1,450 research outputs found
Cardiotoxicity mechanisms of the combination of BRAF-inhibitors and MEK-inhibitors
No full textMany new drugs have appeared in last years in the oncological treatment scenario. Each drug carries an important set of adverse events, not less, cardiovascular adverse events. This aspect is even more important considering the increasing use of combination therapies with two drugs, or three drugs as in some ongoing clinical trials. Besides it represents a growing problem for Cardiologists, that face it in every day clinical practice and that will face it probably more and more in the coming years. This work reviews the mechanism of action of BRAF-inhibitors and MEK-inhibitors used together, the pathophysiological mechanisms that lead to cardiovascular toxicity. Particularly, it focuses on hypertension and ejection fraction reduction development. Then, it follows the examination of published data for each combination therapy. A Literature research was carried out using Pubmed selecting review articles, original studies and clinical trials, but mainly focusing on phase 3 studies. This work aims to summarize the knowledge about BRAF-inhibitor and MEK-inhibitor treatment and its cardiovascular toxicity to make it usable and give the basic tools to Cardiologists and Oncologists for a better management of cancer patient undergoing this treatment. Besides a deeper knowledge of the cardiovascular adverse events linked to this treatment and the magnitude of their expression and frequency can lead to a targeted cardiological treatment
David Audretsch: A Source of Inspiration, a Co-author, and a Friend
No full textIn this chapter, Enrico Santarelli discusses the profound impact that David had on his career. Beginning with a conference in Budapest, Santarelli and David bocame close friends and colleagues. They went on to collaborate on many papers and projects, several of which Santarelli highlights below
Dialogo con Enrico Palandri
No full textA conversation with Enrico Palandri aimed at contextualizing his work as an author
What links BRAF to the heart function? New insights from the cardiotoxicity of BRAF inhibitors in cancer treatment
No full textThe RAS-related signalling cascade has a fundamental role in cell. It activates differentiation and survival. It is particularly important one of its molecules, B-RAF. B-RAF has been a central point for research, especially in melanoma. Indeed, it lacked effective therapeutic weapons since the early years of its study. Molecules targeting B-RAF have been developed. Nowadays, two classes of molecules are approved by FDA. Multi-target molecules, such as Sorafenib and Regorafenib, and selective molecules, such as Vemurafenib and Dabrafenib. Many other molecules are still under investigation. Most of them are studied in phase 1 trials. Clinical studies correlate B-RAF inhibitors and QT prolongation. Though this cardiovascular side effect is not common using these drugs, it must be noticed early and recognize its signals. Indeed, Oncologists and Cardiologists should work in cooperation to prevent lethal events, such as fatal arrhythmias or sudden cardiac death. These events could originate from an uncontrolled QT prolongation
Dyslipidemia management with medical nutrition therapy: current status and perspectives
No full textIn Italy, patients with dyslipidennia account for 15-20% of the adult population with major healthcare and socio-economic impact. According to the ESC/EAS guidelines for the management of dyslipidemias, desirable cholesterol and triglyceride levels can be achieved with a synergy between drug treatment and adequate diet therapy. However, what diets should be adopted? In this review article, different types of dietary treatments are compared, with a special focus on diet education. The new scientific frontier of nutrigenetics is also discussed
Targeted Therapies in Hepatocellular Carcinoma
No full textThe onset of hepatocellular carcinoma (HCC) is related to the development of non-neoplastic liver disease, such as viral infections and cirrhosis. Even though patients with chronic liver diseases undergo clinical surveillance for early diagnosis of HCC, this cancer is often diagnosed in advanced stage. In this case locoregional treatment is not possible and systemic therapies are the best way to control it. Until now sorafenib, a Raf and multi-kinase inhibitor has been the best, choice to treat HCC systemically. It showed a survival benefit in multicenter phase III trials. However the proper patient setting to treat is not well defined, since the results in Child-Pugh B patients are conflicting. To date various new target drugs are under developed and other biological treatments normally indicated in other malignancies are under investigation also for HCC. These strategies aim to target the different biological pathways implicated in HCC development and progression. The target drugs studied in HCC include anti-VEGF and anti-EGFR monoclonal antibodies, tyrosine kinase inhibitors and mTOR inhibitors. The most important challenge is represented by the best integration of these drugs with standard treatments to achieve improvement in overall survival and quality of life
Enrico Cattaneo : Fotografare un'idea
No full textOltre ad aver raccontato l’arte e gli artisti del secondo Novecento attraverso la documentazione di cinquant’anni di mostre, studi e grandi manifestazioni pubbliche in Italia, Enrico Cattaneo (Milano, 1933-2019) ha sviluppato una personalissima ricerca visuale sui modi, i soggetti e i materiali della fotografia.
