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TET2 haploinsufficiency is a driving event in myeloid cancers and is associated with a worse prognosis in patients with acute myeloid leukemia (AML). Enhancing residual TET2 activity using vitamin C increases oxidized 5-methylcytosine (mC) formation and promotes active DNA demethylation via base excision repair (BER), which slows leukemia progression. We utilize genetic and compound library screening approaches to identify rational combination treatment strategies to improve use of vitamin C as an adjuvant therapy for AML. In addition to increasing the efficacy of several US Food and Drug Administration (FDA)-approved drugs, vitamin C treatment with poly-ADP-ribosyl polymerase inhibitors (PARPis) elicits a strong synergistic effect to block AML self-renewal in murine and human AML models. Vitamin-C-mediated TET activation combined with PARPis causes enrichment of chromatin-bound PARP1 at oxidized mCs and γH2AX accumulation during mid-S phase, leading to cell cycle stalling and differentiation. Given that most AML subtypes maintain residual TET2 expression, vitamin C could elicit broad efficacy as a PARPi therapeutic adjuvant., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective and Importance: The presentation, diagnosis, and treatment are described for a patient with a giant ependymoma involving the right cerebellopontine angle extending into the cavernous sinus. This case presents the unusual occurrence of a large extra-axial intracranial ependymoma and is the first reported case of cavernous sinus extension of this tumor., Clinical Presentation: The patient was a 22-year-old woman who presented with a 3-day history of generalized headache and right-sided facial droop. Magnetic resonance imaging revealed a nonhomogeneously enhancing cystic mass that was primarily in the posterior fossa with significant supratentorial extension and no apparent intra-axial or intraventricular involvement., Intervention: Gross total resection of this mass was achieved via two-staged resections using an initial presigmoid transpetrous, transtentorial approach and a subsequent pterional craniotomy. Pathological evaluation confirmed the diagnosis of ependymoma, and adjuvant radiation therapy to the resection bed was administered., Conclusion: Ependymomas can present as entirely extra-axial intracranial masses and rarely may involve the confines of the cavernous sinus.