The new classification announced by the World Health Organization in 2016 recognized five molecular subtypes of diffuse gliomas based on isocitrate dehydrogenase (IDH) and 1p/19q genotypes in addition to histologic phenotypes. We aim to determine whether clinical MRI can stratify these molecular subtypes to benefit the diagnosis and monitoring of gliomas. The data from 456 subjects with gliomas were obtained from The Cancer Imaging Archive. Overall, 214 subjects, including 106 cases of glioblastomas and 108 cases of lower grade gliomas with preoperative MRI, survival data, histology, IDH, and 1p/19q status were included. We proposed a three-level machine-learning model based on multimodal MR radiomics to classify glioma subtypes. An independent dataset with 70 glioma subjects was further collected to verify the model performance. The IDH and 1p/19q status of gliomas can be classified by radiomics and machine-learning approaches, with areas under ROC curves between 0.922 and 0.975 and accuracies between 87.7% and 96.1% estimated on the training dataset. The test on the validation dataset showed a comparable model performance with that on the training dataset, suggesting the efficacy of the trained classifiers. The classification of 5 molecular subtypes solely based on the MR phenotypes achieved an 81.8% accuracy, and a higher accuracy of 89.2% could be achieved if the histology diagnosis is available. The MR radiomics-based method provides a reliable alternative to determine the histology and molecular subtypes of gliomas. .
We designed and synthesized novel theranostic nanoparticles that showed the considerable potential for clinical use in targeted therapy, and non-invasive real-time monitoring of tumors by MRI. Our nanoparticles were ultra-small with superparamagnetic iron oxide cores, conjugated to erlotinib (FeDC-E NPs). Such smart targeted nanoparticles have the preference to release the drug intracellularly rather than into the bloodstream, and specifically recognize and kill cancer cells that overexpress EGFR while being non-toxic to EGFR-negative cells. MRI, transmission electron microscopy and Prussian blue staining results indicated that cellular uptake and intracellular accumulation of FeDC-E NPs in the EGFR overexpressing cells was significantly higher than those of the non-erlotinib-conjugated nanoparticles. FeDC-E NPs inhibited the EGFR–ERK–NF-κB signaling pathways, and subsequently suppressed the migration and invasion capabilities of the highly invasive and migrative CL1-5-F4 cancer cells. In vivo tumor xenograft experiments using BALB/c nude mice showed that FeDC-E NPs could effectively inhibit the growth of tumors. T2-weighted MRI images of the mice showed significant decrease in the normalized signal within the tumor post-treatment with FeDC-E NPs compared to the non-targeted control iron oxide nanoparticles. This is the first study to use erlotinib as a small-molecule targeting agent for nanoparticles.
Mesenchymal stem cells (MSCs) that display homing and infiltration properties towards tumor cells are a promising cellular targeting vector for brain tumor therapy but are limited to local-regional delivery in current preclinical models. Here, we investigated whether placenta-derived MSCs (P-MSCs) are a superior cellular vector for systemic targeting of glioblastoma stem-like cells (GSCs), with an imaging modality to real-time monitor the trafficking P-MSCs to glioblastoma sites. Results demonstrated that P-MSCs had greater migratory activity towards GSCs and across blood-brain barrier compared with bone marrow-derived MSCs, and this activity was enhanced by hypoxia precondition. Chemokine ligand 5 was identified as a chemoattractant responsible for the glioblastoma tropism of P-MSCs. Polyethylene glycol-coated superparamagnetic iron oxide (PEG-SPIO) was synthesized for cellular labelling and imaging P-MSCs, displaying high cellular uptake and no cytotoxic effect on P-MSCs cell proliferation or stemness property. The homing effects of intravenously administered PEG-SPIO-labelled P-MSCs towards intracerebral GSCs were able to be detected in mice models through T2-weighted magnetic resonance imaging (MRI). This study suggests the possibility of innovative systemic P-MSC-based cell therapy for aggressive GSCs, developing a state-of-the-art theranostic technique for real-time tracking of therapeutic P-MSCs tumor infiltration through cellular MRI.
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