Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care

DESIGN FOR CHILDREN: TOWARDS THE DESIGN OF LEARNING ENVIRONMENTS AND OBJECTS FOR CHILDREN

Il paper si concentra sulla progettazione di ambienti e oggetti per bambini, partendo dall'ONU, linee guida ministeriali italiane e dai paradigmi di ricerca di Universal Design for Learning e Design for Children. Declinando queste linee guida in diversi ambienti - digitale, analogico, interno, esterno - il documento sottolinea l'idea di un design che, per migliorare lo sviluppo emotivo, motorio e cognitivo dei bambini e il loro processo di apprendimento, dovrebbe partire ed essere per i bambini

Histone deacetylase inhibitor ITF2357 (Givinostat) reverts transformed phenotype and counteracts stemness in in vitro and in vivo models of human glioblastoma

Purpose Aberrant expression and activity of histone deacetylases (HDACs) sustain glioblastoma (GBM) onset and progression and, therefore, HDAC inhibitors (HDACi) represent a promising class of anti-tumor agents. Here we analyzed the effects of ITF2357 (givinostat), a pan-HDACi, in GBM models for its anti-neoplastic potential. Methods A set of GBM- and patient-derived GBM stem-cell lines was used and the ITF2357 effects on GBM oncophenotype were investigated in in vitro and in vivo xenograft models. Results ITF2357 inhibited HDAC activity and affected GBM cellular fate in a dose dependent manner by inducing G1/S growth arrest (1 to 2.5μM) or caspase-mediated cell death (> 2.5μM). Chronic treatment with low doses (< 1μM) induced autophagy-mediated cell death, neuronal like phenotype and the expression of differentiation markers, such as Glial Fibrillar Actin Protein (GFAP) and Neuron-specific class III beta-tubulin (Tuj-1), this reducing neurosphere formation from patient-derived GBM stem cells. Autophagy inhibition counteracted the ITF2357-induced expression of differentiation markers in p53-expressing GBM cells. Finally, in in vivo experiments, ITF2357 efficiently passed the blood–brain barrier, so rapidly reaching high concentration in the brain tissues, and significantly affected U87MG and U251MG growth in orthotopic xenotransplanted mice. Conclusions The present findings provide evidence of the key role played by HDACs in sustaining transformed and stem phenotype of GBM and strongly suggest that ITF2357 may have a clinical potential for the HDACi -based therapeutic strategies against GBM

Histone deacetylase inhibitor ITF2357 (Givinostat) reverts transformed phenotype and counteracts stemness in in vitro and in vivo models of human glioblastoma

Purpose Aberrant expression and activity of histone deacetylases (HDACs) sustain glioblastoma (GBM) onset and progression and, therefore, HDAC inhibitors (HDACi) represent a promising class of anti-tumor agents. Here we analyzed the effects of ITF2357 (givinostat), a pan-HDACi, in GBM models for its anti-neoplastic potential. Methods A set of GBM- and patient-derived GBM stem-cell lines was used and the ITF2357 effects on GBM oncophenotype were investigated in in vitro and in vivo xenograft models. Results ITF2357 inhibited HDAC activity and affected GBM cellular fate in a dose dependent manner by inducing G1/S growth arrest (1 to 2.5μM) or caspase-mediated cell death (> 2.5μM). Chronic treatment with low doses (< 1μM) induced autophagy-mediated cell death, neuronal like phenotype and the expression of differentiation markers, such as Glial Fibrillar Actin Protein (GFAP) and Neuron-specific class III beta-tubulin (Tuj-1), this reducing neurosphere formation from patient-derived GBM stem cells. Autophagy inhibition counteracted the ITF2357-induced expression of differentiation markers in p53-expressing GBM cells. Finally, in in vivo experiments, ITF2357 efficiently passed the blood–brain barrier, so rapidly reaching high concentration in the brain tissues, and significantly affected U87MG and U251MG growth in orthotopic xenotransplanted mice. Conclusions The present findings provide evidence of the key role played by HDACs in sustaining transformed and stem phenotype of GBM and strongly suggest that ITF2357 may have a clinical potential for the HDACi -based therapeutic strategies against GBM

