Browsing by Author "Nevel, Kathryn S."

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Contemporary Neuroscience Core Curriculum for Medical Schools
    (Wolters Kluwer, 2021-10-04) Gelb, Douglas J.; Kraakevik, Jeff; Safdieh, Joseph E.; Agarwal, Sachin; Odia, Yazmin; Govindarajan, Raghav; Quick, Adam; Soni, Madhu; AAN Undergraduate Education Subcommittee (UES); Bickel, Jennifer; Gamaldo, Charlene; Hannon, Peter; Hatch, Hayden A. M.; Hernandez, Christian; Merlin, Lisa R.; Noble, James M.; Reyes-Iglesias, Yolanda; Salas, Rachel Marie E.; Sandness, David James; Treat, Lauren; AAN Education Committee; Benameur, Karima; Brown, Robert D., Jr.; DeLuca, Gabriele C.; Garg, Neeta; Goldstein, Larry B.; Gutmann, Laurie; Henchcliffe, Claire; Hessler, Amy; Jordan, Justin T.; Kilgore, Shannon M.; Khan, Jaffar; Levin, Kerry H.; Mohile, Nimish A.; Nevel, Kathryn S.; Roberts, Kirk; Said, Rana R.; Simpson, Ericka P.; Sirven, Joseph I.; Smith, A. Gordon; Southerland, Andrew Mebane; Wilson, Rujuta B.; Neurology, School of Medicine
    Medical students need to understand core neuroscience principles as a foundation for their required clinical experiences in neurology. In fact, they need a solid neuroscience foundation for their clinical experiences in all other medical disciplines also because the nervous system plays such a critical role in the function of every organ system. Because of the rapid pace of neuroscience discoveries, it is unrealistic to expect students to master the entire field. It is also unnecessary, as students can expect to have ready access to electronic reference sources no matter where they practice. In the preclerkship phase of medical school, the focus should be on providing students with the foundational knowledge to use those resources effectively and interpret them correctly. This article describes an organizational framework for teaching the essential neuroscience background needed by all physicians. This is particularly germane at a time when many medical schools are reassessing traditional practices and instituting curricular changes such as competency-based approaches, earlier clinical immersion, and increased emphasis on active learning. This article reviews factors that should be considered when developing the preclerkship neuroscience curriculum, including goals and objectives for the curriculum, the general topics to include, teaching and assessment methodology, who should direct the course, and the areas of expertise of faculty who might be enlisted as teachers or content experts. These guidelines were developed by a work group of experienced educators appointed by the Undergraduate Education Subcommittee (UES) of the American Academy of Neurology (AAN). They were then successively reviewed, edited, and approved by the entire UES, the AAN Education Committee, and the AAN Board of Directors.
  • Thumbnail Image
    Item
    Multispecific targeting of glioblastoma with tumor microenvironment-responsive multifunctional engineered NK cells
    (National Academy of Science, 2021) Wang, Jiao; Toregrosa-Allen, Sandra; Elzey, Bennett D.; Utturkar, Sagar; Lanman, Nadia Atallah; Bernal-Crespo, Victor; Behymer, Matthew M.; Knipp, Gregory T.; Yun, Yeonhee; Veronesi, Michael C.; Sinn, Anthony L.; Pollok, Karen E.; Brutkiewicz, Randy R.; Nevel, Kathryn S.; Matosevic, Sandro; Radiology and Imaging Sciences, School of Medicine
    Tumor antigen heterogeneity, a severely immunosuppressive tumor microenvironment (TME) and lymphopenia resulting in inadequate immune intratumoral trafficking, have rendered glioblastoma (GBM) highly resistant to therapy. To address these obstacles, here we describe a unique, sophisticated combinatorial platform for GBM: a cooperative multifunctional immunotherapy based on genetically engineered human natural killer (NK) cells bearing multiple antitumor functions including local tumor responsiveness that addresses key drivers of GBM resistance to therapy: antigen escape, immunometabolic reprogramming of immune responses, and poor immune cell homing. We engineered dual-specific chimeric antigen receptor (CAR) NK cells to bear a third functional moiety that is activated in the GBM TME and addresses immunometabolic suppression of NK cell function: a tumor-specific, locally released antibody fragment which can inhibit the activity of CD73 independently of CAR signaling and decrease the local concentration of adenosine. The multifunctional human NK cells targeted patient-derived GBM xenografts, demonstrated local tumor site-specific activity in the tissue, and potently suppressed adenosine production. We also unveil a complex reorganization of the immunological profile of GBM induced by inhibiting autophagy. Pharmacologic impairment of the autophagic process not only sensitized GBM to antigenic targeting by NK cells but promoted a chemotactic profile favorable to NK infiltration. Taken together, our study demonstrates a promising NK cell-based combinatorial strategy that can target multiple clinically recognized mechanisms of GBM progression simultaneously.
