Le Cellule Staminali Mesenchimali: Aspetti Biologici ed Approcci Terapeutici

The pioneeristic studies, started thirty years ago, were able to uncover an interesting bone marrow derived cell population named as mesenchymal stem cells (MSC). This cell type, used in the last decade in both pre-clinical and clinical phases in several fields of biomedical sciences, opened up innovative branches of translational research. In this review we analyze the biological background of the MSC with the purpose to identify their actual therapeutical applications with a special focus on their possible future role in oncology

Tumor size, node status, grading, HER2 and estrogen receptor status still retain a strong value in patients with operable breast cancer diagnosed in recent years.

Breast cancer prognosis has improved greatly in recent years. Consequently, a thorough search for sensitive prognostic factors, able to help clinicians offer appropriate therapy, has become a priority in this area. In this study, we considered all new cases of invasive breast cancer diagnosed in the Province of Modena, Italy, between 1997 and 2007, registered by the Modena Cancer Registry. The principal endpoint of this study was relapse-free survival (RFS). A set of 11 clinic and pathological parameters was investigated. After a median follow-up of 73 months, 494 relapses were recorded. Tumor size, node status, grading, HER2 and estrogen receptor status were retained as independent factors in a multivariate analysis. Using these variables, a prognostic model was devised to identify three groups at different risk. In the training sample, the 5-year RFS rates resulted 96.0%, 82.9% and 63.7% in patients at low, intermediate and high risk, respectively (p < 0.0001). In the validation sample, the 5-year RFS was 96.2%, 85.4% and 66.9%, respectively. To conclude our study demonstrates that a very simple prognostic index based on easily available clinical data may represent a useful tool for the identification of patients at different risk of relapse and may be a notable device to predict who truly benefits from medical treatment

Radiation Tolerant 3D Laser Scanner for Structural Inspections in Nuclear Reactor Vessels and Fuel Storage Pools

Accurate and timely assessment of displacements and/or structural damages in nuclear reactor vessels' components is a key action in routine inspections for planning maintenance and repairs but also in emergency situations for mitigating consequences of nuclear incidents. Nevertheless, all these components are maintained underwater and reside in high-radiation fields thus imposing harsh operative conditions to inspection devices which must cope with effects such as Cerenkov radiation background, Total Ionizing Radiation (TID), and occlusions in the detectors' field of view. To date, ultrasonic techniques and video cameras are in use for inspection of components' integrity and with measurements of volumetric and surface crack opening displacements, respectively. The present work reports the realization of a radiation tolerant laser scanner and the results of tests in a nuclear research reactor vessel for acquisition of 3D models of critical components. The device, qualified for underwater operation and for withstanding up to 1 MGy of TID, is based on a 515 nm laser diode and a fast-scanning electro-optic unit. To evaluate performances in a significant but controlled environment, the device has been deployed in the vessel of a research reactor operated by ENEA in the Casaccia Research Centre in Rome (Italy). A 3D model of the fuel rods assembly through a cooling water column of 7 m has been acquired. The system includes proprietary postprocessing software that automatically recognizes components of interest and provides dimensional analysis. Possible application fields of the system stretch to dimensional analysis also in spent nuclear fuel storage pools

A high-resolution, integrated system for rice yield forecasting at district level

To meet the growing demands from public and private stakeholders for early yield estimates, a high-resolution (2 km × 2 km) rice yield forecasting system based on the integration of the WARM model and remote sensing (RS) technologies was developed. RS was used to identify rice-cropped area and to derive spatially distributed sowing dates, and for the dynamic assimilation of RS-derived leaf area index (LAI) data within the crop model. The system—tested for the main European rice production districts in Italy, Greece, and Spain—performed satisfactorily; >66% of the inter-annual yield variability was explained in six out of eight combinations of ecotype × district, with a maximum of 89% of the variability explained for the ‘Tropical Japonica’ cultivars in the Vercelli district (Italy). In seven out of eight cases, the assimilation of RS-derived LAI improved the forecasting capability, with minor differences due to the assimilation technology used (updating or recalibration). In particular, RS data reduced uncertainty by capturing factors that were not properly reproduced by the simulation model (given the uncertainty due to large-area simulations). The system, which is an extension of the one used for rice within the EC-JRC-MARS forecasting system, was used pre-operationally in 2015 and 2016 to provide early yield estimates to private companies and institutional stakeholders within the EU-FP7 ERMES project

Real-life effectiveness of tildrakizumab in chronic plaque psoriasis: A 52-week multicentre retrospective study—IL PSO (Italian landscape psoriasis)

