The OGF-OGFr axis utilizes the p21 pathway to restrict progression of human pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is the 4th leading cause of death from cancer in the U.S. The opioid growth factor (OGF; [Met⁵]-enkephalin) and the OGF receptor form an inhibitory growth regulatory system involved in the pathogenesis and treatment of pancreatic cancer. The OGF-OGFr axis influences the G₀/G₁phase of the cell cycle. In this investigation, we elucidate the pathway of OGF in the cell cycle.</p> <p>Results</p> <p>Using BxPC-3 cells, OGF decreased phosphorylation of retinoblastoma (Rb) protein without changing total Rb. This change was correlated with reduced cyclin-dependent kinase protein (Cdk) 2 kinase activity, but not total Cdk2. OGF treatment increased cyclin-dependent kinase inhibitor (CKI) p21 protein expression in comparison to controls, as well levels of p21 complexed with Cdk2. Naloxone abolished the increased expression of p21 protein by OGF, suggesting a receptor-mediated activity. p21 specific siRNAs blocked OGF's repressive action on proliferation in BxPC-3, PANC-1, and Capan-2 cells; cells transfected with negative control siRNA had no alteration in p21 expression, and therefore were inhibited by OGF.</p> <p>Conclusion</p> <p>These data are the first to reveal that the target of cell proliferative inhibitory action of OGF in human pancreatic cancer is a p21 CKI pathway, expanding strategies for diagnosis and treatment of these neoplasias.</p

Il ruolo degli effetti di sito sulla risposta strutturale degli edifici nella conca aquilana

Il terremoto de L’Aquila del 6 aprile 2009 è stato significativamente caratterizzato dagli effetti di sito, evidenziati sia dalla variabilità delle registrazioni accelerometriche in zona near fault che dalla disuniforme distribuzione del danno rilevato. In particolare, nel quartiere aquilano di Pettino, in corrispondenza di un complesso residenziale composto da sette edifici della stessa tipologia strutturale, è stato osservato un danneggiamento molto diversificato. La nota riporta i risultati di una serie di analisi di risposta sismica locale 1D, condotte in corrispondenza di alcuni degli edifici del quartiere, per i quali si disponeva di indagini geotecniche di dettaglio, finalizzate a valutare l’influenza degli effetti di sito sulla risposta delle strutture. I risultati delle analisi condotte in condizioni di campo libero hanno mostrato significative amplificazioni del moto proprio in corrispondenza delle frequenze fondamentali del moto di input. Le analisi del sistema sottosuolo-edificio, condotte mediante l’utilizzo di un codice con formulazione a masse concentrate hanno inoltre consentito di verificare l’incidenza dell’interazione inerziale sul moto in superficie, nonché di riprodurre in forma semplificata il meccanismo di piano soffice osservato

Gemcitabine and oxaliplatin combination chemotherapy in advanced biliary tract cancers

BACKGROUND: Biliary tract cancers are uncommon tumors with a poor prognosis and most patients present with invasive and inoperable disease at diagnosis. Chemotherapy represents a palliative treatment, with poor response rates and a median survival of less than 6 months. Oxaliplatin and gemcitabine have shown an interesting activity as single agents in this group of patients. PATIENTS AND METHODS: We carried out a multicenter phase II study to evaluate the efficacy and safety of combined oxaliplatin and gemcitabine in locally advanced and metastatic biliary tract carcinoma. The schedule of chemotherapy included oxaliplatin 100 mg/m(2) on day 1 and gemcitabine 1000 mg/m(2) on days 1 and 8, every 21 days. RESULTS: All the 24 patients were evaluable for response and toxicity. According to RECIST criteria we observed one complete response and 11 partial responses for an overall response rate of 50%. Overall survival for all the patients on study was 12 months (range 2-30). According to WHO criteria, three patients (12.5%) suffered grade 3 neutropenia and three patients (12.5%) grade 3 thrombocytopenia. Only two patients (8%) suffered grade 3 neuropathy. CONCLUSIONS: Oxaliplatin and gemcitabine chemotherapy seems to be effective with a favorable safety profile in first-line chemotherapy of advanced biliary tract cancers

Generalized FAST approach for seismic assessment of infilled RC MRF buildings: application to the 2011 Lorca earthquake

A generalized formulation of FAST vulnerability method for Reinforced Concrete Moment Resisting Frame (RC-MRF) buildings with non-uniform distribution of masonry infills in elevation is presented. This method belongs to the wider family of spectral-based methodologies. It was already proposed for uniformly infilled frames, and then applied to different earthquakes for benchmarking purposes. The new generalized approach allows us to consider a reduction of the amount of infills at the ground floor. Thus, this new version of FAST is capable of computing all intermediate situations between the opposite cases: uniformly infilled and pilotis (no infills at ground storey) MRF. Finally, this generalized FAST method is applied to the case of the Lorca (Spain) 2011 earthquake, using parameters according to the local construction practice of the area. Results show a fair agreement with damage survey data.Gómez-Martínez, F.; Perez-Garcia, A.; De Luca, F.; Verderame, GM. (2014). Generalized FAST approach for seismic assessment of infilled RC MRF buildings: application to the 2011 Lorca earthquake. WIT Transactions on the Built Environment. 141:427-443. doi:10.2495/SUSI140371S42744314

