Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/353882
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dc.contributor.CRUESPUNIVERSIDADE ESTADUAL DE CAMPINASpt_BR
dc.contributor.authorunicampGarcia, Patrick Vianna-
dc.contributor.authorunicampCarniato, Amanda Pocol-
dc.contributor.authorunicampDuran Caballero, Nelson Eduardo-
dc.contributor.authorunicampOliveira, Alexandre Gabarra de-
dc.contributor.authorunicampFávaro, Wagner José-
dc.typeArtigopt_BR
dc.titleIncreased toll-like receptors and p53 levels regulate apoptosis and angiogenesis in non-muscle invasive bladder cancer: mechanism of action of P-MAPA biological response modifierpt_BR
dc.contributor.authorGarcia, Patrick Vianna-
dc.contributor.authorFerreira Seiva, Fabio Rodrigues-
dc.contributor.authorCarniato, Amanda Pocol-
dc.contributor.authorde Mello Junior, Wilson-
dc.contributor.authorDuran, Nelson-
dc.contributor.authorMacedo, Alda Maria-
dc.contributor.authorde Oliveira, Alexandre Gabarra-
dc.contributor.authorRomih, Rok-
dc.contributor.authorNunes, Iseu da Silva-
dc.contributor.authorNunes, Odilon da Silva-
dc.contributor.authorFavaro, Wagner Jose-
dc.subjectImunoterapiapt_BR
dc.subject.otherlanguageImmunotherapypt_BR
dc.description.abstractBackground: The new modalities for treating patients with non-muscle invasive bladder cancer (NMIBC) for whom BCG (Bacillus Calmette-Guerin) has failed or is contraindicated are recently increasing due to the development of new drugs. Although agents like mitomycin C and BCG are routinely used, there is a need for more potent and/or less-toxic agents. In this scenario, a new perspective is represented by P-MAPA (Protein Aggregate Magnesium-Ammonium Phospholinoleate-Palmitoleate Anhydride), developed by Farmabrasilis (non-profit research network). This study detailed and characterized the mechanisms of action of P-MAPA based on activation of mediators of Toll-like Receptors (TLRs) 2 and 4 signaling pathways and p53 in regulating angiogenesis and apoptosis in an animal model of NMIBC, as well as, compared these mechanisms with BCG treatment. Results: Our results demonstrated the activation of the immune system by BCG (MyD88-dependent pathway) resulted in increased inflammatory cytokines. However, P-MAPA intravesical immunotherapy led to distinct activation of TLRs 2 and 4-mediated innate immune system, resulting in increased interferons signaling pathway (TRIF-dependent pathway), which was more effective in the NMIBC treatment. Interferon signaling pathway activation induced by P-MAPA led to increase of iNOS protein levels, resulting in apoptosis and histopathological recovery. Additionally, P-MAPA immunotherapy increased wild-type p53 protein levels. The increased wild-type p53 protein levels were fundamental to NO-induced apoptosis and the up-regulation of BAX. Furthermore, interferon signaling pathway induction and increased p53 protein levels by P-MAPA led to important antitumor effects, not only suppressing abnormal cell proliferation, but also by preventing continuous expansion of tumor mass through suppression of angiogenesis, which was characterized by decreased VEGF and increased endostatin protein levels. Conclusions: Thus, P-MAPA immunotherapy could be considered an important therapeutic strategy for NMIBC, as well as, opens a new perspective for treatment of patients that are refractory or resistant to BCG intravesical therapypt_BR
dc.relation.ispartofBMC cancerpt_BR
dc.publisher.cityLondonpt_BR
dc.publisher.countryReino Unidopt_BR
dc.publisherSpringer Naturept_BR
dc.date.issued2016-
dc.language.isoengpt_BR
dc.description.volume16pt_BR
dc.rightsAbertopt_BR
dc.sourceWOSpt_BR
dc.identifier.eissn1471-2407pt_BR
dc.identifier.doi10.1186/s12885-016-2474-zpt_BR
dc.identifier.urlhttps://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2474-zpt_BR
dc.description.sponsorshipFUNDAÇÃO ARAUCÁRIA DE APOIO AO DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO DO ESTADO DO PARANÁ - FApt_BR
dc.description.sponsorshipCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQpt_BR
dc.description.sponsorshipFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPpt_BR
dc.description.sponsordocumentnumber490519/2011-3; 475211/2013-8; 402280/2013-0pt_BR
dc.description.sponsordocumentnumber225/2014; 656/2014pt_BR
dc.description.sponsordocumentnumber2011/05726-4; 2012/20706-2; 2012/13585-4; 2014/20465-0pt_BR
dc.date.available2021-01-12T13:00:15Z-
dc.date.accessioned2021-01-12T13:00:15Z-
dc.description.provenanceSubmitted by Sanches Olivia (olivias@unicamp.br) on 2021-01-12T13:00:15Z No. of bitstreams: 0. Added 1 bitstream(s) on 2021-02-25T19:55:42Z : No. of bitstreams: 1 000381196500003.pdf: 3163953 bytes, checksum: 22555593d0e771b0745caafc593c0ac9 (MD5)en
dc.description.provenanceMade available in DSpace on 2021-01-12T13:00:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2016en
dc.identifier.urihttp://repositorio.unicamp.br/jspui/handle/REPOSIP/353882-
dc.contributor.departmentsem informaçãopt_BR
dc.contributor.departmentsem informaçãopt_BR
dc.contributor.departmentDepartamento de Química Orgânicapt_BR
dc.contributor.departmentsem informaçãopt_BR
dc.contributor.departmentDepartamento de Biologia Estrutural e Funcionalpt_BR
dc.contributor.unidadeFaculdade de Ciências Médicaspt_BR
dc.contributor.unidadeInstituto de Biologiapt_BR
dc.contributor.unidadeInstituto de Químicapt_BR
dc.subject.keywordBladder cancerpt_BR
dc.subject.keywordToll-like receptorpt_BR
dc.subject.keywordP53pt_BR
dc.subject.keywordP-MAPApt_BR
dc.subject.keywordAngiogenesispt_BR
dc.subject.keywordBacillus Calmette-Guerinpt_BR
dc.identifier.source000381196500003pt_BR
dc.creator.orcidsem informaçãopt_BR
dc.creator.orcidsem informaçãopt_BR
dc.creator.orcid0000-0001-8372-5143pt_BR
dc.creator.orcid0000-0002-6620-5477pt_BR
dc.creator.orcid0000-0001-5830-8938pt_BR
dc.type.formArtigo de pesquisapt_BR
dc.identifier.articleid422pt_BR
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IB - Artigos e Outros Documentos
FCM - Artigos e Outros Documentos

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