A5070717906- Ultrasound and Hyperthermia Applications
- Glioma Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Nanoplatforms for cancer theranostics
- Electron Spin Resonance Studies
- Photoacoustic and Ultrasonic Imaging
- Mathematical Biology Tumor Growth
- Traumatic Brain Injury and Neurovascular Disturbances
- Ferroptosis and cancer prognosis
- Lanthanide and Transition Metal Complexes
- Medical Imaging Techniques and Applications
- Brain Metastases and Treatment
- Traumatic Brain Injury Research
- Neurogenesis and neuroplasticity mechanisms
- Spinal Fractures and Fixation Techniques
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Artificial Intelligence in Healthcare and Education
- Radiomics and Machine Learning in Medical Imaging
- Spine and Intervertebral Disc Pathology
- Mitochondrial Function and Pathology
- Cardiac, Anesthesia and Surgical Outcomes
- Immunotherapy and Immune Responses
- S100 Proteins and Annexins
- Immune Response and Inflammation
Northwestern University
2023-2025
Northwestern Medicine
2023-2025
Midwestern University
2024-2025
Neurological Surgery
2023-2024
Northwestern University
2024
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
2023-2024
American University of Beirut
2019-2023
Qatar University
2023
Brigham and Women's Hospital
2022-2023
Harvard University
2022-2023
Abstract Given the marginal penetration of most drugs across blood-brain barrier, efficacy various agents remains limited for glioblastoma (GBM). Here we employ low-intensity pulsed ultrasound (LIPU) and intravenously administered microbubbles (MB) to open barrier increase concentration liposomal doxorubicin PD-1 blocking antibodies (aPD-1). We report results on a cohort 4 GBM patients preclinical models treated with this approach. LIPU/MB increases by 2-fold 3.9-fold in human murine brains...
Whereas the contribution of tumor microenvironment to profound immune suppression glioblastoma (GBM) is clear, tumor-cell intrinsic mechanisms that regulate resistance CD8 T cell mediated killing are less understood. Kinases potentially druggable targets drive progression and might influence response. Here, we perform an in vivo CRISPR screen identify glioma kinases contribute evasion cells from recognition. The reveals checkpoint kinase 2 (Chek2) be most important contributing escape T-cell...
Abstract Purpose: We recently reported on clinical trials for patients with recurrent glioblastoma where low-intensity pulsed ultrasound and microbubbles (LIPU/MB) improved paclitaxel or carboplatin delivery into the brain. Here, we report variable local tumor control at maximal/target dose in our phase I trial (NCT04528680). To address this, investigated combination of preclinical glioma models. Experimental Design: performed MRI-based analysis to evaluate disease from trial. studied...
Abstract Background Glioblastoma is a highly aggressive brain cancer that resistant to conventional immunotherapy strategies. Botensilimab, an Fc-enhanced anti-CTLA-4 antibody (FcE-aCTLA-4), has shown durable activity in “cold” and immunotherapy-refractory cancers. Methods We evaluated the efficacy immune microenvironment phenotype of mouse analogue FcE-aCTLA-4 treatment-refractory preclinical models glioblastoma, both as monotherapy combination with doxorubicin delivered via low-intensity...
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality. The innate adaptive immune responses play an important role in the pathogenesis TBI. Gamma-delta (γδ) T cells have been shown to affect immunopathology multiple different conditions, however, their acute chronic TBI largely unknown. Here, we show that γδ pathophysiology as early one day up year following mouse model. TCRδ-/- mice are characterized by reduced inflammation improved neurocognitive functions We find Vγ1...
Abstract Purpose We aimed to investigate surgical outcomes in octogenarians with subaxial cervical spine injuries and determine the predictors of complications mortality. Methods Eligible for inclusion were all patients surgically treated between 2006 2018, either anterior or posterior fixation injuries. A cohort was identified matched 1:1 a corresponding younger adults. Primary perioperative Results Fifty-four included each octogenarian groups (median age: 84.0 vs. 38.5). While risks...
