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Bergamo, Italy

The Mario Negri Institute for Pharmacological Research is a nonprofit research institute dedicated to clinical and biomedical research. It was made possible by a special bequest of Milan philanthropist it:Mario Negri . It was founded in 1961 although it started working in Milan from 1st Feb 1963. There are branches of the institute in Bergamo, Ranica , and at Santa Maria Imbaro, near Chieti.Founder and director from 1961 is prof. it:Silvio Garattini. Wikipedia.

Ricci E.,University of Milan | Cipriani S.,University of Milan | Chiaffarino F.,University of Milan | Malvezzi M.,Mario Negri Institute | Parazzini F.,University of Milan
Journal of Women's Health | Year: 2010

Background: Several randomized controlled trials (RCTs) have compared the effect of phytoestrogens (PEs) vs. placebos on bone density after menopause, with inconsistent results. Methods: We performed a systematic review to assess the overall effect of PEs on bone mineral density (BMD) in menopausal Western women. We searched for all RCTs comparing PEs with placebos conducted on perimenopausal or postmenopausal Western women, published from January 1990 to February 2010. The main outcome measure was the lumbar spine (LS) BMD. Results: We identified 17 studies on soy isoflavone (IFs) bone-sparing effects. Some studies did not report a difference between treated and untreated women, whereas others supported a significant role of IFs on slowing bone loss, although these studies suffered from an internal lack of consistency, as a positive effect emerged in some bone districts but not in others. Data on LS BMD were available in 12 studies including 1433 subjects overall. The effect of PEs on BMD (mg/cm2) was not statistically significant (mean difference 9.86?mg/cm2, 95% confidence interval [CI] -2.64-22.36) under a random-effects model. Excluding the genistein study, however, analyses of IF mixtures did not show a bone-sparing effect (0.73, 95% CI -2.79-4.25). No increasing effect emerged when dose and treatment duration were increased. Conclusions: Our review and meta-analysis suggest that IF mixtures are not effective in decreasing bone loss in perimenopausal and postmenopausal Western women. The role of isolated genistein and individual genetic capacity to metabolize IFs is still open to evaluation. © 2010, Mary Ann Liebert, Inc. Source

Salvati E.,Regina Elena Cancer Institute | Scarsella M.,Regina Elena Cancer Institute | Porru M.,Regina Elena Cancer Institute | Rizzo A.,Regina Elena Cancer Institute | And 11 more authors.
Oncogene | Year: 2010

New anti-telomere strategies represent important goals for the development of selective cancer therapies. In this study, we reported that uncapped telomeres, resulting from pharmacological stabilization of quadruplex DNA by RHPS4 (3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate), trigger specific recruitment and activation of poly-adenosine diphosphate (ADP) ribose polymerase I (PARP1) at the telomeres, forming several ADP-ribose polymers that co-localize with the telomeric repeat binding factor 1 protein and are inhibited by selective PARP(s) inhibitors or PARP1-specific small interfering RNAs. The knockdown of PARP1 prevents repairing of RHPS4-induced telomere DNA breaks, leading to increases in chromosome abnormalities and eventually to the inhibition of tumor cell growth both in vitro and in xenografts. More interestingly, the integration of a TOPO1 inhibitor on the combination treatment proved to have a high therapeutic efficacy ensuing a complete regression of the tumor as well as a significant increase in overall survival and cure of mice even when treatments started at a very late stage of tumor growth. Overall, this work reveals the unexplored link between the PARP1 and G-quadruplex ligands and demonstrates the excellent efficacy of a multi-component strategy based on the use of PARP inhibitors in telomere-based therapy. © 2010 Macmillan Publishers Limited All rights reserved. Source

Levi F.,University of Lausanne | Randimbison L.,University of Lausanne | Maspoli-Conconi M.,Neuchatel Cancer Registry | Blanc-Moya R.,University of Lausanne | And 2 more authors.
Cancer Causes and Control | Year: 2014

