Publications by authors named "A Martin-Alvarez"

Aim: To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments.

Methods: Sequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α), = 49; IFN-α + ribavirin (RBV), = 75; pegylated (peg) IFN-α + RBV, = 47; first-generation direct-acting antivirals (DAAs), = 13; and second-generation DAAs, = 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (NVR).

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Ribavirin remains essential to chronic hepatitis C treatment. This paper investigates the influence of ribavirin priming to steady state before combined pegylated-interferon/ribavirin treatment on viral kinetics, ribavirin trough concentrations, genetic variability within HCV-core, -NS5B and -NS5A, and response to antiviral therapy. A prospective cohort study was made of 27 chronic hepatitis C genotype 1 naïve patients who received four weeks of ribavirin followed by pegIFN-α-2a/ribavirin for 48 weeks (Group A).

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The purpose of this study was to investigate whether PARP-1 inhibition sensitizes human liver cancer cell lines to doxorubicin treatment. Both the addition of PARP-1 inhibitor (ANI) and depletion by means of stable siRNA significantly enhanced the growth inhibition induced by the DNA damage agents used. This effect was associated with an accumulation of unrepaired DNA, with a reduction in EGFR and Bcl-xL gene expression as well as with positive annexin-V staining.

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Article Synopsis
  • Hepatocellular carcinoma (HCC) has a poor prognosis due to limited treatment options, with DNA damage and inflammation playing key roles in the disease.
  • Pharmacological inhibition of PARP-1 using DPQ significantly reduced tumor volume and mitosis in HCC xenografts, which corresponded with increased apoptosis and changes in gene expression related to tumor growth.
  • In mice treated with the carcinogen diethyl-nitrosamine (DEN), PARP-1 inhibition led to a notable decrease in preneoplastic lesions and inflammatory gene expression, suggesting that targeting PARP-1 could be a promising strategy for managing HCC.
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