Avaliação da expressão de proteínas envolvidas na evasão tumoral no carcinoma mucoepidermóide de glândula salivar menor
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFG |
Texto Completo: | http://repositorio.bc.ufg.br/tede/handle/tede/9775 |
Resumo: | Background: The Human Leukocyte Antigen G and E (HLA-G and HLA-E) and Programmed Death Ligand-1 (PD-L1) are molecules which can provide tumor immunosuppression as well as the capacity of neoplastic evasion or escape to the immune system host. Objective: To identify the expression of HLA-G, HLA-E and PD-L1 in oral mucoepidermoid carcinomas (MEC) and assess whether such expressions are related to metastasis, survival, staging, localization and tumor grade. Design: This cross-sectional study selected samples of MEC minor salivary glands (n=30) and classified them according to the World Health Organization (WHO) grading as low grade (LG), intermediate grade (IG) and high grade (HG). HLA-G, HLA-E and PD-L1 were identified by immunohistochemistry and measured by the proportion of positive neoplastic (mucous, epidermoid, intermediate and clear) and stromal cells. The density of positive Cytotoxic T Lymphocytes (CTLs), Natural Killer (NK), and Granzyme B (GB) cells was also evaluated. The Kruskal-Wallis test was used with a 5% significance level. Results: Expressions of HLA-G, HLA-E and PD-L1 were identified in the majority of epidermoid, intermediate and clear cells, but not in the mucous cells of the MECs. Thus, the quantitative analysis of the total percentage of positive neoplastic cells showed an association between the expression of these proteins and histologic grading with the following median values: HLA-G (LG= 79%, IG= 96%, HG= 99%; p=0.0004), HLA-E (LG= 70%, IG= 96%, HG= 99%; p<0.0001) and PD-L1 (LG= 34%, IG= 79%, HG= 80%; p=0.01). In consonance with a microenvironment conducive to inhibiting CTLs and NK cells, low GB density was found in all MEC samples. There was no relationship between the percentage of HLA-G+, HLA-E+ and PD-L1+ cancer cells and the other clinical parameters evaluated. Conclusions: MEC expresses a set of proteins involved in neoplastic cell escape from the anti-tumor immune system. In addition, increased expression of HLA-G, HLA-E and of PD-L1 in the tumoral microenvironment is closely related to the predominant cell type, and consequently to the higher histologic grades of MEC. |
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Batista, Aline Carvalhohttp://lattes.cnpq.br/0199082642322002Aline Carvalho Batista, Aline Carvalho BatistaVêncio, Eneida FrancoAlves, Pollianna Munizhttp://lattes.cnpq.br/7237756043264091Mosconi, Carla2019-07-03T12:32:50Z2017-02-21MOSCONI, Carla. Avaliação da expressão de proteínas envolvidas na evasão tumoral no carcinoma mucoepidermóide de glândula salivar menor. 2017. 36 f. Dissertação (Mestrado em Odontologia) - Universidade Federal de Goiás, Goiânia, 2017.http://repositorio.bc.ufg.br/tede/handle/tede/9775ark:/38995/0013000009sn8Background: The Human Leukocyte Antigen G and E (HLA-G and HLA-E) and Programmed Death Ligand-1 (PD-L1) are molecules which can provide tumor immunosuppression as well as the capacity of neoplastic evasion or escape to the immune system host. Objective: To identify the expression of HLA-G, HLA-E and PD-L1 in oral mucoepidermoid carcinomas (MEC) and assess whether such expressions are related to metastasis, survival, staging, localization and tumor grade. Design: This cross-sectional study selected samples of MEC minor salivary glands (n=30) and classified them according to the World Health Organization (WHO) grading as low grade (LG), intermediate grade (IG) and high grade (HG). HLA-G, HLA-E and PD-L1 were identified by immunohistochemistry and measured by the proportion of positive neoplastic (mucous, epidermoid, intermediate and clear) and stromal cells. The density of positive Cytotoxic T Lymphocytes (CTLs), Natural Killer (NK), and Granzyme B (GB) cells was also evaluated. The Kruskal-Wallis test was used with a 5% significance level. Results: Expressions of HLA-G, HLA-E and PD-L1 were identified in the majority of epidermoid, intermediate