High CD49a+ NK cell infiltrate is associated with poor clinical outcomes in Hepatocellular Carcinoma.

NK cells infiltrating Hepatocellular Carcinoma (HCC) may express residency markers such as Integrin Subunit Alpha 1 (CD49a) that have been associated with nurturing functions in the decidua, and characterized by the production of angiogenic factors as well as loss of cytotoxicity. CIBERSORT, a computational analysis method for quantifying cell fractions from bulk tissue gene expression profiles, was used to estimate the infiltrating immune cell composition of the tumor microenvironment from gene expression profiles of a large cohort of 225 HCCs in the public GEO database. Decidual-like CD49a+ NK cells, in addition to another 22 immune cell populations, were characterized and thoroughly investigated so that HCC cell heterogeneity in a large cohort of 225 HCCs from the public GEO database could be studied.

Targeting Stress Sensor Kinases in Hepatocellular Carcinoma-Infiltrating Human NK Cells as a Novel Immunotherapeutic Strategy for Liver Cancer.

Natural killer (NK) cells may become functionally exhausted entering hepatocellular carcinoma (HCC), and this has been associated with tumor progression and poor clinical outcome. Hypoxia, low nutrients, immunosuppressive cells, and soluble mediators characterize the intratumor microenvironment responsible for the metabolic deregulation of infiltrating immune cells such as NK cells. HCC-infiltrating NK cells from patients undergoing liver resection for HCC were sorted, and genome-wide transcriptome profiling was performed.

Intratumor Regulatory Noncytotoxic NK Cells in Patients with Hepatocellular Carcinoma.

Previous studies support the role of natural killer (NK) cells in controlling hepatocellular carcinoma (HCC) progression. However, ambiguity remains about the multiplicity and the role of different NK cell subsets, as a pro-oncogenic function has been suggested. We performed phenotypic and functional characterization of NK cells infiltrating HCC, with the corresponding nontumorous tissue and liver from patients undergoing liver resection for colorectal liver metastasis used as controls.

Energy metabolism and cell motility defect in NK-cells from patients with hepatocellular carcinoma.

Functional rescue of NK-cells in solid tumors represents a central aim for new immunotherapeutic strategies. We have conducted a genomic, phenotypic and functional analysis of circulating NK-cells from patients with HCV-related liver cirrhosis and hepatocellular carcinoma. NK-cells were sorted from patients with HCC or liver cirrhosis and from healthy donors.

New Direct-Acting Antivirals for the Treatment of Patients With Hepatitis C Virus Infection: A Systematic Review of Randomized Controlled Trials.

Background: New direct-acting antiviral agents (DAAs) approved for the treatment of patients infected by Hepatitis C virus (HCV) are well tolerated and increase sustained virological response (SVR) rate. We summarize current evidence on the efficacy and safety from comparative randomized controlled trials (RCTs) of DAAs.

Methods: We systematically searched MEDLINE, Embase, Scopus, CENTRAL, and Lilacs as well as a list of reference literature.

Immune landscape of hepatocellular carcinoma microenvironment: Implications for prognosis and therapeutic applications.

The development of immunotherapy for solid tumours has boosted interest in the contexture of tumour immune microenvironment (TIME). Several lines of evidence indicate that the interplay between tumour cells and TIME components is a key factor for the evolution of hepatocellular carcinoma (HCC) and for the likelihood of response to immunotherapeutics. The availability of high-resolution methods will be instrumental for a better definition of the complexity and diversity of TIME with the aim of predicting disease outcome, treatment response and possibly new therapeutic targets.

Carbohydrate-deficient transferrin: utility of HPLC in handling atypical samples uninterpretable by capillary electrophoresis.

Aims: Carbohydrate-deficient transferrin (CDT) is a marker of chronic alcohol abuse. Uninterpretable (atypical) CDT patterns have been detected by both capillary electrophoresis (CE) and HPLC. The aim of this study was to evaluate the performance of HPLC as a second-line test for the interpretation of most frequent atypical CDT profiles detected by CE.

