Optical Imaging of tumor cells in hollow fibers: Evaluation of the antitumor activities of anticancer drugs and target validation
Optical Imaging of tumor cells in hollow fibers: Evaluation of the antitumor activities of anticancer drugs and target validation
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DOI：
10.1593/neo.07421
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发表时间：
2007-08-01
期刊：
影响因子：
4.8
通讯作者：
Williams, David L., Jr.
中科院分区：
文献类型：
--
作者：
Zhang, Guo-Jun;Chen, Tsing-Bau;Williams, David L., Jr.
体内中空纤维试验，其中填充有肿瘤细胞的半渗透性中空纤维被植入动物体内，最初开发用于在更复杂的肿瘤模型中评估之前筛选抗癌化合物。为了提高抗癌药物的筛选和评价，我们将光学成像技术应用于该测定。为了证明中空纤维内的肿瘤细胞可以与宿主小鼠交流，我们使用了体内荧光成像和体外CD 31免疫染色，以显示皮下植入后2周，在充满细胞的中空纤维周围发生血管生成。生物发光成像已被用于跟踪植入中空纤维内表达端粒酶的肿瘤细胞的数量;发现多西他赛和伊立替康可显著抑制这些细胞的增殖。我们还使用中空纤维的生物发光成像来监测体内核因子κ B（NF κ B B）通路;在基因工程改造以表达由NF κ B反应元件控制的荧光素酶的肿瘤细胞系中评价脂多糖和肿瘤坏死因子-α对NF κ B B的激活。这些结果表明，含有报告肿瘤细胞的中空纤维的光学成像可用于快速准确地评价抗癌药物的抗肿瘤活性和测量分子途径。
The in vivo hollow fiber assay, in which semipermeable hollow fibers filled with tumor cells, are implanted into animals, was originally developed to screen for anticancer compounds before assessment in more complex tumor models. To enhance screening and evaluation of anticancer drugs, we have applied optical imaging technology to this assay. To demonstrate that tumor cells inside hollow fibers can communicate with the host mice, we have used fluorescence imaging in vivo and CD31 immunostaining ex vivo to show that angiogenesis occurs around cell-filled hollowfibers by 2 weeks after subcutaneous implantation. Bioluminescence imaging has been used to follow the number of luciferase-expressing tumor cells within implanted hollow fibers; proliferation of those cells was found to be significantly inhibited by docetaxel and irinotecan. We also used bioluminescence imaging of hollow fibers to monitor the nuclear factor kappa B (NF kappa B) pathway in vivo; NF kappa B activation by lipopolysaccharide and tumor necrosis factor-alpha was evaluated in tumor cell lines genetically engineered to express luciferase controlled by an NF kappa B-responsive element. These results demonstrate that optical imaging of hollow fibers containing reporter tumor cells can be used for the rapid and accurate evaluation of antitumor activities of anticancer drugs and for measurement of molecular pathways.