and clear cells, but not in the mucous cells of the MECs. Thus, the quantitative analysis of the total percentage of positive neoplastic cells showed an association between the expression of these proteins and histologic grading with the following median values: HLA-G (LG= 79%, IG= 96%, HG= 99%; p=0.0004), HLA-E (LG= 70%, IG= 96%, HG= 99%; p<0.0001) and PD-L1 (LG= 34%, IG= 79%, HG= 80%; p=0.01). In consonance with a microenvironment conducive to inhibiting CTLs and NK cells, low GB density was found in all MEC samples. There was no relationship between the percentage of HLA-G+, HLA-E+ and PD-L1+ cancer cells and the other clinical parameters evaluated. Conclusions: MEC expresses a set of proteins involved in neoplastic cell escape from the anti-tumor immune system. In addition, increased expression of HLA-G, HLA-E and of PD-L1 in the tumoral microenvironment is closely related to the predominant cell type, and consequently to the higher histologic grades of MEC.Contextualização: O antígeno leucocitário humano não clássico G e E (HLA-G e HLAE) e o ligante de morte celular programada 1 (PD-L1) são moléculas que estão envolvidas na imunossupressão tumoral, bem como na capacidade de evasão ou escape das células neoplásicas do sistema imunológico do hospedeiro. Objetivo: Identificar a expressão do HLA-G, HLA-E e PD-L1 em carcinomas mucoepidermóides (CME) de boca e avaliar se essas expressões possuem relação com a metástase, sobrevida, estadiamento, localização e gradação tumoral. Desenho: Este estudo transversal selecionou amostras de CME de glândula salivar menor (n= 30) e as classificou de acordo com a gradação da Organização Mundial de Saúde (OMS) em baixo grau (BG), grau intermediário (GI) e alto grau (AG). HLA-G, HLA-E e PD-L1 foram identificadas pela técnica de imunoistoquímica e mensuradas pela proporção de células neoplásicas (mucosas, epidermóides, intermediárias e claras) e estromais positivas. A densidade de linfócitos T citotóxicos (LTCs) / células Natural Killer (NK) granzima B (GB) positivos também foi avaliada. O teste de Kruskal- Wallis foi utilizado com nível de significância de 5%. Resultados: A expressão de HLA-G, HLA-E e PD-L1 foi identificada na maioria das células epidermóides, intermediárias e claras, mas não nas células mucosas presentes nos CMEs. Desta forma, a análise quantitativa da porcentagem total de células neoplásicas positivas revelou associação entre a expressão dessas proteínas e a gradação histológica com os seguintes valores de mediana: HLA-G (BG= 79%, GI= 96%, AG= 99%; p=0,0004), HLA-E (BG= 70%, GI= 96%, AG= 99%; p< 0,0001) e PD-L1 (BG= 34%, GI= 79%, AG= 80%; p=0,01). Condizente com um microambiente propício a inibição de LTCs e células NK, demonstrou-se baixa densidade de GB em todas as amostras de CME. Não houve relação entre a porcentagem de células neoplásicas HLA-G+, HLA-E+ e PD-L1+ e os demais parâmetros clínicos avaliados. Conclusões: O CME expressa um conjunto de proteínas envolvidas na evasão de células neoplásicas do sistema imunológico antitumoral. Além disso, a maior expressão do HLA-G, HLA-E e do PD-L1 no microambiente tumoral está intimamente relacionada com o tipo celular predominante e, consequentemente, com as maiores gradações histológicas do CME.Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2019-07-02T17:43:08Z No. of bitstreams: 2 Dissertação - Carla Mosconi - 2017.pdf: 1919594 bytes, checksum: 5dbd16dd0796cafecf54277107f44c72 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2019-07-03T12:32:50Z (GMT) No. of bitstreams: 2 Dissertação - Carla Mosconi - 2017.pdf: 1919594 bytes, checksum: 5dbd16dd0796cafecf54277107f44c72 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2019-07-03T12:32:50Z (GMT). No. of bitstreams: 2 Dissertação - Carla Mosconi - 2017.pdf: 1919594 bytes, checksum: 5dbd16dd0796cafecf54277107f44c72 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-02-21Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfporUniversidade Federal de GoiásPrograma de Pós-graduação em Odontologia (FO)UFGBrasilFaculdade de Odontologia - FO (RG)http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessAntígenos HLAProteína 1 ligante de morte celular programada 1Carcinoma mucoepidermóideNeoplasias das glândulas salivaresEvasão da resposta imuneHLA antigensProgrammed cell death 1 ligand 1 proteinMucoepidermoid carcinomaSalivary glandODONTOLOGIA::CLINICA ODONTOLOGICAAvaliação da expressão de proteínas envolvidas na evasão tumoral no carcinoma mucoepidermóide de glândula salivar menorTumor escape mechanisms in mucoepidermoid carcinomainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis-2325576619034292269600600600600-5569154581575113691-18167404498984916572075167498588264571reponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGLICENSElicense.txtlicense.txttext/plain; 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dc.title.eng.fl_str_mv |
Avaliação da expressão de proteínas envolvidas na evasão tumoral no carcinoma mucoepidermóide de glândula salivar menor |
dc.title.alternative.eng.fl_str_mv |
Tumor escape mechanisms in mucoepidermoid carcinoma |
title |
Avaliação da expressão de proteínas envolvidas na evasão tumoral no carcinoma mucoepidermóide de glândula salivar menor |
spellingShingle |
Avaliação da expressão de proteínas envolvidas na evasão tumoral no carcinoma mucoepidermóide de glândula salivar menor Mosconi, Carla Antígenos HLA Proteína 1 ligante de morte celular programada 1 Carcinoma mucoepidermóide Neoplasias das glândulas salivares Evasão da resposta imune HLA antigens Programmed cell death 1 ligand 1 protein Mucoepidermoid carcinoma Salivary gland ODONTOLOGIA::CLINICA ODONTOLOGICA |
title_short |
Avaliação da expressão de proteínas envolvidas na evasão tumoral no carcinoma mucoepidermóide de glândula salivar menor |
title_full |
Avaliação da expressão de proteínas envolvidas na evasão tumoral no carcinoma mucoepidermóide de glândula salivar menor |
title_fullStr |
Avaliação da expressão de proteínas envolvidas na evasão tumoral no carcinoma mucoepidermóide de glândula salivar menor |
title_full_unstemmed |
Avaliação da expressão de proteínas envolvidas na evasão tumoral no carcinoma mucoepidermóide de glândula salivar menor |
title_sort |
Avaliação da expressão de proteínas envolvidas na evasão tumoral no carcinoma mucoepidermóide de glândula salivar menor |
author |
Mosconi, Carla |
author_facet |
Mosconi, Carla |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Batista, Aline Carvalho |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/0199082642322002 |
dc.contributor.referee1.fl_str_mv |
Aline Carvalho Batista, Aline Carvalho Batista |
dc.contributor.referee2.fl_str_mv |
Vêncio, Eneida Franco |
dc.contributor.referee3.fl_str_mv |
Alves, Pollianna Muniz |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/7237756043264091 |
dc.contributor.author.fl_str_mv |
Mosconi, Carla |
contributor_str_mv |
Batista, Aline Carvalho Aline Carvalho Batista, Aline Carvalho Batista Vêncio, Eneida Franco Alves, Pollianna Muniz |
dc.subject.por.fl_str_mv |
Antígenos HLA Proteína 1 ligante de morte celular programada 1 Carcinoma mucoepidermóide Neoplasias das glândulas salivares Evasão da resposta imune |
topic |
Antígenos HLA Proteína 1 ligante de morte celular programada 1 Carcinoma mucoepidermóide Neoplasias das glândulas salivares Evasão da resposta imune HLA antigens Programmed cell death 1 ligand 1 protein Mucoepidermoid carcinoma Salivary gland ODONTOLOGIA::CLINICA ODONTOLOGICA |
dc.subject.eng.fl_str_mv |
HLA antigens Programmed cell death 1 ligand 1 protein Mucoepidermoid carcinoma Salivary gland |
dc.subject.cnpq.fl_str_mv |
ODONTOLOGIA::CLINICA ODONTOLOGICA |
description |
