PubMed | San Raffaele Rome Open University, San Giovanni Hospital Addolorata, University of Chieti Pescara, Interistitutional Multidisciplinary BioBank Bio and University of Rome Tor Vergata
Type: | Journal: International journal of cancer | Year: 2016
The hypothesis that increased oxidative stress in breast cancer (BC) patients could induce enhanced lipid peroxidation, which, in turn, would contribute to platelet activation and poor clinical outcome is attractive. To address this issue, we investigated pre-surgical urinary 8-iso-prostaglandin (PG)F
Hamilton D.H.,U.S. National Cancer Institute |
Roselli M.,University of Rome Tor Vergata |
Ferroni P.,San Raffaele Rome Open University |
Costarelli L.,San Giovanni Hospital Addolorata |
And 5 more authors.
Endocrine-Related Cancer | Year: 2016
Patients diagnosed with triple-negative breast cancer (TNBC) have a high rate of tumor metastasis and a poor prognosis. The treatment option for these patients is currently chemotherapy, which results in very low response rates. Strategies that exploit the immune system for the treatment of cancer have now shown the ability to improve survival in several tumor types. Identifying potential targets for immune therapeutic interventions is an important step in developing novel treatments for TNBC. In this study, in silico analysis of publicly available datasets and immunohistochemical analysis of primary and metastatic tumor biopsies from TNBC patients were conducted to evaluate the expression of the transcription factor brachyury, which is a driver of tumor metastasis and resistance and a target for cancer vaccine approaches. Analysis of breast cancer datasets demonstrated a predominant expression of brachyury mRNA in TNBC and in basal vs luminal or HER2 molecular breast cancer subtypes. At the protein level, variable levels of brachyury expression were detected both in primary and metastatic TNBC lesions. A strong association was observed between nuclear brachyury protein expression and the stage of disease, with nuclear brachyury being more predominant in metastatic vs primary tumors. Survival analysis also demonstrated an association between high levels of brachyury in the primary tumor and poor prognosis. Two brachyury-targeting cancer vaccines are currently undergoing clinical evaluation; the data presented here provide rationale for using brachyury-targeting immunotherapy approaches for the treatment of TNBC. © 2016 Society for Endocrinology Printed in Great Britain.
Ferroni P.,San Raffaele Rome Open University |
Riondino S.,Interinstitutional Multidisciplinary Biobank |
Riondino S.,University of Rome Tor Vergata |
Laudisi A.,University of Rome Tor Vergata |
And 10 more authors.
Oncologist | Year: 2016
Background. Based on the hypothesis that impaired glucose metabolism might be associated with survival outcomes independently of overt diabetes, we sought to investigate the prognostic value of routinely used glycemic parameters in a prospective study of breast cancer (BC) patients. Patients and Methods. Fasting blood glucose, insulin and HbA1c levels, and insulin resistance (assessed by the Homeostasis Model Assessment [HOMA] index) at diagnosis were evaluated in 286 nondiabetic BC patients (249 with primary cancer, 37 with metastatic) with respect to those parameters’ possible associations with clinicopathological features and survival outcomes. As a control group, 143 healthy women matched in a 2:1 ratio for age, blood lipid levels, and body mass index were also investigated. Results. Fasting blood glucose level(mean±SD:99±26vs.85 ± 15 mg/dL), insulin level (median: 10.0 vs. 6.8 μIU/mL), and HOMA index (median: 2.2 vs. 1.4), but not HbA1c level, were significantly elevated in BC patients compared with control subjects. Receiver operating characteristics analysis showed comparable areas for blood glucose and insulin levels, and HOMA index (ranging from 0.668 to 0.671). Using a cutoff level of 13 μIU/mL, insulin had the best specificity (92%) and sensitivity (41%), was significantly associated with disease stage, and acted as a negative prognostic marker of progressionfree survival (hazard ratio: 2.17; 95% confidence interval: 1.13–4.20) independently of menopausal status, disease stage, hormone receptor status, and human epidermal growth factor receptor 2 and Ki67 expression. Conclusion. These results suggest that insulin determination might provide prognostic information in BC and support the hypothesis that lifestyle and/or pharmacological interventions targeting glucose metabolism could be considered to improve survival out come of selected BC patients. © AlphaMed Press 2016.