NF-YA enters cells through cell penetrating peptides.

Cell Penetrating Peptides -CPPs- are short aminoacidic stretches present in proteins that have the ability to translocate the plasma membrane and facilitate delivery of various molecules. They are usually rich in basic residues, and organized as alpha helices. NF-Y is a transcription factor heterotrimer formed by two Histone Fold Domain -HFD- subunits and the sequence-specific NF-YA.

LTR12 promoter activation in a broad range of human tumor cells by HDAC inhibition.

A considerable proportion of the human genome consists of transposable elements, including the long terminal repeats (LTRs) of endogenous retroviruses. During evolution, such LTRs were occasionally inserted upstream of protein-coding genes, contributing to their regulation. We previously identified the LTR12 from endogenous retrovirus 9 (ERV9) as a regulator of proapoptotic genes such as TP63 or TNFRSF10B.

NF-Y activates genes of metabolic pathways altered in cancer cells.

The trimeric transcription factor NF-Y binds to the CCAAT box, an element enriched in promoters of genes overexpressed in tumors. Previous studies on the NF-Y regulome identified the general term metabolism as significantly enriched. We dissect here in detail the targeting of metabolic genes by integrating analysis of NF-Y genomic binding and profilings after inactivation of NF-Y subunits in different cell types.

Utility-based criteria for selecting patients with hepatocellular carcinoma for liver transplantation: A multicenter cohort study using the alpha-fetoprotein model as a survival predictor.

The lifetime utility of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is still controversial. The aim of this study was to ascertain when LT is cost-effective for HCC patients, with a view to proposing new transplant selection criteria. The study involved a real cohort of potentially transplantable Italian HCC patients (n = 2419 selected from the Italian Liver Cancer group database) who received nontransplant therapies.

Prognosis of untreated hepatocellular carcinoma.

Unlabelled: The prognosis of untreated patients with hepatocellular carcinoma (HCC) is heterogeneous, and survival data were mainly obtained from control arms of randomized studies. Clinical practice data on this topic are urgently needed, so as to help plan studies and counsel patients. We assessed the prognosis of 600 untreated patients with HCC managed by the Italian Liver Cancer Group.

Identification of two clinical hepatocellular carcinoma patient phenotypes from results of standard screening parameters.

Previous work has shown that two general processes contribute to hepatocellular cancer (HCC) prognosis: liver damage, monitored by indices such as blood bilirubin, prothrombin time (PT), and aspartate aminostransferase (AST); and tumor biology, monitored by indices such as tumor size, tumor number, presence of portal vein thrombosis (PVT) and blood alpha-fetoprotein (AFP) levels. These processes may affect one another, with prognostically significant interactions between multiple tumor and host parameters. These interactions form a context that provide personalization of the prognostic meaning of these factors for every patient.

Low alpha-fetoprotein HCC and the role of GGTP.

Background: HCC patients are heterogeneous in terms of both tumor and liver factors. Alpha-fetoprotein (AFP) is an important prognostic tumor marker for those patients with elevated AFP levels.

Aims: To examine the differences in HCC patients with high or low AFP levels in blood and evaluate the prognostic parameters in low AFP patients.

Association of abnormal plasma bilirubin with aggressive hepatocellular carcinoma phenotype.

Cirrhosis-related abnormal liver function is associated with predisposition to hepatocellular carcinoma (HCC). It features in several HCC classification systems and is an HCC prognostic factor. The aim of the present study was to examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels.

Factors that affect efficacy of ultrasound surveillance for early stage hepatocellular carcinoma in patients with cirrhosis.

Background & Aims: Ultrasound surveillance does not detect early stage hepatocellular carcinomas (HCCs) in some patients with cirrhosis, although the reasons for this have not been well studied. We assessed the rate at which ultrasound fails to detect early stage HCCs and factors that affect its performance.

Methods: We collected information on 1170 consecutive patients included in the Italian Liver Cancer (ITA.

Significance of platelet and AFP levels and liver function parameters for HCC size and survival.

Background: Hepatocellular carcinoma (HCC) is a heterogeneous disease with both tumor and liver factors being involved.

Aims: To investigate HCC clinical phenotypes and factors related to HCC size.

Methods: Prospectively-collected HCC patients' data from a large Italian database were arranged according to the maximum tumor diameter (MTD) and divided into tumor size terciles, which were then compared in terms of several common clinical parameters and patients' survival.

Rise and fall of HCV-related hepatocellular carcinoma in Italy: a long-term survey from the ITA.LI.CA centres.

Background & Aims: Hepatitis C virus (HCV) is the leading aetiological factor of HCC in the western world where, overall, its incidence is increasing, despite data suggesting an initial drop in some areas. The aim of this study was to evaluate epidemiology, clinical features and survival of HCV-related HCC (HCV-HCC) in a wide time range in Italy.

Methods: Multicentre retrospective study including 3695 patients prospectively recruited by the ITA.

Influence of clinically significant portal hypertension on survival after hepatic resection for hepatocellular carcinoma in cirrhotic patients.

Background: The role of clinically significant portal hypertension on the prognosis of cirrhotic patients undergoing hepatic resection for hepatocellular carcinoma (HCC) is debated.

Aims: In this study, our aim was to assess the role of clinically significant portal hypertension after hepatic resection for HCC in patients with cirrhosis.

