De Marinis F.,San Camillo Hospital |
Atmaca A.,University Cancer Center |
Tiseo M.,University of Parma |
Giuffreda L.,Molinette Hospital |
And 7 more authors.
Journal of Thoracic Oncology | Year: 2013
BACKGROUND: In vitro data suggest that panobinostat (LBH589), a pan-deacetylase inhibitor, may add therapeutic benefit in the treatment of small-cell lung cancer (SCLC) with regression of tumors. METHODS: This multicenter, nonrandomized phase 2 trial was designed to evaluate antitumor activity of LBH589 in patients with previously treated SCLC. Patients received LBH589 administered intravenously at a dose of 20 mg/mq (days 1-8) every 21 days. RESULTS: A total of 21 patients with extensive- or limited-stage SCLC were enrolled. Patients received a median of two cycles (range, 1-6). LBH589 was well tolerated, and the most common toxicities were grade 1 to 2 gastrointestinal disorders (nausea 38%, diarrhea 24%, vomiting 19%), grade 1 to 2 thrombocytopenia (14.3%). Of 19 patients evaluable for efficacy, two cases showed shrinkages more than 30% at first assessment, with time to progression of 14 and 21 weeks, respectively, and there were three long disease stabilizations of 12, 10, and 13 weeks. The study was prematurely closed because of a lack of activity. CONCLUSION: This is the first report of a pan-deacetylase inhibitor inducing tumor shrinkage and sustained stable disease in SCLC. We believe that although the trial was prematurely discontinued, modest clinical activity of LBH589 combined with a favorable safety profile in pretreated SCLC patients was observed, which warrants further exploration of the potential contribution of LBH589 in other trials. © 2013 by the International Association for the Study of Lung Cancer.
Lodi G.,University of Milan |
Pellicano R.,Molinette Hospital |
Carrozzo M.,Northumbria University
Oral Diseases | Year: 2010
Objective: Hepatitis C virus (HCV) is one of the major causes of chronic liver disease worldwide but its morbidity is also due to a variety of extra-hepatic manifestations including mixed cryoglubulinemia, non-Hodgkin lymphoma, diabetes, porphyria cutanea tarda and lichen planus. The aims of this study were to conduct a systematic review and a meta-analysis on the prevalence of HCV in lichen planus patients and on the prevalence of lichen planus in chronic HCV infection. Materials and Method: Bibliographic searches were conducted in several electronic databases. Pooled data were analysed by calculating odds ratios, using a random effects model. Results and Conclusions: Thirty-three studies comparing the seroprevalence of HCV in lichen planus patients and six reporting the prevalence of lichen planus in patients with HCV infection were included in the meta-analysis. The summary estimate showed that LP patients have significantly higher risk (odds ratio 4.85; 95% confidence interval 3.58-6.56) than controls of being HCV seropositive. A similar odds ratio of having lichen planus was found among HCV patients (4.47; 95% confidence interval 1.84-10.86). Sub-analyses indicated that variability of HCVlichen planus association seemed only partially depending on geographic effect. © 2010 John Wiley & Sons AS.
Pellicano R.,Molinette Hospital |
Guerra L.,Medical Service
Minerva Medica | Year: 2012
Chronic or acute pain related to skin ulcers or their management (medication, debridement) is a typical case of mixed pain, both neuropathic and nociceptive. It represents a disabling clinical condition that deteriorates the patient's quality of life. The pharmaceutical therapy must be based on both, intensity and the type of pain. Although NSAIDs, Non Steroidal Anti-Inflammatory Drugs are notoriously effective on nociceptive pain, do not give great results on neuropathic and mixed pain. Also the consumption of NSAIDs is affected by a series of side effects that may involve several organs. In case of neuropathic pain, the benefit deriving from the use of a single active principle is relative. This sets the rational grounds for the use of combined drugs. The paracetamol/tramadol combination represents an innovative solution in the treatment of both the neuropathic and nociceptive components of the pain, since both active principles have a different action mechanism, multiple targets and different pharmacokinetics. It is very interesting, from the clinical point of view, that tramadol is a pure antagonist, not selective, of μ, δ, and κ receptors and carries out and important inhibition action of serotonin and norepinephrine reuptake. This double mechanism, opioid and non-opioid, explains its analgesic efficacy also on neuropathic pain. Besides, since its opioid action is rather weak, it does not induce the severe side effects typical of traditional opioids. The benefit of such com bination comes from their complementary pharmacokinetic profile, since the first has a quick action insurgence, while tramadol has a more prolonged effect. Therefore, this combination allows to obtain a quick and long lasting effect with a high tolerability profile also when treating skin ulcer pain.
Ghigo A.,University of Turin |
Franco I.,University of Turin |
Morello F.,Molinette Hospital |
Hirsch E.,University of Turin
Cardiovascular Research | Year: 2014
Myocardial damage, by different noxious causes, triggers an inflammatory reaction driving post-injury repair mechanisms and chronic remodelling processes that are largely detrimental to cardiac function. Cardiomyocytes have recently emerged as key players in orchestrating this inflammatory response. Injured cardiomyocytes release damage-associated molecular pattern molecules, such as high-mobility group box 1 (HMGB1), DNA fragments, heat shock proteins, and matricellular proteins, which instruct surrounding healthy cadiomyocytes to produce inflammatory mediators. These mediators, mainly interleukin (IL)-1β, IL-6, macrophage chemoattractant protein (MCP)-1, and tumour necrosis factor α (TNF-α), in turn activate versatile signalling networks within surviving cardiomyocytes and trigger leucocyte activation and recruitment. In this review, we will focus on recently characterized signalling pathways activated in cardiomyocytes that mediate inflammatory responses during myocardial infarction, hypertensive heart disease, and myocarditis. © The Author 2014.
Pellicano R.,Molinette Hospital
Minerva Gastroenterologica e Dietologica | Year: 2014
Gastrointestinal (GI) damage by non-steroidal anti-inflammatory drugs (NSAIDs) is an important Public Health problem due to morbility and elevated mortality rate. The logic behind the development and sale of molecules which are selective cyclooxeg-nase-2 (COX-2) inhibitors called coxibs, is to limit the undesired effects of traditional NSAIDs, which should theoretically derive from the inhibition of COX-1. With respect to the emphasis of the initial trials, to now epidemiological studies, open-label studies, meta-analyses and reviews of the same data with longer follow-up, have produced opposite conclusions. Indeed, a recent series of meta-analyses has shown that the risks of GI events are similar for coxib and diclofenac, while they are significantly higher during the assumption of ibuprofen or naproxen. Moreover, the presumed lower gastrolesiv-ity of coxibs is based on a highly simplified hypothesis, that the gastroprotective PGs derive from COX-1 and that the phlogistic processes are related to COX-2. Also in geriatric populations, though less tolerated than coxibs, diclofenac presents minor GI side effects when compared with naproxen and ibuprofen. In this context, in the case of moderate pain intensity, it is possible to use combinations with weak opioids, such as paraceta-mol-tramadol. Though intestinal damage by NSAIDs are a nosological entity of growing interest, to now no trial has been conducted with optimal criteria to demonstrate the superiority of coxibs over traditional NSAIDs. For this reason, chronic inflammation of the intestine still represents a contraindication to the administration of coxibs.