Glioblastoma cusa fluid protein profiling: A comparative investigation of the core and peripheral tumor zones

The present investigation aimed to characterize the protein profile of cavitating ultrasound aspirator fluid of newly diagnosed and recurrent glioblastoma comparing diverse zones of collection, i.e., tumor core and tumor periphery, with the aid of 5\u2010aminolevulinic acid fluorescence. The samples were pooled and analyzed in triplicate by LC\u2010MS following the shotgun proteomic approach. The identified proteins were then grouped to disclose elements exclusive and common to the tumor state or tumor zones and submitted to gene ontology classification and pathway overrepresentation analysis. The proteins common to the distinct zones were further investigated by relative quantitation, following a label free approach, to disclose possible differences of expression. Nine proteins, i.e., tubulin 2B chain, CD59, far upstream element\u2010binding, CD44, histone H1.4, caldesmon, osteopontin, tropomyosin chain and metallothionein\u20102, marked the core of newly diagnosed glioblastoma with respect to tumor periphery. Considering the tumor zone, including the core and the fluorescence positive periphery, the serine glycine biosynthesis, pentose phosphate, 5\u2010 hydroxytryptamine degredation, de novo purine biosynthesis and huntington disease pathways resulted statistically significantly overrepresented with respect to the human genome of reference. The fluorescence negative zone shared several protein elements with the tumor zone, possibly indicating the presence of pathological aspects of glioblastoma rather than of normal brain parenchyma. On the other hand, its exclusive protein elements were considered to represent the healthy zone and, accordingly, exhibiting no pathways overrepresentation. On the contrary to newly diagnosed glioblastoma, pathway overrepresentation was recognized only in the healthy zone of recurrent glioblastoma. The TGF\u3b2 signaling pathway, exclusively classified in the fluorescence negative periphery in newly diagnosed glioblastoma, was instead the exclusive pathway classified in the tumor core of recurrent glioblastoma. These results, preliminary obtained on sample pools, demonstrated the potential of cavitron ultrasonic sur gical aspirate fluid for proteomic profiling of glioblastoma able to distinguish molecular features specific of the diverse tumor zones and tumor states, possibly contributing to the understanding of the highly infiltrative capability and recurrent rate of this aggressive brain tumor and opening to potential clinical applications to be further investigated

Investigating Glioblastoma Multiforme Sub-Proteomes: A Computational Study of CUSA Fluid Proteomic Data

Based on our previous proteomic study on Cavitating Ultrasound Aspirator (CUSA) fluid pools of Newly Diagnosed (ND) and Recurrent (R) glioblastomas (GBMs) of tumor core and periphery, as defined by 5-aminolevulinc acid (5-ALA) metabolite fluorescence, this work aims to apply a bioinformatic approach to investigate specifically into three sub-proteomes, i.e., Not Detected in Brain (NB), Cancer Related (CR) and Extracellular Vesicles (EVs) proteins following selected database classification. The study of these yet unexplored specific datasets aims to understand the high infiltration capability and relapse rate that characterizes this aggressive brain cancer. Out of the 587 proteins highly confidently identified in GBM CUSA pools, 53 proteins were classified as NB. Their gene ontology (GO) analysis showed the over-representation of blood coagulation and plasminogen activating cascade pathways, possibly compatible with Blood Brain Barrier damage in tumor disease and surgery bleeding. However, the NB group also included non-blood proteins and, specifically, histones correlated with oncogenesis. Concerning CR proteins, 159 proteins were found in the characterized GBM proteome. Their GO analysis highlighted the over-representation of many pathways, primarily glycolysis. Interestingly, while CR proteins were identified in ND-GBM exclusively in the tumor zones (fluorescence positive core and periphery zones) as predictable, conversely, in R-GBM they were unexpectedly characterized prevalently in the healthy zone (fluorescence negative tumor periphery). Relative to EVs protein classification, 60 proteins were found. EVs are over-released in tumor disease and are important in the transport of biological macromolecules. Furthermore, the presence of EVs in numerous body fluids makes them a possible low-invasive source of brain tumor biomarkers to be investigated. These results give new hints on the molecular features of GBM in trying to understand its aggressive behavior and open to more in-depth investigations to disclose potential disease biomarkers

Use of Neuronavigation System for Superficial Vein Identification: Safe and Quick Method to Avoid Intraoperative Bleeding and Vein Closure: Technical Note

Background: Contributions on using navigation in neurosurgery have been shared widely. However, few authors have reported their experience identifying superficial vessels before dural opening using indocyanine green\u2013video angiography. Furthermore, this technique has shown some limitations. Methods: For many years, each time we planned a needle biopsy for brain tumors, we set the entry point and trajectory on the navigator before surgery. Regarding the target, we systematically chose both a trajectory, which should avoid any crossing with vessels, and an entry far from veins or granulations. Gadolinium-enhanced magnetic resonance imaging T1-weighted sequences have been demonstrated to be adequate for this purpose. Note that we used the Medtronic StealthStation S8 (Minneapolis, Minnesota, USA) and gadolinium-enhanced magnetic resonance imaging T1-weighted sequences to plan 4 different surgical procedures (needle biopsy, parasagittal meningioma, double metastases, and high-grade glioma). Intraoperatively, after craniotomy and dural exposure, a Passive Planar Blunt Probe and dermographic pen were used to mark superficial vessels on the basis of navigational images. The dura was opened far from any marked line, vessels were dissected, and the dura was opened by a Penfield dissector and Metzenbaum scissors. Results: The mean planning time length was 7 minutes, and the marking procedure time length was 3 minutes. Dural marks perfectly corresponded to the underlying vessels. The correspondence rate of marks to underlying vessels was 100%. No one vessel unmarked was noticed. No superficial vessel injuries were reported. Conclusions: This technique provides a safe and fast method to avoid vessel injuries during dural opening. Furthermore, it could be useful as an educational tool

Geologia della Conca di Arabba

Guide Geologiche Regionali, Società Geologica Italian

Magmatismo e tettonica nelle Dolomiti

Guide Geologiche Regionali, Società Geologica Italian

Application of indocyanine green video angiography in vascular neurosurgery

Indocyanine green video angiography (ICG-VA) is a non-invasive, easy to use and very useful tool for various neurosurgical procedures. The first application was in neurovascular surgery, because it was born as an intravascular tracer for vessels visualization; this has been really useful in aneurysms, atero-venous malformations (AVMs) and dural fistulas surgery where identification, obliteration or patency of vessels is essential. introduced in vascular neurosurgery since 2003, icg-Va applications have broadened over time, both in vascular and in other neurosurgical fields. In 2003 Raabe et al. have been the first to describe the use of ICG-VA for intraoperative assessment of cerebral vascular flow, enabling visualization of vessel patency and aneurysm occlusion during aneurysm surgery. ICG-VA applications in vascular neurosurgery have significantly increased over time including complex aneurysms, bypass, atero-venous malformations (AVM) artero-venous fistulas (AVF), evaluation of cortical perfusion. The procedure can be easily repeated after 5-10 minutes. adverse reactions are comparable to those of other types of contrast media, with frequencies of 0.05% (hypotension, arrhythmia, or, more rarely, anaphylactic shock) to 0.2% (nausea, pruritus, syncope, or skin eruptions. The aim of the present study was to systematically analyze ICG-VA applications in vascular neurosurgery, highlighting the reported advantages and disadvantages, and discussing future perspectives