40 research outputs found

    Androgenic suppression combined with radiotherapy for the treatment of prostate adenocarcinoma: a systematic review

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    <p>Abstract</p> <p>Background</p> <p>Locally advanced prostate cancer is often associated with elevated recurrence rates. Despite the modest response observed, external-beam radiotherapy has been the preferred treatment for this condition. More recent evidence from randomised trials has demonstrated clinical benefit with the combined use of androgen suppression in such cases. The aim of this meta-analysis is to compare the combination of distinct hormone therapy modalities versus radiotherapy alone for overall survival, disease-free survival and toxicity.</p> <p>Methods</p> <p>Databases (MEDLINE, EMBASE, LILACS, Cochrane databases and ClinicalTrials.gov) were scanned for randomised clinical trials involving radiotherapy with or without androgen suppression in local prostate cancer. The search strategy included articles published until October 2011. The studies were examined and the data of interest were plotted for meta-analysis. Survival outcomes were reported as a hazard ratio with corresponding 95% confidence intervals.</p> <p>Results</p> <p>Data from ten trials published from 1988 to 2011 were included, comprising 6555 patients. There was a statistically significant advantage to the use of androgen suppression, in terms of both overall survival and disease free survival, when compared to radiotherapy alone. The use of long-term goserelin (up to three years) was the strategy providing the higher magnitude of clinical benefit. In contrast to goserelin, there were no trials evaluating the use of other luteinizing hormone-releasing hormone (LHRH) analogues as monotherapy. Complete hormonal blockade was not shown to be superior to goserelin monotherapy.</p> <p>Conclusions</p> <p>Based on the findings of this systematic review, the evidence supports the use of androgen suppression with goserelin monotherapy as the standard treatment for patients with prostate cancer treated with radiotherapy, which are at high risk of recurrence or metastases.</p

    Matrix Rigidity Induces Osteolytic Gene Expression of Metastatic Breast Cancer Cells

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    Nearly 70% of breast cancer patients with advanced disease will develop bone metastases. Once established in bone, tumor cells produce factors that cause changes in normal bone remodeling, such as parathyroid hormone-related protein (PTHrP). While enhanced expression of PTHrP is known to stimulate osteoclasts to resorb bone, the environmental factors driving tumor cells to express PTHrP in the early stages of development of metastatic bone disease are unknown. In this study, we have shown that tumor cells known to metastasize to bone respond to 2D substrates with rigidities comparable to that of the bone microenvironment by increasing expression and production of PTHrP. The cellular response is regulated by Rho-dependent actomyosin contractility mediated by TGF-ß signaling. Inhibition of Rho-associated kinase (ROCK) using both pharmacological and genetic approaches decreased PTHrP expression. Furthermore, cells expressing a dominant negative form of the TGF-ß receptor did not respond to substrate rigidity, and inhibition of ROCK decreased PTHrP expression induced by exogenous TGF-ß. These observations suggest a role for the differential rigidity of the mineralized bone microenvironment in early stages of tumor-induced osteolysis, which is especially important in metastatic cancer since many cancers (such as those of the breast and lung) preferentially metastasize to bone

    Semen characteristics and inflammatory mediators in infertile men with different clinical diagnoses

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    This study was aimed at investigating whether semen characteristics in different clinical diagnoses of infertility are associated with PMN elastase, IL-6, IL-8, IL-1b and TNFa levels detected in seminal plasma. Sixty-eight patients were divided into groups according to their clinical diagnosis: idiopathic infertility (group I), varicocele with infections (group II), varicocele (group III), infections (group IV), controls (group V). Physical examination and scrotal Eco-color Doppler was used to detect the varicocele. Patients with positive bacteriological semen analysis were considered as having an infection of the male reproductive tract. Samples were examined by light microscopy and transmission electron microscopy (TEM). TEM data were quantified with a mathematical formula furnishing a fertility index and the percentage of sperm apoptosis, immaturity and necrosis. PMN elastase ⁄ a1-PI complex levels were determined by ELISA and IL-6, IL-8, IL-1b, TNFa by Bio-Plex Cytokine assay. Sperm concentration (I-II: p &lt; 0.005; III-IV: p &lt; 0.0001), motility (I-IV: p &lt; 0.0001) and the fertility index (I: p &lt; 0.005; II-IV: p &lt; 0.0001) were significantly lower in the groups vs. controls, whereas sperm pathologies, except for apoptosis, were significantly higher in group I and apoptosis and necrosis were higher in group III. An increase in immaturity (p &lt; 0.005) with a decrease in necrosis (p &lt; 0.005) were observed in group III vs. group IV. Significantly higher levels of inflammatory mediators were detected in groups III and IV vs. controls. Despite a broad relationship among different inflammatory mediators, no correlation was found among them and the semen parameters, including indices from TEM analysis. In conclusion, patients with idiopathic infertility showed altered semen quality and normal levels of inflammatory mediators. Genitourinary infection and varicocele induced an inflammatory effect which could play a detrimental role in spermatogenesis, revealed by a decrease in sperm motility and the fertility index, concomitant with an increase in immaturity mainly in varicocele and necrosis in infection

    Risk Management in healthcare: Results from a national-level survey and scientometric analysis in Italy

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    Risk management in healthcare, intended as all processes employed to detect, monitor, assess, mitigate, and prevent risks in healthcare facilities and safeguard patient safety, is a crucial component of Italy' National Health Service. Aim of the current study is to assess the role and progress of research and training, in the field of Risk Management. We carried out a scientometric analysis to quantify and describe scientific outputs on Risk Management at the global and national level, over the last forty years; in addiction, we conducted a national-level cross-sectional survey to systematically retrieve and assess research and training activities within Italian postgraduate medical programmes in Hygiene and Preventive Medicine. We report increasing scientific production on Risk Management-related topics from 1980 to 2017 at the global level (12% annual increase rate). Clinical Trials and Systematic reviews/meta-analysis make up for respectively 5% and 6% of global scientific output. Italy ranks 4th for scientific production, after USA, UK and Germany. 88% of Italian postgraduate medical programmes in Hygiene and Preventive medicine research on Risk Management, 42% through international collaborations. The main research themes are Healthcare-Associated Infections (HAIs) (97%), analysis of organizational models for safety in healthcare (62%), while training is focused on internships (87%) and academic lectures (73%). While research provides the evidence required to plan, implement and monitor effective interventions in healthcare risk management, training allows its dissemination in a synergic action to promote the value of patient safety and quality of care. (www.actabiomedica.it)

    Sex-based differences in susceptibility to respiratory and systemic pneumococcal disease in mice.

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    Systemic infection with Streptococcus pneumoniae was investigated in male and female mice in models of invasive pneumonia and sepsis. Male mice were found to be more susceptible to infection, exhibiting greater weight loss, marked decrease in body temperature, and a significantly higher mortality rate compared with female mice. For pneumonia, there were significant differences in survival rates. Female mice cleared their lung infections over time, whereas male mice, compared with female mice, had significantly increased numbers of colony-forming units in early stages of infection accompanied by higher levels of neutrophil recruitment in the first 24 hours after infection. Importantly, there were significant increases in proinflammatory cytokine levels during both sepsis and pneumonia in male compared with female mice. These cytokines were indicative of T-helper 1-type responses. The data presented here describe surprising differences in survival rates, neutrophil recruitment, and proinflammatory cytokine levels, indicating a sex-based difference in susceptibility to respiratory and systemic pneumococcal disease
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