Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomics and transcriptomic evolution.

Extracellular vesicles (EVs) secreted by tumors are abundant in plasma, but their potential for interrogating the molecular features of tumors through multi-omic profiling remains widely unexplored. Genomic and transcriptomic profiling of circulating EV-DNA and EV-RNA isolated from in vitro and in vivo models of metastatic prostate cancer (mPC) reveal a high contribution of tumor material to EV-loaded DNA/RNA, validating the findings in two cohorts of longitudinal plasma samples collected from patients during androgen receptor signaling inhibitor (ARSI) or taxane-based therapy. EV-DNA genomic features recapitulate matched-patient biopsies and circulating tumor DNA (ctDNA) and associate with clinical progression.

Response to interferon alpha treatment and disappearance of cryoglobulinaemia in patients infected by hepatitis C virus.

Background: Mixed cryoglobulinaemia is closely associated with hepatitis C virus (HCV) infection.

Aim: To assess in a prospective open study the efficiency of interferon alpha treatment of cryoglobulinaemia, as reflected by the disappearance of cryoglobulins and clinical manifestations of the disease, and to analyse the factors predictive of a response to interferon.

Method: Eighty seven consecutive patients with chronic hepatitis C treated for the first time with interferon at a dose of 3 x 10(6) international units three times a week for six months were studied.

Comparative evaluation of hepatitis C virus RNA quantitation by branched DNA, NASBA, and monitor assays.

Several studies have shown a relationship between pretreatment hepatitis C virus (HCV) viral load and the response to interferon (IFN) therapy, creating a need for quantitative HCV-RNA assays. Here, we compared three commercial methods: nucleic acid sequence-based amplification NASBA (Organon), branched DNA 2.0 (bDNA) (Chiron), and Monitor (Roche), with reverse-transcription polymerase chain reaction (RT-PCR) as the reference.

Mutations in NS5A region of hepatitis C virus genome correlate with presence of NS5A antibodies and response to interferon therapy for most common European hepatitis C virus genotypes.

A part of the hepatitis C virus (HCV) nonstructural protein 5A (NS5A) amino acid sequence, designated as an interferon (IFN)-sensitive determining region (ISDR), has been shown to be correlated with a response to IFN in Japanese patients. We have shown previously that the presence of NS5A antibodies (Abs) detected by the INNOLIA test (IL-NS5A Ab) is also correlated with a response to IFN. The aim of this study was to investigate, in a wide range of patients, the possible relationship within the NS5A protein between the sequence of ISDR and that used in the INNOLIA test designated as IL3R.

Pattern of HCV antibodies with special reference to NS5A reactivity in HCV-infected patients: relation to viral genotype, cryoglobulinemia and response to interferon.

Background/aims: We aimed to compare the anti-hepatitis C virus reactivity in confirmatory assays (RIBA 3.0 Ortho Diagnostic and INNO-LIA HCV Ab III Innogenetics) among patients infected with different hepatitis C virus genotypes, with or without cryoglobulinemia, and in patients treated with interferon.

Methods: One hundred and three patients followed in our hepatogastroenterology unit were included in the study and compared to 320 consecutive patients tested using RIBA 3.

Variations of serum IgG subclass levels in hepatitis C virus infection during interferon-alpha therapy.

Serum IgG1 levels are selectively increased in patients with chronic hepatitis C virus (HCV) infection. In 15 patients who received interferon (IFN)-alpha therapy, serum levels of immunoglobulin classes and IgG subclasses were measured during treatment and after it was discontinued. In spite of important individual variations, mean IgG, IgG1, IgA and IgM levels decreased during therapy and tended to return to pre-treatment levels afterwards, with no detectable correlation with clinical and biological parameters.

Antibody responses to hepatitis C envelope proteins in patients with acute or chronic hepatitis C.

Antibody responses to the hepatitis C virus (HCV) envelope proteins E1 and E2 were analyzed using two original assays in sera from 86 patients in different stages of disease. A Western blot assay and an immunofluorescence assay (IFA) were developed using envelope proteins produced, respectively, in Escherichia coli and in CV1 cells infected with a recombinant SV40. As a third method, the INNO-LIA HCV Ab III assay including E2 synthetic peptides was used.

Hepatitis C virus genotypes and subtypes in patients with hepatitis C, with and without cryoglobulinemia.

Background/aims: Recent reports have shown a high frequency of anti-hepatitis C virus antibodies in patients with cryoglobulinemia. The factors involved in the production of cryoglobulins in hepatitis C virus-infected patients are unknown. To assess the role of hepatitis C virus genotypes in the pathogenesis of mixed cryoglobulinemia, we analyzed their prevalence in a group of 118 hepatitis C virus-infected patients according to the presence or absence of cryoglobulins.

Essential mixed cryoglobulinemia. A comparative study of dermatologic manifestations in patients infected or noninfected with hepatitis C virus.

Background And Design: An association between essential mixed cryoglobulinemia and hepatitis C virus (HCV) infection has been reported. Dermatologic manifestations are a classic presenting complaint in essential mixed cryoglobulinemia. The aim of this study was to compare the frequency and the nature of dermatologic manifestations in essential mixed cryoglobulinemia according to the presence of anti-HCV antibodies.

Comparative study of conventional and novel strategies for the detection of hepatitis C virus RNA in serum: amplicor, branched-DNA, NASBA and in-house PCR.

The aim of this study was to compare the sensitivity and specificity of conventional procedures (in-house one-stage polymerase chain reaction (PCR) and in-house nested PCR) and of new technologies (rTth DNA polymerase (Amplicor), branched-DNA, NASBA (nucleic acid amplification system)) for the qualitative detection of hepatitis C virus (HCV) RNA in serum of HCV-infected individuals. Serum samples from 37 anti-HCV-positive individuals (15 with a normal alanine aminotransferase (ALT) level, 22 with an elevated ALT level) and 10 anti-HCV-negative individuals as negative controls were studied. A second panel, including 9 diluted serum samples (from 1/10 to 1/100,000) was constituted to establish the differences of sensitivity of the 5 procedures with small quantities of HCV RNA in the serum.

Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage.

Background/aims: Mixed cryoglobulinemia is frequently associated with liver diseases. The respective role of hepatitis C virus (HCV) and liver damage in the pathogenesis of cryoglobulinemia is investigated in this study.

Methods: The prevalence of cryoglobulinemia in 226 consecutive patients with chronic liver diseases (hepatitis C, 127; hepatitis B, 40; other diseases, 59) was studied, and the epidemiological, biological, histological, and virological features in these three groups were analyzed.