Browsing by Subject "Astrocytoma"

Now showing 1 - 5 of 5
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    A Cell-Based Model to Study Factors that Drive Diffuse Astrocytoma Development
    (2016-08) Folck, Anthony F.; Wells, Clark D.; Goebl, Mark G.; Quilliam, Lawrence A.
    Secondary gliomas are an incurable form of brain cancer that are diagnosed in people at a median age of 45 years. Next-generation sequencing has found that secondary glioblastomas have a distinct genetic profile from the more common primary glioblastomas, which are diagnosed in people typically over the age of 60. Over 80% of secondary gliomas contain an IDH1R132H mutation, resulting in neomorphic mutations, which catalyze isocitrate to the oncometabolite D-2-hydroxyglutarate (2-HG) instead of alpha-ketoglutarate (α-KG). As 2-HG accumulates, it induces a hypermethylator phenotype that prevents the cells from differentiating. Acquisition of additional mutations in tumor suppressors such as p53 and/or ATRX likely leads to tumor initiation. Work in the Wells Laboratory has found that loss of the HIPPO adaptor protein AmotL1 is also associated with increased malignancy. AmotL1 inhibits the transcriptional co-activator YAP to suppress both cell growth and migration. To understand the molecular events leading to secondary glioma development, this thesis developed a series of astrocyte cell lines that carry IDH1 and/or p53 mutations. These lines were then studied in 2D and 3D cell culture systems to identify changes that are associated with early secondary glial tumors. Work was also carried out to enable screens for small molecules that can be tested on these cell lines.
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    Cerebrospinal Fluid Drop Metastases of Canine Glioma: Magnetic Resonance Imaging Classification
    (Frontiers Media, 2021-05-03) Bentley, R. Timothy; Yanke, Amy B.; Miller, Margaret A.; Heng, Hock Gan; Cohen-Gadol, Aaron; Rossmeisl, John H.; Neurological Surgery, School of Medicine
    Dissemination of glioma in humans can occur as leptomeningeal nodules, diffuse leptomeningeal lesions, or ependymal lesions. Cerebrospinal fluid (CSF) drop metastasis of glioma is not well-recognized in dogs. Ten dogs with at least two anatomically distinct and histologically confirmed foci of glioma were included in this study. The 10 dogs underwent 28 magnetic resonance imaging (MRI) examinations, with distant CSF drop metastasis revealed in 13 MRIs. The CSF drop metastases appeared as leptomeningeal nodules in four dogs, diffuse leptomeningeal lesions in six dogs, and ependymal lesions in seven dogs; six dogs had a combination of lesion types. Primary tumors were generally T2-heterogeneous and contrast-enhancing. Many metastases were T2-homogeneous and non-enhancing. Diffuse leptomeningeal lesions were seen as widespread extra-axial contrast-enhancement, again very dissimilar to the intra-axial primary mass. Primary masses were rostrotentorial, whereas metastases generally occurred in the direction of CSF flow, in ventricles, CSF cisterns, and the central canal or leptomeninges of the cervical or thoracolumbar spinal cord. Seven of the dogs had received therapy limited to the primary mass, such as surgery or stereotactic radiation, then developed metastasis in the following months. CSF drop metastasis of glioma may take a very different appearance on MRI to the primary mass, including periventricular lesions that are more homogeneous and less contrast-enhancing, rostral horn signal changes, or leptomeningeal enhancement ventral to the brainstem or encircling the spinal cord.
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    Molecular Classification of Gliomas is Associated with Seizure Control: A Retrospective Analysis
    (Springer, 2021) Easwaran, Teresa P.; Lancki, Nicola; Henriquez, Mario; Vortmeyer, Alexander O.; Barbaro, Nicholas M.; Scholtens, Denise M.; Ahmed, Atique U.; Dey, Mahua; Pathology and Laboratory Medicine, School of Medicine
    Classically, histologic grading of gliomas has been used to predict seizure association, with low-grade gliomas associated with an increased incidence of seizures compared to high-grade gliomas. In 2016, WHO reclassified gliomas based on histology and molecular characteristics. We sought to determine whether molecular classification of gliomas is associated with preoperative seizure presentation and/or post-operative seizure control across multiple glioma subtypes. All gliomas operated at our institution from 2007 to 2017 were identified based on ICD 9 and 10 billing codes and were retrospectively assessed for molecular classification of the IDH1 mutation, and 1p/19q codeletion. Logistic regression models were performed to assess associations of seizures at presentation as well as post-operative seizures with IDH status and the new WHO integrated classification. Our study included 376 patients: 82 IDH mutant and 294 IDH wildtype. The presence of IDH mutation was associated with seizures at presentation [OR 3.135 (1.818-5.404), p < 0.001]. IDH-mutant glioblastomas presented with seizures less often than other IDH-mutant glioma subtypes grade II and III [OR 0.104 (0.032-0.340), p < 0.001]. IDH-mutant tumors were associated with worse post-operative seizure outcomes, demonstrated by Engel Class [OR 2.666 (1.592-4.464), p < 0.001]. IDH mutation in gliomas is associated with an increased risk of seizure development and worse post-operative seizure control, in all grades except for GBM.
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    Surgical Neuro-Oncology: Management of Glioma
    (Elsevier, 2022) Mitchell, Dana; Shireman, Jack M.; Dey, Mahua; Pediatrics, School of Medicine
    Gliomas are the most common intrinsic brain tumor in adults. Although maximal tumor resection improves survival, this must be balanced with preservation of neurologic function. Technological advancements have greatly expanded our ability to safely maximize tumor resection and design innovative therapeutic trials that take advantage of intracavitary delivery of therapeutic agents after resection. In this article, we review the role of surgical intervention for both low-grade and high-grade gliomas and the innovations that are driving and expanding the role of surgery in this therapeutically challenging group of malignancies.
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    Thrombus simulating flow void: a pitfall in diagnosing aqueductal patency by high-field MR imaging
    (American Society of Neuroradiology, 1987) Augustyn, Gary T.; D'Amour, Peter G.; Scott, John A.; Worth, Robert M.; Radiology and Imaging Sciences, School of Medicine