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Milano, Italy

Amatu A.,Ospedale Niguarda Ca Granda | Sartore-Bianchi A.,Ospedale Niguarda Ca Granda | Moutinho C.,Bellvitge Biomedical Research Institute IDIBELL | Belotti A.,Ospedale Niguarda Ca Granda | And 10 more authors.
Clinical Cancer Research | Year: 2013

Purpose: O6-methylguanine-DNA-methyltransferase (MGMT) is a DNA repair protein removing mutagenic and cytotoxic adducts from O 6-guanine in DNA. Approximately 40% of colorectal cancers (CRC) display MGMT deficiency due to the promoter hypermethylation leading to silencing of the gene. Alkylating agents, such as dacarbazine, exert their antitumor activity by DNA methylation at the O6-guanine site, inducing base pair mismatch; therefore, activity of dacarbazine could be enhanced in CRCs lacking MGMT. We conducted a phase II study with dacarbazine in CRCs who had failed standard therapies (oxaliplatin, irinotecan, fluoropyrimidines, and cetuximab or panitumumab if KRAS wild-type). Experimental Design: All patients had tumor tissue assessed for MGMT as promoter hypermethylation in double-blind for treatment outcome. Patients received dacarbazine 250 mg/m2 intravenously every day for four consecutive days, every 21 days, until progressive disease or intolerable toxicity. We used a Simon two-stage design to determine whether the overall response rate would be 10% or more. Secondary endpoints included association of response, progression-free survival, and disease control rate with MGMT status. Results: Sixty-eight patients were enrolled from May 2011 to March 2012. Patients received a median of three cycles of dacarbazine (range 1-12). Grades 3 and 4 toxicities included: fatigue (41%), nausea/vomiting (29%), constipation (25%), platelet count decrease (19%), and anemia (18%). Overall, two patients (3%) achieved partial response and eight patients (12%) had stable disease. Disease control rate (partial response + stable disease) was significantly associated with MGMT promoter hypermethylation in the corresponding tumors. Conclusion: Objective clinical responses to dacarbazine in patients with metastatic CRC are confined to those tumors harboring epigenetic inactivation of the DNA repair enzyme MGMT. ©2013 AACR.

Pastorello E.A.,Allergology and Immunology Unit | Stafylaraki C.,Allergology and Immunology Unit | Scibilia J.,Allergology and Immunology Unit | Giuffrida M.G.,CNR Institute of Sciences of Food Production | And 7 more authors.
Journal of Agricultural and Food Chemistry | Year: 2013

Fennel allergy has been rarely reported, and the association with peach allergy has never been described. Our aim was to (i) study the correlation between symptom severity of peach and fennel and (ii) identify fennel allergens and the role of rPru p 3 antibodies in severe reactions to fennel. In 148 patients with peach allergy, we investigated 58 patients with symptoms and IgE antibodies positive to fennel. IgE to rPru p 1, 3, and 4 and rBet v 1, 2, and 4 were measured by immunoblotting, and the N-terminal amino acid sequences and relevant allergens were determined. We found significant association between severe reactions to fennel and peach (p = 0.0009). A major allergen was ∼9 kDa lipid-transfer protein (LTP), cross-reactive with Pru p 3, a 15 kDa protein identified as a pathogenesis-related protein 1 of the Bet v 1 family. In conclusion, peach and fennel severe allergic symptoms are significantly related, and LTP is a major fennel allergen. Fennel should be included in the LTP syndrome. © 2012 American Chemical Society.

Farioli L.,Laboratory Medicine | Di Biase M.,University of Foggia | Nichelatti M.,Service of Biostatistics
International Archives of Allergy and Immunology | Year: 2014

Background: Mast cell tryptase has recently been reported to be involved in atherosclerotic plaque destabilization. However, the results of these reports are conflicting. Methods: The aim of this study was to characterize the role of tryptase as a prognostic marker of patient cardiovascular complexity in acute coronary syndrome (ACS). Furthermore, its association with an angiographic scoring system [defined by the SYNergy between percutaneous coronary intervention (PCI) with the TAXUS drug-eluting stent and the cardiac surgery (SYNTAX) score] was examined. The serum tryptase was measured at admission in 65 consecutive ACS patients and in 35 healthy controls. In the patients with ACS, a composite measure of clinical and angiographic patient cardiovascular complexity was indicated by two of the following: clinical adverse events at hospitalization, at least 2 epicardial coronary arteries involved in the atherosclerotic disease, more than 1 stent implanted or more than 2 coronary artery disease risk factors. Results: The tryptase measurements were lower in patients without the composite measure (p < 0.0005). Linear regression showed a significant relationship between tryptase levels and the SYNTAX score (SX-score). Conversely, high-sensitivity troponin values did not correlate with either the composite outcome or the SX-score. The predictive accuracy of serum tryptase for the composite outcome was set at the cut-off point of 5.22 ng/ml (sensitivity 81% and specificity 95.7%). Conclusion: In ACS patients, serum tryptase levels at admission may predict patient cardiovascular complexity more reliably than currently known biomarkers. Further studies are needed to demonstrate the long-term prognostic role of this biomarker in ACS. © 2014 S. Karger AG, Basel.