Background: Tildrakizumab is a humanized monoclonal antibody that binds selectively the p19 subunit of interleukin-23. It is approved for treatment of moderate– severe chronic plaque psoriasis. Objectives: We conducted a 52-week retrospective study to assess the effectiveness and safety of tildrakizumab in a real-life setting. Methods: Our retrospective study included 237 consecutive adults with moderateto-severe plaque psoriasis, enrolled in 10 different Italian centres, treated with tildrakizumab up to Week 52. Patient characteristics, comorbidities, previous treatmentsand the PASI (Psoriasis Area and Severity Index) score at each visit (baseline, Week 16, Week 28 and Week 52) were retrieved from the electronic medical records. The percentages of patients achieving 75%, 90% and 100% (PASI 75, PASI 90 and PASI 100) improvement in PASI with respect to baseline PASI were registered. Results: At Week 52, 90.91%, 73.55% and 58.68% of patients achieved a PASI reduction ≥75% (PASI 75), PASI 90 and PASI 100, respectively. An absolute PASI≤2 was reached by 85.95% at Week 52. Compared with Phase 3 clinical trials, we observed similar rates of PASI 75/90 responses and higher percentages of patients achieving PASI 100. Patients who had not responded to previous biologic treatments and patients with cardio-metabolic comorbidities were significantly more likely to achieve PASI 100 at Week 28 and PASI 90 at Week 52. The higher body mass index did not interfere with the odds of reaching PASI 75/90/100 at each time point. No significant safety findings were recorded throughout the study, and none of the patients had to interrupt the treatment because of adverse events. Conclusion: Our data suggest that the efficacy of tildrakizumab for plaque psoriasis in ‘real-life’ clinical practice is comparable with Phase 3 clinical trials with higher percentages of patients achieving complete skin clearance (PASI 100) at Weeks 16, 28 and 52

Brodalumab for the treatment of plaque psoriasis in a real-life setting: a 3 years multicenter retrospective study—IL PSO (Italian landscape psoriasis)

Introduction: Brodalumab is a monoclonal antibody that targets the subunit A of the interleukin-17A receptor (IL17RA), inhibiting the signaling of various isoforms of the IL-17 family. It has been approved for the treatment of moderate-to-severe plaque psoriasis after being evaluated in three Phase-3 trials. However, long-term data on brodalumab in a real-life setting are still limited

PIK3CA Mutation in the ShortHER Randomized Adjuvant Trial for Patients with Early HER2\ufe Breast Cancer: Association with Prognosis and Integration with PAM50 Subtype.

Purpose: We explored the prognostic effect of PIK3CA mutation in HER2\ufe patients enrolled in the ShortHER trial. Patients and Methods: The ShortHER trial randomized 1,253 patients with HER2\ufe breast cancer to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. PIK3CA hotspot mutations in exon 9 and 20 were analyzed by pyrosequencing. Expression of 60 genes, including PAM50 genes was measured using the nCounter platform. Results: A mutation of the PIK3CA gene was detected in 21.7% of the 803 genotyped tumors. At a median follow-up of 7.7 years, 5-year disease-free survival (DFS) rates were 90.6% for PIK3CA mutated and 86.2% for PIK3CA wild-type tumors [HR, 0.84; 95% confidence interval (CI), 0.56\u20131.27; P \ubc 0.417]. PIK3CA mutation showed a favorable prognostic impact in the PAM50 HER2-enriched subtype (n \ubc 232): 5-year DFS 91.8% versus 76.1% (log-rank P \ubc 0.049; HR, 0.46; 95% CI, 0.21\u20131.02). HER2-enriched/PIK3CA mutated versus wild-type tumors showed numerically higher tumor-infiltrating lymphocytes (TIL) and significant upregulation of immune-related genes (including CD8A, CD274, PDCD1, and MYBL2, a proliferation gene involved in immune processes). High TILs as well as the upregulation of PDCD1 and MYBL2 were associated with a significant DFS improvement within the HER2-enriched subtype (HR, 0.82; 95% CI, 0.68\u20130.99; P \ubc 0.039 for 10% TILs increment; HR, 0.81; 95% CI, 0.65\u20130.99; P \ubc 0.049 for PDCD1 expression; HR, 0.72; 95% CI, 0.53\u20130.99; P \ubc 0.042 for MYBL2 expression). Conclusions: PIK3CA mutation showed no prognostic impact in the ShortHER trial. Within the HER2-enriched molecular subtype, patients with PIK3CA mutated tumors showed better DFS versus PIK3CA wild-type, which may be partly explained by upregulation of immune-related genes

Effectiveness, Tolerability, and Drug Survival of Risankizumab in a Real-World Setting: A Three-Year Retrospective Multicenter Study—IL PSO (ITALIAN LANDSCAPE PSORIASIS)

Background: Risankizumab is a humanized monoclonal antibody that selectively inhibits interleukin-23. It has been approved for moderate-to-severe plaque psoriasis and has shown efficacy and safety in clinical trials and real-world experiences. This study aimed to evaluate the long-term effectiveness, safety, and drug survival of risankizumab in a real-life setting. Materials and Methods: We included patients treated with risankizumab from January 2019 to February 2023. A Psoriasis Area and Severity Index score (PASI) was collected at weeks 0, 16, 28, 52, 104, and 156, when available. The occurrence of any adverse events was recorded at each visit. Results: We enrolled 1047 patients. At week 52, a ≥90% improvement in PASI was observed in 81.44% of patients, with a continuous improvement throughout the study (88.99% and 99.07% at weeks 104 and 156, respectively). After three years of treatment, all patients involving the scalp, palms/soles, and genitalia and 95% of patients with nail psoriasis achieved a complete or almost complete skin clearance. No significant safety findings were observed, and 90.73% of the patients were still on treatment after 36 months. Conclusions: This study supports the long-term effectiveness and safety of risankizumab in a real- world setting, even in patients involving difficult-to-treat areas