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


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.

SUBMITTER: Shao H 

PROVIDER: S-EPMC3518564 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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

Shao Huilin H   Chung Jaehoon J   Balaj Leonora L   Charest Alain A   Bigner Darell D DD   Carter Bob S BS   Hochberg Fred H FH   Breakefield Xandra O XO   Weissleder Ralph R   Lee Hakho H  

Nature medicine 20121111 12


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 magn  ...[more]

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