Amaro A.A.,Integrated Molecular Pathology |
Esposito A.I.,Integrated Molecular Pathology |
Mirisola V.,Integrated Molecular Pathology |
Mehilli A.,Italian Institute of Technology |
And 5 more authors.
Current Medicinal Chemistry | Year: 2014
Several substances widely dispersed in the environment including hormones, industrial by-products and pollutants exert hormone like activity affecting steroid-responsive physiological systems. These compounds, named endocrine disruptors, are suspected to affect the mammalian reproductive system. However it is still unclear whether these substances are able to elicit estrogen like activity at the low concentrations encountered in the environment. Here we compare the effects of the endocrine disruptor nonylphenol with the effects elicited by 17-β-estradiol on gene transcription in the human breast cancer cell line MCF7. The correlation of the nonylphenol induced gene expression alterations with a reference profile of estradiol treated cells shows that nonylphenol at a concentration of 100 nM exerts a significant effect on estrogen responsive gene transcription in MCF7 cells. Most of the genes regulated by 17-β-estradiol respond to the nonylphenol in the same direction though to a much lesser extent. Molecular modeling of the potential interaction of nonylphenol with the estrogen receptor α shows that nonylphenol is likely to bind to the estrogen receptor α. © 2014 Bentham Science Publishers.
The "pROCAINA (PROstate CAncer INdication Attitudes) Project" (Part II) - A survey among Italian radiation oncologists on radical radiotherapy in prostate cancer [Il progetto PROCAINA (PROstate CAncer INdication Attitudes) (Parte II) - Una survey tra gli oncologi radioterapisti italiani sulla radioterapia radicale per il tumore prostatico]
De Bari B.,Instituto Del Radio O Alberti Spedali Civili |
Alongi F.,Instituto Clinico Humanitas |
Franco P.,TomoTherapy |
Ciammella P.,IRCCS Arcispedale S. Maria Nuova |
And 4 more authors.
Radiologia Medica | Year: 2013
Purpose: Radiotherapy (RT) has an established role in the treatment of prostate cancer patients. Despite the large number of patients treated with RT, some issues about optimal techniques, doses, volumes, timing, and association with androgen deprivation are still subject of debate. The aim of this survey was to determine the patterns of choice of Italian radiation oncologists in two different clinical cases of prostate cancer patients treated with radical RT. Study design: During the 2010 Italian Association of Radiation Oncology (AIRO) National congress, four different clinical cases were presented to attending radiation oncologists. Two of them were prostate cancer cases that could be treated by RT +/- hormonal therapy (HT), different for T stage of primary tumour according to TNM, preoperative diagnostic procedures for staging, initial prostate specific antigen (iPSA), and Gleason Score sum of biopsy. For each clinical case, radiation oncologists were asked to: (a) give indication to pretreatment procedures for staging; (b) give indication to treatment; (c) define specifically, where indicated, total dose, type of fractionation, volumes of treatment, type of technique, type of image-guided setup control; (d) indicate if HT should be prescribed; (e) define criteria that particularly influenced prescription. A descriptive statistical analysis was performed. Results: Three hundred questionnaires were given to radiation oncologists attending the congress, 128 questionnaires were completed and considered for this analysis (41%). Some important differences were shown in prescribing and delivering RT, particularly with regards to treatment volumes and fractionation. Conclusions: Despite the results of clinical trials, several differences still exist among Italian radiation oncologists in the treatment of prostate cancer patients. These patients probably deserve a more uniform approach, based on upto-date, detailed, and evidence-based recommendations. © 2013 Springer-Verlag.
Angeli F.,Teaching Hospital Sm Della Misericordia |
Verdecchia P.,Hospital of Assisi |
Savonitto S.,IRCCS Arcispedale S. Maria Nuova |
Morici N.,Hospital Niguarda Ca Granda |
And 2 more authors.
