Glioblastoma multiforme (GB) is the most malignant primary brain tumor in humans, with an overall survival of approximatively 15 months. The molecular heterogeneity of GB, as well as its rapid progression, invasiveness and the occurrence of drug-resistant cancer stem cells, limits the efficacy of the current treatments. In order to develop an innovative therapeutic strategy, it is mandatory to identify and characterize new molecular players responsible for the GB malignant phenotype. In this study, the RNA-binding ubiquitin ligase MEX3A was selected from a gene expression analysis performed on publicly available datasets, to assess its biological and still-unknown activity in GB tumorigenesis. We find that MEX3A is strongly up-regulated in GB specimens, and this correlates with very low protein levels of RIG-I, a tumor suppressor involved in differentiation, apoptosis and innate immune response. We demonstrate that MEX3A binds RIG-I and induces its ubiquitylation and proteasome-dependent degradation. Further, the genetic depletion of MEX3A leads to an increase of RIG-I protein levels and results in the suppression of GB cell growth. Our findings unveil a novel molecular mechanism involved in GB tumorigenesis and suggest MEX3A and RIG-I as promising therapeutic targets in GB.Cancers 2020, 12, 321 2 of 16 treatments [2]. The current therapeutic protocol for GB patients consists of surgical resection of tumor mass and subsequent concomitant radiotherapy and chemotherapy. However, these approaches show very limited effectiveness, resulting in a high rate of relapse and subsequent deterioration of the patient's neurological and physiological status [2,5].In the recent years, several genetic and epigenetic aberrations in molecular pathways (i.e., WNT and Hedgehog signaling) [6-9] have been associated with GB onset and progression, representing potential therapeutic targets and biomarkers for early prognosis [2,3,5]. Hence, the identification and characterization of new molecular players involved in GB tumorigenesis is essential for developing more effective and innovative therapies against this aggressive malignancy.Ubiquitylation is a post-translational modification that controls a wide range of cellular functions (i.e., protein degradation, endocytosis and trafficking) and the most important physiological processes [10,11]. Ubiquitylation is mediated by an enzymatic cascade, in which the E3-ubiquitin ligases are the main players, responsible for the recognition of specific substrates and the final transferring of ubiquitin moieties onto target proteins.Deregulation or mutations of E3-ubiquitin ligases have been associated with several human tumors; for this reason, they are considered to be promising targets for novel anticancer therapies [12][13][14]. At present, very little information is available about the role of E3 ligases and ubiquitylation processes in GB development and progression [15][16][17].In this regard, we evaluated the expression levels of catalytic E3-ubiquitin ligase complex components [18] and F-b...

No abstract

Background Glioblastoma (GBM) is the most common and aggressive primary brain neoplasia in adults. Seizure is a common manifestation in GBM. Up to 25 to 60% of patients with GBM have seizures. We aim to summarize all the relevant clinical, surgical, radiologic, and molecular features of a cohort of patients suffering from GBM-related epilepsy and measure the outcome, to understand the possible existence of a clinical/phenotypical specificity of this subgroup of patients. Methods We retrospectively analyzed a cohort of 177 patients affected by isocitrate dehydrogenase wild-type (IDH-WT) GBM; 49 patients presented seizure at onset (SaO) and 128 were seizure free (SF). We investigated the relationship between seizures and other prognostic factors of GBMs. Results A statistically significant association between the location of the lesions in the parietal lobe and seizures was observed. The left side was more commonly affected. Interestingly, there was a statistical relationship between tumors involving the subventricular zone (SVZ) and SaO patients. The tumors were also smaller on average at diagnosis, and generalized SaOs were associated with longer overall survival. Conclusions The typical patient with IDH-WT GBM with SaO is a young (<55 year) male without a history of headache. The lesion is typically small to medium in size and located in the temporoparietal dominant lobe, with a high tendency to involve the SVZ.

Pneumocephalus (PC) is an uncommon and life-threatening neurological condition. Air within the ventricular system of the brain is also known as Pneumoventricle (PV). It requires emergency treatments to prevent catastrophic neurological outcomes. Head injury is the most common cause of PV, but there are other well-recognized etiologies in case there is no clear radiological evidence of skull discontinuity. Although this clinical entity has been well described in Literature, our report presents the unique feature of describing a purely ventricular PC without evidence of skull base or cranial vault fracture. Therefore, this case presentation explores mysterious causes of fistulous connections with the atmosphere that may lead to air trapped in and around the cranial vault. The aim of the present paper is to report a case of post-traumatic PV without radiological signs of skull base or convexity fracture in a 72-years-old man, underlining the diagnostic and clinical features, and review the relevant Literature.