Journal of neurosurgery
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Journal of neurosurgery · May 2023
Use of heparin to rescue immunosuppressive monocyte reprogramming by glioblastoma-derived extracellular vesicles.
The profound immunosuppression found in glioblastoma (GBM) patients is a critical barrier to effective immunotherapy. Multiple mechanisms of tumor-mediated immune suppression exist, and the induction of immunosuppressive monocytes such as myeloid-derived suppressor cells (MDSCs) is increasingly appreciated as a key part of this pathology. GBM-derived extracellular vesicles (EVs) can induce the formation of MDSCs. The authors sought to identify the molecular consequences of these interactions in myeloid cells in order to identify potential targets that could pharmacologically disrupt GBM EV-monocyte interaction as a means to ameliorate tumor-mediated immune suppression. Heparin-sulfate proteoglycans (HSPGs) are a general mechanism by which EVs come into association with their target cells, and soluble heparin has been shown to interfere with EV-HSPG interactions. The authors sought to assess the efficacy of heparin treatment for mitigating the effects of GBM EVs on the formation of MDSCs. ⋯ The authors demonstrated that GBM EVs induce broad but reproducible reprogramming in monocytes, with enrichment of pathways that may portend an immunosuppressive phenotype. The authors further demonstrated that GBM EV-monocyte interactions are potentially druggable targets for overcoming tumor-mediated immune suppression, with heparin inhibition of EV-monocyte interactions demonstrating proof of principle.
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Journal of neurosurgery · May 2023
Association of homotopic areas in the right hemisphere with language deficits in the short term after tumor resection.
It is important to identify language deficit and recovery in the week following a tumor resection procedure. The homotopic Broca's area and the superior longitudinal fasciculus in the right hemisphere participate in language functional compensation. However, the nodes in these structures, as well as their contributions to language rehabilitation, remain unknown. In this study, the authors investigated the association of homotopic areas in the right hemisphere with language deficit. ⋯ The decreased ability of nodes A44d, A6dl, and A7m to convey information in the right hemisphere was associated with short-term language deficits after tumor resection. A smaller SDTN induced a worsened postoperative language deficit through a significant decrease in the ability to convey information from these three nodes.
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Journal of neurosurgery · May 2023
ZEB1 loss increases glioma stem cell tumorigenicity and resistance to chemoradiation.
Glioblastoma has been known to be resistant to chemotherapy and radiation, whereas the underlying mechanisms of resistance have not been fully elucidated. The authors studied the role of the transcription factor ZEB1 (zinc finger E-box-binding homeobox 1 protein), which is associated with epithelial-mesenchymal transition (EMT) and is central to the stemness of glioblastoma, to determine its role in therapeutic resistance to radiation and chemotherapy. The authors previously demonstrated that ZEB1 is deleted in a majority of glioblastomas. ⋯ The study results indicate that ZEB1 loss in cancer stem cells confers resistance to chemoradiation and uncovers a potentially targetable cell surface receptor in these resistant cells.
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Journal of neurosurgery · May 2023
Predicting the growth of middle cerebral artery bifurcation aneurysms using differences in the bifurcation angle and inflow coefficient.
Growing intracranial aneurysms (IAs) are prone to rupture. Previous cross-sectional studies using postrupture morphology have shown the morphological or hemodynamic features related to IA rupture. Yet, which morphological or hemodynamic differences of the prerupture status can predict the growth and rupture of smaller IAs remains unknown. The purpose of this longitudinal study was to investigate the effects of morphological features and the hemodynamic environment on the growth of IAs at middle cerebral artery (MCA) bifurcations during the follow-up period. ⋯ The AIRC was a significant independent predictor of the growth of MCA IAs. Sharper bifurcation and inflow angles and wider inclination angles between the M1 and M2 arteries were correlated with the AIRC. MCA IAs with such a bifurcation configuration are more prone to grow and rupture.