No abstract

Our results confirm that endoscopic management of intra- and paraventricular cysts is a valid alternative to open surgery as well as to shunting procedures. Control of clinical symptoms and signs was obtained in around 80% of our patients, while radiological evidence of cyst size reduction occurred in more than 95% of them. These rates are comparable with results of open surgery and shunting. The main advantage of neuroendoscopy is the low incidence of complications, a result that is confirmed by the present series.

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...

Patients with obscure gastrointestinal bleeding and negative CE had a significantly lower rebleeding rate, and further invasive investigations can be deferred.

Endoscopic endonasal surgery can improve the quality of the postoperative course in children regardless of the type of lesions treated and the surgical complications.

Posterior cranial fossa is the most frequent location of pediatric brain tumors. Its diagnosis is currently performed by postsurgery histopathology and the identification of biomarkers in cerebrospinal fluid (CSF) could provide a less invasive tool. Patient CSF was collected during surgery before the tumor removal (PRE-CSF) and 6 days after the resection (POST-CSF) and analyzed by top down LC-MS proteomics for comparison. The PRE-CSFs generally exhibited a less complex LC-MS profile than the relative POST-CSFs suggesting a suppressive role of the tumor toward proteins and peptides production or release. Particularly, a panel of peptides, identified as alpha- and beta-hemoglobin chains fragments, were generally absent in the PRE-CSF and present in the POST ones independently from contaminant blood hemoglobin. Among them, the LVV- and VV-hemorphin-7 showed the most repeatable trend and with a few remarkable exceptions: their unusual absence in POST surgery CSF was in fact interestingly correlated to the presence of tumor in the patient despite surgery due to metastases or to subtotal resection. These results ascribed a relevant biological role to LVV- and VV-h7 peptides in the disease and a strong potential as biomarkers. Their analysis in POST surgery CSF could be used to predict patient prognosis.

Surgery remains the main therapy for intracranial enchondromas. Radiotherapy is required in case of sarcomatous evolution or when a gross total tumor resection is not feasible, as in the present case.

The combination of top-down and bottom-up platforms was utilized for the LC-MS proteomic characterization of the intracystic fluid of adamantinomatous craniopharyngioma pediatric brain tumor disease. Proteins and peptides characterization was achieved by high-resolution LC-ESI-LTQ-Orbitrap-MS analysis while low-resolution LC-ESI-IT-MS was applied for the complete screening of the samples and the evaluation of the protein distribution within patients. Top-down analyses were applied to liquid/liquid extracted samples while bottom-up analyses were performed after trypsin digestion of both untreated and pretreated samples. The two proteomic approaches were complementary for the characterization of the proteome of craniopharyngioma intracystic fluid. Proteins and peptides involved in inflammation, mineralization processes and lipid transport were identified, in agreement with the calcium flecks, cholesterol granules and bone residues characteristic of this fluid. Apolipoprotein A-I, A-II, C-I and J, hemoglobin fragments, ubiquitin, α-2-HS-glycoprotein or fetuin A, α-1-antichymotrypsin, vitamin D binding protein, and α-1-acid glycoprotein were characterized. These data could be relevant for the comprehension of the processes involved in the pathogenesis of the disease and the development of the cyst and could contribute to the individuation of therapeutic targets for the reduction of the cyst volume delaying and/or avoiding invasive surgical treatments.