Browsing by Subject "Meningeal neoplasms"

Now showing 1 - 3 of 3
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    Brigatinib causes tumor shrinkage in both NF2-deficient meningioma and schwannoma through inhibition of multiple tyrosine kinases but not ALK
    (PLOS, 2021-07-15) Chang, Long-Sheng; Oblinger, Janet L.; Smith, Abbi E.; Ferrer, Marc; Angus, Steven P.; Hawley, Eric; Petrilli, Alejandra M.; Beauchamp, Roberta L.; Riecken, Lars Björn; Erdin, Serkan; Poi, Ming; Huang, Jie; Bessler, Waylan K.; Zhang, Xiaohu; Guha, Rajarshi; Thomas, Craig; Burns, Sarah S.; Gilbert, Thomas S.K.; Jiang, Li; Li, Xiaohong; Lu, Qingbo; Yuan, Jin; He, Yongzheng; Dixon, Shelley A.H.; Masters, Andrea; Jones, David R.; Yates, Charles W.; Haggarty, Stephen J.; La Rosa, Salvatore; Welling, D. Bradley; Stemmer-Rachamimov, Anat O.; Plotkin, Scott R.; Gusella, James F.; Guinney, Justin; Morrison, Helen; Ramesh, Vijaya; Fernandez-Valle, Cristina; Johnson, Gary L.; Blakeley, Jaishri O.; Clapp, D. Wade; Pediatrics, School of Medicine
    Neurofibromatosis Type 2 (NF2) is an autosomal dominant genetic syndrome caused by mutations in the NF2 tumor suppressor gene resulting in multiple schwannomas and meningiomas. There are no FDA approved therapies for these tumors and their relentless progression results in high rates of morbidity and mortality. Through a combination of high throughput screens, preclinical in vivo modeling, and evaluation of the kinome en masse, we identified actionable drug targets and efficacious experimental therapeutics for the treatment of NF2 related schwannomas and meningiomas. These efforts identified brigatinib (ALUNBRIG®), an FDA-approved inhibitor of multiple tyrosine kinases including ALK, to be a potent inhibitor of tumor growth in established NF2 deficient xenograft meningiomas and a genetically engineered murine model of spontaneous NF2 schwannomas. Surprisingly, neither meningioma nor schwannoma cells express ALK. Instead, we demonstrate that brigatinib inhibited multiple tyrosine kinases, including EphA2, Fer and focal adhesion kinase 1 (FAK1). These data demonstrate the power of the de novo unbiased approach for drug discovery and represents a major step forward in the advancement of therapeutics for the treatment of NF2 related malignancies.
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    Meningeal myelomatosis: CT and MR appearances
    (American Society of Neuroradiology, 1995-08) Moran, Catherine C.; Anderson, Caryn C.; Caldemeyer, Karen S.; Smith, Richard R.; Radiology and Imaging Sciences, School of Medicine
    Meningeal myelomatosis is a rare feature of multiple myeloma. We report a case of IgG-kappa myeloma presenting as bilateral intracranial extraaxial masses.
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    Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma
    (Springer Nature, 2024) Wang, Justin Z.; Patil, Vikas; Landry, Alexander P.; Gui, Chloe; Ajisebutu, Andrew; Liu, Jeff; Saarela, Olli; Pugh, Stephanie L.; Won, Minhee; Patel, Zeel; Yakubov, Rebeca; Kaloti, Ramneet; Wilson, Christopher; Cohen-Gadol, Aaron; Zaazoue, Mohamed A.; Tabatabai, Ghazaleh; Tatagiba, Marcos; Behling, Felix; Almiron Bonnin, Damian A.; Holland, Eric C.; Kruser, Tim J.; Barnholtz-Sloan, Jill S.; Sloan, Andrew E.; Horbinski, Craig; Chotai, Silky; Chambless, Lola B.; Gao, Andrew; Rebchuk, Alexander D.; Makarenko, Serge; Yip, Stephen; Sahm, Felix; Maas, Sybren L. N.; Tsang, Derek S.; International Consortium on Meningiomas (ICOM); Rogers, C. Leland; Aldape, Kenneth; Nassiri, Farshad; Zadeh, Gelareh; Neurological Surgery, School of Medicine
    Treatment of the tumor and dural margin with surgery and sometimes radiation are cornerstones of therapy for meningioma. Molecular classifications have provided insights into the biology of disease; however, response to treatment remains heterogeneous. In this study, we used retrospective data on 2,824 meningiomas, including molecular data on 1,686 tumors and 100 prospective meningiomas, from the RTOG-0539 phase 2 trial to define molecular biomarkers of treatment response. Using propensity score matching, we found that gross tumor resection was associated with longer progression-free survival (PFS) across all molecular groups and longer overall survival in proliferative meningiomas. Dural margin treatment (Simpson grade 1/2) prolonged PFS compared to no treatment (Simpson grade 3). Molecular group classification predicted response to radiotherapy, including in the RTOG-0539 cohort. We subsequently developed a molecular model to predict response to radiotherapy that discriminates outcome better than standard-of-care classification. This study highlights the potential for molecular profiling to refine surgical and radiotherapy decision-making.