TP63 and TP73 in cancer, an unresolved “family” puzzle of complexity, redundancy and hierarchy

AbstractTP53 belongs to a small gene family that includes, in mammals, two additional paralogs, TP63 and TP73. The p63 and p73 proteins are structurally and functionally similar to p53 and their activity as transcription factors is regulated by a wide repertoire of shared and unique post-translational modifications and interactions with regulatory cofactors. p63 and p73 have important functions in embryonic development and differentiation but are also involved in tumor suppression. The biology of p63 and p73 is complex since both TP63 and TP73 genes are transcribed into a variety of different isoforms that give rise to proteins with antagonistic properties, the TA-isoforms that act as tumor-suppressors and DN-isoforms that behave as proto-oncogenes. The p53 family as a whole behaves as a signaling “network” that integrates developmental, metabolic and stress signals to control cell metabolism, differentiation, longevity, proliferation and death. Despite the progress of our knowledge, the unresolved puzzle of complexity, redundancy and hierarchy in the p53 family continues to represent a formidable challenge

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

EVALITA Evaluation of NLP and Speech Tools for Italian - December 17th, 2020

Welcome to EVALITA 2020! EVALITA is the evaluation campaign of Natural Language Processing and Speech Tools for Italian. EVALITA is an initiative of the Italian Association for Computational Linguistics (AILC, http://www.ai-lc.it) and it is endorsed by the Italian Association for Artificial Intelligence (AIxIA, http://www.aixia.it) and the Italian Association for Speech Sciences (AISV, http://www.aisv.it)

TAp73 regulates ATP7A: possible implications for ageing-related diseases.

The p53 family member p73 controls a wide range of cellular function. Deletion of p73 in mice results in increased tumorigenesis, infertility, neurological defects and altered immune system. Despite the extensive effort directed to define the molecular underlying mechanism of p73 function a clear definition of its transcriptional signature and the extent of overlap with the other p53 family members is still missing. Here we describe a novel TAp73 target, ATP7A a member of a large family of P-type ATPases implicated in human neurogenerative conditions and cancer chemoresistance. Modulation of TAp73 expression influences basal expression level of ATP7A in different cellular models and chromatin immunoprecipitation confirmed a physical direct binding of TAp73 on ATP7A genomic regions. Bioinformatic analysis of expression profile datasets of human lung cancer patients suggests a possible implication of TAp73/ATP7A axis in human cancer. These data provide a novel TAp73-dependent target which might have implications in ageing-related diseases such as cancer and neurodegeneration.Department of Clinical & Experimental Medicine, University of Foggia, Italy 3 Department of Systems Medicine, Nephrology and Hypertension Unit, Tor Vergata University Hospital, Rome, Italy. 4 Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Ital

Extracorporeal shock wave therapy in inflammatory diseases: molecular mechanism that triggers anti-inflammatory action.

Abstract: Shock waves (SW), defined as a sequence of single sonic pulses characterised by high peak pressure (100MPa), a fast rise in pressure (< 10 ns) and a short lifecycle (10 s), are conveyed by an appropriate generator to a specifictarget area at an energy density ranging from 0.03 to 0.11 mJ/mm2. Extracorporeal SW (ESW) therapy was first used onpatients in 1980 to break up kidney stones. During the last ten years, this technique has been successfully employed in orthopaedicdiseases such as pseudoarthosis, tendinitis, calcarea of the shoulder, epicondylitis, plantar fasciitis and severalinflammatory tendon diseases. In particular, treatment of the tendon and muscle tissues was found to induce a long-timetissue regeneration effect in addition to having a more immediate anthalgic and anti-inflammatory outcome. In keepingwith this, an increase in neoangiogenesis in the tendons of dogs was observed after 4-8 weeks of ESW treatment. Furthermore,clinical observations indicate an immediate increase in blood flow around the treated area. Nevertheless, thebiochemical mechanisms underlying these effects have yet to be fully elucidated.In the present review, we briefly detail the physical properties of ESW and clinical cases treated with this therapy. Wethen go on to describe the possible molecular mechanism that triggers the anti-inflammatory action of ESW, focusing onthe possibility that ESW may modulate endogenous nitric oxide (NO) production either under normal or inflammatoryconditions. Data on the rapid enhancement of endothelial NO synthase (eNOS) activity in ESW-treated cells suggest thatincreased NO levels and the subsequent suppression of NF-B activation may account, at least in part, for the clinicallybeneficial action on tissue inflammation

Cell death in cancer in the era of precision medicine

Tumors constitute a large class of diseases that affect different organs and cell lineages. The molecular characterization of cancers of a given type has revealed an extraordinary heterogeneity in terms of genetic alterations and DNA mutations; heterogeneity that is further highlighted by single-cell DNA sequencing of individual patients. To address these issues, drugs that specifically target genes or altered pathways in cancer cells are continuously developed. Indeed, the genetic fingerprint of individual tumors can direct the modern therapeutic approaches to selectively hit the tumor cells while sparing the healthy ones. In this context, the concept of precision medicine finds a vast field of application. In this review, we will briefly list some classes of target drugs (Bcl-2 family modulators, Tyrosine Kinase modulators, PARP inhibitors, and growth factors inhibitors) and discuss the application of immunotherapy in tumors (T cell-mediated immunotherapy and CAR-T cells) that in recent years has drastically changed the prognostic outlook of aggressive cancers. We will also consider how apoptosis could represent a primary end point in modern cancer therapy and how “classic” chemotherapeutic drugs that induce apoptosis are still utilized in therapeutic schedules that involve the use of target drugs or immunotherapy to optimize the antitumor response