Questi due aspetti della sua attività, inseparabili fra loro come le due facce di una medaglia, si ricompongono nella fisionomia unitaria di un autore capace di mettere in questione i presupposti tecnici e concettuali del linguaggio fotografico.
Come lui stesso ha scritto: “L’opera d’arte contemporanea è spesso una cosa più un’idea... Difficile fotografare un’idea”.In addition to having chronicled art and artists of the second half of the 20th century by documenting fifty years of exhibitions, art research, and major public events in Italy, Enrico Cattaneo (Milan, 1933–2019) developed a highly personal visual investigation on the modes, languages, and materials of photography.
These two facets of his activity, indissolubly linked like the two sides of a coin, are recomposed in the overall profile of an author capable of questioning the technical and conceptual foundations of photography.
As he himself has written: ‘The contemporary work of art is often made up of a tangible thing and an idea ... It is difficult to capture an idea on film.
Prostate-specific membrane antigen (PSMA) assembles a macromolecular complex regulating growth and survival of prostate cancer cells "in vitro" and correlating with progression "in vivo"
No full textThe expression of Prostate Specific-Membrane Antigen (PSMA) increases in high-grade prostate carcinoma envisaging a role in growth and progression. We show here that clustering PSMA at LNCaP or PC3-PSMA cell membrane activates AKT and MAPK pathways thus promoting proliferation and survival. PSMA activity was dependent on the assembly of a macromolecular complex including filamin A, beta1 integrin, p130CAS, c-Src and EGFR. Within this complex beta1 integrin became activated thereby inducing a c-Src-dependent EGFR phosphorylation at Y1086 and Y1173 EGF-independent residues. Silencing or blocking experiments with drugs demonstrated that all the complex components were required for full PSMA-dependent promotion of cell growth and/or survival in 3D culture, but that p130CAS and EGFR exerted a major role. All PSMA complex components were found assembled in multiple samples of two high-grade prostate carcinomas and associated with EGFR phosphorylation at Y1086. The expression of p130CAS and pEGFRY1086 was thus analysed by tissue micro array in 16 castration-resistant prostate carcinomas selected from 309 carcinomas and stratified from GS 3+4 to GS 5+5. Patients with Gleason Score ≤5 resulted negative whereas those with GS≥5 expressed p130CAS and pEGFRY1086 in 75% and 60% of the cases, respectively.Collectively, our results demonstrate for the first time that PSMA recruits a functionally active complex which is present in high-grade patients. In addition, two components of this complex, p130CAS and the novel pEGFRY1086, correlate with progression in castration-resistant patients and could be therefore useful in therapeutic or surveillance strategies of these patients
HepatomiRNoma: The proposal of a new network of targets for diagnosis, prognosis and therapy in hepatocellular carcinoma
No full textThe diagnosis and treatment of hepatocellular carcinoma (HCC) underwent a huge advancement in the last years. Recently, microRNAs (miRNAs) have been also studied to provide a new tool for early diagnosis of high risk patients, for prognostic classification to identify those patients who benefit cancer treatment and for predictive definition to select the right targeted drug.In this review we revised all the available data obtained to explore the role of miRNAs in HCC. This analysis led to identification of miRNAs which could gain a diagnostic, prognostic or predictive role.The results of studies on miRNAs involved in HCC are initial and far from providing scientific evidences to translate into clinical practice. We propose a classification of these miRNAs, that we could name HepatomiRNoma as a whole. Anyway prospective studies have to be designed to clarify the real clinical impact of this new tool
Paolo Enrico Arias in Abruzzo
No full textThe author emphasizes P.E.Arias' contribution to archaeological researches in the Abruzzi, thanks to the Pisan Archaeological Mission at Collelongo (AQ)
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