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Tedeschi R.,Microbiology Immunology and Virology Unit | Bidoli E.,Epidemiology and Biostatistic Unit | Bortolin M.T.,Microbiology Immunology and Virology Unit | Schioppa O.,Centro Of Riferimento Oncologico | And 2 more authors.
Oncotarget | Year: 2015

This study aimed to evaluate plasma concentration of selected cancer-associated inflammatory and immune-modulated cytokines in HIV+ patients with advanced Kaposi sarcoma (KS), and to explore candidate biomarkers capable of predicting clinical outcome in response to chemotherapy (CT) plus combination antiretroviral therapy (cART). Thirty-seven plasma cytokines/chemokines were assessed by Luminex technology in 27 consecutive HIV+ KS patients, followed-up during CT and cART of maintanence (m-cART). Associations between plasma concentration of biomarkers and patient clinical response to m-cART were evaluated by means of Hazard Ratios (HRs) and corresponding 95% Confidence Intervals (CIs). Plasma baseline concentration of Granulocyte colony-stimulating factor (G-CSF), Hepatocyte growth factor (HGF) and endoglin were found to be associated with m-cART clinical response (HR:1.56, 95%CI:1.09-2.22, p = 0.01; HR:0.32, 95% CI:0.10-0.99, p = 0.05; HR:0.72, 95% CI:0.54-0.96, p = 0.03, respectively). The multivariate analysis confirmed the associations of baseline plasma G-CSF and HGF concentration with m-cART clinical complete remission response (HR:1.78, 95% CI:1.15-2.74, p = 0.009; HR:0.19, 95% CI:0.04-0.95, p = 0.04). Our exploratory study suggested that plasma G-CSF, HGF and endoglin may be novel predictors of clinical response during m-cART in HIV+ KS patients. Nonetheless, these findings should be further validated in an independent population study. Source


Agborsangaya C.B.,University of Tampere | Agborsangaya C.B.,Finnish National Institute for Health and Welfare | Lehtinen T.,University of Tampere | Toriola A.T.,University of Tampere | And 5 more authors.
European Journal of Cancer | Year: 2011

Background: Few studies have evaluated the role of the ubiquitous Epstein-Barr virus (EBV) infection, together with levels of the immunomodulator, vitamin D, in different breast cancer entities. We studied, prospectively, the association of EBV and vitamin D status with the risk of pregnancy-associated breast cancer (PABC), breast cancer diagnosed during pregnancy or 1 year post-partum, using a nested case-control study. Methods: Serum vitamin D and antibodies to EBV were measured for 108 PABC cases of the Finnish Maternity Cohort, and 208 controls matched for date of birth, date of sampling and parity. The joint effect of vitamin D and EBV on the risk of PABC was evaluated. Results: EBV seropositivity was generally not associated with the risk of PABC. Among individuals with sufficient (≥75 nmol/l) levels of vitamin D, we, however, found similar increased risk estimates for PABC associated with serum immunoglobulin G (IgG) antibodies to EBV early antigens [odds ratio (OR) = 7.7, 95% (confidence interval) CI 1.4-42.3] and the viral reactivator protein, ZEBRA (OR = 7.8, 95% CI 1.1-61.2). Conclusion: Immunological markers of EBV reactivation status among individuals with sufficient vitamin D levels were consistently associated with increased risk of the disease. This suggests that EBV reactivation may be an indicator of the progression of breast cancer occurring soon after pregnancy, while the virus probably is not the aetiological agent. © 2010 Elsevier Ltd. All rights reserved. Source


Bortolin M.T.,Microbiology Immunology and Virology Unit | Tedeschi R.,Microbiology Immunology and Virology Unit | Bidoli E.,Epidemiology Unit | Zanussi S.,Microbiology Immunology and Virology Unit | And 4 more authors.
Cytokine | Year: 2012