Background: The Human Leukocyte Antigen G and E (HLA-G and HLA-E) and Programmed Death Ligand-1 (PD-L1) are molecules which can provide tumor immunosuppression as well as the capacity of neoplastic evasion or escape to the immune system host. Objective: To identify the expression of HLA-G, HLA-E and PD-L1 in oral mucoepidermoid carcinomas (MEC) and assess whether such expressions are related to metastasis, survival, staging, localization and tumor grade. Design: This cross-sectional study selected samples of MEC minor salivary glands (n=30) and classified them according to the World Health Organization (WHO) grading as low grade (LG), intermediate grade (IG) and high grade (HG). HLA-G, HLA-E and PD-L1 were identified by immunohistochemistry and measured by the proportion of positive neoplastic (mucous, epidermoid, intermediate and clear) and stromal cells. The density of positive Cytotoxic T Lymphocytes (CTLs), Natural Killer (NK), and Granzyme B (GB) cells was also evaluated. The Kruskal-Wallis test was used with a 5% significance level. Results: Expressions of HLA-G, HLA-E and PD-L1 were identified in the majority of epidermoid, intermediate and clear cells, but not in the mucous cells of the MECs. Thus, the quantitative analysis of the total percentage of positive neoplastic cells showed an association between the expression of these proteins and histologic grading with the following median values: HLA-G (LG= 79%, IG= 96%, HG= 99%; p=0.0004), HLA-E (LG= 70%, IG= 96%, HG= 99%; p<0.0001) and PD-L1 (LG= 34%, IG= 79%, HG= 80%; p=0.01). In consonance with a microenvironment conducive to inhibiting CTLs and NK cells, low GB density was found in all MEC samples. There was no relationship between the percentage of HLA-G+, HLA-E+ and PD-L1+ cancer cells and the other clinical parameters evaluated. Conclusions: MEC expresses a set of proteins involved in neoplastic cell escape from the anti-tumor immune system. In addition, increased expression of HLA-G, HLA-E and of PD-L1 in the tumoral microenvironment is closely related to the predominant cell type, and consequently to the higher histologic grades of MEC. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017-02-21 |
dc.date.accessioned.fl_str_mv |
2019-07-03T12:32:50Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
MOSCONI, Carla. Avaliação da expressão de proteínas envolvidas na evasão tumoral no carcinoma mucoepidermóide de glândula salivar menor. 2017. 36 f. Dissertação (Mestrado em Odontologia) - Universidade Federal de Goiás, Goiânia, 2017. |
dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/9775 |
dc.identifier.dark.fl_str_mv |
ark:/38995/0013000009sn8 |
identifier_str_mv |
MOSCONI, Carla. Avaliação da expressão de proteínas envolvidas na evasão tumoral no carcinoma mucoepidermóide de glândula salivar menor. 2017. 36 f. Dissertação (Mestrado em Odontologia) - Universidade Federal de Goiás, Goiânia, 2017. ark:/38995/0013000009sn8 |
url |
http://repositorio.bc.ufg.br/tede/handle/tede/9775 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
-2325576619034292269 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 |
dc.relation.department.fl_str_mv |
-5569154581575113691 |
dc.relation.cnpq.fl_str_mv |
-1816740449898491657 |
dc.relation.sponsorship.fl_str_mv |
2075167498588264571 |
dc.rights.driver.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.publisher.program.fl_str_mv |
Programa de Pós-graduação em Odontologia (FO) |
dc.publisher.initials.fl_str_mv |
UFG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Faculdade de Odontologia - FO (RG) |
publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFG instname:Universidade Federal de Goiás (UFG) instacron:UFG |
instname_str |
Universidade Federal de Goiás (UFG) |
instacron_str |
UFG |
institution |
UFG |
reponame_str |
Repositório Institucional da UFG |
collection |
Repositório Institucional da UFG |
bitstream.url.fl_str_mv |
http://repositorio.bc.ufg.br/tede/bitstreams/c3de73ca-54f1-4d1b-9225-134b5a285c96/download http://repositorio.bc.ufg.br/tede/bitstreams/1a9ac0f6-9006-42c9-9f8f-37c1716bb29f/download http://repositorio.bc.ufg.br/tede/bitstreams/35f8fe8c-cef7-44c9-9d48-cd4761081060/download http://repositorio.bc.ufg.br/tede/bitstreams/5aec5b76-6d18-4e0a-9eae-5f791dc07efe/download http://repositorio.bc.ufg.br/tede/bitstreams/40879011-6e75-4c70-b496-9df4571983c8/download |
bitstream.checksum.fl_str_mv |
bd3efa91386c1718a7f26a329fdcb468 4afdbb8c545fd630ea7db775da747b2f d41d8cd98f00b204e9800998ecf8427e d41d8cd98f00b204e9800998ecf8427e 5dbd16dd0796cafecf54277107f44c72 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFG - Universidade Federal de Goiás (UFG) |
repository.mail.fl_str_mv |
tasesdissertacoes.bc@ufg.br |
_version_ |
1811721473581121536 |