Methods: We assessed the prognostic role of the presence of clinically significant portal hypertension (oesophageal/gastric varices/portal hypertensive gastropathy or a platelet count <100 × 10(9) /L associated with splenomegaly) in 152 patients with compensated cirrhosis who underwent hepatic resection for HCC at the Italian Liver Cancer centres.

Hepatocellular carcinoma in patients without cirrhosis in Italy.

Background: In the Western world, hepatocellular carcinoma seldom develops in patients without cirrhosis, and reports describing the characteristics of non-cirrhotic patients with hepatocellular carcinoma are rather infrequent.

Methods: We evaluated the main clinical characteristics, treatment options, and survival of patients with hepatocellular carcinoma developed in non-cirrhotic liver among the 3027 consecutive cases of hepatocellular carcinoma accrued in the Italian Liver Cancer database during the last 20 years.

Results: We identified 52 patients with hepatocellular carcinoma in non-cirrhotic livers (1.

Hepatitis C in the elderly: a multicentre cross-sectional study by the Italian Association for the Study of the Liver.

Background: The prevalence of hepatitis C virus infection increases with advancing age, but elderly hepatitis C virus patients remain an understudied population.

Aim: To define the virological, epidemiological and clinical profiles of Italian outpatients aged 65 years and over infected by hepatitis C virus.

Methods: We evaluated 1544 anti-hepatitis C virus positive patients aged ≥65 years referred to 34 Italian outpatient specialty clinics over a two-year period.

Alpha-fetoprotein has no prognostic role in small hepatocellular carcinoma identified during surveillance in compensated cirrhosis.

Unlabelled: Alpha-fetoprotein is a tumor marker that has been used for surveillance and diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. The prognostic capability of this marker in patients with HCC has not been clearly defined. In this study our aim was to evaluate the prognostic usefulness of serum alpha-fetoprotein in patients with well-compensated cirrhosis, optimal performance status, and small HCC identified during periodic surveillance ultrasound who were treated with curative intent.

Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial.

The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E.

Cost-effectiveness of semi-annual surveillance for hepatocellular carcinoma in cirrhotic patients of the Italian Liver Cancer population.

Background & Aims: It was recently shown that semi-annual surveillance for hepatocellular carcinoma (HCC) in cirrhotic patients provides a prognostic advantage over the annual program; however, its cost-effectiveness (CE) in the general cirrhotic population still needs to be defined.

Methods: A Markov model was built to compare CE of these two strategies, considering literature results and treatment modalities of 918 cirrhotic patients from the Italian Liver Cancer (ITA.LI.

The changing scenario of hepatocellular carcinoma over the last two decades in Italy.

Background & Aims: This study investigates whether the aetiologic changes in liver disease and the improved management of hepatocellular carcinoma (HCC) have modified the clinical scenario of this tumour over the last 20 years in Italy.

Methods: Retrospective study based on the analysis of the ITA.LI.

Barcelona Clinic Liver Cancer staging and transplant survival benefit for patients with hepatocellular carcinoma: a multicentre, cohort study.

Background: Allocation of deceased-donor livers to patients with chronic liver failure is improved by prioritising patients by 5-year liver transplantation survival benefit. The Barcelona Clinic Liver Cancer (BCLC) staging has been proposed as the standard means to assess for prognosis of patients with hepatocellular carcinoma. We aimed to create a prediction model linking the BCLC stage of patients with hepatocellular carcinoma to their 5-year liver transplant benefit.

Relative decrease in the role played by hepatitis B virus infection in the aetiology of hepatocellular carcinoma during a 20-year period: a multicentre Italian study.

Background: Chronic hepatitis B virus (HBV) infection is one of the most frequent aetiological factors associated with the development of hepatocellular carcinoma (HCC).

Aim: This study evaluated the temporal trend in the aetiological role played by HBV infection alone in patients diagnosed with HCC during the last 20 years in Italy.

Methods: Among the 2042 HCC patients included in the Italian Liver Cancer (ITA.

Mass spectrometry measurement of plasma hepcidin for the prediction of iron overload.

Background: Hepcidin has emerged as the primary regulator of iron homeostasis. Previous studies on assessing urinary hepcidin are limited. We developed a method for quantifying hepcidin-25 (Hep-25) in plasma using surface-enhanced laser-desorption-ionization time-of-flight mass spectrometry (SELDI-TOF/MS) and a 25-AA peptide as reference standard.

A 35-year follow-up of a large cohort of patients with primary biliary cirrhosis seen at a single centre.

Background: The natural history of primary biliary cirrhosis (PBC) is still debated.

Aims: To evaluate: (i) long-term survival in a large cohort of PBC patients observed prospectively at a single centre and (ii) mortality in relation to baseline characteristics and ursodeoxycholic acid (UDCA) treatment.

Methods: We considered all consecutive patients between 1973 and 2007 (327 subjects; 310 females, 17 males).

Semiannual surveillance is superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival.

Background & Aims: The current guidelines recommend the surveillance of cirrhotic patients for early diagnosis of hepatocellular carcinoma (HCC), based on liver ultrasonography repetition at either 6 or 12 month intervals, since there is no compelling evidence of superiority of the more stringent program. This study aimed at comparing cancer stage, treatment applicability, and survival between patients on semiannual or annual surveillance.

Methods: We analyzed the clinical records of 649 HCC patients in Child-Pugh class A or B, observed in ITA.