Tumor characterization by ultrasound-release of multiple protein and microRNA biomarkers, preclinical and clinical evidence.
Tumor characterization by ultrasound-release of multiple protein and microRNA biomarkers, preclinical and clinical evidence.
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DOI：
10.1371/journal.pone.0194268
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Gambhir SS
中科院分区：
文献类型：
--
作者：
D'Souza AL;Chevillet JR;Ghanouni P;Yan X;Tewari M;Gambhir SS
我们之前已经证明，低频超声波可以将细胞中的生物标志物释放到小鼠循环中，从而能够放大和定位所释放的生物标志物，从而可以用作基于血液的方法来早期检测癌症并监测治疗。在这项研究中，我们进一步证明，由于培养物、小鼠和患者的细胞中释放了多种蛋白质和核酸生物标志物，该技术可用于表征肿瘤和/或鉴定来源不明的细胞团。我们以 1 MHz 的低频对培养中的结肠 (LS174T) 和前列腺 (LNCaP) 癌细胞系进行超声处理，结果表明，在不同强度和时间的处理下，多种蛋白质和 microRNA (miRNA) 丰度发生了数倍的变化。这种释放取决于两种细胞系超声处理的持续时间和强度。在皮下 LS174T 细胞系异种移植物（针对蛋白质和核酸）的活体小鼠和实验性 LS174T 肝肿瘤模型（仅针对蛋白质）中，经肿瘤超声处理后，还观察到生物标志物释放显着增加。最后，我们展示了使用 MR 引导的高强度聚焦超声在接受子宫肌瘤消融的患者中释放多种生物标志物的方法。 21 个测试样本经超声处理后，血浆中的两种蛋白质生物标志物显着增加。这证明超声放大方法与生物标志物多重技术一起在软组织肿瘤模型中发挥作用，可以为偶发病变、癌症和其他疾病的识别、表征和定位提供一种有效的非侵入性方法。生物标记物的治疗前定量可实现定量比较的个体化。该方法中正常标志物水平的个体化允许生物标志物增加对每个患者、所研究的肿瘤或器官的特异性。
We have previously shown that low frequency ultrasound can release biomarkers from cells into the murine circulation enabling an amplification and localization of the released biomarker that could be used as a blood-based method to detect cancer earlier and monitor therapy. In this study, we further demonstrate that this technique could be used for characterization of tumors and/or identification of cellular masses of unknown origin due to the release of multiple protein and nucleic acid biomarkers in cells in culture, mice and patients. We sonicated colon (LS174T) and prostate (LNCaP) cancer cell lines in culture at a low frequency of 1 MHz and show that there were several-fold changes in multiple protein and microRNA (miRNA) abundance with treatment at various intensities and time. This release was dependent on the duration and intensity of the sonication for both cell lines. Significant increased release in biomarkers was also observed following tumor sonication in living mice bearing subcutaneous LS174T cell line xenografts (for proteins and nucleic acids) and in an experimental LS174T liver tumor model (for proteins only). Finally, we demonstrated this methodology of multiple biomarker release in patients undergoing ablation of uterine fibroids using MR guided high intensity focused ultrasound. Two protein biomarkers significantly increased in the plasma after the ultrasound treatment in 21 samples tested. This proof that ultrasound-amplification method works in soft tissue tumor models together with biomarker multiplexing, could allow for an effective non-invasive method for identification, characterization and localization of incidental lesions, cancer and other disease. Pre-treatment quantification of the biomarkers, allows for individualization of quantitative comparisons. This individualization of normal marker levels in this method allows for specificity of the biomarker-increase to each patient, tumor or organ being studied.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.0903437106
发表时间：
2009-10-06
影响因子：
11.1
作者：
D'Souza, Aloma L.;Tseng, Jeffrey R.;Glazer, Gary M.
通讯作者：
Glazer, Gary M.
DOI：
10.1109/tuffc.2010.1586
发表时间：
2010-07-01
影响因子：
3.6
作者：
Kaddur, Kadija;Lebegue, Loic;Bouakaz, Ayache
通讯作者：
Bouakaz, Ayache
血液和其他体液中基于 microRNA 的生物标志物的问题和前景
DOI：
10.3390/molecules19056080
发表时间：
2014-05-14
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Chevillet JR;Lee I;Briggs HA;He Y;Wang K
通讯作者：
Wang K
DOI：
10.1517/14796694.1.1.37
发表时间：
2005-02-01
期刊：
Future oncology (London, England)
影响因子：
--
作者：
Chatterjee, Sabarni K;Zetter, Bruce R
通讯作者：
Zetter, Bruce R