VST project: mechanical design optimization

The VLT Survey Telescope (VST) is a cooperative program between the European Southern Observatory (ESO) and the INAF Capodimonte Astronomical Observatory (OAC), Naples, for the study, design, and realization of a 2.6-m wide-field optical imaging telescope to be operated at the Paranal Observatory, Chile. The VST has been specifically designed to carry out stand-alone observations in the UV to I spectral range and to supply target databases for the ESO Very Large Telescope (VLT). The telescope design, manufacturing and integration are responsibility of TWG and have been carried out on the base of a model of optimized design not only for mechanics but for all telescope subsystems. The paper is an overview on the telescope mechanical design and optimization

Generation and Characterization of a Tumor Stromal Microenvironment and Analysis of Its Interplay with Breast Cancer Cells: An In Vitro Model to Study Breast Cancer-Associated Fibroblast Inactivation

Breast cancer-associated fibroblasts (BCAFs), the most abundant non-cancer stromal cells of the breast tumor microenvironment (TME), dramatically sustain breast cancer (BC) progression by interacting with BC cells. BCAFs, as well as myofibroblasts, display an up regulation of activation and inflammation markers represented by α-smooth muscle actin (α-SMA) and cyclooxygenase 2 (COX-2). BCAF aggregates have been identified in the peripheral blood of metastatic BC patients. We generated an in vitro stromal model consisting of human primary BCAFs grown as monolayers or 3D cell aggregates, namely spheroids and reverted BCAFs, obtained from BCAF spheroids reverted to 2D cell adhesion growth after 216 h of 3D culture. We firstly evaluated the state of activation and inflammation and the mesenchymal status of the BCAF monolayers, BCAF spheroids and reverted BCAFs. Then, we analyzed the MCF-7 cell viability and migration following treatment with conditioned media from the different BCAF cultures. After 216 h of 3D culture, the BCAFs acquired an inactivated phenotype, associated with a significant reduction in α-SMA and COX-2 protein expression. The deactivation of the BCAF spheroids at 216 h was further confirmed by the cytostatic effect exerted by their conditioned medium on MCF-7 cells. Interestingly, the reverted BCAFs also retained a less activated phenotype as indicated by α-SMA protein expression reduction. Furthermore, the reverted BCAFs exhibited a reduced pro-tumor phenotype as indicated by the anti-migratory effect exerted by their conditioned medium on MCF-7 cells. The deactivation of BCAFs without drug treatment is possible and leads to a reduced capability of BCAFs to sustain BC progression in vitro. Consequently, this study could be a starting point to develop new therapeutic strategies targeting BCAFs and their interactions with cancer cells

The inhibition of lactate dehydrogenase A hinders the transcription of histone 2B gene independently from the block of aerobic glycolysis

Most cancer cells use aerobic glycolysis to fuel their growth and many efforts are made to selectively block this metabolic pathway in cancer cells by inhibiting lactate dehydrogenase A (LDHA). However, LDHA is a moonlighting protein which exerts functions also in the nucleus as a factor associated to transcriptional complexes. Here we found that two small molecules which inhibit the enzymatic activity of LDHA hinder the transcription of histone 2B gene independently from the block of aerobic glycolysis. Moreover, we observed that silencing this gene reduces cell replication, hence suggesting that the inhibition of LDHA can also affect the proliferation of normal non-glycolysing dividing cells

Inhibition of lactate dehydrogenase activity as an approach to cancer therapy

In the attempt of developing innovative anticancer treatments, growing interest has recently focused on the peculiar metabolic properties of cancer cells. In this context, lactate dehydrogenase (LDH), which converts pyruvate to lactate at the end of glycolysis, is emerging as one of the most interesting molecular targets for the development of new inhibitors. In fact, because LDH activity is not needed for pyruvate metabolism through TCA cycle, inhibitors of this enzyme should spare glucose metabolism of normal non-proliferating cells, which usually completely degrade the glucose molecule to CO2. This review is aimed at summarizing the available data on LDH biology in normal and neoplastic cells, which are in support of the anticancer therapeutic approach based on LDH inhibition. These data encouraged Pharmaceutical Industries and Academic Institutions in the search of small molecule inhibitors and promising candidates have recently been identified. The availability of inhibitors with drug-like properties will allow to evaluate in the near future the real potential of LDH inhibition in anticancer treatment, also making possible the identification of the most responsive neoplastic conditions

