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dc.contributor.CRUESPUniversidade Estadual de Campinaspt_BR
dc.typeArtigo de periódicopt_BR
dc.titleMeasurements of CFTR-Mediated Cl- Secretion in Human Rectal Biopsies Constitute a Robust Biomarker for Cystic Fibrosis Diagnosis and Prognosispt_BR
dc.contributor.authorSousa, Mpt_BR
dc.contributor.authorServidoni, MFpt_BR
dc.contributor.authorVinagre, AMpt_BR
dc.contributor.authorRamalho, ASpt_BR
dc.contributor.authorBonadia, LCpt_BR
dc.contributor.authorFelicio, Vpt_BR
dc.contributor.authorRibeiro, MApt_BR
dc.contributor.authorUliyakina, Ipt_BR
dc.contributor.authorMarson, FApt_BR
dc.contributor.authorKmit, Apt_BR
dc.contributor.authorCardoso, SRpt_BR
dc.contributor.authorRibeiro, JDpt_BR
dc.contributor.authorBertuzzo, CSpt_BR
dc.contributor.authorSousa, Lpt_BR
dc.contributor.authorKunzelmann, Kpt_BR
dc.contributor.authorRibeiro, AFpt_BR
dc.contributor.authorAmaral, MDpt_BR
unicamp.author.emailmdamaral@fc.ul.ptpt_BR
unicamp.authorSousa, Marisa Ramalho, Anabela S. Felicio, Veronica Uliyakina, Inna Amaral, Margarida D. Univ Lisbon, BioFIG Ctr Biodivers Funct & Integrat Genom, Fac Sci, P-1699 Lisbon, Portugalpt_BR
unicamp.authorSousa, Marisa Ramalho, Anabela S. Uliyakina, Inna Amaral, Margarida D. Natl Inst Hlth, Dept Genet, Lisbon, Portugalpt_BR
unicamp.authorServidoni, Maria F. Univ Estadual Campinas, Gastroctr, Endoscopy Unit, Campinas, SP, Brazilpt_BR
unicamp.authorServidoni, Maria F. Cardoso, Silvia R. Ribeiro, Jose D. Ribeiro, Antonio F. Univ Estadual Campinas, Dept Pediat, Campinas, SP, Brazilpt_BR
unicamp.authorVinagre, Adriana M. Bonadia, Luciana C. Marson, Fernando A. Kmit, Arthur Ribeiro, Jose D. Bertuzzo, Carmen S. Ribeiro, Antonio F. Univ Estadual Campinas, Fac Med Sci, Campinas, SP, Brazilpt_BR
unicamp.authorRibeiro, Maria A. Ribeiro, Jose D. Ribeiro, Antonio F. Univ Estadual Campinas, CIPED Res Ctr Pediat, Campinas, SP, Brazilpt_BR
unicamp.authorCardoso, Silvia R. Univ Hosp Campinas, Endoscopy Unit, Campinas, SP, Brazilpt_BR
unicamp.authorSousa, Lisete Univ Lisbon, CEAUL Ctr Stat & Applicat, P-1699 Lisbon, Portugalpt_BR
unicamp.authorSousa, Lisete Univ Lisbon, Fac Sci, Dept Stat & Operat Res, P-1699 Lisbon, Portugalpt_BR
unicamp.authorKunzelmann, Karl Univ Regensburg, Inst Physiol, Regensburg, Germanypt_BR
dc.subject.wosTransmembrane Conductance Regulatorpt_BR
dc.subject.wosNasal Potential Differencept_BR
dc.subject.wosNative Human Colonpt_BR
dc.subject.wosAirway Ion-transportpt_BR
dc.subject.wosPulmonary-diseasept_BR
dc.subject.wosLung-functionpt_BR
dc.subject.wosMutationpt_BR
dc.subject.wosIdentificationpt_BR
dc.subject.wosGenept_BR
dc.subject.wosConsensuspt_BR
dc.description.abstractBackground: Cystic Fibrosis (CF) is caused by similar to 1,900 mutations in the CF transmembrane conductance regulator (CFTR) gene encoding for a cAMP-regulated chloride (Cl-) channel expressed in several epithelia. Clinical features are dominated by respiratory symptoms, but there is variable organ involvement thus causing diagnostic dilemmas, especially for non-classic cases. Methodology/Principal Findings: To further establish measurement of CFTR function as a sensitive and robust biomarker for diagnosis and prognosis of CF, we herein assessed cholinergic and cAMP-CFTR-mediated Cl- secretion in 524 freshly excised rectal biopsies from 118 individuals, including