Showing papers by "Giulia Pasello published in 2013"

Effects of Sulfonylureas on Tumor Growth: A Review of the Literature

Abstract: Type 2 diabetes mellitus patients are at higher cancer risk, probably because of hyperinsulinemia and insulin growth factor 1 pathway activation. The effects of antidiabetic drugs on cancer risk have been described and discussed in several studies suggesting opposite effects of the biguanide metformin and sulfonylureas on cancer incidence and mortality. The anticancer mechanisms of metformin have been clarified, and some clinical studies, particularly in breast cancer patients, have been published or are currently ongoing; however, data about the effects of sulfonylureas on cancer growth are less consistent. The aims of this work are to review preclinical evidence of second-generation sulfonylureas effects on tumor growth, to clarify the potential mechanisms of action, and to identify possible metabolic targets for patient selection. Most evidence is on the adenosine triphosphate-sensitive potassium channels inhibitor glibenclamide, which interacts with reactive oxygen species production thus inducing cancer cell death. Among diarylsulfonylureas, next-generation DW2282 derivatives are particularly promising because of the proapoptotic activity in multidrug-resistant cells.

Outcomes and prognostic factors of non-small-cell lung cancer with lymph node involvement treated with induction treatment and surgical resection

Abstract: OBJECTIVES: Induction therapy (IT) has gained popularity in recent years, becoming a standard of treatment in resectable lymph nodepositive NSCLC. IT aims to downstage the disease (shrinkage of tumour and clearance of lymph node-metastases), clear distant micrometastases and prolong survival. Potential disadvantages are increased morbidity and/or mortality after surgery and risk of progression of disease that could have been initially resected. The purpose of this study was to evaluate the outcomes and prognostic factors in a series of patients with lymph node-positive NSCLC receiving IT followed by surgery. METHODS: A total of 86 patients (75.6% males, median age 63 years) affected by NSCLC in clinical stage IIIA (n= 80) or IIIB (n= 6), with pathologically proven lymph node involvement, underwent platinum-based IT followed by surgery between 2000 and 2009. RESULTS: Eighty (93%) patients received a median of 3 cycles of chemotherapy, and 6 (7%) underwent induction chemoradiotherapy. Response to IT was complete in 3.5%, partial in 59.3% and stable disease in 37.2% of patients. Postoperative morbidity and mortality were 25.6 and 2.3%, respectively. At pathological evaluation, 38.4% of patients had a downstaging of disease with a complete lymph node clearance in 31.4%. Median overall survival was 23 months (5-year survival 33%). Univariate analysis found clinical stage (P= 0.02), histology (P= 0.01), response to IT (P= 0.02) and type of intervention (P= 0.047) to have predictive roles in survival. A better but not significant survival was also found for pN0 vs pN+ (P= 0.22), downstaged tumours (P= 0.08) and left side (P= 0.06). On multivariate analysis, clinical response to neoadjuvant therapy (P= 0.01) and age (P= 0.03) were the only independent predictors of survival. CONCLUSIONS: The use of IT for lymph node-positive NSCLC seems justified by low morbidity and/or mortality and good survival rates. Patients with response to IT showed greater benefit in the long term.

Changes in pulmonary function tests predict radiological response to chemotherapy in malignant pleural mesothelioma.

Abstract: OBJECTIVES: Response to chemotherapy in malignant pleural mesothelioma (MPM) is usually evaluated by radiological criteria, but no common agreement exists on their validity, yet. The cytoreductive effect of chemotherapy on pleural thickening may make the lung more expansible, reducing the restrictive ventilatory impairment. The aim of this study was to evaluate the changes in pulmonary function following chemotherapy in patients with MPM and to correlate these findings with radiological changes. METHODS: Between 2004 and 2011, 62 consecutive patients (74% males, median age 63 years) were prospectively investigated. Modified RECIST criteria were used for radiological evaluation of response to chemotherapy. All patients underwent pulmonary function tests before and after three cycles of platinum-based chemotherapy. Changes between baseline and post-chemotherapy pulmonary function values (Δ) and their differences were assessed by means of Student’s paired and unpaired t-test, respectively. Receiver operating characteristic (ROC) curve analysis was performed on spirometric parameters significantly associated with response. RESULTS: Thirty (48.4%) patients had a radiological stable disease (S), 23 (37.1%) a partial response (R) and 9 (14.5%) a progressive disease (P). ΔFEV1%pred (R: 18.1 ± 18.5%; S: 0.5 ± 9.3%; P: −11 ± 13.5%; P< 0.0001), ΔFVC%pred (R: 16.1 ± 11.8%; S: 0.4 ± 11.2%; P: −9.2 ± 14.6%; P< 0.0001) and ΔVC%pred (R: 12.9 ± 15.7%; S: 1.5 ± 12.1%; P: −6.1 ± 13.2%; P= 0.001) were significantly associated with radiological response. A significant correlation was observed between ΔFEV1%pred (r = 0.46, P= 0.01), ΔFVC%pred (r = 0.43, P= 0.02) and % change in linear tumour measurement. ROC curve analysis using dichotomized radiological response (P/S vs R) as classification variables showed AUC = 0.88 (95%CI: 0.77–0.95) for ΔFEV1%pred (optimal cut-off value: +7%, sensitivity: 83%, specificity: 82%, PPV: 73%, NPV: 89%) and AUC = 0.86 (95%CI: 0.75–0.94) for ΔFVC%pred (optimal cut-off value: +6%, sensitivity: 82%, specificity: 74%, PPV: 64%, NPV: 88%). CONCLUSIONS: Dynamic lung volumes and radiological changes after chemotherapy seem directly related. Lung function changes could be an additional tool to better evaluate the response to chemotherapy in MPM.