Catheterization and Cardiovascular Interventions | Year: 2014
Background It is unclear whether the benefits of an early invasive strategy (EIS) in patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) equally apply to younger and older individuals. Elderly patients are generally less likely to undergo EIS when compared with younger patients. Objectives We conducted a meta-analysis to compare the benefit of an EIS versus a selectively invasive strategy (SIS) in patients with NSTEACS. We tested the hypothesis that the magnitude of benefit of an EIS over a SIS mainly applies to older individuals. Methods We extracted data from randomized controlled trials (RCTs) identified through search methodology filters the primary outcome of the analysis was the composite of all-cause death and myocardial infarction (MI). Secondary outcomes were death and MI taken alone and re-hospitalization. Results Nine trials (n = 9,400 patients) were eligible the incidence of the composite end-point of MI and all-cause death was 16.0% with the EIS and 18.3% with the SIS (OR: 0.85, 95% CI: 0.76-0.95) the incidence of MI was 8.4% with the EIS and 10.9% with the SIS (OR: 0.75, 95% CI: 0.66-0.87). Similar results were obtained for rehospitalization (OR: 0.71, 95% CI: 0.55-0.90) the incidence of all-cause death did not differ between the two groups the EIS reduced the composite end-point and re-hospitalization to a greater extent in elderly than in younger patients (P for interaction = 0.044 and <0.0001, respectively) these findings were confirmed in meta-regression analyses. Conclusions In patients with NSTEACS, a routine EIS reduces the risk of rehospitalization and the composite end point of recurrent MI and death to a greater extent in elderly than in younger individuals. © 2013 Wiley Periodicals, Inc. Copyright © 2013 Wiley Periodicals, Inc.
Menozzi A.,U.O. Cardiologia |
Savonitto S.,IRCCS Arcispedale S. Maria Nuova
Giornale Italiano di Cardiologia | Year: 2014
Background. Nei pazienti sottoposti a procedura coronarica percutanea (PCI) primaria, la bivalirudina, rispetto all'associazione eparina più inibitore della glicoproteina IIb/IIa, si è dimostrata efficace nel ridurre le complicanze emorragiche e la mortalità. Resta tuttavia da definire se tale beneficio persista anche nell'era moderna con somministrazione del trattamento in fase preospedaliera, uso opzionale degli inibitori della glicoproteina IIb/IIIa e dei nuovi inibitori del recettore P2Y12 e utilizzo dell'approccio radiale nella PCI. Metodi. 2218 pazienti con infarto miocardico acuto con sopraslivellamento del tratto ST (STEMI) trasportati in ambulanza per essere sottoposti a PCI primaria sono stati randomizzati a ricevere bivalirudina da sola o eparina non frazionata o a basso peso molecolare in associazione o meno ad inibitore della glicoproteina IIb/IIIa (gruppo di controllo). L'outcome primario a 30 giorni era rappresentato da un composito di morte o sanguinamenti maggiori non correlati all'intervento di bypass aortocoronarico (CABG), mentre l'outcome secondario principale era costituito da un composito di morte, reinfarto o sanguinamenti maggiori non correlati all'intervento di CABG. Risultati. La bivalirudina, rispetto al trattamento convenzionale, ha determinato una riduzione dell'outcome primario (5.1 vs 8.5%; rischio relativo 0.60; intervallo di confidenza [IC] 95% 0.43-0.82; p=0.001) e dell'outcome secondario principale (6.6 vs 9.2%; rischio relativo 0.72; IC 95% 0.54-0.96; p=0.02), nonché una riduzione del tasso di sanguinamenti maggiori (2.6 vs 6.0%; rischio relativo 0.43; IC 95% 0.28-0.66; p<0.001). Il rischio di trombosi acuta dello stent è risultato maggiore nei pazienti trattati con bivalirudina (1.1 vs 0.2%; rischio relativo 6.11; IC 95% 1.37-27.24; p=0.007). Non sono state riscontrate differenze significative nella mortalità (2.9 vs 3.1%) e nell'incidenza di reinfarto (1.7 vs 0.9%). I risultati sono stati sovrapponibili in tutti i sottogruppi di pazienti. Conclusioni. Il trattamento con bivalirudina in fase preospedaliera nei pazienti trasportati per PCI primaria ha determinato un miglioramento dell'outcome clinico a 30 giorni oltre ad una riduzione del tasso di sanguinamenti maggiori, ma a fronte di un aumento di trombosi acuta dello stent. [N Engl J Med 2013;369:2207-17]. © 2014 Il Pensiero Scientifico Editore.
The PROCAINA (PROstate CAncer INdication Attitudes) Project (Part I): A survey among Italian radiation oncologists on postoperative radiotherapy in prostate cancer [Il progetto PROCAINA (PROstate CAncer INdication Attitudes) (Parte I): una survey tra gli oncologi radioterapisti italiani sulla radioterapia postoperatoria per il tumore prostatico]
Alongi F.,Instituto Clinico Humanitas |
De Bari B.,Instituto Del Radio O Alberti |
Franco P.,TomoTherapy |
Ciammella P.,IRCCS Arcispedale S. Maria Nuova |
And 4 more authors.
