Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer.

Purpose The prognosis of gastric cancer (GC) is poor, and the molecular pathogenesis players are vastly unknown. Surgery remains the primary option in GC treatment. The aim of this study was to investigate the impact of somatic CDH1 alterations in prognosis and survival of patients with GC. Patients and Methods A series of patients with sporadic and familial GC (diffuse and intestinal; n _ 246) were analyzed for somatic CDH1 mutations, promoter hypermethylation, and loss of heterozygosity (LOH) by polymerase chain reaction sequencing. E-cadherin protein expression was determined by immunohistochemistry. Associations between molecular, clinicopathologic, and survival data were analyzed. Results CDH1 somatic alterations were found in approximately 30% of all patients with GC. Both histologic types of sporadic GC displayed LOH in 7.5%, mutations in 1.7%, and hypermethylation in 18.4% of patients. Primary tumors from hereditary diffuse GC, lacking germline CDH1 alterations, showed exclusively CDH1 promoter hypermethylation in 50% of patients. Familial intestinal GC (FIGC) tumors showed LOH in 9.4% and hypermethylation in 17.0%. CDH1 alterations did not associate with a particular pattern of E-cadherin expression. Importantly, the worst patient survival rate among all GCs analyzed was seen in patients with tumors carrying CDH1 structural alterations, preferentially those belonging to FIGC families. Conclusion CDH1 somatic alterations exist in all clinical settings and histotypes of GC and associate with different survival rates. Their screening at GC diagnosis may predict patient prognosis and is likely to improve management of patients with this disease.Supported by the Portuguese Foundation for Science and Technology (Projects No. POCTI/SAUOBS/58111/2004, PIC/IC/82923/2007, PTDC/SAU-GMG/72168/2006, PTDC/SAUGMG/110785/2009, and PTDC/SAU-ONC/110294/2009; PhD Grants No. SFRH/BD/40090/2007-GC and SFRH/BD/44074/2008-JC); salary support to C.O. from POPHQREN/Type 4.2; European Social Fund and Portuguese Ministry of Science and Technology; European Molecular Biology Organization short-term fellowship (ASTF 338.00-2008-JC); Calouste Gulbenkian Foundation short-term fellowship (nr 92352-JC); and Istituto Toscano Tumori (Grant No. ITT-2007). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology, and Higher Education and is partially supported by the Portuguese Foundation for Science and Technology

Molybdenum sputtering film characterization for high gradient accelerating structures

Technological advancements are strongly required to fulfill the demands of new accelerator devices with the highest accelerating gradients and operation reliability for the future colliders. To this purpose an extensive R&D regarding molybdenum coatings on copper is in progress. In this contribution we describe chemical composition, deposition quality and resistivity properties of different molybdenum coatings obtained via sputtering. The deposited films are thick metallic disorder layers with different resistivity values above and below the molibdenum dioxide reference value. Chemical and electrical properties of these sputtered coatings have been characterized by Rutherford backscattering, XANES and photoemission spectroscopy. We will also present a three cells standing wave section coated by a molybdenum layer $\sim$ 500 nm thick designed to improve the performance of X-Band accelerating systems.Comment: manuscript has been submitted and accepted by Chinese Physics C (2012

Phytochemical and biological characterization of dry outer scales extract from Tropea red onion (Allium cepa L. var. Tropea)–A promising inhibitor of pancreatic lipase

Background: Allium cepa L. var. Tropea is typically cultivated in Calabria (Italy) and it is certified as “Cipolla Rossa di Tropea Calabria-PGI” (Tropea red onion). The use of clinically available anti-obesity drugs such as Orlistat is being gradually dismissed due to their side-effects and this has encouraged the search for alternative inhibitors of intestinal lipases such as phytochemicals showing less side-effects. In this study we aimed to evaluate for the first time the anti-obesity potential of the hydroalcoholic extract from the dry outer scales of Tropea red onion by the assesment of its capacity to inhibit pancreatic lipase. Its possible mechanism of action was also studied with planar lipid membranes (PLMs) surrogate of intestinal membranes. Methods: Specialized metabolites in the extract were determined by GC–MS, HPLC-DAD, HPLC-UV-DAD and HPLC-HRMS analyses. Inhibition of pancreatic lipase was studied in vitro against crude lipase Type II from porcine pancreas. PLMs used in the electrophysiology measurements were made up of DOPS:DOPE:POPC. Results: The extract contained quercetin-4′-O-glucoside, quercetin and quercetin-3,4′-O-diglucoside as the most abundant phenolics. Among apolar constituents, γ-sitosterol, linoleic and stearic acids were dominant. The lipase inhibitory effect of the extract had an IC50 value equal to 0.77±0.03 mg/mL (positive control, IC50 = 0.018 mg/mL). The electrophysiological study demonstrated that the extract is able to incorporate into PLMs and to form transient channel-like events Conclusions: Taken altogether, the results allow us to suggest that the hydroalcoholic extract from the dry outer scales of Tropea red onion could prevent lipid ester hydrolysis and it has a protective effect against phospholipase as found for interfacially active compounds

Mechanical influence of tissue culture plates and extracellular matrix on mesenchymal stem cell behavior: A topical review

