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Pivetta E.,CRO IRCCS | Wassermann B.,CRO IRCCS | Bulian P.,Clinical and Experimental Onco Hematology Unit | Steffan A.,Oncologic Pathology Unit | And 3 more authors.
Oncotarget | Year: 2015

Mononuclear osteoclast precursors circulate in the monocyte fraction of peripheral blood and form multinuclear cells with all osteoclastic phenotypic characteristics when cultured in the presence of macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor kB ligand (RANKL). The method to obtain osteoclast precursors from peripheral blood is simple but the number of recovered osteoclasts is often largely insufficient for functional analyses. The original aim of this study was to develop a rapid and efficient method that could overcome the donor variability and enrich the osteoclast precursors from a small volume of peripheral blood as a basis for future clinical studies to correlate the differentiation potential of circulating osteoclast precursors with bone lesions in cancer patients. We improved the efficiency of osteoclastogenesis by reducing isolation and purification times and overcame the use of flow cytometry and immunomagnetic purification procedures. In our culture system the osteoclast number was increased severalfold and the precursors were able to reach a full differentiation within seven days of culture. Both age as well as gender differences in osteoclastogenesis efficiency were no longer evident by processing limited volume blood samples with this simple and rapid method.


PubMed | Unit of Epidemiology and Biostatistics, Scientific Institute of Hospitalization and Treatment and University of Bologna
Type: Journal Article | Journal: International journal of molecular sciences | Year: 2015

One challenge in colorectal cancer (CRC) is identifying novel biomarkers to be introduced in screening programs. The present study investigated the promoter methylation status of the SEPT9 gene in peripheral blood samples of subjects positive fecal occult blood test (FOBT). In order to add new insights, we investigated the association between SEPT9 promoter methylation and micronuclei frequency, and polymorphisms in the folate-related pathway genes. SEPT9 promoter methylation, micronuclei frequency, and genotypes were evaluated on 74 individuals FOBT positive. Individuals were subjected to a colonoscopy that provided written informed consent for study participation. SEPT9 promoter methylation status was significantly lower in the CRC group than controls (p = 0.0006). In contrast, the CaCo2 cell-line, analyzed as a tissue specific model of colon adenocarcinoma, showed a significantly higher percentage of SEPT9 promoter methylation compared to the CRC group (p < 0.0001). Linear regression analysis showed an inverse correlation between micronuclei frequency and the decrease in the methylation levels of SEPT9 promoter region among CRC patients ( = -0.926, p = 0.0001). With regard to genotype analysis, we showed the involvement of the DHFR polymorphism (rs70991108) in SEPT9 promoter methylation level in CRC patients only. In particular, the presence of at least one 19 bp del allele significantly correlates with decreased SEPT9 promoter methylation, compared to the 19 bp ins/ins genotype (p = 0.007). While remaining aware of the strengths and limitations of the study, this represents the first evidence of a novel approach for the early detection of CRC, using SEPT9 promoter methylation, micronuclei frequency and genotypes, with the potential to improve CRC risk assessment.


PubMed | Unit of Epidemiology and Biostatistics, CRO IRCCS, Clinical and Experimental Onco Hematology Unit and Oncologic Pathology Unit
Type: Journal Article | Journal: Oncotarget | Year: 2015

Mononuclear osteoclast precursors circulate in the monocyte fraction of peripheral blood and form multinuclear cells with all osteoclastic phenotypic characteristics when cultured in the presence of macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor kB ligand (RANKL). The method to obtain osteoclast precursors from peripheral blood is simple but the number of recovered osteoclasts is often largely insufficient for functional analyses. The original aim of this study was to develop a rapid and efficient method that could overcome the donor variability and enrich the osteoclast precursors from a small volume of peripheral blood as a basis for future clinical studies to correlate the differentiation potential of circulating osteoclast precursors with bone lesions in cancer patients. We improved the efficiency of osteoclastogenesis by reducing isolation and purification times and overcame the use of flow cytometry and immunomagnetic purification procedures. In our culture system the osteoclast number was increased several-fold and the precursors were able to reach a full differentiation within seven days of culture. Both age as well as gender differences in osteoclastogenesis efficiency were no longer evident by processing limited volume blood samples with this simple and rapid method.