patients with confirmed CF clinical diagnosis (n = 51), individuals with clinical CF suspicion (n = 49) and age-matched non-CF controls (n = 18). Conclusive measurements were obtained for 96% of cases. Patients with "Classic CF'', presenting earlier onset of symptoms, pancreatic insufficiency, severe lung disease and low Shwachman-Kulczycki scores were found to lack CFTR-mediated Cl- secretion (<5%). Individuals with milder CF disease presented residual CFTR-mediated Cl- secretion (10-57%) and non-CF controls show CFTR-mediated Cl- secretion >= 30-35% and data evidenced good correlations with various clinical parameters. Finally, comparison of these values with those in "CF suspicion'' individuals allowed to confirm CF in 16/49 individuals (33%) and exclude it in 28/49 (57%). Statistical discriminant analyses showed that colonic measurements of CFTR-mediated Cl- secretion are the best discriminator among Classic/Non-Classic CF and non-CF groups. Conclusions/Significance: Determination of CFTR-mediated Cl- secretion in rectal biopsies is demonstrated here to be a sensitive, reproducible and robust predictive biomarker for the diagnosis and prognosis of CF. The method also has very high potential for (pre-) clinical trials of CFTR-modulator therapies.pt
dc.relation.ispartofPlos Onept_BR
dc.relation.ispartofabbreviationPLoS Onept_BR
dc.publisher.citySan Franciscopt_BR
dc.publisher.countryEUApt_BR
dc.publisherPublic Library Sciencept_BR
dc.date.issued2012pt_BR
dc.date.monthofcirculationOCT 17pt_BR
dc.identifier.citationPlos One. Public Library Science, v. 7, n. 10, 2012.pt_BR
dc.language.isoenpt_BR
dc.description.volume7pt_BR
dc.description.issuenumber10pt_BR
dc.rightsabertopt_BR
dc.sourceWeb of Sciencept_BR
unicamp.cruespUSPpt_BR
dc.identifier.issn1932-6203pt_BR
dc.identifier.wosidWOS:000311146900095pt_BR
dc.identifier.doi10.1371/journal.pone.0047708pt_BR
dc.description.sponsorshipTargetScreen2 [EU/FP6/LSH/2005/037365, PIC/IC/83103/2007]pt_BR
dc.description.sponsorshipFCT (Portugal) [PEstOE/BIA/UI4046/2011, PEstOE/MAT/UI0006/2011, SFRH/BD/35936/2007, SFRH/BD/69180/2010]pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsorshipMukoviszidose e.V. (Germany) [S02/10]pt_BR
dc.description.sponsorship[PTDC/MAT/118335/2010]pt_BR
dc.description.sponsorship1Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorship1Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsordocumentnumberTargetScreen2 [EU/FP6/LSH/2005/037365, PIC/IC/83103/2007]pt
dc.description.sponsordocumentnumberFCT (Portugal) [PEstOE/BIA/UI4046/2011, PEstOE/MAT/UI0006/2011, SFRH/BD/35936/2007, SFRH/BD/69180/2010]pt
dc.description.sponsordocumentnumberCNPq [40.8924/2006/3]pt
dc.description.sponsordocumentnumberMukoviszidose e.V. (Germany) [S02/10]pt
dc.description.sponsordocumentnumber[PTDC/MAT/118335/2010]pt
dc.date.available2014-07-30T13:40:43Z
dc.date.available2015-11-26T16:40:52Z-
dc.date.accessioned2014-07-30T13:40:43Z
dc.date.accessioned2015-11-26T16:40:52Z-
dc.description.provenanceMade available in DSpace on 2014-07-30T13:40:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2012en
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dc.identifier.urihttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/53441
dc.identifier.urihttp://repositorio.unicamp.br/jspui/handle/REPOSIP/53441-
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