Gli inibitori dell'istone deacetilasi nel trattamento del linfoma non hodgkin diffuso a grandi cellule ricaduto/refrattario dell'adulto: studio di fase II con Panobinostat

Backgrounds:Treatment of patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) not eligible to high dose therapy represents an unmet medical need. Panobinostat showed encouraging therapeutic activity in studies conducted in lymphoma cell lines and in vivo in patients with advanced hematologic malignancies.Purpose:FIL-PanAL10 (NCT01523834) is a phase II, prospective multicenter trial of the Fondazione Italiana Linfomi (FIL) to evaluate safety and efficacy of single agent Panobinostat as salvage therapy for R/R DLBCL patients and to evaluate a possible relationships between response and any biological features. Patients and Methods:Patients with R/R DLBCL were included. The treatment plan included 6 induction courses with Panobinostat monotherapy followed by other 6 courses of consolidation. The primary objective was to evaluate Panobinostat activity in terms of overall response (OR); secondary objectives were: CR rate, time to response (TTR), progression-free survival (PFS), safety and feasibility of Panobinostat. We included evaluation of the impact of pharmacogenetics, immunohistochemical patterns and patient’s specific gene expression and mutations as potential predictors of response to Panobinostat as explorative objectives. To this aim a pre-enrollment new tissue biopsy was mandatory. ResultsThirty-five patients, 21 males (60%), were enrolled between June 2011 and March 2014. At the end of induction phase, 7 responses (20%) were observed, including 4 CR (11%), while 28 patients (80%) discontinued treatment due to progressive disease (PD) in 21 (60%) or adverse events in 7 (20%). Median TTR in 9 responders was 2.6 months (range 1.8-12). With a median follow up of 6 months (range 1-34), the estimated 12 months PFS and OS were 27% and 30.5%, respectively. Grade 3-4 thrombocytopenia and neutropenia were the most common toxicities (in 29 (83%) and 12 (34%) patients, respectively. Conclusions The results of this study indicate that Panobinostat might be remarkably active in some patients with R/R DLBCL, showing durable C

Prolonged disease-free survival in elderly relapsed diffuse large B-cell lymphoma patients treated with lenalidomide plus rituximab

open4non/aopenZinzani, PIER LUIGI; Pellegrini, Cinzia; Argnani, Lisa; Broccoli, AlessandroZinzani, PIER LUIGI; Pellegrini, Cinzia; Argnani, Lisa; Broccoli, Alessandr

PKM mechatronic clamping adaptive device

This study proposes a novel adaptive fixturing device based on active clamping systems for smart micropositioning of thin-walled precision parts. The modular architecture and the structure flexibility make the system suitable for various industrial applications. The proposed device is realized as a Parallel Kinematic Machine (PKM), opportunely sensorized and controlled, able to perform automatic error-free workpiece clamping procedures, drastically reducing the overall fixturing set-up time. The paper describes the kinematics and dynamics of this mechatronic system. A first campaign of experimental trails has been carried out on the prototype, obtaining promising results

Public and patient involvement: a survey on knowledge, experience and opinions among researchers within a precision oncology European project

Participatory research; Patient engagement; Precision oncologyInvestigación participativa; Compromiso del paciente; Oncología de precisiónRecerca participativa; Compromís del pacient; Oncologia de precisióBackground Patient and Public Involvement (PPI) is slowly but steadily being implemented in all phases of clinical research. As part of the European project “Building Data Rich Clinical Trials” a survey was launched to investigate the knowledge, experiences and opinions on this topic of clinicians and researchers from seven European clinical and non-clinical centers (Cancer Core Europe). Methods An invitation to take part in a cross-sectional web survey was sent to 199 clinicians and researchers working in the field of precision oncology. The questionnaire was developed ad hoc because no existing questionnaires met the purpose of this study. The analysis takes account of whether respondents had experience on PPI or not. Results On a total of 101 respondents, this survey reveals that 76.2% of them knew about PPI before answering the questionnaire, 54.5% had experience in the previous five years and 86.1% were interested in a training course on this topic. PPI knowledge grew together with career seniority (peak of 86.5% for established career professionals), while the group most interested in a course was the early-career professionals (100.0%). Finally, the majority of respondents stated they had no training or education on PPI (67.3% of experienced and 82.6% of not-experienced respondents). Conclusions This survey shows that most cancer researchers knew the term PPI, even if only a little more than half of them had any relative experience. Opinions on PPI benefits, negative effects, barriers and requirements differed between the groups of PPI experienced and not-experienced respondents, showing that experience itself can influence respondents’ opinions. Most of respondents reported they would prefer a training course based on practical rather than theoretical tools.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 965397