Ways to improve breast cancer patients' management and clinical outcome: The 2020 Assisi Think Tank Meeting

We report on the third Assisi Think Tank Meeting (ATTM) on breast cancer, a brainstorming project which involved European radiation and clinical oncologists who were dedicated to breast cancer research and treatment. Held on February 2020, the ATTM aimed at identifying key clinical questions in current clinical practice and "grey" areas requiring research to improve management and outcomes. Before the meeting, three key topics were selected: 1) managing patients with frailty due to either age and/or multi-morbidity; 2) stereotactic radiation therapy and systemic therapy in the management of oligometastatic disease; 3) contralateral breast tumour prevention in BCRA-mutated patients. Clinical practice in these areas was investigated by means of an online questionnaire. In the lapse period between the survey and the meeting, the working groups reviewed data, on-going studies and the clinical challenges which were then discussed in-depth and subjected to intense brainstorming during the meeting; research protocols were also proposed. Methodology, outcome of discussions, conclusions and study proposals are summarized in the present paper. In conclusion, this report presents an in-depth analysis of the state of the art, grey areas and controversies in breast cancer radiation therapy and discusses how to confront them in the absence of evidence-based data to guide clinical decision-making

Ways to improve breast cancer patients' management and clinical outcome: The 2020 Assisi Think Tank Meeting.

We report on the third Assisi Think Tank Meeting (ATTM) on breast cancer, a brainstorming project which involved European radiation and clinical oncologists who were dedicated to breast cancer research and treatment. Held on February 2020, the ATTM aimed at identifying key clinical questions in current clinical practice and "grey" areas requiring research to improve management and outcomes. Before the meeting, three key topics were selected: 1) managing patients with frailty due to either age and/or multi-morbidity; 2) stereotactic radiation therapy and systemic therapy in the management of oligometastatic disease; 3) contralateral breast tumour prevention in BCRA-mutated patients. Clinical practice in these areas was investigated by means of an online questionnaire. In the lapse period between the survey and the meeting, the working groups reviewed data, on-going studies and the clinical challenges which were then discussed in-depth and subjected to intense brainstorming during the meeting; research protocols were also proposed. Methodology, outcome of discussions, conclusions and study proposals are summarized in the present paper. In conclusion, this report presents an in-depth analysis of the state of the art, grey areas and controversies in breast cancer radiation therapy and discusses how to confront them in the absence of evidence-based data to guide clinical decision-making

Ways to improve breast cancer patients' management and clinical outcome: The 2020 Assisi Think Tank Meeting

We report on the third Assisi Think Tank Meeting (ATTM) on breast cancer, a brainstorming project which involved European radiation and clinical oncologists who were dedicated to breast cancer research and treatment. Held on February 2020, the ATTM aimed at identifying key clinical questions in current clinical practice and "grey" areas requiring research to improve management and outcomes. Before the meeting, three key topics were selected: 1) managing patients with frailty due to either age and/or multi-morbidity; 2) stereotactic radiation therapy and systemic therapy in the management of oligometastatic disease; 3) contralateral breast tumour prevention in BCRA-mutated patients. Clinical practice in these areas was investigated by means of an online questionnaire. In the lapse period between the survey and the meeting, the working groups reviewed data, on-going studies and the clinical challenges which were then discussed in-depth and subjected to intense brainstorming during the meeting; research protocols were also proposed. Methodology, outcome of discussions, conclusions and study proposals are summarized in the present paper. In conclusion, this report presents an in-depth analysis of the state of the art, grey areas and controversies in breast cancer radiation therapy and discusses how to confront them in the absence of evidence-based data to guide clinical decision-making

Additional file 2: Table S1. of Chromogranin-A production and fragmentation in patients with Takayasu arteritis

CgA peptides in TA patients with and without arterial hypertension, stratified for therapy with PPIs. (DOC 49 kb