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

Age-Related Changes in the Epithelial and Stromal Compartments of the Mammary Gland in Normocalcemic Mice Lacking the Vitamin D3 Receptor

The vitamin D3 receptor (VDR) serves as a negative growth regulator during mammary gland development via suppression of branching morphogenesis during puberty and modulation of differentiation and apoptosis during pregnancy, lactation and involution. To assess the role of the VDR in the aging mammary gland, we utilized 12, 14, and 16 month old VDR knockout (KO) and wild type (WT) mice for assessment of integrity of the epithelial and stromal compartments, steroid hormone levels and signaling pathways. Our data indicate that VDR ablation is associated with ductal ectasia of the primary mammary ducts, loss of secondary and tertiary ductal branches and atrophy of the mammary fat pad. In association with loss of the white adipose tissue compartment, smooth muscle actin staining is increased in glands from VDR KO mice, suggesting a change in the stromal microenviroment. Activation of caspase-3 and increased Bax expression in mammary tissue of VDR KO mice suggests that enhanced apoptosis may contribute to loss of ductal branching. These morphological changes in the glands of VDR KO mice are associated with ovarian failure and reduced serum 17β-estradiol. VDR KO mice also exhibit progressive loss of adipose tissue stores, hypoleptinemia and increased metabolic rate with age. These developmental studies indicate that, under normocalcemic conditions, loss of VDR signaling is associated with age-related estrogen deficiency, disruption of epithelial ductal branching, abnormal energy expenditure and atrophy of the mammary adipose compartment

Mineralogy, petrography and evolution of Triassic magmatites of the Cima Pape Complex, eastern Dolomites

Middle Triassic magmatic products in the Cima Pape area (Eastern Dolomites) are examined. Stratigraphically the volcanic rocks are placed between the Livinallongo formation and the "Conglomerato della Marmolada' formation. The succession starts with the "agglomerati' (a tabular sheet of chaotic deposits derived from submarine slidings) followed by pillow lavas, pillow breccias and small subvolcanic bodies. A thick hyaloclastite sequence marks the end of volcanic activity. A sill varying in thickness from 50 to 300 m is injected inside the Livinallongo formation and controls the distribution of the overlying volcanics. The sill has undergone important differentiation. The chemical characteristics of the volcanic rocks show a clear affinity with shoshonitic series. The rocks could be derived from high alumina basalt primary magmas by high-pressure fractional crystallisation near the base of a thick crust. The "Conglomerato della Marmolada' is a thick conglomeratic sequence made almost exclusively of volcanic elements. This formation marks the end of an upper-Ladinian tectonic phase with extensive uplifting, faulting and erosions. -from English summar

Fe-Mn carbonate concretions in the Reno-Limentra fluvial deposits near Vergato (Bologna province, Northern Apennines): A petrographic and geochemical study

Ferromanganese carbonate concretions of extremely variable compositions mineralogical, petrographic and geochemical features. The obtained results lead to a genetic model by which concretions appear to be diagenetic rather than hydrogenic or hydrothermal. This origin is particularly supported by trace metal concentrations, REE patterns and stable isotope compositions

Monte Cavaloro: Small differences in outcrop lithology (Fe-Ti-P diorite) of a complex olistolith (Apennines Bologna)

At Monte Cavaloro near Bologna, outcrops a small olistolith of the ophiolite sequences of the Northern Apeninnes. This small outcrop is known in the geological literature as Bombicci (1868) find out a new type of rock which he named "oligoclasite". Cappellini (1878) studying the same outcrop, named the rock "Cavalorite". These two terms are still present (although obsclete) in the geological nomenclature. The same outcrop was studied by various authors which gave contrasting description of the mineralogy and recognized different rock types, from oligoclase bearing gabbro to quartzdiorite. The last study was by Gazzi (1961) who recognized the presence of stilpnomelane and classified the rock as stilpnomelane-oligoclase bearing gabbro. The present work lead us to the finding of several litothypes in the Monte Cavaloro olistolith: Fe-gabbros, Fe-gabbrobrodiorites, Fe-Ti-P diorites, Fe-Ti-P meladiorites, quartzdiorites and amphibole bearing albitite dikes. The Fe-Ti-P diorites are made up by oligoclase, ferroaugite, ferrohortonolite, ferrosilite, apatite, titanomagnetite and Fe-edenite and appear to be the product of cumulus processes from Fe-rich andesitic magmas which concentrate Fe-Ti oxides when apatite appeared as a liquidus phase. The other associated rocks are genetically linked through flow differentiation processes which generated the Fe-Ti-P meladiorites and the zircon rich quartzdiorites. The differentiation processes, took place in a closed system under low oxygen fugacity; during the late magmatic stages the high volatile content promoted the formation of hydrous minerals (mainly amphiboles) and the peculiar association biotite, cummingtonite-grunerite, stilpnomelane, chlorite. Stilpnomelane is variable in composition and in spite of its chemical features, it may correspond to that find in late stage granophyre of the Skaergaard pluton. This fact is a clear indication of the highly evoluted nature of our stilpnomelane bearing rock in keeping with the presence of stilpnomelane relics in the quartzdiorites. REE and trace elements abundances and composition of apatites and titano-magnetites agree with this genetic interpretation. Liquid immiscibility, as responsible of Fe-Ti-P rock, would seem to be not a viable genetic mechanism. The amphibole bearing albitite dikes represent a late injection of a slightly evolved gabbric magma

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