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PubMed | Italian National Cancer Institute, University of Udine, Catholic University ore, University of Turin and 2 more.
Type: | Journal: BMC medical genetics | Year: 2016

About 20 % of hereditary breast cancers are caused by mutations in BRCA1 and BRCA2 genes. Since BRCA1 and BRCA2 mutations may be spread throughout the gene, genetic testing is usually performed by direct sequencing of entire coding regions. In some populations, especially if relatively isolated, a few number of recurrent mutations is reported, sometimes caused by founder effect.BRCA1 and BRCA2 screening for mutations was carried out on 1114 breast and/or ovarian cancer patients complying with the eligibility criteria for BRCA testing. Haplotype analysis was performed on the probands carrying recurrent mutations and their relatives, using two sets of microsatellite markers covering the BRCA1 (D17S588, D17S806, D17S902, D17S1325, D17S855, D17S1328, D17S800, and D17S250) and BRCA2 (D13S220, D13S267, D13S171, D13S1701, D13S1698, D13S260, D13S290, D13S1246) loci. The DMLE + 2.2 software was used to estimate the age of BRCA1 c.676delT and BRCA2 c.7806-2A > G. A multiplex PCR and two different primer extension assays were optimized and used for genotyping the recurrent mutations of the two genes.In the time frame of almost 20 years of genetic testing, we have found that five BRCA1 and three BRCA2 mutations are recurrent in a substantial subset of carriers from North-East Italy and neighboring Istria, where they represent more than 50 % of all mutations. Microsatellite analyses identified a common haplotype of different length for each mutation. Age estimation of BRCA1 c.676delT and BRCA2 c.7806-2A > G mutations revealed that they arose in the Friuli Venezia Giulia area about 86 and 94 generations ago, respectively. Suggestion of an association between BRCA2 c.7806-2A > G and risk of breast cancer in males has emerged. Finally, we developed a simple and efficient pre-screening test, performing an in-house primer extension SNaPshot assay for the rapid identification of the eight recurrent mutations.Proofs of common ancestry has been obtained for the eight recurrent mutations. The observed genotype-phenotype correlation and the proposed rapid mutation detection strategy could improve the clinical management of breast and ovarian patients in North-East of Italy and neighboring geographic areas.


Tisi M.C.,University Cattolica ore | Bozzoli V.,University Cattolica ore | Giachelia M.,University Cattolica ore | Massini G.,University Cattolica ore | And 10 more authors.
Leukemia and Lymphoma | Year: 2014

Anemia is a frequent sign in patients with diffuse large B-cell lymphoma (DLBCL) at diagnosis. We determined erythropoietin, hepcidin and interleukin-6 (IL-6) in plasma samples of 53 patients with DLBCL The majority of patients (40/53, 75%) showed defective endogenous erythropoietin production, in particular when anemia was present (p = 0.01). Hepcidin plasma levels were significantly higher in patients compared to controls (p = 0.006), particularly in those with characteristics associated with a more active disease, including elevated lactate dehydrogenase (LDH) (p = 0.0004), B-symptoms (p = 0.07) and an age-adjusted international prognostic index (IPI) score > 1 (p = 0.01). Hepcidin levels correlated strongly to ferritin (r=0.77, p< 0.0001) and weakly to IL-6 concentrations (r = 0.30, p = 0.03), but not to hemoglobin values. IL-6 inversely correlated to hemoglobin values in both univariate and multivariate analysis (p = 0.04), including hepcidin and erythropoietin as variables. Our findings suggest that elevated hepcidin levels and inadequate erythropoietin response are frequent in DLBCL, but elevated IL-6 plays the major role for the development of anemia. © 2014 Informa UK, Ltd.


Roversi A.,Catholic University ore
Bulgarian Journal of Agricultural Science | Year: 2015

To obtain a good number of rooted hazelnut plants from no-suckering hazelnut clones of “Tonda Gentile delle Langhe” (TGL) a modified layering was devised. Before the sprouting the branches of hazelnut no-suckering plants were cut at 35 cm from the ground. The water sprouts so obtained were ringed, as usual for mounding layering application. The ringed water sprouts were surrounded by a container and covered with an appropriate substrate. The plants so obtained are very vigorous with a good height and diameter at the collar and rich roots mass and therefore immediately suitable to plantation in orchard. It seems that this new method could be adopted by nurseryman for its simplicity and very good results. © 2015, National Centre for Agrarian Sciences. All Rights reserved.


Hohaus S.,Catholic University ore | Giachelia M.,Catholic University ore | Cuccaro A.,Catholic University ore | Voso M.T.,Catholic University ore | Leone G.,Catholic University ore
Critical Reviews in Oncogenesis | Year: 2013

Anemia is a frequent finding of Hodgkin's lymphoma (HL) diagnosis. It is usually mild, with hemoglobin levels between 10 and 12 g/dl; it is rarely (<10% of cases) a result of bone marrow infiltration; and it displays the characteristics of the anemia of chronic disease due to abnormalities in iron metabolism. The inflammatory cytokine IL-6 is frequently up-regulated in Hodgkin's lymphoma, and IL-6 levels are strongly associated with hepcidin, the main regulator of iron metabolism. Elevated hepcidin levels result in iron restriction and signs of anemia of chronic disease. In addition, the abundant microenvironment surrounding the neoplastic Hodgkin's and Reed-Sternberg cells may contribute to alterations in iron metabolism. Tumor-infiltrating macrophages can sequester iron using scavenger receptors. Iron-restricted anemia at HL diagnosis can be aggravated by intensive chemotherapy, and iron overload may become clinically relevant in heavily treated patients with relapsed or refractory disease undergoing high-dose chemotherapy and stem cell transplantation. © 2013 by Begell House, Inc.


