Does hyperthermia increase adenoviral transgene expression or dissemination in tumors?
Does hyperthermia increase adenoviral transgene expression or dissemination in tumors?
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DOI：
10.1080/02656730902913248
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发表时间：
2009-06
期刊：
影响因子：
--
通讯作者：
Kim JH
中科院分区：
文献类型：
--
作者：
Siddiqui F;Kolozsvary A;Barton KN;Freytag SO;Brown SL;Kim JH
用于癌症基因治疗的病毒载体通常通过直接瘤内给药来递送。我们在体外和体内研究了热疗 (HT) 的作用，试图实现更高的转染率（特别是更大的扩散体积）。使用含有人类碘化钠同向转运蛋白（Ad5-CMV-hNIS）或绿色荧光蛋白（Ad5-CMV-eGFP）作为报告基因的复制缺陷型腺病毒。对于体外研究，用病毒转染人肺癌 A549 细胞，并在存在和不存在 HT 的情况下分别使用伽玛计数器或荧光镜通过放射性高锝酸盐吸收或绿色荧光活性来测定 hNIS 表达。对于体内研究，在 CD1 无胸腺小鼠中肌内建立 A549 肿瘤。当肿瘤直径达到 10-11 毫米时，将腺病毒构建体（1010 个病毒颗粒/肿瘤）注射到瘤内。检查了 HT 的不同时序，并使用锝放射自显影术或 GFP 荧光显微镜评估了病毒传播。在体外研究中，用腺病毒构建体感染的A549细胞在存在或不存在HT的情况下没有表现出基因表达水平的任何差异。在体内，HT 对 A549 肿瘤中基因表达量的影响变化很大，一些小鼠组在 HT 存在下表现出更好的扩散，而另一些小鼠则表现出 HT 使扩散减少。在使用基因表达的两个定量终点的小鼠肿瘤模型中，并没有一致地观察到热疗引起的瘤内腺病毒扩散的改善。
Viral vectors used for cancer gene therapy are usually delivered by direct intratumoral administration. We studied the role of hyperthermia (HT) in vitro and in vivo in an attempt to achieve higher transfection rates (especially, larger volume of spread). Replication-deficient adenoviruses containing either the human sodium-iodide symporter (Ad5-CMV-hNIS) or green fluorescent protein (Ad5-CMV-eGFP) as reporter genes were used. For in vitro studies, human lung cancer A549 cells were transfected with the virus and assayed for hNIS expression by radioactive pertechnetate uptake or green fluorescence activity using a gamma-counter or fluoroscopy respectively in the presence and absence of HT. For in vivo studies, A549 tumors were established intramuscularly in CD1 athymic mice. The adenoviral constructs (1010 viral particles/tumor) were injected intratumorally when the tumors reached 10–11 mm in diameter. Different timing sequences of HT were examined and viral spread was assessed using technetium-autoradiography or GFP-fluorescence microscopy. In the in vitro studies, A549 cells infected with the adenoviral construct did not show any difference in gene expression level in the presence or absence of HT. In vivo, the effect of HT on the volume of gene expression in A549 tumors was highly variable with some groups of mice showing better spread in the presence of HT and others showing reduced spread with HT. Improvements in intratumoral adenoviral spread in response to hyperthermia were not consistently observed in a mouse tumor model using two quantitative endpoints of gene expression.
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影响因子：
4.2
作者：
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