Role of yUbp8 in Mitochondria and Hypoxia Entangles the Finding of Human Ortholog Usp22 in the Glioblastoma Pseudo-Palisade Microlayer

KAT Gcn5 and DUB Ubp8 are required for respiration and mitochondria functions in budding yeast, and in this study we show that loss of respiratory activity is acquired over time. Interestingly, we show that absence of Ubp8 allows cells to grow in hypoxic conditions with altered mitophagy. Comparatively, the aggressive glioblastoma (GBM) multiforme tumor shows survival mechanisms able to overcome hypoxia in the brain. Starting from yeast and our findings on the role of Ubp8 in hypoxia, we extended our analysis to the human ortholog and signature cancer gene Usp22 in glioblastoma tumor specimens. Here we demonstrate that Usp22 is localized and overexpressed in the pseudo-palisade tissue around the necrotic area of the tumor. In addition, Usp22 colocalizes with the mitophagy marker Parkin, indicating a link with mitochondria function in GBM. Collectively, this evidence suggests that altered expression of Usp22 might provide a way for tumor cells to survive in hypoxic conditions, allowing the escape of cells from the necrotic area toward vascularized tissues. Collectively, our experimental data suggest a model for a possible mechanism of uncontrolled proliferation and invasion in glioblastoma

Post-operative segmental cerebral venous sinus thrombosis : risk factors, clinical implications, and therapeutic considerations

Cerebral venous sinus thromboses (CVSTs) are rare complications of neurosurgical interventions and their management remains controversial as most of cases appear clinically silent. Here, we analyzed our institutional series of patients with CVSTs evaluating clinical and neuroradiological characteristics, risk factors, and outcome. From the analysis of our institutional PACS, we collected a total of 59 patients showing postoperative CVSTs after supratentorial or infratentorial craniotomies. For every patient, we collected demographics and relevant clinical and laboratory data. Details on thrombosis trend were retrieved and compared along the serial radiological assessment. A supratentorial craniotomy was performed in 57.6% of cases, an infratentorial in 37.3%, while the remaining were a single cases of trans-sphenoidal and neck surgery (1.7%, respectively). A sinus infiltration was present in almost a quarter of patients, and in 52.5% of cases the thrombosed sinus was exposed during the craniotomy. Radiological signs of CVST were evident in 32.2% of patients, but only 8.5% of them developed a hemorrhagic infarct. CVST-related symptoms were complained by 13 patients (22%), but these were minor symptoms in about 90%, and only 10% experienced hemiparesis or impaired consciousness. The majority of patients (78%) remained completely asymptomatic along the follow-up. Risk factors for symptoms occurrence were interruption of preoperative anticoagulants, infratentorial sinuses involvement and evidence of vasogenic edema and venous infarction. Overall, a good outcome defined mRS 0-2 was observed in about 88% of patients at follow-up. CVST is a complication of surgical approaches in proximity of dural venous sinuses. CVST usually does not show progression and courses uneventfully in the vast majority of cases. The systematic use of post-operative anticoagulants seems to not significantly influence its clinical and radiological outcome.Peer reviewe