  • Thumbnail Image
    Item
    Practical guidance for telemedicine use in neuro-oncology
    (Oxford University Press, 2022-01-17) Strowd, Roy E.; Dunbar, Erin M.; Gan, Hui K.; Kurz, Sylvia; Jordan, Justin T.; Mandel, Jacob J.; Mohile, Nimish A.; Nevel, Kathryn S.; Taylor, Jennie W.; Ullrich, Nicole J.; Welch, Mary R.; Wasilewski, Andrea; Mrugala, Maciej M.; Neurology, School of Medicine
    While the COVID-19 pandemic has catalyzed the expansion of telemedicine into nearly every specialty of medicine, few articles have summarized current practices and recommendations for integrating virtual care in the practice of neuro-oncology. This article identifies current telemedicine practice, provides practical guidance for conducting telemedicine visits, and generates recommendations for integrating virtual care into neuro-oncology practice. Practical aspects of telemedicine are summarized including when to use and not use telemedicine, how to conduct a virtual visit, who to include in the virtual encounter, unique aspects of telehealth in neuro-oncology, and emerging innovations.
  • Thumbnail Image
    Item
    Preoperative MRI-radiomics features improve prediction of survival in glioblastoma patients over MGMT methylation status alone
    (Impact Journals, 2019-01-18) Tixier, Florent; Um, Hyemin; Bermudez, Dalton; Iyer, Aditi; Apte, Aditya; Graham, Maya S.; Nevel, Kathryn S.; Deasy, Joseph O.; Young, Robert J.; Veeraraghavan, Harini; Neurology, School of Medicine
    Background: Glioblastoma (GBM) is the most common malignant central nervous system tumor, and MGMT promoter hypermethylation in this tumor has been shown to be associated with better prognosis. We evaluated the capacity of radiomics features to add complementary information to MGMT status, to improve the ability to predict prognosis. Methods: 159 patients with untreated GBM were included in this study and divided into training and independent test sets. 286 radiomics features were extracted from the magnetic resonance images acquired prior to any treatments. A least absolute shrinkage selection operator (LASSO) selection followed by Kaplan-Meier analysis was used to determine the prognostic value of radiomics features to predict overall survival (OS). The combination of MGMT status with radiomics was also investigated and all results were validated on the independent test set. Results: LASSO analysis identified 8 out of the 286 radiomic features to be relevant which were then used for determining association to OS. One feature (edge descriptor) remained significant on the external validation cohort after multiple testing (p=0.04) and the combination with MGMT identified a group of patients with the best prognosis with a survival probability of 0.61 after 43 months (p=0.0005). Conclusion: Our results suggest that combining radiomics with MGMT is more accurate in stratifying patients into groups of different survival risks when compared to with using these predictors in isolation. We identified two subgroups within patients who have methylated MGMT: one with a similar survival to unmethylated MGMT patients and the other with a significantly longer OS.
  • Thumbnail Image
    Item
    Tumor-responsive, multifunctional CAR-NK cells cooperate with impaired autophagy to infiltrate and target glioblastoma
    (bioRxiv, 2020) Wang, Jiao; Toregrosa-Allen, Sandra; Elzey, Bennett D.; Utturkar, Sagar; Lanman, Nadia Atallah; Bernal-Crespo, Victor; Behymer, Matthew M.; Knipp, Gregory T.; Yun, Yeonhee; Veronesi, Michael C.; Sinn, Anthony L.; Pollok, Karen E.; Brutkiewicz, Randy R.; Nevel, Kathryn S.; Matosevic, Sandro; Radiology and Imaging Sciences, School of Medicine
    Tumor antigen heterogeneity, a severely immunosuppressive tumor microenvironment (TME) and lymphopenia resulting in inadequate immune intratumoral trafficking have rendered glioblastoma (GBM) highly resistant to therapy. As a result, GBM immunotherapies have failed to demonstrate sustained clinical improvements in patient overall survival (OS). To overcome these obstacles, here we describe a novel, sophisticated combinatorial platform for GBM: the first multifunctional immunotherapy based on genetically-engineered, human NK cells bearing multiple anti-tumor functions, including local tumor responsiveness, that addresses key drivers of GBM resistance to therapy: antigen escape, poor immune cell homing, and immunometabolic reprogramming of immune responses. We engineered dual-specific CAR-NK cells to bear a third functional moiety that is activated in the GBM TME and addresses immunometabolic suppression of NK cell function: a tumor-specific, locally-released antibody fragment which can inhibit the activity of CD73 independently of CAR signaling and decrease the local concentration of adenosine. The multifunctional human NK cells targeted patient-derived GBM xenografts, demonstrated local tumor site specific activity in the tissue and potently suppressed adenosine production. We also unveil a complex reorganization of the immunological profile of GBM induced by inhibiting autophagy. Pharmacologic impairment of the autophagic process not only sensitized GBM to antigenic targeting by NK cells, but promoted a chemotactic profile favorable to NK infiltration. Taken together, our study demonstrates a promising new NK cell-based combinatorial strategy that can target multiple clinically-recognized mechanisms of GBM progression simultaneously.