The Role of Granulocytes Following Intravesical BCG Prophylaxis

Abstract Objectives The antitumour effect of bacillus Calmette-Guérin (BCG) still remains relatively undefined. Most investigations on its mechanism of action have focused on mononuclear cells; little consideration has been given to granulocytes. We analysed urine of patients with bladder cancer dur...

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Veröffentlicht in:European urology 2007-06, Vol.51 (6), p.1589-1599
Hauptverfasser: Siracusano, Salvatore, Vita, Francesca, Abbate, Rita, Ciciliato, Stefano, Borelli, Violetta, Bernabei, Massimiliano, Zabucchi, Giuliano
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container_end_page 1599
container_issue 6
container_start_page 1589
container_title European urology
container_volume 51
creator Siracusano, Salvatore
Vita, Francesca
Abbate, Rita
Ciciliato, Stefano
Borelli, Violetta
Bernabei, Massimiliano
Zabucchi, Giuliano
description Abstract Objectives The antitumour effect of bacillus Calmette-Guérin (BCG) still remains relatively undefined. Most investigations on its mechanism of action have focused on mononuclear cells; little consideration has been given to granulocytes. We analysed urine of patients with bladder cancer during 8 wk of intravesical BCG prophylaxis. The number of polymorphonuclear neutrophils (PMNs) and urothelial cells (UCs) was evaluated. We examined the in vitro response of the T24 UC line to human PMNs after BCG treatment. Methods Seventeen patients were enrolled in the study. Cytologic analyses were performed on urine samples collected before each BCG instillation and after 2 h from the first voided urine after BCG instillation. Elastase activity was determined on these samples to evaluate PMN activation. PMN-induced damage was measured on the T24 cell line treated with BCG. Results After BCG treatment, a large number of PMNs transmigrated through the urothelium and PMNs adherent to detached UCs were found. One patient, who did not respond with significant PMN transmigration, experienced recurrent disease. The number of eosinophils that transmigrated was low, with the exception of three patients with recurrent disease. In vitro, PMNs adhered to BCG-primed T24 cells and damaged the monolayer. Conclusions The results agree with recent evidence that PMNs may play an important role in the antitumour action of BCG during the BCG induction period. This role is probably nonspecific because both normal UCs in vivo and tumour cells in vitro appeared to be injured. As suggested by results obtained from a limited number of patients, a high number of eosinophils in the urine may indicate therapy failure.
doi_str_mv 10.1016/j.eururo.2006.11.045
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Most investigations on its mechanism of action have focused on mononuclear cells; little consideration has been given to granulocytes. We analysed urine of patients with bladder cancer during 8 wk of intravesical BCG prophylaxis. The number of polymorphonuclear neutrophils (PMNs) and urothelial cells (UCs) was evaluated. We examined the in vitro response of the T24 UC line to human PMNs after BCG treatment. Methods Seventeen patients were enrolled in the study. Cytologic analyses were performed on urine samples collected before each BCG instillation and after 2 h from the first voided urine after BCG instillation. Elastase activity was determined on these samples to evaluate PMN activation. PMN-induced damage was measured on the T24 cell line treated with BCG. Results After BCG treatment, a large number of PMNs transmigrated through the urothelium and PMNs adherent to detached UCs were found. One patient, who did not respond with significant PMN transmigration, experienced recurrent disease. The number of eosinophils that transmigrated was low, with the exception of three patients with recurrent disease. In vitro, PMNs adhered to BCG-primed T24 cells and damaged the monolayer. Conclusions The results agree with recent evidence that PMNs may play an important role in the antitumour action of BCG during the BCG induction period. This role is probably nonspecific because both normal UCs in vivo and tumour cells in vitro appeared to be injured. As suggested by results obtained from a limited number of patients, a high number of eosinophils in the urine may indicate therapy failure.