Search results for "temi"
showing 10 items of 3194 documents
HCC therapies--lessons learned.
2014
The antiangiogenic multikinase inhibitor sorafenib was the first systemic agent to demonstrate a significant improvement in the overall survival of patients with advanced hepatocellular carcinoma (HCC), thereby introducing molecularly-targeted therapy in a therapeutic field of unmet needs. However, survival benefits for patients on sorafenib treatment are modest in clinical practice and advancing the field is far more challenging than initially anticipated. Molecular and clinical heterogeneity diminishes signals of potential activity in unselected populations, and underlying liver cirrhosis seals the fate of many novel targeted agents by causing relevant toxicity and mortality. The failure …
Outcomes of hepatocellular carcinoma patients treated with sorafenib: a meta-analysis of Phase III trials
2019
Aim: To benchmark overall survival (OS) and time to radiological progression (TTP) of patients enrolled in randomized controlled trials (RCTs) assessing sorafenib in advanced hepatocellular carcinoma using individual participant survival data, and to meta-analyze prognostic factors for OS and TTP. Methods: RCTs were identified through literature search until December 2018. Individual participant survival was reconstructed with an algorithm from published Kaplan–Meier curves. Results: Ten RCTs were included. Median OS was 10.0 months (95% CI: 9.6–10.5), and median TTP was 4.1 months (95% CI: 3.8–4.3). Multivariable analyses showed HCV positivity, absence of macrovascular invasion and extra-…
Optimizing Sequential Systemic Therapies for Advanced Hepatocellular Carcinoma: A Decision Analysis
2020
Background: An optimal sequential systemic therapy for advanced hepatocellular carcinoma (HCC) has not been discovered. We developed a decision model based on available clinical trials to identify an optimal risk/benefit strategy for sequences of novel systemic agents. Methods: A Markov model was built to simulate overall survival (OS) among patients with advanced HCC. Three first-line (single-agent Sorafenib or Lenvatinib, and combination of Atezolizumab plus Bevacizumab) followed by five second-line treatments (Regorafenib, Cabozantinib, Ramucirumab, Nivolumab, Pembrolizumab) were compared in fifteen sequential strategies. The likelihood of transition between states (initial treatment, ca…
Treatment of Hepatocellular Carcinoma with Immune Checkpoint Inhibitors and Applicability of First-Line Atezolizumab/Bevacizumab in a Real-Life Setti…
2021
Immune checkpoint inhibitors (ICIs) are the new frontier for the treatment of advanced hepatocellular carcinoma (HCC). Since the first trial with tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 inhibitor, increasing evidence has confirmed that these drugs can significantly extend the survival of patients with advanced hepatocellular carcinoma (HCC). As a matter of fact, the overall survival and objective response rates reported in patients with advanced HCC treated with ICIs are the highest ever reported in the second-line setting and, most recently, the combination of the anti-programmed death ligand protein-1 atezolizumab with bevacizumab—an anti-vascular endothelial growth fa…
Sorafenib in advanced hepatocellular carcinoma – We have won a battle not the war
2008
Sorafenib in advanced hepatocellular carcinoma. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Background No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multi-kinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. Methods In this multicente…
La gestione della qualità ambientale e gli eco-regolamenti edilizi - Environmental quality management and eco-building regulations
2012
The Italian municipalities have taken only the first steps on the road to smart cities. By 2020 thanks to the European Community and the Mayors agreement in 2008, cities aiming to be smart (for energy management,transport, digital technologies, social policy) will focus on sustainable development, by innovations and adequate partners. The general goal of resource saving and use of renewable energy has become a strategic necessity, fully involving architecture, whose environmental load in industrialized countries has become unsustainable. The national regulatory framework is constantly evolving, because the new European Directive 31/2010/CE, repealing the E.D. 91/2002/CE, obliges from Januar…
Linee guida per la redazione di Eco-Regolamenti Edilizi nella Regione Sicilia
2014
In vista degli obiettivi di Horizon2020, e all’interno del dibattito sulle Smart Cities, il tema della sostenibilità dell’ambiente costruito risulta di grande attualità, specie se coniugato con la necessità di garantire un’elevata qualità della vita e una crescita individuale e sociale della comunità, ottimizzando risorse e spazi comuni. Gli attori di questo cambiamento sono i Comuni, che attraverso i propri Regolamenti Edilizi, devono governare la trasformazione del territorio e la realizzazione di nuovi edifici, tecnologicamente all’altezza delle nuove esigenze, anche introducendo incentivi, premi volumetrici, per il perseguimento dei nuovi obiettivi energetici ed ambientali.. In tale qua…
Organizing a sonic space through vocal imitations
2016
A two-dimensional space is proposed for exploration and interactive design in the sonic space of a sound model. A number of reference items, positioned as landmarks in the space, contain both a synthetic sound and its vocal imitation, and the space is geometrically arranged based on the acoustic features of these imitations. The designer may specify new points in the space either by geometric interpolation or by direct vocalization. In order to understand how the vast and complex space of the human voice could be organized in two dimensions, we collected a database of short excerpts of vocal imitations. By clustering the sound samples on a space whose dimensionality has been reduced to the …
Psoriatic arthritis and COVID ‐19 pandemic: Consequences in medical treatment?
2020
The COVID‐19 pandemic has a strong negative impact on human society world‐wide. Patients with immune‐mediated disease may be prone to an increased risk of infection and/ or more severe course. We review the available data for patients with psoriatic arthritis (PSA) and systemic treatments. Current treatment options are summarized. Based upon the experience with COVID‐19 the following problems are addressed: (a) Can systemic treatment reduce comorbidities of PsA that are also comorbidities for COVID‐19? Does systemic medical treatment pose an increased risk of infection with SARS‐CoV‐2? Does systemic drug therapy have an impact on the risk of pulmonary fibrosis ‐ a factor with strong negativ…
Cytotoxicity of Artesunic Acid Homo- and Heterodimer Molecules toward Sensitive and Multidrug-Resistant CCRF-CEM Leukemia Cells
2010
A novel approach to circumvent multidrug resistance is hybridization of natural products in dimers. We analyzed homodimers of two artesunic acid molecules and heterohybrids of artesunic acid and betulin in human CCRF-CEM and multidrug-resistant P-glycoprotein-overexpressing CEM/ADR5000 leukemia cells. Multidrug-resistant cells were not cross-resistant to the novel compounds. Collateral sensitivity was observed for artesunic acid homodimer. Artesunic acid and artesunic acid homodimer induced G0/G1 cell cycle arrest, apoptosis, and formation of reactive oxygen species.