Purine Nucleoside Derivative

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Marçal Pastor-anglada - One of the best experts on this subject based on the ideXlab platform.

  • Ribavirin uptake into human hepatocyte HHL5 cells is enhanced by interferon-α via up-regulation of the human concentrative Nucleoside transporter (hCNT2).
    Molecular pharmaceutics, 2014
    Co-Authors: Itziar Pinilla-macua, Paula Fernández-calotti, Sofía Pérez-del-pulgar, Marçal Pastor-anglada
    Abstract:

    Ribavirin is a broad spectrum antiviral that increases the response rate in chronic hepatitis C patients when administered in combination with IFNα. Ribavirin is a Purine Nucleoside Derivative, transported into hepatocytes by Nucleoside transporters. hCNT2 is the best candidate to mediate ribavirin uptake into hepatocytes due to its high-affinity for Purines and its capacity to concentrate its substrates intracellularly. The aim of this study was to determine whether hCNT2 function is under IFNα modulation. IFNα treatment of the nontransformed human hepatocyte-derived cell line HHL5 induced a rapid and transient increase in hCNT2 activity after cytokine addition. hCNT2 activity up-regulation was associated with increased ribavirin accumulation into cells. This increase was consistent with the translocation of hCNT2-containing vesicles to the plasma membrane via a mechanism requiring ERK 1/2 and ROCK activation and cytoskeleton integrity. Longer treatments with IFNα induced transcriptional activation of th...

Itziar Pinilla-macua - One of the best experts on this subject based on the ideXlab platform.

  • Ribavirin uptake into human hepatocyte HHL5 cells is enhanced by interferon-α via up-regulation of the human concentrative Nucleoside transporter (hCNT2).
    Molecular pharmaceutics, 2014
    Co-Authors: Itziar Pinilla-macua, Paula Fernández-calotti, Sofía Pérez-del-pulgar, Marçal Pastor-anglada
    Abstract:

    Ribavirin is a broad spectrum antiviral that increases the response rate in chronic hepatitis C patients when administered in combination with IFNα. Ribavirin is a Purine Nucleoside Derivative, transported into hepatocytes by Nucleoside transporters. hCNT2 is the best candidate to mediate ribavirin uptake into hepatocytes due to its high-affinity for Purines and its capacity to concentrate its substrates intracellularly. The aim of this study was to determine whether hCNT2 function is under IFNα modulation. IFNα treatment of the nontransformed human hepatocyte-derived cell line HHL5 induced a rapid and transient increase in hCNT2 activity after cytokine addition. hCNT2 activity up-regulation was associated with increased ribavirin accumulation into cells. This increase was consistent with the translocation of hCNT2-containing vesicles to the plasma membrane via a mechanism requiring ERK 1/2 and ROCK activation and cytoskeleton integrity. Longer treatments with IFNα induced transcriptional activation of th...

Sofía Pérez-del-pulgar - One of the best experts on this subject based on the ideXlab platform.

  • Ribavirin uptake into human hepatocyte HHL5 cells is enhanced by interferon-α via up-regulation of the human concentrative Nucleoside transporter (hCNT2).
    Molecular pharmaceutics, 2014
    Co-Authors: Itziar Pinilla-macua, Paula Fernández-calotti, Sofía Pérez-del-pulgar, Marçal Pastor-anglada
    Abstract:

    Ribavirin is a broad spectrum antiviral that increases the response rate in chronic hepatitis C patients when administered in combination with IFNα. Ribavirin is a Purine Nucleoside Derivative, transported into hepatocytes by Nucleoside transporters. hCNT2 is the best candidate to mediate ribavirin uptake into hepatocytes due to its high-affinity for Purines and its capacity to concentrate its substrates intracellularly. The aim of this study was to determine whether hCNT2 function is under IFNα modulation. IFNα treatment of the nontransformed human hepatocyte-derived cell line HHL5 induced a rapid and transient increase in hCNT2 activity after cytokine addition. hCNT2 activity up-regulation was associated with increased ribavirin accumulation into cells. This increase was consistent with the translocation of hCNT2-containing vesicles to the plasma membrane via a mechanism requiring ERK 1/2 and ROCK activation and cytoskeleton integrity. Longer treatments with IFNα induced transcriptional activation of th...

Paula Fernández-calotti - One of the best experts on this subject based on the ideXlab platform.

  • Ribavirin uptake into human hepatocyte HHL5 cells is enhanced by interferon-α via up-regulation of the human concentrative Nucleoside transporter (hCNT2).
    Molecular pharmaceutics, 2014
    Co-Authors: Itziar Pinilla-macua, Paula Fernández-calotti, Sofía Pérez-del-pulgar, Marçal Pastor-anglada
    Abstract:

    Ribavirin is a broad spectrum antiviral that increases the response rate in chronic hepatitis C patients when administered in combination with IFNα. Ribavirin is a Purine Nucleoside Derivative, transported into hepatocytes by Nucleoside transporters. hCNT2 is the best candidate to mediate ribavirin uptake into hepatocytes due to its high-affinity for Purines and its capacity to concentrate its substrates intracellularly. The aim of this study was to determine whether hCNT2 function is under IFNα modulation. IFNα treatment of the nontransformed human hepatocyte-derived cell line HHL5 induced a rapid and transient increase in hCNT2 activity after cytokine addition. hCNT2 activity up-regulation was associated with increased ribavirin accumulation into cells. This increase was consistent with the translocation of hCNT2-containing vesicles to the plasma membrane via a mechanism requiring ERK 1/2 and ROCK activation and cytoskeleton integrity. Longer treatments with IFNα induced transcriptional activation of th...

Ryuzo Ohno - One of the best experts on this subject based on the ideXlab platform.

  • Phase I clinical study of SH L573 (fludarabine phosphate) in patients with chronic lymphocytic leukemia and adult T-cell leukemia/lymphoma
    Gan to kagaku ryoho. Cancer & chemotherapy, 1999
    Co-Authors: Naomichi Arima, Mizoguchi H, Shigeru Shirakawa, Tomonaga M, Kiyoshi Takatsuki, Ryuzo Ohno
    Abstract:

    We have conducted a phase I clinical study of fludarabine phosphate, a new Purine Nucleoside Derivative, in patients with chronic lymphocytic leukemia and adult T-cell leukemia/lymphoma. The patients were given intravenous administration at a dose of 15 mg/m2/day followed by 20 mg/m2/day and 25 mg/m2/day, each dose given consecutively for 5 days. The dose limiting factors were thrombocytopenia and neutropenia. The thrombocyte count and neutrocyte count dropped to their lowest value in week 1 to 2 after administration, but the changes were reversible, and these counts recovered in most patients. The maximum tolerated dose of the study drug was 25 mg/m2/day, and it was decided to administer 20 mg/m2/day as the recommended dose for the subsequent phase II clinical study.