Background: Recent studies suggest a powerful prognostic value for blood cytokine levels in different diseases. Non-Hodgkin lymphoma (NHL) still represents one of the main causes of death in the HIV setting, with a wide variation in outcome and survival among patients.We measured blood concentrations of 11 cytokines from HIV-NHL patients at diagnosis and correlated these with the patient outcome to evaluate the prognostic value. Methods: Luminex technology was used to simultaneously measure serum levels of interleukin IL-2/5/6/7/8/10/13/15, INF-γ, TNF-α and VEGF. Eighty-one consecutive HIV-NHL patients, at diagnosis, were studied. Hazard Ratios (HRs) and corresponding 95% confidence intervals (CIs) of disease-free survival (DFS) and overall survival (OS) were computed according to cytokine levels. HRs were also calculated for continuous variation of IL-7. Results: In the multivariate analysis, statistically significant associations to both DFS and OS were found for IL-7 serum levels ≥3.2. pg/mL (HR=5.55, 95%CI:2.38-12.95; HR=3.53, 95%CI:1.60-7.77, respectively), IL-8 ≥ 18. pg/mL (HR=2.69, 95%CI:1.15-6.30; HR=2.35, 95%CI:1.01-5.51, respectively) and IL-10 ≥ 13. pg/mL (HR=2.82, 95%CI: 1.19-6.71; HR=2.98, 95%CI:1.21-7.30, respectively). When the multivariate analyses were mutually adjusted for INF-γ, IL-7, IL-8, IL-10 and IL-15, serum IL-7 ≥ 3.2. pg/mL emerged as factor independently associated to increased risk of DFS (HR=3.63, 95%CI:1.47-8.93) and OS (HR=3.97, 95%CI:1.49-10.57). Conclusions: IL-7, measured at NHL diagnosis, was the only cytokine strongly and independently associated to both DFS and OS. The multiplex analysis of different blood cytokines' concentration might be useful in defining additive predictive markers in HIV-NHL management and ascertainment of their outcome. © 2012 Elsevier Ltd. Source


Tedeschi R.,Microbiology Immunology and Virology Unit | Bortolin M.T.,Microbiology Immunology and Virology Unit | Bidoli E.,Epidemiology Unit | Zanussi S.,Microbiology Immunology and Virology Unit | And 4 more authors.
Journal of Clinical Virology | Year: 2012

Background: Despite the era of highly active antiretroviral therapy, non-Hodgkin lymphoma (NHL) remains one of the main causes of death in HIV-infected patients, with a wide variation on the outcome. Objectives: We investigated immunological status and EBV, HHV8, HIV viral load in a group of HIV-infected patients at diagnosis of NHL to evaluate their prognostic significance. Study design: Eighty-one consecutive HIV+ NHL patients were studied. CD4 and CD8 cell counts, HHV8 DNA, EBV DNA, HIV RNA and HIV DNA were assessed at diagnosis and at 3 months after chemotherapy initiation. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of disease free survival (DFS) and overall survival (OS) were computed according to CD4 and CD8 cell counts, EBV DNA, HIV RNA and HIV DNA. HRs were, thereafter, computed also for continuous variation of CD4, CD8 cell counts and EBV DNA. Results: In the multivariate analysis, CD4 < 160 and CD8 < 590. cell/μl and EBV DNA ≥ 300. c/ml were independently associated to DFS (HR = 2.98; 95%CI: 1.26-7.03; HR = 2.65, 95%CI: 1.13-6.19; HR = 4.01; 95%CI: 1.81-8.91) and OS (HR = 3.32; 95%CI: 1.41-7.83; HR = 4.62, 95%CI: 1.91-11.19; HR = 3.11, 95%CI: 1.42-6.80). HRs for DFS and OS decreased continuously with increasing CD4 and CD8 cell counts, while they increased continuously with increasing EBV DNA levels. Conclusions: The association with survival of low CD4 and CD8 cell counts and detectable EBV viremia, measured at lymphoma's diagnosis, identified three independent prognostic biomarkers that might help in the management of NHL HIV+ patients, offering complementary information in the ascertainment of their outcome. © 2012 Elsevier B.V. Source


Bortolin M.T.,Microbiology Immunology and Virology Unit | Tedeschi R.,Microbiology Immunology and Virology Unit | Bidoli E.,Epidemiology and Biostatistic Unit | Furlan C.,Oncology Reference Center | And 6 more authors.
Biomarkers | Year: 2015

Objective: To evaluate whether plasma cell-free DNA (cfDNA) was related to clinical outcome in inoperable stage I non-small cell lung cancer (NSCLC) patients undergoing stereotactic body radiotherapy (SBRT).Materials and methods: Plasma cfDNA was assessed at baseline, before the last day and 45 days after the end of SBRT, in 22 NSCLC patients. Twenty-two healthy controls were also evaluated.Results: Plasma cfDNA was higher in patients than in controls. An association with unfavourable disease-free survival was found for continuous baseline cfDNA increments (HR = 5.9, 95%CI: 1.7-19.8, p = 0.04).Conclusion: Plasma cfDNA may be a promising prognostic biomarker in high-risk NSCLC patients. © 2015 Taylor & Francis. Source

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