Zanet E.,Italian National Cancer Institute | Taborelli M.,Unit of Epidemiology and Biostatistics | Rupolo M.,Italian National Cancer Institute | Durante C.,Unit of Stem Cells Collection and Processing | And 7 more authors.
AIDS | Year: 2015

Objectives: To describe survival data, CD4 + T-cell long-term dynamics and the correlation between dynamics and events occurrence in 26 HIV-positive patients with refractory lymphoma in complete response after autologous stem cell transplantation (ASCT). Design: Retrospective single-centre study. Methods: Lymphoma relapse, second cancers and opportunistic infections were considered after ASCT. Group A included patients experiencing events after ASCT and group B the remaining patients. Overall survival, progression-free survival and event-free survival probabilities were estimated by Kaplan-Meier method. The comparison of median CD4 + T-cell count at cancer diagnosis with matched values was investigated by Wilcoxon signed-rank test and between group A and B by Mann-Whitney U test. Results: With a median of 6-year follow-up, the overall survival, the progression-free survival and the event-free survival at 10 years were 91, 86 and 36%. Compared with CD4 + T-cell count at cancer diagnosis a higher amount was maintained over time after ASCT. Two patients experienced a lymphoma relapse at 4.3 and 3.1 years; five patients had secondary malignancies and nine patients opportunistic infections at a median time of 2.2 and 0.4 years from ASCT. At 6 and 12 months after ASCT, a significant difference in CD4 + T-cell count was found between group A and B. Conclusion: ASCT has a dramatic impact on survival of HIV-positive patients with refractory lymphoma. We support surveillance of opportunistic infections early after ASCT and of second cancers or lymphoma relapses later from ASCT. Both opportunistic infections and second malignancies were successfully managed and the only long-term death occurred due to lymphoma relapse. ASCT seems to contribute to immune recovery. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Bearz A.,Medical Oncology | Bearz A.,Italian National Cancer Institute | Talamini R.,Unit of Epidemiology and Biostatistics | Rossoni G.,Medical Oncology | And 10 more authors.
BMC Research Notes | Year: 2012

Background: Although first-line therapy for patients affected by advanced mesothelioma is well established, there is a lack of data regarding the impact of second-line treatment. Methods. We retrospectively collected data of patients affected by advanced mesothelioma, already treated with first-line therapy based on pemetrexed and platin, with a response (partial response or stable disease) lasting at least 6 months, and re-treated with a pemetrexed-based therapy at progression. The primary objective was to describe time to progression and overall survival after re-treatment. Results: Overall across several Italian oncological Institutions we found 30 patients affected by advanced mesothelioma, in progression after a 6-month lasting clinical benefit following a first-line treatment with cisplatin and pemetrexed, and re-challenged with a pemetrexed-based therapy. In these patients we found a disease control rate of 66%, with reduction of pain in 43% of patients. Overall time to progression and survival were promising for a second-line setting of patients with advanced mesothelioma, being 5.1 and 13.6 months, respectively. Conclusions: In our opinion, when a patient has a long-lasting benefit from previous treatment with pemetrexed combined with a platin compound, the same treatment should be offered at progression. © 2012 Bearz et al.


Ferro P.,Azienda Sanitaria Locale n | Canessa P.A.,Azienda Sanitaria Locale n | Battolla E.,Azienda Sanitaria Locale n | Dessanti P.,Azienda Sanitaria Locale n | And 8 more authors.
Anticancer Research | Year: 2013

Background/Aim: Soluble mesothelin-related peptide (SMRP) is regarded as a biomarker of malignant pleural mesothelioma (MPM). Herein, we compared the diagnostic performances of SMRP in matched pleural effusion (PE-SMRP) and serum (S-SMRP). Materials and Methods: Diagnosis on pleural biopsies was performed for all patients including 43 with MPM, 23 with non-MPM pleural metastases (MTS) and 36 with benign (BNG) pleural diseases. SMRP was measured by a MesoMark ELISA (Cis-Bio International Gif/Yvette; France). Results: Using the receiver operating characteristic (ROC) analysis, 12.70 and 1.08 nM were detected as cut-off values to optimal discrimination for PESMRP and S-SMRP, respectively. PE-SMRP showed a better diagnostic accuracy than S-SMRP in MPM vs. MTS+BNG (area under the ROC curve=81.6 vs. 70.5; sensitivity=69.8% vs. 46.5%; specificity=88.1% vs. 84.7%; diagnostic odds ratio (DOR)=17.1 vs. 4.8). In S-SMRP-negative patients, PE-SMRP maintained an acceptable performance (Sensitivity=47.8%; DOR=8.3; p=0.001), whereas in PE-SMRP-negative patients, S-SMRP performed very poorly (Sensitivity=15.4%; DOR=1.2; p=0.858). Conclusion: PE-SMRP detection has a superior diagnostic accuracy than S-SMRP detection in the diagnosis of MPM.


