Letter to the Editor Regarding “Efficacy of Paravertebral Injection of Interferon-α2b Combined with High-Voltage, Long-Term Pulsed Radiofrequency in DRG in Mitigation of Postherpetic Neuralgia: A Retrospective Study”

Article

作者: Kumar, Aashish ; Okon, Inibehe Ime ; Iqbal, Umer ; Arsal, Syed Ali

2013-06-01·Experimental Cell Research3区 · 医学

A chimeric cyclic interferon-α2b peptide induces apoptosis by sequential activation of phosphatidylinositol 3-kinase, protein kinase Cδ and p38 MAP kinase

3区 · 医学

Article

作者: Veronica Julieta Marino ; Clara Peña ; Verónica Alejandra Furmento ; Lucila Bertucci ; Leonor Patricia Roguin ; Viviana Claudia Blank

We have previously demonstrated that tyrosine phosphorylation of STAT1/3 and p38 mitogen-activated protein kinase (p38 MAPK) activation are involved in the apoptotic response triggered by a chimeric cyclic peptide of the interferon-α2b (IFN-α2b) in WISH cells. Since the peptide also induced serine phosphorylation of STAT proteins, in the present study we examined the kinase involved in serine STAT1 phosphorylation and the signaling effectors acting upstream such activation. We first found that p38 MAPK is involved in serine STAT1 phosphorylation, since a reduction of phophoserine-STAT1 levels was evident after incubating WISH cells with cyclic peptide in the presence of a p38 pharmacological inhibitor or a dominant-negative p38 mutant. Next, we demonstrated that the peptide induced activation of protein kinase Cδ (PKCδ). Based on this finding, the role of this kinase was then evaluated. After incubating WISH cells with a PKCδ inhibitor or after decreasing PKCδ expression levels by RNA interference, both peptide-induced serine STAT1 and p38 phosphorylation levels were significantly decreased, indicating that PKCδ functions as an upstream regulator of p38. We also showed that PKCδ and p38 activation stimulated by the peptide was inhibited by a specific pharmacological inhibitor of phosphatidylinositol 3-kinase (PI3K) or by a dominant-negative p85 PI3K-regulatory subunit, suggesting that PI3K is upstream in the signaling cascade. In addition, the role of PI3K and PKCδ in cyclic peptide-induced apoptosis was examined. Both signaling effectors were found to regulate the antiproliferative activity and the apoptotic response triggered by the cyclic peptide in WISH cells. In conclusion, we herein demonstrated that STAT1 serine phosphorylation is mediated by the sequential activation of PI3K, PKCδ and p38 MAPK. This signaling cascade contributes to the antitumor effect induced by the chimeric IFN-α2b cyclic peptide in WISH cells.

2005-04-01·Nature Clinical Practice Oncology

Can outpatient interleukin-2 and interferon replace high-dose interleukin-2 for metastatic renal cell carcinoma?

Article

作者: Vieweg, Johannes

A review.The article is a review of the study and results by McDermott DF et al. (2005) entitled "Randomized Phase III trial of high-dose interleukin-2 vs. s.c. interleukin-2 and interferon in patients with metastatic renal cell carcinoma.".A commentary by Johannes Vieweg, Associate Professor in the Departments of Urol. and Immunol. at Duke University Medical Center, Durham, North Carolina is provided.A randomized phase III trial of 193 patients with progressive metastatic renal cell carcinoma (RCC) showed that high-dose i.v. bolus interleukin-2 (HDIB IL-2) demonstrated a superior response rate and more durable complete response rate than IL-2 plus interferon-α2b.Patients with liver or bone metastases or primary tumor in place had improved response rates and survival with HDIB IL-2, relative to lower-dose IL-2 and interferon-α2b.This study, however, failed to demonstrate an improvement in patient survival, probably because only few patients benefited from such treatment.The Cytokine Working Group study confirms that, for patients with good performance status, HDIB IL-2 should remain the preferred therapy for patient with metastatic RCC.Such treatment will still require referral to specialized centers with the necessary skills and equipment.Applicability of high-dose IL-2 remains limited.Fortunately, newer compounds that target tyrosine receptor kinases or angiogenic pathways seem quite promising in the treatment of metastatic RCC and, if proven effective, may supplant IL-2 in the foreseeable future.

100 项与 Interferon-α2b(University Hospital Tuebingen) 相关的药物交易

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