The Ectodomain of Herpes Simplex Virus Glycoprotein H Contains a Membrane α-Helix with Attributes of an Internal Fusion Peptide, Positionally Conserved in the Herpesviridae Family

Human herpesviruses enter cells by fusion with target membranes, a process that requires three conserved glycoproteins: gB, gH, and gL. How these glycoproteins execute fusion is unknown. Neural network bioinformatics predicted a membrane α-helix contained within the ectodomain of herpes simplex virus (HSV) gH, positionally conserved in the gH of all examined herpesviruses. Evidence that it has attributes of an internal fusion peptide rests on the following lines of evidence. (i) The predicted membrane α-helix has the attribute of a membrane segment, since it transformed a soluble form of gD into a membrane-bound gD. (ii) It represents a critical domain of gH. Its partial or entire deletion, or substitution of critical residues inhibited HSV infectivity and fusion in the cell-cell fusion assay. (iii) Its replacement with the fusion peptide from human immunodeficiency virus gp41 or from vesicular stomatitis virus G partially rescued HSV infectivity and cell-cell fusion. The corresponding antisense sequences did not. (iv) The predicted α-helix located in the varicella-zoster virus gH ectodomain can functionally substitute the native HSV gH membrane α-helix, suggesting a conserved function in the human herpesviruses. We conclude that HSV gH exhibits features typical of viral fusion glycoproteins and that this property is likely conserved in the Herpesviridae family

Lactate dehydrogenase inhibition: Exploring possible applications beyond cancer treatment

Lactate dehydrogenase (LDH) inhibition is considered a worthwhile attempt in the development of innovative anticancer strategies. Unfortunately, in spite of the involvement of several research institutions and pharma-companies, the discovery of LDH inhibitors with drug-like properties seems a hardly resolvable challenge. While awaiting new advancements, in the present review we will examine other pathologic conditions characterized by increased glycolysis and LDH activity, which could potentially benefit from LDH inhibition. The rationale for targeting LDH activity in these contexts is the same justifying the LDH-based approach in anticancer therapy: because of the enzyme position at the end of glycolytic pathway, LDH inhibitors are not expected to hinder glucose metabolism of normal cells. Moreover, we will summarize the latest contributions in the discovery of enzyme inhibitors and try to glance over the reasons underlying the complexity of this research

Surgical management of acutely presenting gastrointestinal stromal tumors of the stomach among elderly: experience of an emergency surgery department

Introduction: The incidence of gastrointestinal stromal tumors (GISTs), requiring often an emergency surgical management, is extremely rare among elderly. We aimed to present the experience of the Emergency Surgery Department, Brotzu Hospital, in the management of elderly patients with GIST related emergencies.Methods: This study was carried out on 12 patients with gastrointestinal stromal tumors who presented to in an emergency situation during the period from January 2010 to December 2013. All patients' data, clinical presentations, surgical procedures, complications, and survival data were collected and analyzed.Results: Between 2010 and 2013, 12 patients (8 males and 4 females), with a mean age of 70 years (range: 65-79 years) were admitted with different emergency presentations of clinically and radiologically suspected GISTs. The incidence of proximal obstruction was 41.7% of all gastric GIST cases, resulting acute gastrointestinal bleeding and perforation in 41.7% and 16.6% respectively. The mean length of hospitalization was 9.1 +/- 2.3 days and there were no posterative complications or mortalities. At a mean follow-up of 21 months, 11 patients (91.6%) were alive and disease free.Discussions: Although GISTs are uncommon among elderly, their incidence is increasing especially in their emergency presentation and surgeon should be prepared to treat this condition following the principles of GIST surgery as stated by the GIST consensus conference.Conclusions: In conclusion our data demonstrate that age itself does not affect the outcome of surgical treatment of GISTs in emergency situation. (C) 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved