ABSTRACT
Brain tumor-initiating cells (BTICs) are self-renewing multipotent cells critical for tumor maintenance and growth. Using single-cell microfluidic profiling, we identified multiple subpopulations of BTICs coexisting in human glioblastoma, characterized by distinct surface marker expression and single-cell molecular profiles relating to divergent bulk tissue molecular subtypes. These data suggest BTIC subpopulation heterogeneity as an underlying source of intra-tumoral bulk tissue molecular heterogeneity, and will support future studies into BTIC subpopulation-specific therapies. Stem Cells 2016;34:1702-1707.
Subject(s)
Brain Neoplasms/pathology , Glioblastoma/pathology , Neoplastic Stem Cells/pathology , Biomarkers, Tumor/metabolism , Brain Neoplasms/genetics , Cell Line, Tumor , Glioblastoma/genetics , Humans , Phenotype , Single-Cell Analysis , Transcription, GeneticABSTRACT
Telehealth and telemedicine services can be a solution for improving accessibility and reducing the cost of health care. Challenges remain in designing, implementing, and sustainably scaling telehealth solutions. Research is lacking on the health impacts and cost-effectiveness of telehealth; more data are needed in the evaluation of telehealth programs, adjusting for potential participant bias and extending the time frame of evaluating impact. In addition, rethinking and addressing the economic incentives and payment for telehealth services, as well as the medical-legal framework for provider competition across geographic regions (and jurisdictions), are needed for greater adoption of telehealth services.
Subject(s)
Program Development/methods , Telemedicine/organization & administration , Computer Security , Cost-Benefit Analysis , Health Services Accessibility , Humans , Medical Record Linkage , Telemedicine/economics , Telemedicine/instrumentationABSTRACT
BACKGROUND: In previous clinical trials, antiangiogenic therapies such as bevacizumab did not show efficacy in patients with newly diagnosed glioblastoma (GBM). This may be a result of the heterogeneity of GBM, which has a variety of imaging-based phenotypes and gene expression patterns. In this study, we sought to identify a phenotypic subtype of GBM patients who have distinct tumor-image features and molecular activities and who may benefit from antiangiogenic therapies. METHODS: Quantitative image features characterizing subregions of tumors and the whole tumor were extracted from preoperative and pretherapy perfusion magnetic resonance (MR) images of 117 GBM patients in 2 independent cohorts. Unsupervised consensus clustering was performed to identify robust clusters of GBM in each cohort. Cox survival and gene set enrichment analyses were conducted to characterize the clinical significance and molecular pathway activities of the clusters. The differential treatment efficacy of antiangiogenic therapy between the clusters was evaluated. RESULTS: A subgroup of patients with elevated perfusion features was identified and was significantly associated with poor patient survival after accounting for other clinical covariates (P values <.01; hazard ratios > 3) consistently found in both cohorts. Angiogenesis and hypoxia pathways were enriched in this subgroup of patients, suggesting the potential efficacy of antiangiogenic therapy. Patients of the angiogenic subgroups pooled from both cohorts, who had chemotherapy information available, had significantly longer survival when treated with antiangiogenic therapy (log-rank P=.022). CONCLUSIONS: Our findings suggest that an angiogenic subtype of GBM patients may benefit from antiangiogenic therapy with improved overall survival.