Tissue engineering applications need a continuous development of new biomaterials able to generate an ideal cell-extracellular matrix interaction. The stem cell fate is regulated by several factors, such as growth factors or transcription factors. The most recent literature has reported several publications able to demonstrate that environmental factors also contribute to the regulation of stem cell behavior, leading to the opinion that the environment plays the major role in the cell differentiation. The interaction between mesenchymal stem cells (MSCs) and extracellular environment has been widely described, and it has a crucial role in regulating the cell phenotype. In our laboratory (Tecnologica Research Institute, Crotone, Italy), we have recently studied how several physical factors influence the distribution and the morphology of MSCs isolated from dental pulp, and how they are able to regulate stem cell differentiation. Mechanical and geometrical factors are only a small part of the environmental factors able to influence stem cell behavior, however, this influence should be properly known: in fact, this assumption must be clearly considered during those studies involving MSCs; furthermore, these interactions should be considered as an important bias that involves an high number of studies on the MSCs, since in worldwide laboratories the scientists mostly use tissue culture plates for their experiments

A new device used in the restoration of kinematics after total facet arthroplasty

Facet degeneration can lead to spinal stenosis and instability, and often requires stabilization. Interbody fusion is commonly performed, but it can lead to adjacent-segment disease. Dynamic posterior stabilization was performed using a total facet arthroplasty system. The total facet arthroplasty system was originally intended to restore the natural motion of the posterior stabilizers, but follow-up studies are lacking due to limited clinical use. We studied the first 14 cases (long-term follow-up) treated with this new device in our clinic. All patients were diagnosed with lumbar stenosis due to hypertrophy of the articular facets on one to three levels (maximum). Disk space was of normal height. The design of this implant allows its use only at levels L3-L4 and L4-L5. We implanted nine patients at the L4-L5 level and four patients at level L3-L4. Postoperative follow-up of the patients was obtained for an average of 3.7 years. All patients reported persistent improvement of symptoms, visual analog scale score, and Oswestry Disability Index score. Functional scores and dynamic radiographic imaging demonstrated the functional efficacy of this new implant, which represents an alternative technique and a new approach to dynamic stabilization of the vertebral column after interventions for spine decompression. The total facet arthroplasty system represents a viable option for dynamic posterior stabilization after spinal decompression. For the observed follow-up, it preserved motion without significant complications or apparent intradisk or adjacent-disk degeneration. © 2014 Vermesan et al

Exosomes from human periapical Cyst-MSCs: Theranostic application in Parkinson’s disease

The scientific community continuously strives to get new disease models, to discover early markers or novel therapeutic approaches, improving the diagnosis and prognosis of several human pathologies. Parkinson’s Disease (PD) is characterized by a long asymptomatic phase, characterized by a selective loss of dopaminergic neurons. Recently, the human Periapical Cyst-Mesenchymal Stem Cells (hPCy-MSCs) have been differentiated in functional dopaminergic neurons: such oral-derived MSCs and the hPCy-MSCs-derived exosomes may represent a strategic and useful in vitro study-model, as well as intriguing therapeutic carriers. Circadian rhythm (CR) alteration variously impacts on PD pathways: an interesting research target is represented by the analysis of the exosomes released by dopaminergic neurons, derived from neural-differentiated hPCy-MSCs, after having reproduced in-vitro PD-like conditions. This review aims to describe the crosstalk among some aspects of circadian rhythm related to the onset of PD and the exosomes released by cells of PD patients. More in detail: the first part of this article will describe the main characteristics of circadian rhythm and the involvement of the exosomes found to be effective in the pathogenesis of PD. Finally, the authors will suggest how those exosomes derived from dopaminergic neurons, obtained by oral-derived stem cells (hPCy-MSCs) may represent a smart model for the in vitro research on PD, to find new biomarkers, to test new drugs or, fatally, to find new pathways applicable in future therapeutic approaches

In vitro comparative study on the mechanical behavior of Zirconia and Polyetheretherketone in applied dental sciences

OBJECTIVE: Recently, Zirconia and polyaryletherketone (PEEK) have attracted increasing interest as reliable and safe materials in dental applications, mainly because of their good biomechanical characteristics. The aim of this study was to investigate the response to different loads by prosthetic frameworks for supported fixed partial dentures (FPDs), thus simulating osseointegrated implants. MATERIALS AND METHODS: The specimens were divided into two groups (n= 5 each). Group A: FDPs in zirconia-ceramic; Group B: FDPs in PEEK-composite. These 2 groups were subjected to vertical loads so to evaluate structural deformation; then, they have been analyzed by scanning electron microscopy (SEM) at different magnifications. RESULTS: In tested samples, different types of mechanical failures have been observed. In Zirconia-specimens, chipping is the main failure noticed in this study, mostly in distal margins of the structure. Also, peek-specimens show failure and fracture. CONCLUSIONS: Zirconia and PEEK could be considered both good materials, but several investigations are needed to use these materials as an alternative to metals for fixed partial dentures

Cytoreductive Surgery (CRS) and HIPEC for Advanced Ovarian Cancer with Peritoneal Metastases: Italian PSM Oncoteam Evidence and Study Purposes

Ovarian cancer is the eighth most common neoplasm in women with a high mortality rate mainly due to a marked propensity for peritoneal spread directly at diagnosis, as well as tumor recurrence after radical surgical treatment. Treatments for peritoneal metastases have to be designed from a patient’s perspective and focus on meaningful measures of benefit. Hyperthermic intraperitoneal chemotherapy (HIPEC), a strategy combining maximal cytoreductive surgery with regional chemotherapy, has been proposed to treat advanced ovarian cancer. Preliminary results to date have shown promising results, with improved survival outcomes and tumor regression. As knowledge about the disease process increases, practice guidelines will continue to evolve. In this review, we have reported a broad overview of advanced ovarian cancer management, and an update of the current evidence. The future perspectives of the Italian Society of Surgical Oncology (SICO) are discussed conclusively