Moderate exercise improves cardiac hypertrophy in female aged mice

Age-related diastolic dysfunction has a significant impact on the elderly health, in fact the left ventricular filling is impaired, limiting intense exercise tolerance and reducing the quality of life. Pathological hypertrophy is commonly associated with up-regulation of fetal genes, fibrosis, cardiac dysfunction, fat deposits and increased mortality. Regular and moderate physical activity improves cardiac performance in elderly people. Type 5 cyclic nucleotide phosphodiesterase (PDE5) regulates intracellular cGMP levels and its increased expression has an important role in the development of cardiac hypertrophy (1). Our hypothesis is to assess if moderate exercise modulates PDE5 expression and reduces cardiac hypertrophy in old mice. CD1 female mice were grouped in young (2 months) sedentary (YS), young trained (YE), old 20 months sedentary (OS) and old old trained (OE). Exercise was performed at moderate intensity (speed of 13 m/min, for 30 minutes) on tapis roulant for 5 days/week. Morphometric (left ventricular weight/tibial length ratio) and histological (cardiomyocyte size) analyses showed that cardiac hypertrophy is present in OS compared to YS and YE and significantly reduced in OE group compared to OS. Moderate exercise also attenuated cardiac fibrosis in OE group. Molecular analysis revealed that hypertrophic markers such as ANP, BNP, GATA 4 and NKX 2.5 were significantly down-regulated in OE group. SIRT1 and PPARα, two regulators of oxidative stress and fat metabolism, were up-regulated in aged trained mice. PDE5 expression is down-regulated after exercise in OE group. These results suggest that exercise leads to a beneficial effect in old mice. Interestingly PDE5 expression correlates with the anti-hypertrophic effect of training in old mice

Brentuximab vedotin in the treatment of elderly Hodgkin lymphoma patients at first relapse or with primary refractory disease: a phase 2 study of FIL ONLUS

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A phase II study on the role of gemcitabine plus romidepsin (GEMRO regimen) in the treatment of relapsed/refractory peripheral T-cell lymphoma patients

Background: There is no consensus regarding optimal treatment for peripheral T-cell lymphomas (PTCL), especially in relapsed or refractory cases, which have very poor prognosis and a dismal outcome, with 5-year overall survival of 30 %. Methods: A multicenter prospective phase II trial was conducted to investigate the role of the combination of gemcitabine plus romidepsin (GEMRO regimen) in relapsed/refractory PTCL, looking for a potential synergistic effect of the two drugs. GEMRO regimen contemplates an induction with romidepsin plus gemcitabine for six 28-day cycles followed by maintenance with romidepsin for patients in at least partial remission. The primary endpoint was the overall response rate (ORR); secondary endpoints were survival, duration of response, and safety of the regimen. Results: The ORR was 30 % (6/20) with 15 % (3) complete response (CR) rate. Two-year overall survival was 50 % and progression-free survival 11.2 %. Grade >= 3 adverse events were represented by thrombocytopenia (60 %), neutropenia (50 %), and anemia (20 %). Two patients are still in CR with median response duration of 18 months. The majority of non-hematological toxicities were mild and transient. No treatment-related death occurred and no toxicity led to treatment interruption. Conclusions: GEMRO combination regimen shows efficacy data similar to those of single-agent romidepsin with additional hematologic toxicities. Synergy observed in preclinical phase did not turn into ability to improve clinical outcomes

Single-agent rituximab is an effective salvage therapy in pretreated patients with hairy cell leukemia

No abstract availabl

The experience of regular exercise participation for women moving into their middle years : its nature, meaning and its benefits