Radiologia Medica | Year: 2013
Purpose: Radiotherapy (RT) has an established role in the postoperative treatment of prostate cancer patients with extracapsular extension, positive surgical margins or a detectable post-operative prostate-specific antigen (PSA). Despite the large number of patients treated with postoperative RT, some issues about optimal technique, doses, volumes, timing and association with androgen deprivation are still subject of debate. The aim of this survey was to determine the patterns of choice of Italian radiation oncologists in two different clinical cases of postoperative prostate cancer patients. Study design: During the 2010 National Congress of the Italian Association of Radiation Oncology (AIRO), four clinical cases were presented to the attending radiation oncologists. Two of them were cases of postoperative prostate cancer, differing in T stage of the primary tumour according to the TNM classification, preoperative staging procedures, preoperative PSA (iPSA), Gleason score of biopsies and definitive pathological specimen after surgery and postoperative PSA. For each clinical case, the radiation oncologists were asked to: (a) give indication to new pre-treatment procedures for staging; b) give indication to postoperative treatment; (c) to define specifically, where indicated, the total dose, type of fractionation, treatment volumes, type of technique, type of image-guided setup control; (d) indicate whether adjuvant hormonal therapy should be prescribed; (e) define criteria that mostly influenced the prescription. A descriptive statistical analysis was then performed. Results: A total of 300 questionnaires were distributed amongst radiation oncologists attending the congress; 128 were completed and considered for this analysis (41%). Some important differences were shown in prescribing and performing postoperative radiotherapy, and some significant differences with international guidelines and data available from the literature were also reviewed and discussed. Conclusions: Despite the results of clinical trials, significant differences still exist among Italian radiation oncologists in deciding postoperative treatment in prostate cancer patients. These patients probably deserve a more uniform approach based on updated, detailed and evidencebased recommendations. © 2013 Springer-Verlag Italia.
PubMed | Ospedali Riuniti, IRCCS Arcispedale S. Maria Nuova, Casa di Cura IGEA, Ospedale SantAnna and 15 more.
Type: Journal Article | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2016
Colorectal cancer is the third most common and the third most lethal cancer in both men and women in developed countries. About 75% of cases are first diagnosed when the disease is classified as localized or regional, undergo potentially curative treatment and enter a post-treatment surveillance program. Although such programs drain significant resources from health systems, empirical evidence of their efficacy is scanty.Dukes B2-C colorectal cancer patients who had no evidence of disease at the end of their front-line treatment (surgery and adjuvant radiochemotherapy, if indicated) were eligible for the trial and randomized to two different surveillance programs. These programs differed greatly in the frequency of diagnostic imaging. They had similar schedules of physical examinations and carcinoembryonic antigen (CEA) assessments. Patients received baseline and yearly health-related quality-of-life (HR-QoL) questionnaires. Primary outcomes were overall survival (OS) and QoL.From 1998 to 2006, 1228 assessable patients were randomized, 933 with colon cancer and 295 with rectal cancer. More than 90% of patients had the expected number of diagnostic procedures. Median follow-up duration was 62 months [interquartile range (IQR) 51-86] in the minimal surveillance group and 62 months (IQR 50-85) in the intensive group. At primary analysis, 250 patients had recurred and 218 had died. Intensive surveillance anticipated recurrence, as shown by a significant difference in mean disease-free survival of 5.9 months. Comparison of OS curves of the whole intention-to-treat population showed no statistically significant differences. HR-QoL of life scores did not differ between regimens.Our findings support the conclusions of other randomized clinical trials, which show that early diagnosis of cancer recurrence is not associated with OS benefit.NCT02409472.
PubMed | Laboratory of Translational Research, IRCCS Arcispedale S. Maria Nuova, Clinical Governance and International Research Activities, Nottingham Trent University and 2 more.
Type: | Journal: Journal of translational medicine | Year: 2016
Although survival rates for lymphoproliferative disorders are steadily increasing both in the US and in Europe, there is need for optimizing front-line therapies and developing more effective salvage strategies. Recent advances in molecular genetics have highlighted the biological diversity of lymphoproliferative disorders. In particular, integrative approaches including whole genome sequencing, whole exome sequencing, and transcriptome or RNA sequencing have been instrumental to the identification of molecular targets for treatment. Herein, we will discuss how genomic, epigenomic and proteomic approaches in lymphoproliferative disorders have supported the discovery of molecular lesions and their therapeutic targeting in the clinic.
PubMed | Humanitas Clinical and Research Center, Cardiologia Prima, Ospedale San Giovanni Addolorata and Centro per la Lotta contro l Infarto CLI Foundation, Ospedale Manzoni and 9 more.
