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Malignant gliomas are heterogeneous tumors, mostly incurable, arising in the central nervous system (CNS) driven by genetic, epigenetic, and metabolic aberrations. Mutations in isocitrate dehydrogenase (IDH1/2) enzymes are predominantly found in low-grade gliomas and secondary high-grade gliomas, with IDH1 mutations being more prevalent. Mutant-IDH1/2 confers a gain-of-function activity that favors the conversion of a-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), resulting in an aberrant hypermethylation phenotype.

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Matrigel/BME, a basement membrane-like preparation, supports long-term growth of epithelial 3D organoids from adult stem cells [T. Sato , , 262-265 (2009); T. Sato , , 1762-1772 (2011)].

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Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within preexisting benign lesions called plexiform neurofibromas (PNs). PNs are solely driven by biallelic loss eliciting RAS pathway activation, and they respond favorably to MEK inhibitor therapy.

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VCP controls KCC2 degradation through FAF1 recruitment and accelerates emergence from anesthesia.

Proc Natl Acad Sci U S A

January 2025

Department of Medical Neuroscience, SUSTech Center for Pain Medicine, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China.

Ubiquitin-proteasomal degradation of K/Cl cotransporter 2 (KCC2) in the ventral posteromedial nucleus (VPM) has been demonstrated to serve as a common mechanism by which the brain emerges from anesthesia and regains consciousness. Ubiquitin-proteasomal degradation of KCC2 during anesthesia is driven by E3 ligase Fbxl4. However, the mechanism by which ubiquitinated KCC2 is targeted to the proteasome has not been elucidated.

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Background Introduction: Vestibular schwannoma (VS) tumors typically present with sensorineural hearing loss (SNHL). Losartan has recently demonstrated prevention of tumor-associated SNHL in a mouse model of VS through suppression of inflammatory and pro-fibrotic factors, and the current study investigates this association in humans.

Methods: This is a retrospective study of patients with unilateral VS and hypertension followed with sequential audiometry at a tertiary referral hospital from January 1994 to June 2023.

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