereby achieving a significant in-situ amplification effect after initial administration. We conclude that delivery of RRV into the glioma by CED provides much wider vector distribution than simple, injection, and this correlated with better therapeutic outcomes.
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影响因子：
5.3
作者：
Saito, R;Krauze, MT;Bankiewicz, KS
通讯作者：
Bankiewicz, KS
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Heywood, P
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Saito, R;Bringas, JR;Bankiewicz, KS
通讯作者：
Bankiewicz, KS