Background: In high-quality cancer registration systems, about one in eight incident cancers are second primary cancers. This is due to a combination of careful diagnostic ascertainment, shared genetic determinants, shared exposure to environmental factors and consequences of treatment for first cancer. Methods: We used data derived from the Swiss population-based cancer Registries of Vaud and Neuchâtel, including 885,000 inhabitants. Results: Among 107,238 (52% males) first cancers occurring between 1976 and 2010, a total of 126 second sarcomas were observed through active and passive follow-up versus 68.2 expected, corresponding to a standardized incidence ratio (SIR) of 1.85 (95 % CI 1.5-2.2). Significant excess sarcoma risks were observed after skin melanoma (SIR = 3.0), breast cancer (2.2), corpus uteri (2.7), testicular (7.5), thyroid cancer (4.2), Hodgkin lymphoma (5.7) and leukemias (4.0). For breast cancer, the SIR was 3.4 ≥5 years after sarcoma diagnosis. Conclusions: The common denominator of these neoplasms is the utilization of radiotherapy in their management. Some sarcomas following breast cancer may be due to shared genetic components (i.e., in the Li-Fraumeni syndrome), as well as possibly to shared environmental factors, with sarcomas, including overweight, selected dietary and reproductive factors which are, however, too little defined for any quantitative risk assessment. © 2014 Springer International Publishing. Source

Kaguelidou F.,APHP | Pandolfini C.,Mario Negri Institute | Manzoni P.,Neonatology and Hospital Neonatal Intensive Care Unit | Choonara I.,University of Nottingham | And 2 more authors.
European Journal of Pediatrics | Year: 2012

Neonatal fungal infections are associated with substantial mortality and morbidity. Although prophylactic use of several antifungals has been proposed, this practice remains controversial. In order to evaluate the use of fluconazole prophylaxis in European NICUs, we conducted a cross-sectional survey by means of a structured questionnaire that was sent to European level II and III neonatal intensive care units, over a 9-month period, as part of a neonatal research FP7 European project. A total of 193 questionnaires from 28 countries were analysed. Use of antifungal prophylaxis was reported by 55% of the responders, and the most frequently used antifungal agent was fluconazole (92%). Main indications for prophylaxis were low gestational age (<28 weeks) and birth weight (<1,000 g). A dose of 3 mg/kg was used in 66% of NICUs using fluconazole, with an administration interval of 72 h in 52% of them. All responders acknowledged the need for additional trials on the efficacy of prophylactic fluconazole. Non-users of fluconazole prophylaxis were more likely to be influenced by the local incidence of candidiasis, the risk of increasing antifungal resistance and the absence of specific recommendations by paediatric societies. Conclusions: Major concerns about the use of fluconazole prophylaxis include its efficacy, the risk of emergence of resistant species and the absence of clear consensus to support routine use. Future studies that address these issues will contribute to a more rational use of fluconazole prophylaxis. © Springer-Verlag 2011. Source

Erba G.,University of Rochester | Giussani G.,Mario Negri Institute | Juersivich A.,University of Rochester | Magaudda A.,Messina University | And 6 more authors.
Epilepsia | Year: 2016

Objective To investigate if, when, and to what extent visual information contained in a video-recorded event allows experienced epileptologists to predict the diagnosis of psychogenic nonepileptic seizures (PNES) without the aid of electroencephalography (EEG). Methods Five neurologists actively practicing in epilepsy centers in Italy and the United States were asked to review 23 videos capturing representative events of 21 unselected consecutive patients admitted for long-term video-EEG monitoring (VEM). Four raters were blind to EEG and clinical information; one rater was not. They were requested to (1) rate the videos for quality and content; (2) choose among four diagnoses: (a) epileptic seizures (ES); (b) PNES; (c) Other nonepileptic seizures (NES; (syncope, movement disorder, migraine, etc.); (d) "Cannot Say"; and (3) explain in their own words the main reasons leading to the diagnosis of choice. Results All raters predicted the diagnosis correctly in 7 of 23 videos (all ES or PNES) (30.4%), whereas all raters failed in 5 of 23 cases (three Other NES, one PNES, one Cannot Say) (21.7%). The conditions that facilitate, and those that interfere with, a confident diagnosis were predictable. Degree of accuracy among raters was not uniform and was consistently better in three raters. Two among the four blind raters were as accurate as the rater who was not blinded. Interrater agreement was "moderate" (k = 0.52) for the overall group; "moderate" for ES (k = 0.53); "substantial" for PNES (k = 0.63); "fair" for Other NES (k = 0.21) - similar to the results obtained in a previous study evaluating the reliability of combined video-EEG. Significance In about one third of cases, a confident diagnosis of PNES/ES can be established on clinical grounds based on video data alone. Our results benefit all affected patients, particularly those with no access to video-EEG monitoring units. © 2016 International League Against Epilepsy. Source

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