Near infrared imaging of EGFR of oral squamous cell carcinoma in mice administered arsenic trioxide.
Near infrared imaging of EGFR of oral squamous cell carcinoma in mice administered arsenic trioxide.
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给予三氧化二砷的小鼠口腔鳞状细胞癌 EGFR 的近红外成像
DOI：
10.1371/journal.pone.0046255
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zhang B
中科院分区：
文献类型：
--
作者：
Zhang L;Wang K;Zhao F;Hu W;Chen J;Lanza GM;Shen B;Zhang B
研究了近红外成像（NIR）检测表皮生长因子受体（EGFR）表达作为口腔鳞状细胞癌（OSCC）对三氧化二砷治疗反应的敏感生物标志物的有效性。材料与方法体外培养的A431口腔鳞癌细胞分别暴露于0 μM、0.5 μM、2.5 μM和5 μM的As 2 O3溶液中0、24、48和72 h。共聚焦显微镜和流式细胞术证实了EGFR的表达，并证明了灵敏度剂量相关的信号下降与As 2 O3治疗。接下来，从第0天到第10天，植入咽部A431细胞的小鼠每48小时接受0.0、0.5、2.5或5 mg/kg/天的As 2 O3 i. p.（n = 6/组）。 在基线和第4、8和12天注射静脉内NIR探针EGF-Cy 5.5用于动态NIR成像。每周三次测量肿瘤体积和体重。结果在体外培养条件下，A431 EGFR在正常对照组中的表达明显增加，随着As 2 O3剂量的增加和作用时间的延长，A431 EGFR的表达逐渐降低（p<0.05）。从第4天到第12天，As 2 O3处理组与对照组相比，体内EGFR NIR肿瘤信号强度降低（p<0.05），与剂量增加一致。肿瘤体积以剂量相关方式减小，而体重不受影响。切除的肿瘤的免疫组织化学染色证实，EGFR的表达减少As 2 O3治疗的剂量响应模式。结论本研究首次证实了EGFR的近红外分子成像可以在体内对OSCC进行检测，并且该生物标志物可有效用于纵向评估OSCC对As 2 O3治疗的反应。
Background The effectiveness of near-infrared imaging (NIR) interrogation of epidermal growth factor receptor (EGFR) expression as a sensitive biomarker of oral squamous cell carcinoma (OSCC) response to arsenic trioxide therapy was studied in mice. Material and Methods A431 OSCC in vitro were exposed to 0 µM, 0.5 µM, 2.5 µM, or 5 µM of As2O3 for 0 h, 24 h, 48 h and 72 h. Confocal microscopy and flow cytometry confirmed EGFR expression and demonstrated a sensitivity dose-related signal decline with As2O3 treatment. Next, mice with pharynx-implanted A431 cells received As2O3 i.p. every 48 h at 0.0, 0.5, 2.5, or 5 mg/kg/day (n = 6/group) from day 0 to 10. An intravenous NIR probe, EGF-Cy5.5, was injected at baseline and on days 4, 8, and 12 for dynamic NIR imaging. Tumor volume and body weights were measured three times weekly. Results In vitro, A431 EGFR expression was well appreciated in the controls and decreased (p<0.05) with increasing As2O3 dose and treatment duration. In vivo EGFR NIR tumor signal intensity decreased (p<0.05) in As2O3 treated groups versus controls from days 4 to 12, consistent with increasing dosage. Tumor volume diminished in a dose-related manner while body weight was unaffected. Immunohistochemical staining of excised tumors confirmed that EGFR expression was reduced by As2O3 treatment in a dose responsive pattern. Conclusion This study demonstrates for the first time that OSCC can be interrogated in vivo by NIR molecular imaging of the EGFR and that this biomarker is effective for the longitudinal assessment of OSCC response to As2O3 treatment.
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1002/hed.20782
发表时间：
2008-06-01
影响因子：
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作者：
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