GENE EXPRESSION TIME-SERIES ANALYSIS OF CAMPTHOTECIN EFFECTS IN U-87-MG AND DBTRG-05 GLIOBLASTOMA CELL LINES

The clinical efficacy of camptothecin (CPT), a drug specifically targetingtopoisomerase I (TopoI), is under evaluation for the treatment of malignant gliomas. Due to thehigh unresponsiveness of these tumours to chemotherapy, it would be very important to study thesignalling network that drives camptothecin outcome in this type of cancer cells. To address thisissue, we had previously compared the expression profile of human U87-MG glioblastoma cellswith that of a CPT-resistant counterpart, giving evidence that the development of a robustinflammatory response was the main transcriptional effect associated with CPT resistance.Here we report time-related changes and cell line specific patterns of gene expression after CPTtreatment by using two p53 wild-type glioblastoma cell lines, U87-MG and DBTRG-05, withdifferent sensitivities to TopoI inhibition

Guidelines on the diagnosis, treatment and management of visceral and renal arteries aneurysms: a joint assessment by the Italian Societies of Vascular and Endovascular Surgery (SICVE) and Medical and Interventional Radiology (SIRM)

: The objective of these Guidelines is to provide recommendations for the classification, indication, treatment and management of patients suffering from aneurysmal pathology of the visceral and renal arteries. The methodology applied was the GRADE-SIGN version, and followed the instructions of the AGREE quality of reporting checklist. Clinical questions, structured according to the PICO (Population, Intervention, Comparator, Outcome) model, were formulated, and systematic literature reviews were carried out according to them. Selected articles were evaluated through specific methodological checklists. Considered Judgments were compiled for each clinical question in which the characteristics of the body of available evidence were evaluated in order to establish recommendations. Overall, 79 clinical practice recommendations were proposed. Indications for treatment and therapeutic options were discussed for each arterial district, as well as follow-up and medical management, in both candidate patients for conservative therapy and patients who underwent treatment. The recommendations provided by these guidelines simplify and improve decision-making processes and diagnostic-therapeutic pathways of patients with visceral and renal arteries aneurysms. Their widespread use is recommended

Gene expression profiles as endpoints in hazard identification of environmental exposure

La trascrittomica consente di identificare meglio i fattori di rischio e sperabilmente di migliorare il risk assessmen

Extracorporeal hemoadsorption therapy as a potential therapeutic option for rapid removal of Apixaban in high risk-surgical patients: a case report

Abstract Background Apixaban is a non-vitamin K antagonist oral anticoagulant (NOACs) recently emerged as an effective alternative to conventional vitamin K antagonists (VKAs) in the treatment of several thromboembolic disorders. However, in case of overdose or in patients requiring emergency surgery there is a high bleeding rate and severe adverse side effects due to the absence of an antidote. There is promising data from in vitro and clinical studies, that certain antithrombotic agents (that is Rivaroxaban and Ticagrelor) have been successfully removed by the extracorporeal hemoadsorption therapy CytoSorb. Here, we present the case of a patient successfully treated with CytoSorb as a kind of antidote to enable emergency surgery for bilateral nephrostomy. Case presentation A 82-year-old Caucasian man was admitted to the Emergency Room with acute kidney injury (AKI) in the context of severe bilateral hydroureteronephrosis. The patient’s medical history included chronic obstructive pulmonary disease, arterial hypertension, atrial fibrillation (anticoagulated with Apixaban) and a locally advanced prostate adenocarcinoma treated with trans-ureteral resection of the bladder and radiotherapy in the previous months. The indication for a bilateral nephrostomy could not be considered immediately given the major bleeding risk due to Apixaban, which was discontinued and replaced with calciparin. After 36 hours of continuous renal replacement therapy (CRRT), the Apixaban blood level was still elevated and it was decided to install CytoSorb into the running CRRT to accelerate the drug clearance. After 2 hours 30 minutes, there was good reduction of Apixaban from 139 to 72 ng/ml (reduction rate of 48.2%) registered, and this allowed for an easy placement of bilateral nephrostomies without complications. Four days after surgery renal function parameters further normalized, the patient did not require additional dialysis treatments and Apixaban therapy was prescribed again once the patient returned home. Conclusions In this case we report the findings of a patient with post-renal AKI requiring emergency nephrostomy placement while on chronic anticoagulation with Apixaban therapy. Combined treatment with CRRT and CytoSorb was associated with the rapid and effective removal of Apixaban allowing for prompt and urgent surgery while simultaneously ensuring the low risk of bleeding as well as an uneventful post-operative course

