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Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy

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2012

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Nature Research
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Shao, Huilin, Jaehoon Chung, Leonora Balaj, Alain Charest, Darell D Bigner, Bob S Carter, Fred H Hochberg, Xandra O Breakefield, Ralph Weissleder, and Hakho Lee. 2012. “Protein Typing of Circulating Microvesicles Allows Real-Time Monitoring of Glioblastoma Therapy.” Nature Medicine 18 (12): 1835–40. https://doi.org/10.1038/nm.2994.

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Abstract

Glioblastomas shed large quantities of small, membrane-bound microvesicles into the circulation. Although these hold promise as potential biomarkers of therapeutic response, their identification and quantification remain challenging. Here, we describe a highly sensitive and rapid analytical technique for profiling circulating microvesicles directly from blood samples of patients with glioblastoma. Microvesicles, introduced onto a dedicated microfluidic chip, are labeled with target-specific magnetic nanoparticles and detected by a miniaturized nuclear magnetic resonance system. Compared with current methods, this integrated system has a much higher detection sensitivity and can differentiate glioblastoma multiforme (GBM) microvesicles from nontumor host cell-derived microvesicles. We also show that circulating GBM microvesicles can be used to analyze primary tumor mutations and as a predictive metric of treatment-induced changes. This platform could provide both an early indicator of drug efficacy and a potential molecular stratifier for human clinical trials.

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