Giovanni Pietro Beretta

Role of proliferation in HER2 status predicted response to doxorubicin

The role of HER2 in predicting response to doxorubicin (DXR) therapy in breast cancer was evaluated in vivo in a series of breast carcinomas from 220 patients with tumors larger than 2.5 cm and treated with 3 cycles of DXR (75 mg/m2) as neoadjuvant chemotherapy. Patients with HER2‐positive tumors were more frequently responsive to DXR treatment compared with HER2‐negative patients (p = 0.05; Mantel‐Haenszel X2 = 0.009). Progesterone receptor (PgR) negativity, but not mutated p53, was also associated with response to DXR (p = 0.05; Mantel‐Haenszel X2 = 0.004). Further analysis of those correlations using breast carcinoma cell lines characterized for different biologic parameters revealed a trend between HER2 positivity/PgR negativity and greater DXR sensitivity, but the strongest direct correlation was found between the proliferation rate and sensitivity to DXR (r = 0.82, p = 0.00009). Neither p53 nor the DXR target molecule topoisomerase‐II‐α was significantly associated with in vitro sensitivity to DXR. Thus, whereas data showed that the major biologic parameter associated with in vitro response to DXR in breast cancer cells appears to be the tumor proliferation rate, HER2 expression together with PgR negativity may serve as the counterpart of the proliferation marker in predicting the in vivo response to DXR.

Reliability of groundwater vulnerability maps obtained through statistical methods

Statistical methods are widely used in environmental studies to evaluate natural hazards. Within groundwater vulnerability in particular, statistical methods are used to support decisions about environmental planning and management. The production of vulnerability maps obtained by statistical methods can greatly help decision making. One of the key points in all of these studies is the validation of the model outputs, which is performed through the application of various techniques to analyze the quality and reliability of the final results and to evaluate the model having the best performance. In this study, a groundwater vulnerability assessment to nitrate contamination was performed for the shallow aquifer located in the Province of Milan (Italy). The Weights of Evidence modeling technique was used to generate six model outputs, each one with a different number of input predictive factors. Considering that a vulnerability map is meaningful and useful only if it represents the study area through a limited number of classes with different degrees of vulnerability, the spatial agreement of different reclassified maps has been evaluated through the kappa statistics and a series of validation procedures has been proposed and applied to evaluate the reliability of the reclassified maps. Results show that performance is not directly related to the number of input predictor factors and that is possible to identify, among apparently similar maps, those best representing groundwater vulnerability in the study area. Thus, vulnerability maps generated using statistical modeling techniques have to be carefully handled before they are disseminated. Indeed, the results may appear to be excellent and final maps may perform quite well when, in fact, the depicted spatial distribution of vulnerability is greatly different from the actual one. For this reason, it is necessary to carefully evaluate the obtained results using multiple statistical techniques that are capable of providing quantitative insight into the analysis of the results. This evaluation should be done at least to reduce the questionability of the results and so to limit the number of potential choices.

Point and nonpoint pollution and restoring groundwater quality in Italy: 30 years of experience

In Italy, a significant portion of the drinking water supply is provided by groundwater, hence also the importance given to its protection. For nonpoint pollutants, the paper describes the experimental approach (field trials) and cartographic materials (vulnerability maps) used to assess the nitrogen dynamics and the consequent presence of nitrates in groundwater. In the high vulnerability areas, there are limitations on the use of agricultural fertilizers, while in urban areas, various interventions on water discharges must be undertaken. Little information is available from the monitoring network with regard to emerging pollutants. For point pollutants in contaminated sites, an estimate is given of the distribution of the most frequently found substances; after a detailed description of these substances, possible remediation technologies are discussed. Despite the recovery of the mass of pollutants even as much as 90–99%, the cleanup values (expected concentrations expressed as µg/L) established by national legislation have not been achieved. It can be stated that the scientific community is considering the new paradigm expressed by the “order of magnitude of the flow of pollutant mass” to replace the old paradigm consisting in the “limit value of final concentrations”.