Pistoia Hospital

Pistoia, Italy

Pistoia Hospital

Pistoia, Italy
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Caldarella A.,Institute for Study and Cancer Prevention ISPO | Buzzoni C.,Institute for Study and Cancer Prevention ISPO | Crocetti E.,Institute for Study and Cancer Prevention ISPO | Bianchi S.,University of Florence | And 7 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2013

Introduction: The special types of breast cancer seem to have not only distinct morphological features but also distinct biological features. Materials and methods: Women diagnosed with a first primary invasive breast cancer in the 2004-2005 period were identified through Tuscan Cancer Registry. Information on age, tumor size, lymph node status, histological type and grade, hormonal receptors, HER2 immunohistochemical expression were collected. Five subtypes were defined: luminal A, luminal B HER2+, luminal B HER2-, triple negative, and HER2 positive. The association between the histological type and molecular subgroups was assessed by a Fisher's exact test, and a multinomial logistic regression model was used. Results: Out of 1,487 patients, 34 % were luminal A subtype, 25 % luminal B HER2-, 11 % luminal B HER2+, 19 % triple negative, and 10.2 % HER2+; 58.5 % of cancers were ductal NOS types. With luminal A as reference, histological types distribution was significantly different between the subgroups. Mucinous, tubular, and cribriform histotypes were found among luminal A cancers more than in other subgroups; all medullary carcinomas were triple negative cancers. Pathological stage at diagnosis was more advanced, and histological grade was lower among subgroups other than luminal A. Conclusions: Significant association between breast cancer histotypes and molecular subgroups was found. © 2012 Springer-Verlag Berlin Heidelberg.

Caldarella A.,Institute for Study and Cancer Prevention ISPO | Puliti D.,Institute for Study and Cancer Prevention ISPO | Crocetti E.,Institute for Study and Cancer Prevention ISPO | Bianchi S.,University of Florence | And 7 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2013

Introduction: In a population-based screening program, a percentage of tumors remain undetected; these tumors comprise a heterogeneous group, and they are more likely to have adverse prognostic features. The aim of this study was to identify differences in biological characteristics of screen-detected versus interval breast cancers in a population-based screening program according to molecular subtypes. Materials and methods: We analyzed the population-based data from a long-running screening program in the area of Florence. Data on screening history and on age, T and N status, grade, histotype, hormonal status and Ki-67 and HER2 expression were retrieved. Subtypes of breast cancer were defined on the expression of ER, PR, Ki-67 and HER2: luminal A if ER/PR+, HER2- and Ki67 <14 %, luminal B (HER2 negative) if ER/PR+, HER2- and Ki67 ≥14 %, luminal B (HER2 positive) if ER/PR+ and HER2+, triple negative if ER/PR-and HER2-, HER2 positive if ER/PR- and HER2+. Association between molecular subtypes and mode of detection will be evaluated by a logistic regression model adjusted for the potential confounding variables. Results: Information about biomarkers was known for 277 cases, 211 screening-detected and 66 interval cancers. Among interval cases, the triple-negative cancers were more represented than luminal A (OR = 3.52; CI, 1.112-11.13; p = 0.0319), while the proportion of HER2+ was quite similar (OR = 1.57; p = 0.4709). Conclusion: Although made on a small number of cases, our results suggest a difference in distribution of molecular subtypes according to mode detection, confirming the results of earlier studies. © 2012 Springer-Verlag.

