Targeting lysine-specific demethylase 1 (KDM1A/LSD1) impairs colorectal cancer tumorigenesis by affecting cancer cells stemness, motility, and differentiation

: Among all cancers, colorectal cancer (CRC) is the 3rd most common and the 2nd leading cause of death worldwide. New therapeutic strategies are required to target cancer stem cells (CSCs), a subset of tumor cells highly resistant to present-day therapy and responsible for tumor relapse. CSCs display dynamic genetic and epigenetic alterations that allow quick adaptations to perturbations. Lysine-specific histone demethylase 1A (KDM1A also known as LSD1), a FAD-dependent H3K4me1/2 and H3K9me1/2 demethylase, was found to be upregulated in several tumors and associated with a poor prognosis due to its ability to maintain CSCs staminal features. Here, we explored the potential role of KDM1A targeting in CRC by characterizing the effect of KDM1A silencing in differentiated and CRC stem cells (CRC-SCs). In CRC samples, KDM1A overexpression was associated with a worse prognosis, confirming its role as an independent negative prognostic factor of CRC. Consistently, biological assays such as methylcellulose colony formation, invasion, and migration assays demonstrated a significantly decreased self-renewal potential, as well as migration and invasion potential upon KDM1A silencing. Our untargeted multi-omics approach (transcriptomic and proteomic) revealed the association of KDM1A silencing with CRC-SCs cytoskeletal and metabolism remodeling towards a differentiated phenotype, supporting the role of KDM1A in CRC cells stemness maintenance. Also, KDM1A silencing resulted in up-regulation of miR-506-3p, previously reported to play a tumor-suppressive role in CRC. Lastly, loss of KDM1A markedly reduced 53BP1 DNA repair foci, implying the involvement of KDM1A in the DNA damage response. Overall, our results indicate that KDM1A impacts CRC progression in several non-overlapping ways, and therefore it represents a promising epigenetic target to prevent tumor relapse

The first SARS-CoV-2 wave among pregnant women in Italy: results from a prospective population-based study

Introduction. This study aimed to estimate the incidence of SARS-CoV-2 infection among pregnant women during the first pandemic wave in Italy, and to describe COVID-19 disease characteristics and maternal and perinatal outcomes. Materials and methods. National population-based prospective cohort study collecting information on women with SARS-CoV-2 diagnosis, confirmed within 7 days from hospital admission. Results. The national SARS-CoV-2 rate was 6.04 per 1,000 births (95% CI 5.62-6.49) among pregnant women and 7.54 (95% CI 7.47-7.61) among women in reproductive age. 72.1% of the cohort developed mild COVID-19 disease without pneumonia nor need for ventilatory support. Severe disease was significantly associated with women's previous comorbidities (OR 2.55; 95% CI 0.98-6.90), obesity (OR 4.76; 95% CI 1.79-12.66) and citizenship from High Migration Pressure Countries (OR 3.43; 95% CI 1.27-9.25). Conclusions. During the first pandemic wave in Italy, the SARS-CoV-2 rate among pregnant women was lower compared to that detected among women of reproductive age, and risks of severe COVID-19 disease and adverse maternal and perinatal outcomes were rare

L’attività dei Centri Antifumo italiani tra problematiche e aree da potenziare: i risultati di un’indagine svolta attraverso un questionario on-line

Introduzione. In Italia sono 295 i Servizi per la cessazione dal fumo di tabacco (Centri Antifumo - CA) afferenti al Servizio Sanitario Nazionale (SSN) censiti nel 2011 dall’Osservatorio Fumo, Alcol e Droga (OssFAD) dell’Istituto Superiore di Sanità. La presente indagine, condotta dall’OssFAD in collaborazione con i CA, è stata volta a rilevare alcune delle problematiche con le quali il personale dei CA si confronta per portare avanti la propria attività e le iniziative ritenute utili per migliorarla. Materiali e metodi. L’indagine è stata condotta dal 7 al 21 maggio 2012, mediante un questionario compilabile on-line composto da 5 brevi sezioni di domande con un totale di 38 items da completare. Il link al questionario on-line è stato inviato per e-mail a 322 indirizzi dei CA censiti nel 2011 dall’OssFAD. I dati raccolti sono stati elaborati statisticamente con il programma SPSS 20. Risultati. All’indagine hanno risposto 146 operatori dei CA (45,3%). Sebbene ci siano aspetti ormai consolidati dell’attività dei CA, sono ancora molte le criticità che gli operatori riscontrano nella loro attività. Le principali problematiche che influiscono in modo fondamentale/rilevante per la buona attività del centro sono le “Scarse o nulle risorse economiche” per il 60,7% del personale, “la mancanza di personale dedicato” per il 52,4% del personale; il “riconoscimento/mandato istituzionale del CA” per il 40,9% del personale. Tra le azioni ritenute più efficaci per facilitare l’accesso ai CA sono risultate la sensibilizzazione del personale sanitario (91%), in particolare dei medici di famiglia e l’inserimento delle prestazioni antitabagiche nei LEA (76,8%). Conclusioni. È auspicabile che l’attività dei CA riceva una maggiore attenzione, attraverso la dotazione di strutture, personale e finanziamenti adeguati a svolgere un importante ruolo nella tutela e promozione della salute