Counter-regulation of regulatory T cells by autoreactive CD8 T cells in rheumatoid arthritis.

The mechanisms whereby autoreactive T cells escape peripheral tolerance establishing thus autoimmune diseases in humans remain an unresolved question. Here, we demonstrate that autoreactive polyfunctional CD8 T cells recognizing self-antigens (i.e.

Immune Gene Expression Profile in Hepatocellular Carcinoma and Surrounding Tissue Predicts Time to Tumor Recurrence.

Background: The antitumor immune response may play a major role in the clinical outcome of hepatocellular carcinoma (HCC). We characterized the liver immune microenvironment by direct hybridization of RNA extracted from HCC and nontumorous tissues.

Methods: RNA was extracted from frozen liver tissue samples of HCC (T; = 30) and nontumorous tissues (NT; = 33) obtained from 38 patients.

Natural killer cells phenotypic characterization as an outcome predictor of HCV-linked HCC after curative treatments.

NK-cell number and function have been associated with cancer progression. A detailed analysis of phenotypic and functional characteristics of NK-cells in HCC is still lacking. NK-cell function is regulated by activating and inhibitory receptors determined by genetic factors and engagement with cognate ligands on transformed or infected cells.

Optimisation of triple therapy for patients with chronic hepatitis C: a systematic review.

Background: Triple therapy with Pegylated-Interferon α (PEG-IFNα)/Ribavirin (RBV) and Boceprevir (Boc) or Telaprevir (Tel) significantly improved sustained virological response (SVR) rates for patients with genotype 1 HCV infection compared to PEG-IFNα/RBV alone (dual therapy). However, less is known about factors associated with rates of SVR and of adverse events (AEs).

Material And Methods: The aim of this systematic review was to evaluate the evidence regarding the factors affecting response and rate of AEs associated with triple therapy.

Carbohydrate-Deficient Transferrin Determination in a Clinical Setting: Consistency Between Capillary Electrophoresis Assays and Utility of HPLC as a Confirmatory Test.

Background: Carbohydrate-deficient transferrin (CDT) is used to assess chronic alcohol consumption in administrative and forensic context. The aim of the present study was the optimization of the diagnostic strategy for CDT determination in a clinical laboratory setting.

Methods: Two capillary zone electrophoresis (CZE) assays, the CEofix CDT (Analis, Suarlée, Belgium) run on single capillary MDQ instrument and the muticapillary (Sebia, Lisses, France), were compared as screening methods and a commercial high-performance liquid chromatography (HPLC) assay (Recipe, Munich, Germany) was used for confirmation.

Interferon lambda-3 is not associated with clinical outcome in patients with HCV-induced compensated cirrhosis: a long-term cohort study.

Background: Interferon Lambda-3 (IFN-λ3) gene polymorphism is associated with spontaneous clearance of hepatitis C virus (HCV) and response to IFN-based therapy (IFN). However, very few data are available about its value in predicting sustained virologic response (SVR) in patients with cirrhosis, and whether IFN-λ3 genotype influences liver disease progression remains unclear.

Methods: We determined IFN-λ3 genotype by PCR in a cohort of patients with compensated HCV-related cirrhosis, enrolled between 1989 and 1992.

KIR/HLA immunogenetic background influences the evolution of hepatocellular carcinoma.

Natural killer (NK) cells play a major role in antitumor immune responses. Recent results from our laboratory demonstrate the impact of the immunogenetic background on the activity of NK cells and hence on the outcome of hepatocellular carcinoma, disclosing perspectives for the development of NK-cell based therapies.

A serially coupled stationary phase method for the determination of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine by liquid chromatography ion trap tandem mass spectrometry.

