Characterisation of systemic dissemination of nonreplicating adenoviral vectors from tumours in local gene delivery.
Characterisation of systemic dissemination of nonreplicating adenoviral vectors from tumours in local gene delivery.
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来自肿瘤的非复制腺病毒载体在局部基因传递中的系统传播的特征。
DOI：
10.1038/sj.bjc.6602494
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发表时间：
2005-04-25
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
全身性病毒传播是实体瘤局部基因传递过程中的一个潜在问题。然而，输注开始后 24 小时内的传播动力学和途径尚未得到很好的表征。为此，我们将荧光素酶或增强型绿色荧光蛋白的腺病毒载体注入三种不同的小鼠肿瘤模型中。在输注期间和/或之后，我们测定了肿瘤、血液和肝脏中腺病毒的量，并检查了肝脏、肺、血液和肿瘤中的转基因表达。此外，我们静脉注射表达荧光素酶的肿瘤细胞，并检查这些细胞在体内的生物分布。我们在输注后24小时观察到肝脏和肿瘤中的转基因表达，但无法检测到血液和肺部中的转基因表达。血浆中病毒载体的峰值浓度出现在瘤内输注期间。输注后10分钟，血液中残留的病毒载体很少，80%的小鼠肝脏和肿瘤之间的腺病毒拷贝数比率>2，40%的小鼠>10。大多数静脉注射的肿瘤细胞在最初的 24 小时内积聚在肺部。综上所述，这些数据表明，全身性病毒传播主要发生在肿瘤内输注开始后的前10分钟内，并且传播是由于输注引起的病毒载体对流转运至渗漏的肿瘤微血管中所致。
Systemic virus dissemination is a potential problem during local gene delivery in solid tumours. However, the kinetics and pathways of the dissemination have not been well characterised during the first 24 h after the infusion is started. To this end, we infused adenoviral vectors for luciferase or enhanced green fluorescence protein into three different tumour models in mice. During and/or after the infusion, we determined the amount of adenoviruses in the tumour, blood, and liver, and examined the transgene expression in the liver, lung, blood, and tumour. In addition, we intravenously injected tumour cells expressing luciferase and examined the biodistribution of these cells in the body. We observed transgene expression in the liver and tumour at 24 h after the infusion, but could not detect transgene expression in the blood and lung. The peak concentration of viral vectors in the plasma occurred during the intratumoral infusion. At 10 min after the infusion, few viral vectors remained in the blood and the ratio of copy numbers of adenoviruses between liver and tumour was >2 in 80% and ⩾10 in 40% of the mice. Most tumour cells injected intravenously accumulated in the lung within the first 24 h. Taken together, these data indicated that systemic virus dissemination occurred mainly during the first 10 min after the intratumoral infusion was started, and that the dissemination was due to infusion-induced convective transport of viral vectors into leaky tumour microvessels.
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影响因子：
46.9
作者：
Douglas, JT;Rogers, BE;Curiel, DT
通讯作者：
Curiel, DT
影响因子：
12.4
作者：
Hackett, NR;El Sawy, T;Crystal, RG
通讯作者：
Crystal, RG
影响因子：
4.2
作者：
Jaggar, RT;Chan, HY;Bicknell, R
通讯作者：
Bicknell, R
影响因子：
3.8
作者：
Alemany, R;Suzuki, K;Curiel, DT
通讯作者：
Curiel, DT
影响因子：
5.1
作者：
Bramson, JL;Hitt, M;Graham, FL
通讯作者：
Graham, FL