Circulating microRNAs, miR-939, miR-595, miR-519d and miR-494, Identify Cirrhotic Patients with HCC.

The performance of circulating biomarkers for the diagnosis of hepatocellular carcinoma (HCC) is sub-optimal. In this study we tested circulating microRNAs as biomarkers for HCC in cirrhotic patients by performing a two stage study: a discovery phase conducted by microarray and a validation phase performed by qRT-PCR in an independent series of 118 patients. Beside miRNAs emerged from the discovery phase, miR-21, miR-221, miR-519d were also tested in the validation setting on the basis of literary and tissue findings. Deregulated microRNAs were assayed in HCC-derived cells in the intracellular compartment, cell culture supernatant and exosomal fraction. Serum and tissue microRNA levels were compared in 14 patients surgically treated for HCC. From the discovery study, it emerged that seven circulating microRNAs were differentially expressed in cirrhotic patients with and without HCC. In the validation set, miR-939, miR-595 and miR-519d were shown to differentiate cirrhotic patients with and without HCC. MiR-939 and miR-595 are independent factors for HCC. ROC curves of miR-939, miR-595 and miR-519d displayed that AUC was higher than AFP. An exosomal secretion of miR-519d, miR-21, miR-221 and miR-1228 and a correlation between circulating and tissue levels of miR-519d, miR-494 and miR-21 were found in HCC patients. Therefore, we show that circulating microRNAs deserve attention as non-invasive biomarkers in the diagnostic setting of HCC and that exosomal secretion contributes to discharging a subset of microRNAs into the extracellular compartment.

Efficacy, safety, and modulation of immunologic markers by immunotherapy with honeybee venom: comparison of standardized quality depot versus aqueous extract.

Venom immunotherapy (IT) is a very effective method for the treatment of Hymenoptera venom allergy. We compared safety, efficacy, and modulation of specific immunologic parameters in 70 patients sensitized to Apis mellifera, treated for > or = 5 years with standardized quality (SQ) aqueous IT, either with a rush (n = 20) or with a cluster (n = 20) induction protocol, or with an SQ depot extract and a cluster induction protocol (n = 30). We made an open, noncontrolled study. Side effects were monitored and the effects of field stings during the maintenance phase of the treatment and after its interruption were recorded. Skin reactivity to Apis was measured by end point dilution and specific serum immunoglobulin E (IgE) were measured by a solid-phase-based assay. The depot IT was better tolerated than aqueous IT with rush induction. This was caused by mainly the lower frequency in the induction phase of systemic side effects (3.4% versus 36.8% [p < 0.0041] on a "per patient" and 0.1% versus 0.9% [p = 0.0092] on a "per dose "basis, respectively). The cluster protocol with the aqueous extract tended to be better tolerated that the rush protocol. About one-half of patients from each group were re-stung during the study and all suffered only minor discomfort. Reduction of skin reactivity and of serum-specific IgE was significant in the three groups (p < 0.02 in all cases). SQ Depot IT to Apis venom allergy administered with a cluster protocol induces less side effects and is equally effective then IT with SQ aqueous extract administered with a rush protocol.

Biomarkers to assess the genetic damage induced by alcohol abuse in human lymphocytes.

Alcohol abuse is a major risk factor for cancer of the upper alimentary tract, the upper respiratory tract, and liver. Chromosome damage is used as early effect biomarker in the surveillance of human exposure to genotoxic carcinogens. In the present study, two genetic markers, namely chromosome aberrations (CAs) and micronuclei (MN), were used to evaluate genetic damage in peripheral lymphocytes from 20 alcoholics, 20 abstinent alcoholics, and 20 controls. Composition of the three groups was fairly similar as regards sex, age and smoking habits. A highly significant increase was observed in the frequencies of CA and MN in lymphocytes of alcoholics as compared both with controls and abstinent alcoholics. However, no correlation was found between the length of alcohol abuse and the frequencies of either biomarkers in alcoholics. CA and MN frequencies in abstinent alcoholics were similar than those in controls. Our data indicate that CA and MN can be two useful biomarkers to assess genetic damage associated with alcohol abuse. They could be included in programs for cancer prevention in alcoholics. Abstinence appears to normalize the frequency of both MN and CA. This could offer therapists another tool to help alcoholics change their lifestyle.