title: 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.
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Huilin
authors.initials: H
authors.lastname: Shao
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Chung
authors.forename: Leonora
authors.initials: L
authors.lastname: Balaj
authors.forename: Alain
authors.initials: A
authors.lastname: Charest
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
authors.forename: Bob S
authors.initials: BS
authors.lastname: Carter
authors.forename: Fred H
authors.initials: FH
authors.lastname: Hochberg
authors.forename: Xandra O
authors.initials: XO
authors.lastname: Breakefield
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Hakho
authors.initials: H
authors.lastname: Lee
mesh_terms: D014408:Biomarkers, Tumor / Q000737:chemistry*; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles; D046210:Microfluidic Analytical Techniques; D022161:Transport Vesicles / Q000737:chemistry*
chemical_list: D014408:Biomarkers, Tumor; D058185:Magnetite Nanoparticles