RINTC-E: Towards seismic risk assessment of existing residential reinforced concrete buildings in Italy

The RINTC research project (RINTC Workgroup, 2018), financed by the Italian Department of Civil Protection, is aimed at evaluating the seismic risk of buildings conforming to the Italian building code. Within the framework of this project, the attention has been recently focused on existing buildings, too. In this study, case-study structures, representative of the existing residential reinforced concrete (RC) building stock in Italy, are analyzed. These structures are three-storey buildings with compact rectangular plan, and they have been defined through a simulated design process, in order to represent two types of buildings, namely designed for gravity loads only during 1970s (gravity load designed, GLD) or for moderate seismic loads during 1990s (seismic load designed, SLD). GLD buildings are assumed to be located in three different sites, namely Milan, Naples and Catania, in increasing order of seismic hazard. SLD buildings are assumed to be located in L'Aquila. The assumed design typologies are consistent with the seismic classification of the sites at the assumed ages of construction. The presence of typical nonstructural masonry infill walls (uniformly distributed in plan as external enclosure walls) is taken into account, assuming three configurations along height, namely “bare” (without infills), uniformly infilled and “pilotis” (without infills at the bottom storey) buildings. Two (not code-based) Limit States are investigated, namely Usability-Preventing Damage, corresponding to an interruption of the building use, and Collapse. RC elements are modelled with a lumped plasticity approach, through an empirical-based macromodel. The possible occurrence of shear failures in columns is taken into account through a preliminary classification of the expected failure mode (flexure- or shear-controlled, in the latter case prior to or following flexural yielding) and, if needed, a modification of the backbone of the nonlinear moment-chord rotation response, through empirical models providing the expected deformation capacity at shear and axial failure, the latter meant as the (initiation of) loss of axial-load-carrying-capacity. The nonlinear response of beam-column joints is modelled, too, with a “scissors model” based on concentrated springs representing the nonlinear response of the joint panel, at the intersection of beams' and columns' centerlines, through a preliminary evaluation of the expected failure mode (i.e. prior to or following yielding of adjacent beam/column elements). Materials properties are provided by literature studies, consistent with the age of construction of the buildings. The in-plane response of infills is modelled, taking into account the presence of openings, too. Modeling should be considered as simplified and, from some points of view, still preliminary, since advances are foreseen within the project in order to capture further failure modes that can occur in structural and nonstructural elements of older, nonductile RC buildings. Nonlinear static analyses, allowing to identify the (top) displacement capacity at the investigated Limit States, are carried out. Multiple stripe nonlinear time history bi-directional analyses of the three-dimensional structural models are carried out in order to evaluate the demand, for ten stripes - each corresponding to a return period ranging from 10 to 105 years - and for twenty couples of records for each stripe. Records were selected, within the activities of the research project, based on a Probabilistic Seismic Hazard Analysis at the sites of interest for the selected return periods. Results are illustrated, highlighting the role of a - although obsolete - seismic design in the response of the buildings and in their capacity, more specifically in terms of displacement capacity at Collapse, but also in terms of demand estimated from multiple stripe analyses. Finally, demand-to-capacity ratios at the investigated Limit States are analyzed, which allow, within the scope of the project, the assessment of the seismic risk of the case study structures

320pnab paclitaxel nab p in metastatic breast cancer mbc in elderly patients a real life setting nereide study

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Virtual Multidisciplinary Tumor Boards: A Narrative Review Focused on Lung Cancer

To date, the virtual multidisciplinary tumor boards (vMTBs) are increasingly used to achieve high-quality treatment recommendations across health-care regions, which expands and develops the local MTB team to a regional or national expert network. This review describes the process of lung cancer-specific MTBs and the transition process from face-to-face tumor boards to virtual ones. The review also focuses on the project organization's description, advantages, and disadvantages. Semi-structured interviews identified five major themes for MTBs: current practice, attitudes, enablers, barriers, and benefits for the MTB. MTB teams exhibited positive responses to modeled data feedback. Virtualization reduces time spent for travel, allowing easier and timely patient discussions. This process requires a secure web platform to assure the respect of patients’ privacy and presents the same unanswered problems. The implementation of vMTB also permits the implementation of networks especially in areas with geographical barriers facilitating interaction between large referral cancer centers and tertiary or community hospitals as well as easier access to clinical trial opportunities. Studies aimed to improve preparations, structure, and conduct of MTBs, research methods to monitor their performance, teamwork, and outcomes are also outlined in this article. Analysis of literature shows that MTB participants discuss 5–8 cases per meeting and that the use of a vMTB for lung cancer and in particular stage III NSCLC and complex stage IV cases is widely accepted by most health professionals.&nbsp;Despite still-existing gaps, overall vMTB represents a unique opportunity to optimize patient management in a&nbsp;patient-centered&nbsp;approach