Molecular Analyte Profiling of the Early Events and Tissue Conditioning Following Intravesical Bacillus Calmette-Guerin Therapy in Patients With Superficial Bladder Cancer

No AccessJournal of UrologyAdult Urology1 Apr 2009Molecular Analyte Profiling of the Early Events and Tissue Conditioning Following Intravesical Bacillus Calmette-Guerin Therapy in Patients With Superficial Bladder Canceris accompanied byIncreased Infiltration of Tumor Associated Macrophages is Associated With Poor Prognosis of Bladder Carcinoma In Situ After Intravesical Bacillus Calmette-Guerin InstillationPrevention and Treatment of Transitional Cell Carcinomatosis With Intraperitoneal Chemotherapy in a Rat Model Aurélie Bisiaux, Nicolas Thiounn, Marc-Olivier Timsit, Ahmed Eladaoui, Huey-Hsuan Chang, James Mapes, Agnès Mogenet, Jean-Louis Bresson, Dominique Prié, Stéphane Béchet, Camille Baron, Christine Sadorge, Stéphanie Thomas, Elaine B. Albert, Peter S. Albert, and Matthew L. Albert Aurélie BisiauxAurélie Bisiaux Laboratoire d'Immunobiologie des Cellules Dendritiques, Department of Immunology, Institut Pasteur, Paris, France INSERM U818, Paris, France More articles by this author , Nicolas ThiounnNicolas Thiounn Service d'Urologie, Université René Descartes, Hôpital Necker, Paris, France More articles by this author , Marc-Olivier TimsitMarc-Olivier Timsit Service d'Urologie, Université René Descartes, Hôpital Necker, Paris, France More articles by this author , Ahmed EladaouiAhmed Eladaoui Centre d'Investigation Clinique AP-HP/INSERM, Université René Descartes, Paris, France More articles by this author , Huey-Hsuan ChangHuey-Hsuan Chang Laboratoire d'Immunobiologie des Cellules Dendritiques, Department of Immunology, Institut Pasteur, Paris, France INSERM U818, Paris, France More articles by this author , James MapesJames Mapes Rules Based Medicine, Inc., Austin, Texas More articles by this author , Agnès MogenetAgnès Mogenet Centre d'Investigation Clinique AP-HP/INSERM, Université René Descartes, Paris, France More articles by this author , Jean-Louis BressonJean-Louis Bresson Centre d'Investigation Clinique AP-HP/INSERM, Université René Descartes, Paris, France More articles by this author , Dominique PriéDominique Prié Service des Explorations Fonctionnelles, INSERM U845, Université René Descartes, Hôpital Necker, Paris, France More articles by this author , Stéphane BéchetStéphane Béchet Centre de Recherche Vaccinale et Biomédicale, Institut Pasteur, Paris, France More articles by this author , Camille BaronCamille Baron Centre de Recherche Vaccinale et Biomédicale, Institut Pasteur, Paris, France More articles by this author , Christine SadorgeChristine Sadorge Centre de Recherche Vaccinale et Biomédicale, Institut Pasteur, Paris, France More articles by this author , Stéphanie ThomasStéphanie Thomas Laboratoire d'Immunobiologie des Cellules Dendritiques, Department of Immunology, Institut Pasteur, Paris, France INSERM U818, Paris, France More articles by this author , Elaine B. AlbertElaine B. Albert Staten Island Urological, Staten Island, New York More articles by this author , Peter S. AlbertPeter S. Albert Staten Island Urological, Staten Island, New York More articles by this author , and Matthew L. AlbertMatthew L. Albert Laboratoire d'Immunobiologie des Cellules Dendritiques, Department of Immunology, Institut Pasteur, Paris, France INSERM U818, Paris, France More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2008.11.124AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We characterized the innate immune response to intravesical bacillus Calmette-Guerin therapy using a systems approach based on proteomic and cytometric screens. Materials and Methods: Blood and urine were collected from patients receiving intravesical bacillus Calmette-Guerin therapy before, and 2 and 4 hours after bacillus Calmette-Guerin treatment, at the first and third instillation. Proteomic and cytometry based screens were performed. Results: Molecular analyte profiling revealed a prime/boost pattern to the innate response to intravesical bacillus Calmette-Guerin. We identified 36 statistically significant changes in the proteins induced during the third instillation compared to the initial treatment. These analytes were classified into 3 categories of 1) plasma proteins that leaked into the urine, 2) cytokines/chemokines produced locally