Papers by Simona Santangelo
European Respiratory Journal, 2015
European Respiratory Journal, 2015
European Respiratory Journal, 2015
Expert Review of Molecular Diagnostics, 2013
European Respiratory Journal, Sep 1, 2013
Material and methods: we included 74 patients (51 OSAS and 23 COPD-6 hypoxemic). Exhaled breath o... more Material and methods: we included 74 patients (51 OSAS and 23 COPD-6 hypoxemic). Exhaled breath of all participants was analyzed using an innovative multisensorial system based on an array of seven quartz microbalance (QMB) sensors covered with thin films of seven different biomaterials. Sensors responses to VOCs result in seven frequency shifts of each of the QMB respect to their typical resonance frequency. This technology has been validated and its performance has been evaluated in gases and vapours calibration experiments for both single compounds and mixtures Background: the diagnosis of two major respiratory causes of sleep disturbances, Obstructive Sleep Apnea Syndrome (OSAS) and Chronic Obstructive Pulmonary Disease (COPD), is technically demanding, cost-intensive and time consuming. The measurement of volatile organic compounds (VOCs) by an electronic nose device is an innovative method to determine distinct molecular patterns of exhaled breath in different patient groups, and its potential use in OSAS and COPD, distinctly, has recently been evaluated.
Leukemia Research, 2013
Gene profile and functional changes upon IgD cross-linking were evaluated in chronic lymphocytic ... more Gene profile and functional changes upon IgD cross-linking were evaluated in chronic lymphocytic leukemia (CLL). Microarrays highlighted responsiveness to IgD in all cases, independently of clinicobiological characteristics. Stimulated samples exhibited the down-regulation of transcripts of B-cell receptor signaling and cell-adhesion at 24 h and the up-modulation of differentiation and apoptosis genes at 48 h. A significant increase in apoptosis upon ligation was also documented. Furthermore, comparison between IgD and IgM stimulation displayed a differential transcriptional/functional response.
Leukemia Research, 2010
To investigate the role of protein kinases (PKs) in chronic lymphocytic leukemia (CLL), we perfor... more To investigate the role of protein kinases (PKs) in chronic lymphocytic leukemia (CLL), we performed gene expression profile on 505 PK genes. Comparison between CLL with acute lymphocytic leukemia (ALL) patients highlighted an homogeneous up-modulation of several PKs in CLL, 16 also overexpressed in two additional CLL cohorts. Q-PCR analysis confirmed these findings. No differences were observed in the main prognostic subclasses, indicating that PK overexpression is specific of the disease itself. Tests in vitro showed that Dasatinib partially reduced CLL cells viability, mostly in IGHV germline patients. These findings suggest that treatment with second generation tyrosine kinase (TK) inhibitors may represent an attractive therapeutic strategy for CLL patients.
Journal of Medical Screening, 2013
Haematologica, 2011
blood cell count at diagnosis and immunoglobulin variable region gene mutations are independent p... more blood cell count at diagnosis and immunoglobulin variable region gene mutations are independent predictors of treatment-free survival in young patients with stage A chronic lymphocytic leukemia. Haematologica 2011;96(4):626-630.
Genes, Chromosomes and Cancer, 2011
Given that TP53 alterations predict prognosis and response to therapy in chronic lymphocytic leuk... more Given that TP53 alterations predict prognosis and response to therapy in chronic lymphocytic leukemia (CLL), screening for TP53 mutations has an increasing role in patient management. TP53 direct sequencing is a time-consuming method, while the AmpliChip p53 Research Test is a novel non time-consuming microarray-based resequencing assay and queries Exons 2-11. We evaluated the impact of TP53 mutations on clinical outcome by analyzing 98 untreated CLL using the AmpliChip p53 Research Test and direct sequencing and performed microarrays analysis on TP53 mutated and/or deleted cases. The AmpliChip p53 Research Test detected 17 mutations in 14 patients (17.3%); a significant association between TP53 mutations and del(17p) was recorded. From a clinical standpoint, a higher percentage of mutation was found in CLL with unfavorable outcome (17.2% vs. 7.1% in progressive vs. stable cases). Detection of TP53 mutations by the AmpliChip p53 Research Test was associated with a significantly worse survival (P = 0.0002). Comparison of the array and direct sequencing tests showed that the p53 Research Test detected more mutations, although it failed to identify two microdeletions. Finally, microarrays analysis showed a more distinctive signature associated with del(17p) than with TP53 mutations, likely due to a concomitant gene dosage effect. The AmpliChip p53 Research Test is a straightforward method that bears prognostic value. This study confirms a high percentage of TP53 mutations in CLL with unfavorable outcome and a significant association between TP53 aberrations and del(17p). Finally, specific gene expression profiles are recognized for TP53 alterations.