PubMed | Unit of Epidemiology and Biostatistics, Scientific Institute of Hospitalization and Treatment and University of Bologna
Type: | Journal: Angiogenesis | Year: 2016

The angiogenic pathway plays a pivotal role in tumor growth, invasiveness and metastasis. The most important actors in the angiogenic pathway are VEGFA and its receptors VEGFR1, 2 and 3. These genes are polymorphic, and the presence of single nucleotide polymorphisms may result in angiogenic deregulation. Herein, we hypothesized that germline variants may affect sunitinib efficacy (TTP and OS) and/or toxicity. Therefore, we investigated 19 polymorphisms, in four genes, in 54 GIST patients, treated with second-line sunitinib and 147 healthy controls. Through a multiple candidate gene approach, we also investigated, for the first time, any possible significant associations with GIST susceptibility and clinical pathological features. The most important result shows two associations between polymorphisms in VEGFR3 rs6877011 (CC vs. CG, OR 9.7, 95% CI 3.31-28.4; P<0.001) and rs7709359 (AA+AG vs. GG, OR 5.01, 95% CI 1.33-18.8; P=0.017) and TTP. Interestingly, the association between VEGFR3 rs6877011 and TTP maintained the significance after applying the Bonferroni correction for multiple testing (P=0.017). We also highlighted the association with sunitinib-related toxicity; in particular, VEGFA polymorphism rs3025039 (CT+TT vs. CC, OR 15.3, 95% CI 2.2-102.1; P=0.005) is associated with severe toxicity, with the presence of the variant T allele associated with a grade 3 AE. Because of the small sample size and large number of tests performed, we cannot ignore the possibility that some associations have been retrieved by chance. However, the influence of VEGF polymorphisms in angiogenesis is a hypothesis worthy of exploration in cellular models and confirmation in a sizeable cohort of patients.


Collee A.,Unit of Epidemiology and Biostatistics | Legrand C.,Catholic University of Louvain | Govaerts B.,Catholic University of Louvain | Der Veken Paul V.,Queen Astrid Military Hospital | And 2 more authors.
Noise and Health | Year: 2011

The armed forces are highly exposed to occupational noise. The aim of this study was to evaluate the prevalence and noise exposures associated with the severity of hearing loss (HL) in a Belgian military population. A cross-sectional study was carried out at the Centre for Medical Expertise (CME) and in four Units of Occupational Medicine (UOM). Hearing thresholds were determined by audiometry. The examination included a questionnaire on hearing-related medical history, and noise exposure in military and leisure time activity. A multinomial logistic regression model was used to assess the association of the severity of HL with tinnitus, with the military occupation, and with noise exposures. Of the 2055 subjects aged 18-55 years, 661 (32.2%) had a slight HL (25-40 dB), 280 (13.6%) had a moderate HL (45-60 dB) and 206 (10.0%) had a severe HL (>60 dB) of 4 and 6 kHz for both ears. The prevalence of slight, moderate and severe HL increased significantly with age and was higher for subjects from Paracommando and infantry units. Fighting in Built-Up Area (FIBUA) training, shooting with large caliber weapons, and participation in military exercises were the best determinants of HL in this population. These results suggest that subjects from infantry and Paracommando units run the highest risk of HL because they are exposed to very loud noises in their professional life, like large caliber shooting and FIBUA training.


Cerruto M.A.,University of Verona | D'Elia C.,University of Verona | Cacciamani G.,University of Verona | De Marchi D.,University of Verona | And 15 more authors.
Health and Quality of Life Outcomes | Year: 2014

Background: There is a lack of good data in the literature evaluating the Health-Related Quality of Life (HR- QoL) in patients with urinary diversions. The aim of this study was to examine the changes in expectation and needs in terms of human adaptation and behavioural profiles in patients with ileal conduit (IC) after radical cystectomy (RC) for bladder cancer (BC).Materials and methods: A qualitative, multicenter cross-sectional study using a " narrative based" approach was planned. We proceed with a sampling reasoned choice (purposive), selecting groups of patients with follow-up from one up to more than 7 years after surgery. Data were collected through individual interviews.Results: Thirty patients participated in the study. The processing of the interviews allowed us to identify 2 major profiles: positive and negative. Patients with a positive profile resumed normal daily activities with no or limited restrictions both on the personal and the social level. This profile reflects a good HR-QoL. The negative profile reflects the patients for whom the ostomy has meant a worsening of HR-QoL. A positive profile was statistically more frequent in older patients (p = 0.023), with a longer follow-up (p = 0.042) and less complications rates (p = 0.0002). According to the length of follow-up and the occurrence of complitations, we identified further 5 intermediate profiles.Conclusions: Patients' satisfaction is related to the degree of adaptation to their new life with an urinary stoma and its correct management. Live " with urinary diversion" represents a new phase of life and not a deterioration. © 2014 Cerruto et al.; licensee BioMed Central Ltd.

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