Guzzetta A.,Stella Maris Scientific Institute | D'Acunto M.G.,University of Pisa | Carotenuto M.,The Second University of Naples | Berardi N.,National Research Council Italy | And 7 more authors.
Developmental Medicine and Child Neurology | Year: 2011

Aim Early intervention programmes based on the manipulation of the extra-uterine environment have been used in preterm infants with the aim of improving development and functional outcome. Infant massage, among them, has proved effective for weight gain and reduced length of stay in the neonatal intensive care unit. We have recently shown that infant massage accelerates brain maturation of low-risk preterm infants without brain abnormalities as measured by global parameters of electroencephalography (EEG) activity. In the present study we further analyse the same cohort of preterm infants, testing the hypothesis that massage determines changes in EEG spectral activity, a highly sensitive index of brain maturation. Method Infants were randomly allocated to a massage or comparison group. Intervention consisted of standard care only (comparison group) or standard care plus infant massage (massage group). Massage was started at around 10days after birth and was provided for 12days during a 2-week period. EEG was performed at around 1 and 4weeks, i.e. before and after intervention. Spectral EEG analysis was performed on 80seconds of active sleep, applying the fast Fourier transform on the signal obtained from eight monopolar derivations. Results The modification in global EEG spectral power between the two assessments was significantly different for the two groups, especially for the delta band activity; the spectral power did not change in massaged infants although, not surprisingly, it decreased significantly in the comparison group, as shown by previous studies. Interpretation We propose that massage intervention affects the maturation of brain electrical activity and favours a process more similar to that observed in utero in term infants. © 2011 Mac Keith Press.

PubMed | Italian National Cancer Institute, Pistoia Hospital, Azienda Ospedaliero, San Donato Hospital and 2 more.
Type: | Journal: International journal of radiation oncology, biology, physics | Year: 2016

We report a subgroup analysis primarily focused on human papillomavirus (HPV)-related oropharyngeal cancer (OPC) from the Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer (CTXMAB+RT; ClinicalTrials.gov identifier NCT01216020) trial comparing radiation therapy with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced head and neck cancer.The data from all the patients in the CTXMAB+RT trial were reviewed and separately analyzed in 3 groups: p16-positive OPC, p16-negative OPC, and all other cancer sites. The endpoints of interest were locoregionalcontrol (LC), metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS). Severe and fatal infectious complications were also reanalyzed to more thoroughly investigate the association between CTX treatment and potentially life-threatening reactions.A total of 33 patients had OPC. The HPV status was available for 30 of the 33 patients. Thus, 3 patients treated with CDDP but with unknown HPV status were excluded from the survival analysis. The small number of patients in each group did not allow for significance to be reached for any of the outcomes analyzed. A trend favored the CDDP arm in the p16-positive group for the 2-year LC and OS/CSS rates (100% vs 72.9% and 100% vs 77.8% for CDDP vs CTX). In this group of patients, the hazard ratio for the treatment arm (CTX vs CDDP) was 4.7 (95% confidence interval [CI] 0.5-40.3) for LC, 3.4 (95% CI 0.4-30.5) for OS, and 2.4 for CSS (95% CI 0.2-23.2). A survival benefit favoring the CDDP arm was not evident in the p16-negative OPC group or for patients with cancer located in other sites. Serious or fatal infectious complications occurred only in the CTX arm.In patients with p16-positive OPC in the CTXMAB+RT trial, CTX had lower efficacy than CDDP, with possible implications for treatment selection in this clinical setting.

PubMed | San Filippo Neri Hospital, University of Rome La Sapienza, Azienda USL, Italian National Cancer Institute and 10 more.
Type: Journal Article | Journal: The British journal of radiology | Year: 2016

Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure.Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 ((125)I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. (125)I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes.Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p<0.0001) and V100 (p=0.09) were correlated with BFFS, with V100 effect significantly different between patients at low risk and those at intermediate/high risk (p=0.04). Short follow-up and lack of toxicity data represent the main limitations for a global evaluation of LDR-BT.This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer.Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome.

