A strategy for blood biomarker amplification and localization using ultrasound
A strategy for blood biomarker amplification and localization using ultrasound
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DOI：
10.1073/pnas.0903437106
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发表时间：
2009-10-06
影响因子：
11.1
通讯作者：
Glazer, Gary M.
中科院分区：
文献类型：
--
作者：
D'Souza, Aloma L.;Tseng, Jeffrey R.;Glazer, Gary M.
血液生物标志物在包括癌症在内的各种疾病的早期检测和管理中具有重要的潜在应用。大多数生物标记物在血液中的浓度很低，很难从噪音中区分出来。此外，生物标志物的血液测量不能提供有关其产生位置的信息。我们假设了一种先前描述的策略，可以增加血液中生物标志物的浓度，并使用直接应用于肿瘤细胞的超声能量来定位生物标志物信号的来源。我们使用人结肠癌细胞系LS174T在细胞培养实验和小鼠肿瘤异种移植模型中验证了我们的假设，同时测量了超声从肿瘤细胞中释放生物标志物癌胚抗原（CEA）前后的生物标志物。结果表明，低频超声作用于肿瘤细胞后，肿瘤生物标志物显著释放，可在血液中检测到。此外，我们确定这种释放对超声直接应用于肿瘤是特异性的，从而实现了生物标志物生产的定位方法。这项工作表明，有可能使用超声波来放大和定位肿瘤小鼠血液中CEA水平的来源，并将允许以前未描述的方法来确定疾病的存在和定位，使用相对简单和非侵入性的策略。
Blood biomarkers have significant potential applications in early detection and management of various diseases, including cancer. Most biomarkers are present in low concentrations in blood and are difficult to discriminate from noise. Furthermore, blood measurements of a biomarker do not provide information about the location(s) where it is produced. We hypothesize a previously undescribed strategy to increase the concentration of biomarkers in blood as well as localize the source of biomarker signal using ultrasound energy directly applied to tumor cells. We test and validate our hypothesis in cell culture experiments and mouse tumor xenograft models using the human colon cancer cell line LS174T, while measuring the biomarker carcinoembryonic antigen (CEA) before and after the use of ultrasound to liberate the biomarker from the tumor cells. The results demonstrate that the application of low-frequency ultrasound to tumor cells causes a significant release of tumor biomarker, which can be measured in the blood. Furthermore, we establish that this release is specific to the direct application of the ultrasound to the tumor, enabling a method for localization of biomarker production. This work shows that it is possible to use ultrasound to amplify and localize the source of CEA levels in blood of tumor-bearing mice and will allow for a previously undescribed way to determine the presence and localization of disease more accurately using a relatively simple and noninvasive strategy.