Ricotta R.,Ospedale Niguarda Ca Granda | Vanzulli A.,Ospedale Niguarda Ca Granda | Moroni M.,Ospedale Niguarda Ca Granda | Colnago B.,Ospedale Niguarda Ca Granda | And 9 more authors.
Clinical Colorectal Cancer | Year: 2013

Purpose: The early identification of patients with metastatic colorectal carcinoma who are likely to benefit from treatment with panitumumab or cetuximab remains of paramount importance. We evaluated whether the early tumor shrinkage assessed by magnetic resonance imaging (MRI) is predictive of long-term outcome to these epidermal growth factor receptor-targeted therapies. Patients and Methods: Thirty-nine patients with chemorefractory metastatic colorectal carcinoma were treated with cetuximab or panitumumab. The patients were evaluated by unenhanced MRI at baseline, week 2, and week 8 after the beginning of the treatment and by contrast-enhanced computed tomography within 3 months. Early response was defined as a tumor shrinkage ≥10% at week-2 MRI, whereas response by contrast-enhanced computed tomography was defined according to standard Response Evaluation Criteria in Solid Tumors 1.1. Results: At week-2 MRI, 15 (38.5%) of 39 patients had an early response. Eleven (73.3%) of these 15 early responders then presented a partial response by contrast-enhanced computed tomography, whereas none of the 24 early nonresponders obtained a partial response (P <.0005, Fisher exact test). Median progression-free survival (PFS) was 29.7 and 8 weeks in patients with or without early response, respectively (hazard ratio [HR] 0.156 [95% CI, 0.069-0.355]; P <.0001)]. The median overall survival (OS) was 80 weeks in patients with early response and 23.3 weeks in those without early response, respectively (HR 0.154 [95% CI, 0.057-0.420]; P <.00005]). Conclusions: Early detection of tumor response by week-2 MRI without contrast medium is associated with a prediction of clinical outcome in patients with metastatic colorectal carcinoma treated with cetuximab or panitumumab. © 2013 Elsevier Inc. All rights reserved.

Pastorello E.A.,Allergology and Immunology Unit | Stafylaraki C.,Allergology and Immunology Unit | Mascheri A.,Allergology and Immunology Unit | Scibilia J.,Allergology and Immunology Unit | And 5 more authors.
International Archives of Allergy and Immunology | Year: 2013

Sensitisation to peach lipid transfer protein (LTP; Pru p 3) is significantly associated with severe allergic symptoms in adults, but little is known about the age at onset of peach allergy. We investigated a possible correlation between specific IgE levels to Pru p 3 and the age at onset of peach allergy. One hundred and forty-eight patients allergic to peach were divided into 6 classes according to the age at onset. Sera were analyzed for IgE antibodies to peach, rPru p 3, rPru p 1, rPru p 4, rBet v 1, rBet v 2, total IgE titre, and tryptase; all collected data were statistically analysed. A significant inverse correlation was found between the age at onset of peach allergy and anti-rPru p 3 IgE levels at diagnosis (p < 0.0005; Spearman's ρ = -0.3833). In contrast, the age at onset was directly correlated with both anti-rPru p 1 IgE levels (p = 0.0001; Spearman's ρ = 0.3197) and anti-rBet v 1 IgE levels (p = 0.0006; Spearman's ρ = 0.2914) at diagnosis. No correlations were detected between the reported age at onset and anti-peach, anti-rPru p 4, anti-rBet v 2 IgE and total IgE values and serum tryptase levels. At diagnosis, when peach allergy starts at a younger age, it is likely associated with Pru p 3 sensitisation, and the younger the onset, the higher the IgE titres. When peach allergy starts at an older age, it is more likely the result of cross-reactivity to Bet v1. Copyright © 2013 S. Karger AG, Basel.

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