Tumor-associated neutrophil (TAN) effects on glioblastoma (GBM) biology remain under-characterized. We show here that neutrophils with dendritic features-including morphological complexity, expression of antigen presentation genes, and the ability to process exogenous peptide and stimulate major histocompatibility complex (MHC)II-dependent T cell activation-accumulate intratumorally and suppress tumor growth in vivo. Trajectory analysis of patient TAN scRNA-seq identifies this "hybrid" dendritic-neutrophil phenotype as a polarization state that is distinct from canonical cytotoxic TANs, and which differentiates from local precursors.
View Article and Find Full Text PDFObjective: The escalating healthcare expenditures in the United States, particularly in neurosurgery, necessitate effective tools for predicting patient outcomes and optimizing resource allocation. This study explores the utility of combining frailty and comorbidity indices, specifically the Johns Hopkins Adjusted Clinical Groups (JHACG) frailty index and the Elixhauser Comorbidity Index (ECI), in predicting hospital length of stay (LOS), non-routine discharge, and one-year readmission in patients undergoing craniotomy for benign and malignant primary brain tumors.
Methods: Leveraging the Nationwide Readmissions Database (NRD) for 2016-2019, we analyzed data from 645 patients with benign and 30,991 with malignant tumors.
Pancreatic ductal adenocarcinoma (PDAC) represents one of the only cancers with an increasing incidence rate and is often associated with intra- and peri-tumoral scarring, referred to as desmoplasia. This scarring is highly heterogeneous in extracellular matrix (ECM) architecture and plays complex roles in both tumor biology and clinical outcomes that are not yet fully understood. Using hematoxylin and eosin (H&E), a routine histological stain utilized in existing clinical workflows, we quantified ECM architecture in 85 patient samples to assess relationships between desmoplastic architecture and clinical outcomes such as survival time and disease recurrence.
View Article and Find Full Text PDFPancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related death. Hallmarks include desmoplasia with variable extracellular matrix (ECM) architecture and a complex microenvironment with spatially defined tumor, stromal, and immune populations. Nevertheless, the role of desmoplastic spatial organization in patient/tumor variability remains underexplored, which we elucidate using two technologies.
View Article and Find Full Text PDFTumor-associated neutrophil (TAN) effects on glioblastoma biology remain under-characterized. We show here that 'hybrid' neutrophils with dendritic features - including morphological complexity, expression of antigen presentation genes, and the ability to process exogenous peptide and stimulate MHCII-dependent T cell activation - accumulate intratumorally and suppress tumor growth . Trajectory analysis of patient TAN scRNA-seq identifies this phenotype as a polarization state which is distinct from canonical cytotoxic TANs and differentiates intratumorally from immature precursors absent in circulation.
View Article and Find Full Text PDFCancer-associated fibroblasts (CAFs) were presumed absent in glioblastoma given the lack of brain fibroblasts. Serial trypsinization of glioblastoma specimens yielded cells with CAF morphology and single-cell transcriptomic profiles based on their lack of copy number variations (CNVs) and elevated individual cell CAF probability scores derived from the expression of 9 CAF markers and absence of 5 markers from non-CAF stromal cells sharing features with CAFs. Cells without CNVs and with high CAF probability scores were identified in single-cell RNA-Seq of 12 patient glioblastomas.
View Article and Find Full Text PDFCancer-associated fibroblasts (CAFs) are integral to the solid tumor microenvironment. CAFs were once thought to be a relatively uniform population of matrix-producing cells, but single-cell RNA sequencing has revealed diverse CAF phenotypes. Here, we further probed CAF heterogeneity with a comprehensive multiomics approach.
View Article and Find Full Text PDFVirtual reality (VR) technology has seen increasing use in physical rehabilitation and in the management of acute and chronic pain. Functional movement disorders (FMDs) are a source of disability with no known association to neurologic pathology, and patients are generally offered multidisciplinary treatment approaches to improve functional movement. However, patients who are not compliant with rehabilitation may have persistent FMD and long-term disability.
View Article and Find Full Text PDFGlioblastoma (GBM) is the most common primary brain tumor with a median survival under two years. Using in silico and in vitro techniques, we demonstrate heterogeneous expression of CD97, a leukocyte adhesion marker, in human GBM. Beyond its previous demonstrated role in tumor invasion, we show that CD97 is also associated with upregulation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/Erk) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways in GBM.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2021
In the skin, tissue injury results in fibrosis in the form of scars composed of dense extracellular matrix deposited by fibroblasts. The therapeutic goal of regenerative wound healing has remained elusive, in part because principles of fibroblast programming and adaptive response to injury remain incompletely understood. Here, we present a multimodal -omics platform for the comprehensive study of cell populations in complex tissue, which has allowed us to characterize the cells involved in wound healing across both time and space.
View Article and Find Full Text PDFMetastases cause 90% of human cancer deaths. The metastatic cascade involves local invasion, intravasation, extravasation, metastatic site colonization, and proliferation. Although individual mediators of these processes have been investigated, interactions between these mediators remain less well defined.
View Article and Find Full Text PDFGlioblastoma (GBM) responses to bevacizumab are invariably transient with acquired resistance. We profiled paired patient specimens and bevacizumab-resistant xenograft models pre- and post-resistance toward the primary goal of identifying regulators whose targeting could prolong the therapeutic window, and the secondary goal of identifying biomarkers of therapeutic window closure. Bevacizumab-resistant patient specimens and xenografts exhibited decreased vessel density and increased hypoxia versus pre-resistance, suggesting that resistance occurs despite effective therapeutic devascularization.
View Article and Find Full Text PDFFluorescent proteins are used extensively in transgenic animal models to label and study specific cell and tissue types. Expression of these proteins can be imaged and analyzed using fluorescent and confocal microscopy. Conventional confocal microscopes cannot penetrate through tissue more than 4-6 μm thick.
View Article and Find Full Text PDFInitial studies on cancer primarily focused on malignant cells themselves. The overarching narrative of cancer revolved around unchecked and rapidly proliferating cells. Special attention was given to the molecular, genetic, and metabolic profiles of isolated cancer cells in hopes of elucidating a critical factor in malignancy.
View Article and Find Full Text PDFObjective: Glioblastoma (GBM) carries a high economic burden for patients and caregivers, much of which is associated with initial surgery. The authors investigated the impact of insurance status on the inpatient hospital costs of surgery for patients with GBM.
Methods: The authors conducted a retrospective review of patients with GBM (2010-2015) undergoing their first resection at the University of California, San Francisco, and corresponding inpatient hospital costs.
Background: Resection may be appropriate for select patients with recurrent glioblastoma. The incidence of histopathological findings related to prior treatment and their prognostic implications are incompletely characterized.
Objective: To quantify the incidence and survival outcomes associated with treatment effect at resection of recurrent glioblastoma (GBM).
OBJECTIVE Glioblastoma (GBM) is an aggressive brain malignancy with a short overall patient survival, yet there remains significant heterogeneity in outcomes. Although access to health care has previously been linked to impact on prognosis in several malignancies, this question remains incompletely answered in GBM. METHODS This study was a retrospective analysis of 354 newly diagnosed patients with GBM who underwent first resection at the authors' institution (2007-2015).
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