Experimental Hematology, 2012
Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by defects in the DNA... more Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by defects in the DNA damage response and apoptosis. Among the factors involved in these pathways, we focused on the enzyme poly(ADP-ribose) polymerase 1 (PARP1) and on its substrate Che-1 by evaluating their basal expression and functional changes upon irradiation (IR). Microarray experiments were performed on 98 untreated CLL cases. Next, freshly isolated primary cells from 21 untreated patients were analyzed for in vitro response to irradiation through Western blot, PARP activity assay, Annexin-V analysis, and PARP1 basal expression by quantitative polymerase chain reaction. Microarray analysis showed that PARP1 and CHE1 were constitutively expressed in CLL and had a high degree of correlation with each other and with TP53. PARP1 and TP53 downmodulation was associated with worse clinical outcomes, especially in TP53-mutated cases. Next, CLL samples from 21 untreated patients were classified as responders and nonresponders based on IR-induced PARP1 cleavage. Notably, while responder samples were characterized by Che-1 and p53 induction at 8 hours and reduction at 24 hours post-IR, nonresponders included both samples with p53 dysfunctions and cases with a normal IR-induced Che-1 and/or p53 response. Finally, we observed that PARP1 was downregulated in nonresponder vs responder samples and that its basal expression was positively correlated with PARP1 cleavage after IR. In conclusion, we showed that reduced expression of PARP1 is associated with an impairment of CLL responsiveness to cell death. Ó
British Journal of Haematology, 2012
British Journal of Haematology, 2011
Blood, 2008
leukemia (CLL) cells unmutated chronic lymphocytic H functional changes only in IgV BCR ligation ... more leukemia (CLL) cells unmutated chronic lymphocytic H functional changes only in IgV BCR ligation induced by IgM stimulation results in gene expression and http://bloodjournal.hematologylibrary.org/content/112/3/782.full.html Updated information and services can be found at: (4217 articles) Neoplasia Articles on similar topics can be found in the following Blood collections http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub_requests Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#reprints Information about ordering reprints may be found online at: http://bloodjournal.hematologylibrary.org/site/subscriptions/index.xhtml Information about subscriptions and ASH membership may be found online at: Chronic lymphocytic leukemia (CLL) patients exhibit a variable clinical course. To investigate the association between clinicobiologic features and responsiveness of CLL cells to anti-IgM stimulation, we evaluated gene expression changes and modifications in cell-cycle distribution, proliferation, and apoptosis of IgV H mutated (M) and unmutated (UM) samples upon BCR crosslinking. Unsupervised analysis highlighted a different response profile to BCR stimulation between UM and M samples. Super-vised analysis identified several genes modulated exclusively in the UM cases upon BCR cross-linking. Functional gene groups, including signal transduction, transcription, cell-cycle regulation, and cytoskeleton organization, were up-regulated upon stimulation in UM cases. Cell-cycle and proliferation analyses confirmed that IgM crosslinking induced a significant progression into the G 1 phase and a moderate increase of proliferative activity exclusively in UM patients. Moreover, we observed only a small reduction in the percentage of subG 0/1 cells, without changes in apoptosis, in UM cases; contrariwise, a significant increase of apoptotic levels was observed in stimulated cells from M cases. These results document that a differential genotypic and functional response to BCR ligation between IgV H M and UM cases is operational in CLL, indicating that response to antigenic stimulation plays a pivotal role in disease progression. (Blood. 2008;112:782-792)
Blood, 2009
biologic features of 9 cases Spontaneous regression of chronic lymphocytic leukemia: clinical and... more biologic features of 9 cases Spontaneous regression of chronic lymphocytic leukemia: clinical and http://bloodjournal.hematologylibrary.org/content/114/3/638.full.html Updated information and services can be found at: (896 articles) Lymphoid Neoplasia (1258 articles) Free Research Articles (3309 articles) Clinical Trials and Observations Articles on similar topics can be found in the following Blood collections http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub_requests Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#reprints Information about ordering reprints may be found online at: http://bloodjournal.hematologylibrary.org/site/subscriptions/index.xhtml Information about subscriptions and ASH membership may be found online at: In chronic lymphocytic leukemia (CLL), spontaneous regressions are an exceptional phenomenon, whose biologic features are unknown. We describe 9 CLL patients who underwent a spontaneous clinical regression over an 11-year followup, despite a residual neoplastic clone detected by flow cytometry. CD38 and ZAP-70 were negative in all cases. Immunoglobulin heavy chain variable region (IgVH) genes, mutated in all 7 evaluable patients, were restricted to the VH3 family in 6, with the usage of V H 3-30 gene in 2. The light chain variable region genes were mutated in 6 of 8 cases, with the use of V 4-1 gene in 3. Microarray analysis of CLL cells showed a distinctive genomic profile with an overrepresentation of BCRrelated and ribosomal genes, regulators of signal transduction and transcription. The number of activated T lymphocytes expressing IFN-␥, TNF-␣, and IL-4 was similar between CLL in spontaneous regression and healthy persons. In conclu-sion, spontaneous clinical regressions can occur in CLL despite the persistence of the neoplastic clone, and the biologic features include negative CD38 and ZAP-70, mutated V H 3-30 and V 4-1 genes. The peculiar gene profile suggests that BCR signaling may play an important role in this scenario as the most significant feature of the leukemic clone in regression. (Blood. 2009;114:638-646)
Annals of Hematology, 2011
American Journal of Hematology, 2014
word count: 199 N° of figures: 4 (2 Supplemental) N° of tables: 3 (2 Supplemental)
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Papers by Simona Santangelo