Abstract Background The blood-brain barrier (BBB) impedes the passage of most circulating drugs into brain. Low-intensity pulsed ultrasound with microbubbles (LIPU/MB) transiently opens BBB, improving parenchymal drug penetration. Parenchymal permanence upon short-lived BBB opening is unknown. We compared temozolomide, carboplatin, and fluorescein, investigated effect LIPU/MB on concentration carboplatin fluorescein. Methods analyzed four patients who underwent intraoperative intravenous...
Although GBM's immunosuppressive environment is well known, the tumor's resistance to CD8+ T cell killing not fully understood. Our previous study identified Checkpoint Kinase 2 (Chek2) as key driver of in mouse glioma through an vivo CRISPR screen and demonstrated that Chk2 inhibition, combined with PD-1/PD-L1 blockade, significantly enhanced cell-mediated tumor improved survival preclinical model. Here, we aimed elucidate function Chek2. Immunoprecipitation (IP) followed by mass...
Abstract While chimeric antigen receptor (CAR) T-cell therapies present novel therapeutic opportunities, their clinical success has been limited when targeting malignant brain tumors, such as gliomas. Marked antigenic heterogeneity of those tumors underlies treatment resistance. Ultimately, it is crucial to promote endogenous T cell responses against tumor cells not targeted by the CAR (“epitope-spreading”). However, natural anatomical barriers and an immunosuppressive environment allow...
Abstract Although the immunosuppressive microenvironment of glioblastoma (GBM) is well-established, tumor-intrinsic mechanisms underlying resistance to CD8+ T cell-mediated killing remain incompletely understood. Our previous study identified Checkpoint Kinase 2 (Chek2) as top contributor cell in GBM through an vivo CRISPR screen. Therapeutic evaluation demonstrated that Chek2 inhibition, combined with PD-1/PD-L1 immune checkpoint blockade, significantly enhanced tumor and improved survival...
Abstract Background Glioblastoma (GB) remains a formidable challenge in neuro-oncology, with immune checkpoint blockade (ICB) showing limited efficacy unselected patients. We previously recently established that MAPK/ERK signaling is associated overall survival following anti-PD-1 and anti-CTLA-4 treatment recurrent GB. However, the causal relationship between susceptibility to ICB, as well mechanisms underlying this association, remain poorly understood. Method conducted vivo kinome-wide...
This cross-sectional study uses the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis reporting guideline to assess 120 published studies about surgical prediction models.
BACKGROUND AND OBJECTIVES: Carotid endarterectomy (CEA) is a well-established treatment option for carotid stenosis. The choice between general anesthesia (GA) and nongeneral (non-GA) during CEA remains subject of debate, with concerns regarding perioperative complications, particularly myocardial infarctions. This study aimed to evaluate the outcomes associated GA vs non-GA using large, nationwide database. METHODS: National Surgical Quality Improvement Project database was queried patients...
Abstract Glioblastoma (GBM) is a highly aggressive tumor of the brain. Current techniques detection like magnetic resonance imaging and tissue biopsy are inaccurate or invasive, requiring alternatives liquid biopsy. Exosomes nanosized vesicles that contain cargo, reflective their cellular origin have been used for early diagnosis cancer. However, in GBM, blood-brain barrier (BBB) leads to paucity pathological information blood. This study investigates effect opening BBB on circulating...
// Alberto Moscona-Nissan 1 , Karl J. Habashy 2 3 Victor A. Arrieta 4 Adam M. Sonabend and Crismita Dmello Universidad Panamericana School of Medicine, Mexico City, Department Neurological Surgery, Feinberg Northwestern University, Chicago IL 60611, USA Malnati Brain Tumor Institute the Lurie Comprehensive Cancer Center, PECEM, Facultad de Medicina, Nacional Autónoma México, Correspondence to: Dmello, email: crismita.dmello@northwestern.edu Sonabend,...
Abstract While immune checkpoint blockade (ICB) is not effective in unselected glioblastoma (GBM) patients, we previously established that MAPK/ERK signaling associated with overall survival following anti-PD-1 and anti-CTLA-4 treatment recurrent GBM. However, the causal relationship between susceptibility to ICB, as well mechanisms underlying this association, remain be determined. We conducted vivo kinome-wide CRISPR/Cas9 screenings murine gliomas identify key regulators of CD8+ T-cell...