Silva S.,Catholic University ore | Baffi C.,Catholic University ore | Spalla S.,Catholic University ore | Cassinari C.,Catholic University ore | Lodigiani P.,Catholic University ore
Agrochimica | Year: 2010

The determination of CEC and exchangeable bases in calcareous soils has always been very difficult, because partial dissolution of the phases (e.g. CaCO3) is observed in these matrices as a result of interaction with the exchange solution rich in electrolytes. The proposed method foresees, on 10 g of soil, a saturation step with use of IN NH4OAc, followed by washing with deionized water, contact with a solution of 0.4N NaCl and re-extraction of Na+ with the IN NH4OAc solution. The exchangeable bases were determined in the supernatant after the Ist saturation step and CEC by measuring the concentration of Na+ removed by NH4 + and collected in the 2nd step. For both measurements optical emission spectrometry with inductively coupled plasma (ICP-OES) was used. For the trials two soil profiles of Vertisols were chosen, collected in the experimental farm "124" in Foggia (Italy), both with seven diagnostic horizons, with the amount of carbonates expressed as CaCO 3 %, ranging from 10% (topsoil) to 30% (subsoil). The proposed method is well correlated with the official method for single and the sum of exchangeable bases; but not for CEC.


Bozzoli V.,Catholic University ore | Tisi M.C.,Catholic University ore | Maiolo E.,Catholic University ore | Alma E.,Catholic University ore | And 5 more authors.
British Journal of Haematology | Year: 2015

Summary: The primary objective of this prospective, randomized study was to compare the efficacy of a reduced regimen of only four doses of unpegylated filgrastim from day +8 to +11 per cycle with a standard once per cycle administration of pegylated filgrastim to maintain dose-intensity of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone given every 14 d) in previously untreated elderly patients with diffuse large B-cell lymphoma (DLBCL). We included 51 patients (median age 66 years, range 60-76). Median dose intensity did not differ between the group of 24 patients receiving four doses of unpegylated filgrastim of each cycle (87·5%) and the group of 27 patients receiving pegylated filgrastim once per cycle on day 2 (89·4%) (P = 0·9). There was also no difference in the frequency of adverse events, such as episodes of neutropenic fever and unplanned hospitalizations. Patient characteristics that negatively influenced dose intensity were reduced performance status, advanced stage disease and poor-risk International Prognostic Index, with Eastern Cooperative Oncology Group performance status ≥2 being the most significant factor. In conclusion, a limited support with 4 d of filgrastim appears to be equivalent to pegylated filgrastim administered once per cycle, and appears to be sufficient to maintain dose-intensity of the R-CHOP-14 regimen in elderly patients with DLBCL without risk factors. © 2015 John Wiley & Sons Ltd.


Hohaus S.,Catholic University ore | Santangelo R.,Catholic University ore | Giachelia M.,Catholic University ore | Vannata B.,Catholic University ore | And 10 more authors.
Clinical Cancer Research | Year: 2011

Purpose: The Epstein-Barr virus (EBV) is present in the malignant Hodgkin/Reed-Sternberg (HRS) cells of 20% to 40% cases of Hodgkin lymphoma (HL) in Western countries. We were interested in the detection and quantification of cell-free plasma EBV-DNA as an indicator of biological and clinical characteristics in EBV-associated HL. Experimental Design: EBV was detected in peripheral blood compartments (whole blood, plasma, and mononuclear cells) at diagnosis by real-time PCR for the EBNA (EB nuclear antigen) region (n = 93) and in HRS cells by in situ hybridization for EBV-encoded small RNAs (EBER; n = 63). These data were correlated to histological and clinical characteristics, EBV serology, circulating cell-free DNA, and interleukin (IL)-6 levels. Results: Detection of EBV-DNA in plasma had a high specificity (90%), but a relatively low sensitivity (65%) to predict for EBV association. The viral load was higher in patients with advanced stage disease, older age in the presence of B-symptoms, and international prognostic score more than 2. The presence of EBV in HRS cells and higher plasma EBV-DNA copy numbers correlated to an increased frequency of tumor-infiltrating CD68+ macrophages in lymph node biopsies. Plasma EBV-DNA load correlated to circulating cell-free DNA and IL-6 levels, and inversely correlated to lymphocyte counts and EBNA1 antibody titers. Conclusion: Although the presence of EBV-DNA in peripheral blood cannot be regarded as a surrogate marker for EBER, the plasma EBV-DNA load at HL diagnosis is an indicator of disease activity and biological characteristics associated with negative prognosis. Moreover, the inverse correlation to EBNA1 antibody titers and lymphocyte counts may indicate a reduction in immunosurveillance, favoring the expansion of EBV-HRS cells in HL. ©2011 AACR.


PubMed | Catholic University ore
Type: Journal Article | Journal: Leukemia & lymphoma | Year: 2016

An association between Epstein-Barr Virus (EBV) infection and lymphoproliferative diseases has been reported with EBV+diffuse large B cell-lymphoma (DLBCL) of the elderly described as a distinct entity. In a cohort of 218 human immunodeficiency virus (HIV)-negative patients with diffuse large B-cell lymphomas, we detected EBV-DNA in 25% of whole blood (WB) samples at diagnosis. Presence and viral load in WB, mononuclear cells or plasma did not predict the presence of EBV in the tumor biopsy. Positive Hepatitis C virus (HCV) serology was associated with a higher frequency of EBV in WB. Patients with EBV-DNA in WB had a significantly shorter progression-free (p=0.02) and overall survival (p=0.05) after immunochemotherapy with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone). We conclude that detection of EBV in WB is not a surrogate marker for EBV-association in diffuse large B-cell lymphoma, however it associates with worse outcome.

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