Type: Journal Article | Journal: The American journal of medicine | Year: 2016
Epidemiological studies have shown a higher risk of cardiovascular mortality associated with early menopause, but the relation between menopausal age and extent of coronary artery disease after menopause is unknown. We assessed the relation between menopausal age and extent of coronary disease in postmenopausal women with an acute coronary syndrome.A prospective study was conducted in patients 55 years old undergoing coronary angiography for an acute coronary syndrome. Enrollment was stratified by sex (women/men ratio 2:1) and age (55-64, 65-74, 75-85, and >85 years). Women were administered menopause questionnaires during admission. An independent core lab quantified coronary artery disease extent using the Gensini Score, which classifies both significant (>50%) and nonsignificant lesions. Linear correlation was used to appraise the association between the Gensini score and menopausal age.We enrolled 675 patients, 249 men and 426 women (mean age 74 years). The mean Gensini score was 60 36 in men vs 50 32 in women (P <.001), being higher among men at any age. The median menopausal age of women was 50 years. Risk factors and age at first acute coronary syndrome were identical among women below and above the median menopausal age. The Gensini score in women showed a weak association with age (R= 0.127; P= .0129), but not with menopausal age (R= 0.063; P= .228). At multivariable analysis, ejection fraction, female sex, and ST elevation myocardial infarction were independent predictors of the Gensini score in the overall population.Menopausal age was not associated with the extent of coronary artery disease. Age at first acute coronary syndrome presentation, risk factors, and prior cardiovascular events were not affected by menopausal age. (The LADIES ACS study: NCT01997307).
PubMed | Fatebenefratelli Hospital, University of Turin, S Maria Misericordia Hospital, University of Modena and Reggio Emilia and 19 more.
Type: Journal Article | Journal: Journal of Cancer | Year: 2016
Early integration of palliative care in oncology practice (simultaneous care, SC) has been shown to provide better care resulting in improved quality-of-life and also survival. We evaluated the opinions of Italian Association of Medical Oncology (AIOM) members.A 37-item questionnaire was delivered to 1119 AIOM members. Main areas covered were: social, ethical, relational aspects of disease and communication, training, research, organizational and management models in SC. Three open questions explored the definition of Quality of Life, Medical Oncologist and Palliative Care.Four hundred and forty-nine (40.1%) medical oncologists returned the questionnaires. Forty-nine percent stated they address non-curability when giving a diagnosis of metastatic tumor, and 43% give the information only to patients who clearly ask for it. Fifty-five percent say the main formative activity in palliative medicine came from attending meetings and 90% agree that specific palliative care training should be part of the core curriculum in oncology. Twenty-two percent stated they consulted guidelines for symptom management, 45% relied upon personal experience and 26% make a referral to a palliative care specialist. Seventy-four percent were in favor of more research in palliative medicine. An integration between Units of Oncology and Palliative Care Services early in the course of advanced disease was advocated by 86%. Diverse and multifaceted definitions were given for the concepts of Quality of Life, Palliative Care and Medical Oncologist.SC is felt as an important task, as well as training of medical oncologists in symptom management and research in this field.
A comparison of reduced-dose prasugrel and standard-dose clopidogrel in elderly patients with acute coronary syndromes undergoing early percutaneous revascularization: Design and rationale of the randomized Elderly-ACS 2 study
PubMed | Humanitas Clinical and Research Center, IRCCS Fondazione Policlinico S. Matteo, Ospedale Manzoni, Ospedale Ruggi D Aragona and 13 more.
Type: | Journal: American heart journal | Year: 2016
Elderly patients display higher on clopidogrel platelet reactivity as compared with younger patients. Treatment with prasugrel 5mg has been shown to provide more predictable and homogenous antiplatelet effect, as compared with clopidogrel, suggesting the possibility of reducing ischemic events after an acute coronary syndrome (ACS) without increasing bleeding.The Elderly-ACS 2 study is a multicenter, randomized, parallel-group, open-label trial designed to demonstrate the superiority of a strategy of dual antiplatelet treatment using a reduced 5-mg daily dose of prasugrel over a standard strategy with a daily clopidogrel dose of 75mg in patients older than 74years with ACS (either ST- or non-ST-elevation myocardial infarction) undergoing early percutaneous revascularization. The primary end point is the composite of all-cause mortality, myocardial reinfarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. Taking advantage of the planned size of 2,000 patients, the secondary objective is to assess the prognostic impact of selected prerandomization variables (age, sex, diabetic status, serum creatinine level, electrocardiogram changes, abnormal troponin levels, basal and residual SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery [SYNTAX] score).The Elderly-ACS 2 study is a multicenter, randomized trial comparing a strategy of dual antiplatelet therapy with a reduced dose of prasugrel with a standard dose of clopidogrel in elderly patients with ACS undergoing percutaneous revascularization (the Elderly ACS 2 trial: NCT01777503).