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 |
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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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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.</description><identifier>ISSN: 1079-9907</identifier><identifier>PMID: 15626159</identifier><language>eng</language><publisher>United States</publisher><subject>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</subject><ispartof>Journal of interferon & cytokine research, 2004-10, Vol.24 (10), p.621-626</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15626159$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mitropoulos, Dionisios</creatorcontrib><creatorcontrib>Deliconstantinos, George</creatorcontrib><creatorcontrib>Adamakis, Ioannis</creatorcontrib><creatorcontrib>Zervas, Anastasios</creatorcontrib><creatorcontrib>Karakaidos, Panagiotis</creatorcontrib><creatorcontrib>Gorgoulis, Vassilis G</creatorcontrib><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</title><title>Journal of interferon & cytokine research</title><addtitle>J Interferon Cytokine Res</addtitle><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.</description><subject>Administration, Intravesical</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Carcinoma, Transitional Cell - drug therapy</subject><subject>Carcinoma, Transitional Cell - metabolism</subject><subject>Carcinoma, Transitional Cell - pathology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Interferon-alpha - administration & dosage</subject><subject>Nitric Oxide - urine</subject><subject>Nitric Oxide Synthase - biosynthesis</subject><subject>Nitric Oxide Synthase Type II</subject><subject>Peroxynitrous Acid - urine</subject><subject>Recombinant Proteins</subject><subject>Urinary Bladder - drug effects</subject><subject>Urinary Bladder - enzymology</subject><subject>Urinary Bladder - metabolism</subject><subject>Urinary Bladder Neoplasms - drug therapy</subject><subject>Urinary Bladder Neoplasms - metabolism</subject><subject>Urinary Bladder Neoplasms - pathology</subject><issn>1079-9907</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNplkL9OwzAQxjOAaCm8AvLEFsmxk9geUUWhUgVL98iOL61R6gRfgtoX4jlxaJmYTnff7_59V8k8o0KlSlExS24RPyilpWTqJpllRcnKrFDz5Hu5134HSJwn4C3pQ2fHekDSNcS7IbiadEdnYdLH4DwQHSnnJ8h1_h-GJz_sNQKBYx8AcWIurTqciGm1tRCInQq7qAxBfwG6WrcxwcG1rZ7m_u5fr95S3fZ7zcxdct3oFuH-EhfJdvW8Xb6mm_eX9fJpk_ZFrlJZ80YWVvIMSkFBZDLPa-BWMqag4YY1OZdRkRmYUkaJKsZkLgQzEpQ0fJE8nsdGGz5HwKE6OKwhHuWhG7EqBaNcqiKCDxdwNAewVR_cIf5X_RnLfwCENXbJ</recordid><startdate>200410</startdate><enddate>200410</enddate><creator>Mitropoulos, Dionisios</creator><creator>Deliconstantinos, George</creator><creator>Adamakis, Ioannis</creator><creator>Zervas, Anastasios</creator><creator>Karakaidos, Panagiotis</creator><creator>Gorgoulis, Vassilis G</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200410</creationdate><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</title><author>Mitropoulos, Dionisios ; Deliconstantinos, George ; Adamakis, Ioannis ; Zervas, Anastasios ; Karakaidos, Panagiotis ; Gorgoulis, Vassilis G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p549-8c3f85d831e670e71844ce3d8229ef3b2f43867081eb684ce092284772b8e98b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Administration, Intravesical</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Carcinoma, Transitional Cell - drug therapy</topic><topic>Carcinoma, Transitional Cell - metabolism</topic><topic>Carcinoma, Transitional Cell - pathology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Interferon-alpha - administration & dosage</topic><topic>Nitric Oxide - urine</topic><topic>Nitric Oxide Synthase - biosynthesis</topic><topic>Nitric Oxide Synthase Type II</topic><topic>Peroxynitrous Acid - urine</topic><topic>Recombinant Proteins</topic><topic>Urinary Bladder - drug effects</topic><topic>Urinary Bladder - enzymology</topic><topic>Urinary Bladder - metabolism</topic><topic>Urinary Bladder Neoplasms - drug therapy</topic><topic>Urinary Bladder Neoplasms - metabolism</topic><topic>Urinary Bladder Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mitropoulos, Dionisios</creatorcontrib><creatorcontrib>Deliconstantinos, George</creatorcontrib><creatorcontrib>Adamakis, Ioannis</creatorcontrib><creatorcontrib>Zervas, Anastasios</creatorcontrib><creatorcontrib>Karakaidos, Panagiotis</creatorcontrib><creatorcontrib>Gorgoulis, Vassilis G</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of interferon & cytokine research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mitropoulos, Dionisios</au><au>Deliconstantinos, George</au><au>Adamakis, Ioannis</au><au>Zervas, Anastasios</au><au>Karakaidos, Panagiotis</au><au>Gorgoulis, Vassilis G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Journal of interferon & cytokine research</jtitle><addtitle>J Interferon Cytokine Res</addtitle><date>2004-10</date><risdate>2004</risdate><volume>24</volume><issue>10</issue><spage>621</spage><epage>626</epage><pages>621-626</pages><issn>1079-9907</issn><abstract>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.</abstract><cop>United States</cop><pmid>15626159</pmid><tpages>6</tpages></addata></record> |
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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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