Changes in end products of nitric oxide in urine and induction of nitric oxide synthase expression in urinary bladder during intravesical instillations of IFN-alpha2b

Interferon-alpha2b (IFN-alpha2b) is being used intravesically for preventing recurrence and progression of superficial transitional cell carcinoma of the bladder. However, its mechanism of action when instilled intravesically is not yet elucidated. We monitored end products of nitric oxide (NO) in u...

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Veröffentlicht in:Journal of interferon & cytokine research 2004-10, Vol.24 (10), p.621-626
Hauptverfasser: Mitropoulos, Dionisios, Deliconstantinos, George, Adamakis, Ioannis, Zervas, Anastasios, Karakaidos, Panagiotis, Gorgoulis, Vassilis G
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container_end_page 626
container_issue 10
container_start_page 621
container_title Journal of interferon & cytokine research
container_volume 24
creator Mitropoulos, Dionisios
Deliconstantinos, George
Adamakis, Ioannis
Zervas, Anastasios
Karakaidos, Panagiotis
Gorgoulis, Vassilis G
description Interferon-alpha2b (IFN-alpha2b) is being used intravesically for preventing recurrence and progression of superficial transitional cell carcinoma of the bladder. However, its mechanism of action when instilled intravesically is not yet elucidated. We monitored end products of nitric oxide (NO) in urine in 12 bladder cancer patients undergoing intravesical instillations of IFN-alpha2b. Urine end products of NO levels rose gradually after each instillation, reaching a peak value after the third instillation. Although the patients continued their treatment for 5 more weeks, no further alteration was observed. Inducible nitric oxide synthase (iNOS) expression was immunohistochemically evaluated in urinary bladder biopsy specimens before and after IFN-alpha2b instillations. It was shown that IFN-alpha2b induced urothelial iNOS expression, with subsequent oxidative stress. The peroxynitrite (ONOO-) formed from the combination of NO with superoxide (O2-) provides important clues in the role of ONOO- as a causative factor in the antineoplastic action of IFN-alpha2b.
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subjects Administration, Intravesical
Antineoplastic Agents - administration & dosage
Carcinoma, Transitional Cell - drug therapy
Carcinoma, Transitional Cell - metabolism
Carcinoma, Transitional Cell - pathology
Humans
Immunohistochemistry
Interferon-alpha - administration & dosage
Nitric Oxide - urine
Nitric Oxide Synthase - biosynthesis
Nitric Oxide Synthase Type II
Peroxynitrous Acid - urine
Recombinant Proteins
Urinary Bladder - drug effects
Urinary Bladder - enzymology
Urinary Bladder - metabolism
Urinary Bladder Neoplasms - drug therapy
Urinary Bladder Neoplasms - metabolism
Urinary Bladder Neoplasms - pathology
title Changes in end products of nitric oxide in urine and induction of nitric oxide synthase expression in urinary bladder during intravesical instillations of IFN-alpha2b
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