Oxidative attack to DNA is of particular interest since DNA modifications can lead to heritable mutations. The most studied product of DNA oxidation is 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). While 8-oxodG determination in blood and tissue cells is prone to artifacts, its measurement in urine employing liquid chromatography tandem mass spectrometry (LC-MS/MS) has gained more and more interest for increased reliability.

HLA and killer immunoglobulin-like receptor genes as outcome predictors of hepatitis C virus-related hepatocellular carcinoma.

Purpose: We evaluated the impact of the killer immunoglobulin-like receptors (KIR) of natural killer (NK) cells and of their HLA ligands over the clinical outcome of hepatitis C virus (HCV)-related hepatocellular carcinoma after curative treatment by either surgical resection or radiofrequency thermal ablation (RTA).

Experimental Design: Sixty-one consecutive patients with HCV-related hepatocellular carcinoma underwent KIR genotyping and HLA typing. A phenotypic/functional characterization of NK cells was carried out in patients with different KIR/KIR-ligand genotype.

Immunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma.

The definition of the risk of hepatocellular carcinoma (HCC) recurrence after resection represents a central issue to improve the clinical management of patients. In this study we examined the prognostic relevance of infiltrating immune cell subsets in the tumor (TIL) and in nontumorous (NT) liver (LIL), and the expression of immune-related and lineage-specific mRNAs in HCC and NT liver derived from 42 patients. The phenotype of infiltrating cells was analyzed by flow cytometry, and mRNA expression in liver tissue was examined by real-time reverse transcription (RT)-PCR.

A system consisting of cation-exchange chromatography, combined surface-activated chemical and electrospray ionization, and ion-trap analysis for the analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine in urine.

Rationale: 8-Hydroxy-2'-deoxyguanosine has served as a biomarker for oxidative damage to DNA from different types of biological samples, and various techniques have been used to analyze it. In particular, liquid chromatography coupled to mass spectrometry has been used to identify 8-hydroxy-2'-deoxyguanosine in urine samples. Usually, a triple quadrupole analyzer and multiple reaction monitoring have been employed for its detection.

Interleukin 28B genotype determination using DNA from different sources: A simple and reliable tool for the epidemiological and clinical characterization of hepatitis C.

Recent studies reported a close correlation between polymorphisms in the Interleukin (IL)28B gene and rates of resolution of hepatitis C virus infection occurring spontaneously or induced by treatment. The diagnostic utility of IL28B genotype, however, is not understood completely. For rapid data collection on the natural history of HCV infection in patients with different IL28B genotype, simple, sensitive and rapid methods suitable for non-invasive and archival clinical samples are needed urgently.

Translating pharmacogenetics into clinical practice: interleukin (IL)28B and inosine triphosphatase (ITPA) polymophisms in hepatitis C virus (HCV) infection.

Hepatitis C virus (HCV) infection is frequently characterized by evolution to chronicity and by a variable clinical course of the disease. The clinical heterogeneities of HCV infection and the imperfect predictability of the response to interferon (IFN) have suggested the need to search for a genetic basis of clinical features. This led to the discovery of genetic polymorphisms playing a major role in the evolution of infection, as well as on treatment response and adverse effects.

[Analytical quality in biological monitoring of workers exposed to chemicals: experience of the Prevention and Safety at the Workplace Service in Modena].

Background: The quality of laboratory data is one of the main factors in guaranteeing efficacy of biological monitoring.

Objectives: To analyze the quality of laboratory data used for biological monitoring of exposed workers.

Methods: A survey involving 18 companies employing 945 workers in the area of Modena, Italy, was carried out in 2008.

Effectiveness of the biological monitoring of chemical exposure in the workplace: results of a survey in an area of Northern Italy.

A survey of biological monitoring results from 2000 to 2008 was carried out as a part of institutional activities performed by the Workplace Prevention and Safety Service (SPSAL) of the south area of Modena district (Italy). The survey involved 18 companies employing 945 workers altogether. According to workplace exposure, routine biological monitoring had been carried out yearly or 6-monthly in private laboratories chosen by each company.