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Glioblastoma (GBM) is the most common primary malignant brain tumor, with a universally poor prognosis. The emergence of molecular biomarkers has had a significant impact on histological typing and diagnosis, as well as predicting patient survival and response to treatment. The methylation status of the O6-methylguanine-DNA methyl-transferase (MGMT) gene promoter is one such molecular biomarker. Despite the strong evidence supporting the role of MGMT methylation status in prognostication, its routine implem...
Isocitrate Deyhydrogenase (IDH) mutant gliomas are comprised of the majority of grade II-III gliomas and nearly all secondary glioblastomas. These progressive gliomas arise from mutations in IDH1 or IDH2 that pathologically produces D-2-hydroxyglutarate (2HG). 2-HG interferes with cell reactions using alpha ketoglutarate leading to a hypermethylated genome and epigenetic dysregulation of gene expression initiating tumorigenesis.
Diffuse Intrinsic Pontine Glioma (DIPG) is a uniformly fatal CNS tumor diagnosed in 300 American children per year. Radiation is the only effective treatment and extends overall survival to a median of 11 months. Due to its location in the brainstem, DIPG tumors cannot be surgically resected. Immunotherapy has the ability to target tumor cells specifically, however, little is known about the tumor microenvironment in DIPGs. We sought to characterize infiltrating immune cells and immunosuppressive factor exp...
The genomic characterization of sporadically arising gliomas has delineated molecularly and clinically distinct subclasses of disease. However, less is known about the molecular nature of gliomas that are familial in origin. We performed molecular subtyping of 163 tumor specimens from individuals with a family history of glioma and integrated germline and somatic genomic data to characterize the pathogenesis of 20 tumors in additional detail.
This study aims to evaluate the impact of tumor location on key molecular alterations on a single voxel level in patients with newly-diagnosed glioma.
Pseudoprogression is a diagnostic challenge in early post-treatment glioblastoma. We therefore developed and validated a radiomics model using multiparametric MRI to differentiate pseudoprogression from early tumor progression in patients with glioblastoma.
A high heterogeneity and activation of multiple oncogenic pathways have been implicated in failure of targeted therapies in glioblastoma.
Aerobic glycolysis confers several advantages to tumor cells, including shunting of metabolites into anabolic pathways. In glioblastoma cells, hypoxia induces a flux shift from the pentose phosphate pathway towards glycolysis and a switch from proliferation to migration. The mechanistic link between glycolysis and migration is poorly understood. Since glucose-6-phosphate isomerase (GPI) is identical to the secreted autocrine motility factor (AMF), we investigated whether GPI/AMF regulates glioblastoma cell ...
Ependymal tumors are glial tumors that commonly manifest in children and young adults. Their classification has remained entirely morphological until recently, and surgery and radiotherapy are the main treatment options, especially in adults. Here we sought to correlate DNA methylation profiles with clinical and pathological characteristics in the prospective cohort of the German Glioma Network.
Noninvasive and accurate modality to predict Isocitrate dehydrogenase (IDH) mutant glioma may have great potential in routine clinical practice. We aimed to investigate the diagnostic performance of 2-hydroxyglutarate (2HG) magnetic resonance spectroscopy (MRS) for prediction of IDH mutant glioma and provide an optimal cut-off value for 2HG.
Recently, three molecular subgroups of atypical teratoid/rhabdoid tumor (ATRT) were identified, but little is known on their clinical and magnetic resonance imaging (MRI) characteristics.
Meningiomas are mostly benign tumors tending to progress to higher-grade lesions. Mutations in the telomerase reverse transcriptase (TERT) gene promoter are comparably rare in meningioma, but were recently suggested to predict risk of recurrence and progression. Here we have analyzed a cohort of World Health Organization grades I-III meningiomas regarding the impact of TERT promoter mutations on patient prognosis and in vitro cell propagation feasibility.
Survival alone is no longer an adequate outcome for persons with brain tumors; the quality of the survivorship experience should be viewed with equal importance. Symptom management is a significant component of quality survivorship care. Regardless of their histology, brain tumors and therapies used to treat them produce symptoms that affect an individual's ability to function in everyday life. Common symptoms include fatigue, cognitive impairment, distress, and sleep disturbance. Symptom-based intervention...
Glioblastoma (GBM) is a difficult-to-treat brain cancer that nearly uniformly recurs, and recurrent tumors are largely therapy-resistant. Our prior work has demonstrated an important role for the TWEAK receptor Fn14 in GBM patho-biology. In this study, we investigated Fn14 expression in recurrent GBM and in the setting of temozolomide (TMZ) resistance.
In the current study we used contrast-enhanced T1 subtraction maps to test whether early changes in enhancing tumor volume are prognostic for overall survival (OS) in newly diagnosed GBM patients treated with chemoradiation with or without bevacizumab (BV).
Perineuronal satellitosis, the microanatomical clustering of glioma cells around neurons in the tumor microenvironment, has been recognized as a histopathological hallmark of high-grade gliomas since the seminal observations of Scherer in the 1930s. In this review, we explore the emerging understanding that neuron - glioma cell interactions regulate malignancy, and that neuronal activity is a critical determinant of glioma growth and progression. Elucidation of the interplay between normal and malignant neu...
Corticosteroids are the mainstay of treatment for peritumor edema but are often associated with significant side effects. Therapies that can reduce corticosteroid use would potentially be of significant benefit to patients. However, currently there are no standardized endpoints evaluating corticosteroid use in neuro-oncology clinical trials.