Different sensitivity of BALB/c 3T3 cell clones in the response to carcinogens

none11Cell transformation assays (CTAs) are currently regarded as the only possible in vitro alternative to animal testing for carcinogenesis studies. CTAs have been proposed as screening tests for the carcinogenic potential of compounds that have no evidence of genotoxicity but present structural alerts for carcinogenicity. We have extensively used the BALB/c 3T3 model based on the A31 cell clone to test single chemicals, complex mixtures and environmental pollutants. In the prevalidation study carried out by ECVAM, the improved protocol is based on BALB /c 3T3 A31-1-1 cells, a clone derived by A31 cells, that is very sensitive to PAH-induced transformation. The present study was performed in the aim to compare the results obtained with the two different clones exposed to different classes of carcinogens. Cells were treated with PAHs (3-methylcholanthrene, benzo(a)pyrene), alkylating agents (melphalan) and aloethanes (1,2-dibromoethane). The induction of cytotoxicity and the onset of chemically transformed foci were evaluated by two experimental protocols, differing for cell seeding density and chemical treatment duration. The A31-1-1 cells showed higher inherent transformation rate after PAHs treatment, but they were insensitive to 1,2-dibromoethane at concentrations that usually induced transformation in A31 cells. As 1,2-dibromoethane is bioactivated to reactive forms able to bind DNA mainly through the conjugation with intracellular glutathione, these results suggested a reduced activity of phase-2 enzymes involved in glutathione conjugation in A31-1-1 cells. Our results give evidence that inherent metabolic capacity of cells may play a critical role in in vitro cell transformation, cautioning against possible misclassification of chemicals.The knowledge of both metabolic pathways of carcinogens and the effective ability by cell lines to perform such metabolic activation is a key point. In fact, they allow to avoid possible misclassification of various agents as to their ability to increase cancer incidence in mammals by means of extrapolation of the results obtained in in vitro cell transformation. Epub ahead of print 2011 June 6mixedColacci A.; Mascolo M.G.; Perdichizzi S.; Gazzilli A.; Quercioli D.; Rotondo F.; Morandi E.; Guerrini A.; Silingardi P.; Grilli S.; Vaccari M.Colacci A.; Mascolo M.G.; Perdichizzi S.; Gazzilli A.; Quercioli D.; Rotondo F.; Morandi E.; Guerrini A.; Silingardi P.; Grilli S.; Vaccari M

All together now:collective intelligence for computer-supported collective action

In this position paper, we argue that a new methodological paradigm and software platform is required for developing citizen-oriented social computing applications. The platform that we propose is based on the idea of 'Collective Intelligence as a Service', and is grounded in the formalisation of computational models derived from an empirical analysis of psychological processes and social practices. This in turn provides the enablers for developing radically innovative tools for computational sustainability and computer-supported collective action in smart communities (e.g. Smart cities). Our vision is illustrated with two exemplars, one a healthcare application for patients with peripheral arterial disease, and the other an application for collaborative energy conservation to meet targets set out in a city's Sustainable Energy Action Plan

Angiopoietin-2 expression in B-cell chronic lymphocytic leukemia: association with clinical outcome and immunoglobulin heavy-chain mutational status

Our results regarding the adverse prognostic significance of high expression of Ang-2 by CLL cells are substantially in keeping with Hu¨ttmann et al. Importantly, in our series, CLL patients expressing at diagnosis high levels of Ang-2 usually had more advanced clinical stage and a higher percentage of CD38þ cells, had unmutated immunoglobulin status and unfavorable cytogenetics and had a shorter progression-free survival. These associations support the idea of the involvement of Ang-2 in the mechanisms of CLL disease progression. In addition, both circulating and BM-infiltrating Ig-unmutated CLL B-cells are able to express higher levels of Ang-2 than Ig-mutated CLL and normal B cells, suggesting the presence of an intrinsic defect in Ang-2 expression that could be pathogenetically relevant in CLL marrow microenvironment and could be involved in the differential clinical behavior of Ig-mutated and Ig-unmutated CLL cases

Angiopoietin-2 expression in B-cell chronic lymphocytic leukemia: association with clinical outcome and immunoglobulin heavy-chain mutational status

Chronic lymphocytic leukemia (CLL) has been considered for several years a disease of accumulation of relentless mature-looking malignant monoclonal B cells due to a presumeddefect in programmed cell death. However, several observations suggest that CLL cells are not immortal and that they require signals from microenvironment to maintain viability. Increased microvessel density in marrow and lymph node and increased levels of certain proangiogenetic factors in blood and urine of CLL patients were observed.2 Angiopoietin-2 (Ang-2) has a pivotal role in the disruption of stability and quiescence of mature vasculature that coincides with the reinitiation of vascular remodelling and angiogenic sprouting in adult, as occurs in tumors