Publications

<div>Abstract<p>Cyclic fasting–mimicking diet (FMD) is an experimental nutritional intervention with potent antitumor activity in preclinical models of solid malignancies. FMD cycles are also safe and active metabolically and immunologically in cancer patients. Here, we reported on the outcome of FMD cycles in two patients with chronic lymphocytic leukemia (CLL) and investigated the effects of fasting and FMD cycles in preclinical CLL models. Fasting-mimicking conditions in murine CLL models had mild cytotoxic effects, which resulted in apoptosis activation mediated in part by lowered insulin and IGF1 concentrations. In CLL cells, fasting conditions promoted an increase in proteasome activity that served as a starvation escape pathway. Pharmacologic inhibition of this escape mechanism with the proteasome inhibitor bortezomib resulted in a strong enhancement of the proapoptotic effects of starvation conditions <i>in vitro</i>. In mouse CLL models, combining cyclic fasting/FMD with bortezomib and rituximab, an anti-CD20 antibody, delayed CLL progression and resulted in significant prolongation of mouse survival. Overall, the effect of proteasome inhibition in combination with FMD cycles in promoting CLL death supports the targeting of starvation escape pathways as an effective treatment strategy that should be tested in clinical trials.</p>Significance:<p>Chronic lymphocytic leukemia cells resist fasting-mimicking diet by inducing proteasome activation to escape starvation, which can be targeted using proteasome inhibition by bortezomib treatment to impede leukemia progression and prolong survival.</p></div>

Trastuzumab-based regimens for the adjuvant treatment of HER2-positive early breast cancer significantly prolonged overall survival (OS) and disease free survival (DFS) in large randomized trials, with sustained benefits at four-year follow-up. We assessed long-term survival estimates and predictors in a large cohort of Italian women with early breast cancer treated with trastuzumab in clinical practice. Through a record linkage between five regional healthcare databases, we identified women treated with trastuzumab for early breast cancer in Lombardy (2006-2009). DFS and OS were estimated using the Kaplan-Meier method, and independent predictors were assessed using proportional hazard models. 2046 women received trastuzumab in early breast cancer adjuvant setting. Overall, the proportion of patients surviving free of disease was 93.9% at one year, 85.8% at 2 years, 79.4% at 3 years, and 75.0% at 4 years. OS estimates were 98.7%, 95.4%, 91.5% and 89.4% at 1, 2, 3 and 4 years, respectively. Significant independent predictors of worse survival outcomes were age <40 or ≥70 years compared to age 40-69 years, positive nodal status, radical breast surgery, combination therapy with paclitaxel, having at least one comorbidity (i.e. diabetes, cardiovascular disease), and a trastuzumab-based regimen lasting less than six months. Long term survival rates of women treated with trastuzumab for early breast cancer in clinical practice were consistent with estimates from clinical trials testing the drug in the adjuvant setting.

Several studies have assessed the relationship between exposure to particulate matter with aerodynamic diameters ≤2.5 μm (PM2.5) and ≤10 μm (PM10) and assisted reproduction technology (ART) success rates, with controversial findings. This review aimed to consolidate the current evidence from fresh ART cycles and explore sources of heterogeneity across studies. The outcomes of interest were biochemical and clinical pregnancy, and live birth. Four exposure timeframes were considered: T0 (within 90 days before starting the stimulation protocol), T1 (from the first day of stimulation protocol to oocyte retrieval), T2 (from oocyte retrieval to embryo transfer), and T3 (from embryo transfer to pregnancy). Database searches were conducted on PubMed/Medline and Embase up to April 2025, using a combination of MeSH/Emtree and generic terms relating to ART patients and air pollution exposure. Fourteen studies, involving 333,438 cycles, were included in the meta-analysis. The studies were conducted between 2010 and 2024 primarily in China (10/14), while 3 were from the USA and one from Korea. We estimated pooled relative risks (RRs) and the corresponding 95% confidence intervals (CIs) for a 10 μg/m3 increase in PM2.5 and PM10 for biochemical pregnancy, clinical pregnancy, and live births, using random-effects meta-analytic models. The pooled RRs for 10 μg/m3 increment in PM2.5 and PM10 at T0 were respectively 0.97 (95%CI: 0.91–1.04) and 0.98 (95%CI: 0.95–1.02) for biochemical pregnancy; for clinical pregnancy they were respectively 0.98 (95%CI: 0.96–1.01) and 0.99 (95%CI: 0.98–1.00). All other findings were close to unity. Substantial heterogeneity was observed across studies for selected outcomes and exposure periods for both pollutants. This systematic review found no significant association between PM2.5 and PM10 exposure and ART outcomes after fresh embryo transfer for any of the four exposure windows.

&lt;p&gt;Number of enhancers associated with genes and the number of mutations in the lower right quadrant of figure 4c Overlap with Msigdb C2 dataset&lt;/p&gt;

Identifying clusters of comorbidity in patients with BC may help understand their effects and enable clinicians and policymakers to better organise patient and healthcare management.