</description><identifier>ISSN: 0302-2838</identifier><identifier>EISSN: 1873-7560</identifier><identifier>DOI: 10.1016/j.eururo.2006.11.045</identifier><identifier>PMID: 17222501</identifier><language>eng</language><publisher>Switzerland: Elsevier B.V</publisher><subject>Administration, Intravesical ; BCG ; BCG Vaccine - administration &amp; dosage ; Biomarkers, Tumor - urine ; Bladder cancer ; Blotting, Western ; Carcinoma, Transitional Cell - immunology ; Carcinoma, Transitional Cell - therapy ; Carcinoma, Transitional Cell - urine ; Electrophoresis, Polyacrylamide Gel ; Granulocyte ; Granulocytes - immunology ; Humans ; Immunotherapy ; Luminescence ; Urinalysis ; Urinary Bladder Neoplasms - immunology ; Urinary Bladder Neoplasms - therapy ; Urinary Bladder Neoplasms - urine ; Urology</subject><ispartof>European urology, 2007-06, Vol.51 (6), p.1589-1599</ispartof><rights>2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-ab1c53ac2cbd858f3cf2b95f2cb6885ea886aa1de445f344edbc25eecf077c4c3</citedby><cites>FETCH-LOGICAL-c481t-ab1c53ac2cbd858f3cf2b95f2cb6885ea886aa1de445f344edbc25eecf077c4c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0302283806014771$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17222501$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Siracusano, Salvatore</creatorcontrib><creatorcontrib>Vita, Francesca</creatorcontrib><creatorcontrib>Abbate, Rita</creatorcontrib><creatorcontrib>Ciciliato, Stefano</creatorcontrib><creatorcontrib>Borelli, Violetta</creatorcontrib><creatorcontrib>Bernabei, Massimiliano</creatorcontrib><creatorcontrib>Zabucchi, Giuliano</creatorcontrib><title>The Role of Granulocytes Following Intravesical BCG Prophylaxis</title><title>European urology</title><addtitle>Eur Urol</addtitle><description>Abstract Objectives The antitumour effect of bacillus Calmette-Guérin (BCG) still remains relatively undefined. Most investigations on its mechanism of action have focused on mononuclear cells; little consideration has been given to granulocytes. We analysed urine of patients with bladder cancer during 8 wk of intravesical BCG prophylaxis. The number of polymorphonuclear neutrophils (PMNs) and urothelial cells (UCs) was evaluated. We examined the in vitro response of the T24 UC line to human PMNs after BCG treatment. Methods Seventeen patients were enrolled in the study. Cytologic analyses were performed on urine samples collected before each BCG instillation and after 2 h from the first voided urine after BCG instillation. Elastase activity was determined on these samples to evaluate PMN activation. PMN-induced damage was measured on the T24 cell line treated with BCG. Results After BCG treatment, a large number of PMNs transmigrated through the urothelium and PMNs adherent to detached UCs were found. One patient, who did not respond with significant PMN transmigration, experienced recurrent disease. The number of eosinophils that transmigrated was low, with the exception of three patients with recurrent disease. In vitro, PMNs adhered to BCG-primed T24 cells and damaged the monolayer. Conclusions The results agree with recent evidence that PMNs may play an important role in the antitumour action of BCG during the BCG induction period. This role is probably nonspecific because both normal UCs in vivo and tumour cells in vitro appeared to be injured. As suggested by results obtained from a limited number of patients, a high number of eosinophils in the urine may indicate therapy failure.</description><subject>Administration, Intravesical</subject><subject>BCG</subject><subject>BCG Vaccine - administration &amp; dosage</subject><subject>Biomarkers, Tumor - urine</subject><subject>Bladder cancer</subject><subject>Blotting, Western</subject><subject>Carcinoma, Transitional Cell - immunology</subject><subject>Carcinoma, Transitional Cell - therapy</subject><subject>Carcinoma, Transitional Cell - urine</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Granulocyte</subject><subject>Granulocytes - immunology</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Luminescence</subject><subject>Urinalysis</subject><subject>Urinary Bladder Neoplasms - immunology</subject><subject>Urinary Bladder Neoplasms - therapy</subject><subject>Urinary Bladder Neoplasms - urine</subject><subject>Urology</subject><issn>0302-2838</issn><issn>1873-7560</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU-L1EAQxRtR3HH1G4jk5C2x-l_Sc1HcwR0XFhRdz02nUnF77EmP3cnqfHsTZkDw4qkoeO8V9XuMveRQceD1m11FU5pSrARAXXFegdKP2IqbRpaNruExW4EEUQojzQV7lvMOAKRey6fsgjdCCA18xd7d3VPxJQYqYl9skxumEPE4Ui6uYwjxlx--FzfDmNwDZY8uFFebbfE5xcP9MbjfPj9nT3oXMr04z0v27frD3eZjeftpe7N5f1uiMnwsXctRS4cC285o00vsRbvW_bzXxmhyxtTO8Y6U0r1UiroWhSbCHpoGFcpL9vqUe0jx50R5tHufkUJwA8Up2waUXCtRz0J1EmKKOSfq7SH5vUtHy8Eu4OzOnsDZBZzl3M7gZturc_7U7qn7azqTmgVvTwKav3zwlGxGTwNS5xPhaLvo_3fh3wAMfliY_qAj5V2c0jATtNxmYcF-XcpbuoMauGoaLv8AFOaWoQ</recordid><startdate>20070601</startdate><enddate>20070601</enddate><creator>Siracusano, Salvatore</creator><creator>Vita, Francesca</creator><creator>Abbate, Rita</creator><creator>Ciciliato, Stefano</creator><creator>Borelli, Violetta</creator><creator>Bernabei, Massimiliano</creator><creator>Zabucchi, Giuliano</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20070601</creationdate><title>The