Importance: Previous histologic classifications of brain tumors have been limited by discrepancies in diagnoses reported by neuropathologists and variability in outcomes and response to therapies. Such diagnostic discrepancies have impaired clinicians' ability to select the most appropriate therapies for patients and have allowed heterogeneous populations of patients to be enrolled in clinical trials, hindering the development of more effective therapies. In adult-type diffuse gliomas, histologic classification has a particularly important effect on clinical care.
View Article and Find Full Text PDFAs the most recent innovation in cancer therapy that utilizes properties of the electromagnetic spectrum, tumor treating fields (TTFields) are non-invasive alternating electrical fields that target rapidly dividing tumor cells. In the patient, TTFields are delivered as regional treatment via two pairs of orthogonally positioned transducer arrays applied to the head or elsewhere on the body surface. Side effects are primarily localized to the skin.
View Article and Find Full Text PDFPolyglutamine-repeat disorders are part of a larger family of neurodegenerative diseases characterized by protein misfolding and aggregation. In spinal and bulbar muscular atrophy (SBMA), polyglutamine expansion within the androgen receptor (AR) causes progressive debilitating muscular atrophy and lower motor neuron loss in males. Although soluble polyglutamine-expanded aggregation species are considered toxic intermediates in the aggregation process, relatively little is known about the spectrum of structures that are formed.
View Article and Find Full Text PDFProteolysis of polyglutamine-expanded proteins is thought to be a required step in the pathogenesis of several neurodegenerative diseases. The accepted view for many polyglutamine proteins is that proteolysis of the mutant protein produces a "toxic fragment" that induces neuronal dysfunction and death in a soluble form; toxicity of the fragment is buffered by its incorporation into amyloid-like inclusions. In contrast to this view, we show that, in the polyglutamine disease spinal and bulbar muscular atrophy, proteolysis of the mutant androgen receptor (AR) is a late event.
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