Moretti S.,University of Florence | Massi D.,University of Florence | Farini V.,University of Florence | Baroni G.,University of Florence | And 4 more authors.
Laboratory Investigation | Year: 2013

Recent studies sight β-adrenergic receptor (AR) antagonists as novel therapeutic agents for melanoma, as they may reduce disease progression. Here within, we evaluated the expression of β-ARs in a series of human cutaneous melanocytic lesions, and studied the effect of their endogenous agonists, norepinephrine (NE) and epinephrine (E), on primary and metastatic human melanoma cell lines. Using immunohistochemistry, we found that both β1- and β2-ARs are expressed in tissues from benign melanocytic naevi, atypical naevi and malignant melanomas and that expression was significantly higher in malignant tumours. Melanoma cell lines (human A375 primary melanoma cell line and human Hs29-4T metastatic melanoma cell lines) also expressed β1- and β2-ARs by measuring transcripts and proteins. NE or E increased metalloprotease-dependent motility, released interleukin-6 and 8 (IL-6, IL-8) and vascular endothelial growth factor (VEGF). These effects of catecholamines were inhibited by the unselective β-AR antagonist propranolol. The role of soluble factors elicited by catecholamines seemed pleiotropic as VEGF synergized with NE increased melanoma invasiveness through 3D barriers, while IL-6 participated in stromal fibroblast activation towards a myofibroblastic phenotype. Our results indicate that NE and E produce in vitro via β-ARs activation a number of biological responses that may exert a pro-tumorigenic effect in melanoma cell lines. The observation that β-ARs are upregulated in malignant melanoma tissues support the hypothesis that circulating catecholamines NE and E, by activating their receptors, favour melanoma progression in vivo. © 2013 USCAP, Inc All rights reserved.

Bernini P.,University of Florence | Bernini P.,FiorGen Foundation | Bertini I.,University of Florence | Bertini I.,FiorGen Foundation | And 3 more authors.
Journal of Proteome Research | Year: 2011

The identification and the present wide acceptance of cardiovascular risk factors such as age, sex, hypertension, hyperlipidemia, smoking, obesity, diabetes, and physical inactivity have led to dramatic reductions in cardiovascular morbidity and mortality. However, novel risk predictors present opportunities to identify more patients at risk and to more accurately define the biochemical signature of that risk. In this paper, we present a comprehensive metabonomic analysis of 864 plasma samples from healthy volunteers, through Nuclear Magnetic Resonance (NMR) and multivariate statistical analysis (regression and classification). We have found that subjects that are classified as at high or at low risk using the common clinical markers can also be discriminated using NMR metabonomics. This discrimination is not only due to common markers (such as total cholesterol, triglycerides, LDL, HDL), but also to (p < 0.05 after Bonferroni correction) other metabolites (e.g., 3-hydroxybutyrate, α-ketoglutarate, threonine, dimethylglycine) previously not associated with cardiovascular diseases. © 2011 American Chemical Society.

Calvani M.,University of Florence | Pelon F.,University of Florence | Comito G.,University of Florence | Taddei M.L.,University of Florence | And 9 more authors.
Oncotarget | Year: 2015

Stress has an emerging role in cancer and targeting stress-related β-adrenergic receptors (AR) has been proposed as a potential therapeutic approach in melanoma. Here we report that β3-AR expression correlates with melanoma aggressiveness. In addition, we highlight that β3-AR expression is not only restricted to cancer cells, but it is also expressed in vivo in stromal, inflammatory and vascular cells of the melanoma microenvironment. Particularly, we demonstrated that β3-AR can (i) instruct melanoma cells to respond to environmental stimuli, (ii) enhance melanoma cells response to stromal fibroblasts and macrophages, (iii) increase melanoma cell motility and (iv) induce stem-like traits. Noteworthy, β3-AR activation in melanoma accessory cells drives stromal reactivity by inducing pro-inflammatory cytokines secretion and de novo angiogenesis, sustaining tumor growth and melanoma aggressiveness. β3-ARs also play a mandatory role in the recruitment to tumor sites of circulating stromal cells precursors, in the differentiation of these cells towards different lineages, further favoring tumor inflammation, angiogenesis and ultimately melanoma malignancy. Our findings validate selective β3-AR antagonists as potential promising anti-metastatic agents. These could be used to complement current therapeutic approaches for melanoma patients (e.g. propranolol) by targeting non-neoplastic stromal cells, hence reducing therapy resistance of melanoma.

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