Role of Granulocytes Following Intravesical BCG Prophylaxis</title><author>Siracusano, Salvatore ; Vita, Francesca ; Abbate, Rita ; Ciciliato, Stefano ; Borelli, Violetta ; Bernabei, Massimiliano ; Zabucchi, Giuliano</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-ab1c53ac2cbd858f3cf2b95f2cb6885ea886aa1de445f344edbc25eecf077c4c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Administration, Intravesical</topic><topic>BCG</topic><topic>BCG Vaccine - administration &amp; dosage</topic><topic>Biomarkers, Tumor - urine</topic><topic>Bladder cancer</topic><topic>Blotting, Western</topic><topic>Carcinoma, Transitional Cell - immunology</topic><topic>Carcinoma, Transitional Cell - therapy</topic><topic>Carcinoma, Transitional Cell - urine</topic><topic>Electrophoresis, Polyacrylamide Gel</topic><topic>Granulocyte</topic><topic>Granulocytes - immunology</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Luminescence</topic><topic>Urinalysis</topic><topic>Urinary Bladder Neoplasms - immunology</topic><topic>Urinary Bladder Neoplasms - therapy</topic><topic>Urinary Bladder Neoplasms - urine</topic><topic>Urology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Siracusano, Salvatore</creatorcontrib><creatorcontrib>Vita, Francesca</creatorcontrib><creatorcontrib>Abbate, Rita</creatorcontrib><creatorcontrib>Ciciliato, Stefano</creatorcontrib><creatorcontrib>Borelli, Violetta</creatorcontrib><creatorcontrib>Bernabei, Massimiliano</creatorcontrib><creatorcontrib>Zabucchi, Giuliano</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European urology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Siracusano, Salvatore</au><au>Vita, Francesca</au><au>Abbate, Rita</au><au>Ciciliato, Stefano</au><au>Borelli, Violetta</au><au>Bernabei, Massimiliano</au><au>Zabucchi, Giuliano</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Role of Granulocytes Following Intravesical BCG Prophylaxis</atitle><jtitle>European urology</jtitle><addtitle>Eur Urol</addtitle><date>2007-06-01</date><risdate>2007</risdate><volume>51</volume><issue>6</issue><spage>1589</spage><epage>1599</epage><pages>1589-1599</pages><issn>0302-2838</issn><eissn>1873-7560</eissn><abstract>Abstract Objectives The antitumour effect of bacillus Calmette-Guérin (BCG) still remains relatively undefined. Most investigations on its mechanism of action have focused on mononuclear cells; little consideration has been given to granulocytes. We analysed urine of patients with bladder cancer during 8 wk of intravesical BCG prophylaxis. The number of polymorphonuclear neutrophils (PMNs) and urothelial cells (UCs) was evaluated. We examined the in vitro response of the T24 UC line to human PMNs after BCG treatment. Methods Seventeen patients were enrolled in the study. Cytologic analyses were performed on urine samples collected before each BCG instillation and after 2 h from the first voided urine after BCG instillation. Elastase activity was determined on these samples to evaluate PMN activation. PMN-induced damage was measured on the T24 cell line treated with BCG. Results After BCG treatment, a large number of PMNs transmigrated through the urothelium and PMNs adherent to detached UCs were found. One patient, who did not respond with significant PMN transmigration, experienced recurrent disease. The number of eosinophils that transmigrated was low, with the exception of three patients with recurrent disease. In vitro, PMNs adhered to BCG-primed T24 cells and damaged the monolayer. Conclusions The results agree with recent evidence that PMNs may play an important role in the antitumour action of BCG during the BCG induction period. This role is probably nonspecific because both normal UCs in vivo and tumour cells in vitro appeared to be injured. As suggested by results obtained from a limited number of patients, a high number of eosinophils in the urine may indicate therapy failure.</abstract><cop>Switzerland</cop><pub>Elsevier B.V</pub><pmid>17222501</pmid><doi>10.1016/j.eururo.2006.11.045</doi><tpages>11</tpages></addata></record>
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subjects Administration, Intravesical
BCG
BCG Vaccine - administration & dosage
Biomarkers, Tumor - urine
Bladder cancer
Blotting, Western
Carcinoma, Transitional Cell - immunology
Carcinoma, Transitional Cell - therapy
Carcinoma, Transitional Cell - urine
Electrophoresis, Polyacrylamide Gel
Granulocyte
Granulocytes - immunology
Humans
Immunotherapy
Luminescence
Urinalysis
Urinary Bladder Neoplasms - immunology
Urinary Bladder Neoplasms - therapy
Urinary Bladder Neoplasms - urine
Urology
title The Role of Granulocytes Following Intravesical BCG Prophylaxis
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