during the first hours of inflammation and 3) other innate molecules that modulate the bladder microenvironment. To characterize the marked increase in the inflammatory response after multiple treatments we evaluated the cells present in the urine and again a prime/boost response was revealed. For the locally produced analytes it was possible to define the cell source(s) and, thus, provide a first generation map of what occurs during the initial phase of bacillus Calmette-Guerin therapy. Conclusions: This study provides in vivo information concerning the ability of bacillus Calmette-Guerin to sensitize the tissue microenvironment to enhance innate responses and establishes a framework for improving vaccination strategies while decreasing adverse events. References 1 : Bladder cancer. Curr Opin Oncol2002; 14: 265. Google Scholar 2 : BCG immunotherapy of bladder cancer: 20 years on. Lancet1999; 353: 1689. Google Scholar 3 : Thirty years of BCG immunotherapy for non-muscle invasive bladder cancer: a success story with room for improvement. Biomed Pharmacother2007; 61: 299. Google Scholar 4 : Intracavitary bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol1976; 116: 180. 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Google Scholar © 2009 by American Urological AssociationFiguresReferencesRelatedDetailsRelated articlesJournal of Urology23 Feb 2009Increased Infiltration of Tumor Associated Macrophages is Associated With Poor Prognosis of Bladder Carcinoma In Situ After Intravesical Bacillus Calmette-Guerin InstillationJournal of Urology23 Feb 2009Prevention and Treatment of Transitional Cell Carcinomatosis With Intraperitoneal Chemotherapy in a Rat Model Volume 181Issue 4April 2009Page: 1571-1580 Advertisement Copyright & Permissions© 2009 by American Urological AssociationKeywordsimmunotherapyurinary bladder neoplasmsinnateimmunityactiveAcknowledgmentsThe nursing staff of the Department of Urology, Necker Hospital provided assistance, Ms. Mayu Frank and Dr. Douglas Scherr assisted during the early phase of this project, and the Center for Human Immunology provided clinical support.MetricsAuthor Information Aurélie Bisiaux Laboratoire d'Immunobiologie des Cellules Dendritiques, Department of Immunology, Institut Pasteur, Paris, France INSERM U818, Paris, France More articles by this author Nicolas Thiounn Service d'Urologie, Université René Descartes, Hôpital Necker, Paris, France More articles by this author Marc-Olivier Timsit Service d'Urologie, Université René Descartes, Hôpital Necker, Paris, France More articles by this author Ahmed Eladaoui Centre d'Investigation Clinique AP-HP/INSERM, Université René Descartes, Paris, France More articles by this author Huey-Hsuan Chang Laboratoire d'Immunobiologie des Cellules Dendritiques, Department of Immunology, Institut Pasteur, Paris, France INSERM U818, Paris, France More articles by this author James Mapes Rules Based Medicine, Inc., Austin, Texas More articles by this author Agnès Mogenet Centre d'Investigation Clinique AP-HP/INSERM, Université René Descartes, Paris, France More articles by this author Jean-Louis Bresson Centre d'Investigation Clinique AP-HP/INSERM, Université René Descartes, Paris, France More articles by this author Dominique Prié Service des Explorations Fonctionnelles, INSERM U845, Université René Descartes, Hôpital Necker, Paris, France More articles by this author Stéphane Béchet Centre de Recherche Vaccinale et Biomédicale, Institut Pasteur, Paris, France More articles by this author Camille Baron Centre de Recherche Vaccinale et Biomédicale, Institut Pasteur, Paris, France More articles by this author Christine Sadorge Centre de Recherche Vaccinale et Biomédicale, Institut Pasteur, Paris, France More articles by this author Stéphanie Thomas Laboratoire d'Immunobiologie des Cellules Dendritiques, Department of Immunology, Institut Pasteur, Paris, France INSERM U818, Paris, France More articles by this author Elaine B. Albert Staten Island Urological, Staten Island, New York More articles by this author Peter S. Albert Staten Island Urological, Staten Island, New York More articles by this author Matthew L. Albert Laboratoire d'Immunobiologie des Cellules Dendritiques, Department of Immunology, Institut Pasteur, Paris, France INSERM U818, Paris, France More articles by this author Expand All Advertisement PDF downloadLoading ...