title: FGFR3 Down-Regulation is Involved in bacillus Calmette-Guérin Induced Bladder Tumor Growth Inhibition.
abstract: OBJECTIVE
  Bacillus Calmette-Guérin is the standard treatment for patients with nonmuscle invasive high histological grade bladder cancer. Previously we found that bacillus Calmette-Guérin induces murine bladder cancer MB49 cell death in vitro and in vivo, generating tissue remodeling, which involves the release of fibroblast growth factor (FGF)-2.
  
  
  METHODS
  We studied the effect of bacillus Calmette-Guérin treatment on FGF-2 and FGF receptor (FGFR) expression in bladder cancer.
  
  
  RESULTS
  In vitro FGF-2 increased MB49 cell proliferation but did not reverse bacillus Calmette-Guérin induced cell death. Increased FGF-2 expression was detected after bacillus Calmette-Guérin treatment. Moreover MB49 cells expressed high FGFR3 levels, which decreased after treatment. Similar results were observed in human T24 bladder cancer cells. In vivo MB49 tumors expressed higher FGFR3 levels than normal urothelium. Tumor FGFR3 decreased after treatment and correlated with tumor growth inhibition in response to bacillus Calmette-Guérin. In a pilot bioassay using 11 human bladder tumors treated ex vivo with bacillus Calmette-Guérin we found a subgroup of 41% of patients in whom FGFR3 was decreased after treatment.
  
  
  CONCLUSIONS
  Based on bladder cancer murine model results we infer that down-regulation of FGFR3 is a predictive marker of a good response to bacillus Calmette-Guérin therapy. The decrease in FGFR3 in response to bacillus Calmette-Guérin occurred not only in a murine model but also in a human bladder cancer cell line and in some patient samples. More patients and increased followup are needed to establish the predictive role of FGFR3 as a marker in human bladder cancer.
authors.affiliation: Área de Investigación, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina; Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (AS, AG, AB, CL, CL), Buenos Aires, Buenos Aires, Argentina.
authors.forename: Yanina V
authors.initials: YV
authors.lastname: Langle
authors.affiliation: Área de Investigación, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina; Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (AS, AG, AB, CL, CL), Buenos Aires, Buenos Aires, Argentina.
authors.forename: Denise
authors.initials: D
authors.lastname: Belgorosky
authors.affiliation: Área de Investigación, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina; Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (AS, AG, AB, CL, CL), Buenos Aires, Buenos Aires, Argentina.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Prack McCormick
authors.affiliation: Área de Investigación, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina; Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (AS, AG, AB, CL, CL), Buenos Aires, Buenos Aires, Argentina.
authors.forename: Ana
authors.initials: A
authors.lastname: Sahores
authors.affiliation: Área de Investigación, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina; Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (AS, AG, AB, CL, CL), Buenos Aires, Buenos Aires, Argentina.
authors.forename: Adrián
authors.initials: A
authors.lastname: Góngora
authors.affiliation: Área de Investigación, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina; Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (AS, AG, AB, CL, CL), Buenos Aires, Buenos Aires, Argentina.
authors.forename: Alberto
authors.initials: A
authors.lastname: Baldi
authors.affiliation: Área de Investigación, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina; Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (AS, AG, AB, CL, CL), Buenos Aires, Buenos Aires, Argentina.
authors.forename: Claudia
authors.initials: C
authors.lastname: Lanari
authors.affiliation: Área de Investigación, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina; Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (AS, AG, AB, CL, CL), Buenos Aires, Buenos Aires, Argentina.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lamb
authors.affiliation: Área de Investigación, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina; Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (AS, AG, AB, CL, CL), Buenos Aires, Buenos Aires, Argentina. Electronic address: grupoeijan@gmail.com.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Eiján
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001500:BCG Vaccine / Q000627:therapeutic use*; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3
keywords: BCG vaccine; biological markers; fibroblast growth factors; receptors, fibroblast growth factor; urinary bladder neoplasms