This study added to the limited research on positive aspects of the human condition. It highlighted the perspective that women in western society recognise that there are wider health benefits to be taken from exercise than science suggests. Whilst this study acknowledged the customary fragmentary view, it took a holistic approach to exploring the nature and meaning of regular participation in exercise from the perspective of 41 women aged 30 to 50 years. This qualitative study included the views of regular participants in facility based and non-facility based exercise, along with the views of exercise instructors and the researcher. The study was contextualised within the traditional theories of related disciplines, namely health, women's studies, and exercise science. Also it was founded on the fitness industry's perspective on its service provision and its instructor training. Theory was compared with the experiences of a sector of the female population who, despite all the accepted calls on their time and energy, consistently maintained regular involvement in exercise. The study provided a holistic perspective on the nature, meaning and benefits of regular participation in exercise. Semi-structured interviews and focus groups were utilised in the data gathering process. In each case, the process consisted of a series of questions designed to explore a subjective perception of experience in accordance with the Neuro-Logical Levels process, a model from within the field of Neuro-Linguistic Programming (Dilts, 1990; Dilts, Hallbom and Smith, 1990; O'Connor and Seymour, 1995). This model acknowledges that behaviours and actions, witnessed on a surface level, are driven by internal systems, including personal beliefs and identity structures. It was utilised as an exploratory technique to identify unconscious triggers for behaviour. The use of this process in the interviews facilitated individual exploration of the research topic at increasingly deep levels of awareness. Focus groups demonstrated a consensus on, as well as further individual differences in, the beliefs, attitudes, experiences and feelings of the participants as they arose from the interactive context. The heuristic methodology utilised in the analysis and presentation of the data offered a holistic, person-centred and reflective perspective on the nature, meaning and benefits of exercise (Moustakas, 1990). Individual and exemplary portraits depicted the experience and personal meaning of exercise as it emerged from the data. Composite depictions conveyed the nature of exercise participation from the perspectives of participants and instructors. The researcher's involvement in the complete study facilitated the emergence of a creative synthesis of the essence of exercise. Exercise provided emotional and spiritual gains that extended beyond the traditional lifestyle benefits. Individuals indicated a range of 'special' qualities in exercise, along with benefits to the mind. They noted unique personal benefits and enhanced interpersonal relationships in all spheres of life. Regular participation in exercise greatly enhanced the lives of those involved and contributed to an individual and collective evolutionary process. Effective exercise delivery consisted of interactional and motivational elements beyond the scientific and mechanistic topics traditionally recognised in instructor training programmes and was founded on empathy, facilitation, passion, love and positive energy.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

90-yttrium-ibritumomab tiuxetan consolidation of fludarabine, mitoxantrone, rituximab in intermediate/high-risk follicular lymphoma: updated long-term results after a median follow-up of 7\ua0years

Radioimmunotherapy (RIT) after an induction phase with conventional chemoimmunotherapy became an attractive strategy of consolidation for patients with advanced follicular lymphoma: in particular, in many studies RIT was represented by yttrium-90-ibritumomab tiuxetan (90Y-IT). Independently by the different front-line treatment, updates on the long-term follow-up of these studies are needed because the disease course of follicular lymphoma is characterised by multiple relapses and progressively shorter durations of response. We report updated long-term efficacy and toxicity results of a multicenter phase II study on sequential treatment with four cycles of fludarabine, mitoxantrone, and rituximab followed by 90Y-IT as front-line therapy for untreated patients with intermediate/high-risk follicular lymphoma. With a median follow-up of 84 months, only 19/49 (38.8%) complete response patients relapsed, yielding an estimated long-term disease-free survival of 62.6%. The 7-year overall survival was 72.7%. Four (7.3%) second acute myeloid leukemia occurred, with a median time following RIT of 42 months. A relevant patients' responsiveness to subsequent therapies occurred: approximately 65% of relapsed patients obtained a good clinical response after the second-line treatment. These data represented the first evidence of a real role even in the long period of 90Y-IT after a fludarabine-containing regimen plus rituximab in the treatment of high-risk follicular lymphoma