Alterações em genes relacionados à via glicolítica em tumores de carcinoma epidermoide de esôfago
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UERJ |
Texto Completo: | http://www.bdtd.uerj.br/handle/1/16256 |
Resumo: | The esophageal squamous cell carcinoma (ESCC) represents 90% of cases of esophageal cancer in Brazil. The ESCC has late diagnosis, highly aggressive behavior and poor survival. ESCC is an interesting target to the study of mechanism involved in its carcinogenesis, in order to identify potential drug targets or biomarkers to help clinical practice. Changes in tumor cell energy metabolism appear to have a prominent role in malignant transformation. Tumor cells consume glucose avidly and produce lactic acid, even under normoxia. Among the factors that may contribute to the stimulation of glycolysis in tumor cells, there are changes in the glycolytic pathway enzymes such as: pyruvate kinase M1 and M2 (PKM2 and PKM1), hexokinase II (HKII), glucose transporter isoform 1, GLUT-1, and transcription factor induced by hypoxia (HIF1α), responsible for the transcription of proteins cited. The goal of the study is to evaluate the relationship between the expression of HIF1α, HK2, PKM2, PKM1 and GLUT-1 and clinicopathological data in ESCC. Biopsy of the esophagus in patients without esophageal disease were collected, who underwent endoscopy at University Hospital Pedro Ernesto (HUPE). Tissue samples were collected from 44 patients with a histologically confirmed diagnosis of ESCC recruted from Hospital Universitário Pedro Ernesto (HUPE-UERJ), and Instituto Nacional de Câncer (INCA). Tissue samples from healthy individuals submitted to endoscopic routine examination, not related to cancer or esophageal disorders, at HUPE-UERJ were also included in this study. The expression of proteins in tissues was evaluated by immunohistochemistry, while mRNA expression of GLUT-1 was also evaluated in the control samples. It was observed that the control samples express HK2, PKM1, PKM2, HIF1α layers of the esophageal epithelium. GLUT-1 and Ki-67 are seen only in the basal layer. Furthermore, expression of GLUT-1 mRNA did not correlate with disease etiological factors. In ESCC expression of HK2, PKM2 and GLUT-1 was seen in all tumors, and the expression of HIF1α and PKM1 was variable. We found that increased expression of HIF-1α correlates with lymph node invasion and differentiation, whereas the expression of HK2 is related to survival, and differentiation with PKM1. The clinical correlations found suggest that alterations in energy metabolism are an interesting subject of study for development of biomarkers that help clinical practice. |
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Albano, Rodolpho Mattoshttp://lattes.cnpq.br/1268859650338952Pinto, Luis Felipe Ribeirohttp://lattes.cnpq.br/0774809439237135Teixeira, Ana Maria Rossinihttp://lattes.cnpq.br/0370020634398898Viola, João Paulo de Biasohttp://lattes.cnpq.br/7032301842334963http://lattes.cnpq.br/9174662235152595Barreto, Ester de Andrade2021-04-26T01:15:34Z2013-10-182013-03-07BARRETO, Ester de Andrade. Alterações em genes relacionados à via glicolítica em tumores de carcinoma epidermoide de esôfago. 2013. 140 f. Dissertação (Mestrado em Biociências Nucleares; Ecologia) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2013.http://www.bdtd.uerj.br/handle/1/16256The esophageal squamous cell carcinoma (ESCC) represents 90% of cases of esophageal cancer in Brazil. The ESCC has late diagnosis, highly aggressive behavior and poor survival. ESCC is an interesting target to the study of mechanism involved in its carcinogenesis, in order to identify potential drug targets or biomarkers to help clinical practice. Changes in tumor cell energy metabolism appear to have a prominent role in malignant transformation. Tumor cells consume glucose avidly and produce lactic acid, even under normoxia. Among the factors that may contribute to the stimulation of glycolysis in tumor cells, there are changes in the glycolytic pathway enzymes such as: pyruvate kinase M1 and M2 (PKM2 and PKM1), hexokinase II (HKII), glucose transporter isoform 1, GLUT-1, and transcription factor induced by hypoxia (HIF1α), responsible for the transcription of proteins cited. The goal of the study is to evaluate the relationship between the expression of HIF1α, HK2, PKM2, PKM1 and GLUT-1 and clinicopathological data in ESCC. Biopsy of the esophagus in patients without esophageal disease were collected, who underwent endoscopy at University Hospital Pedro Ernesto (HUPE). Tissue samples were collected from 44 patients with a histologically confirmed diagnosis of ESCC recruted from Hospital Universitário Pedro Ernesto (HUPE-UERJ), and Instituto Nacional de Câncer (INCA). Tissue samples from healthy individuals submitted to endoscopic routine examination, not related to cancer or esophageal disorders, at HUPE-UERJ were also included in this study. The expression of proteins in tissues was evaluated by immunohistochemistry, while mRNA expression of GLUT-1 was also evaluated in the control samples. It was observed that the control samples express HK2, PKM1, PKM2, HIF1α layers of the esophageal epithelium. GLUT-1 and Ki-67 are seen only in the basal layer. Furthermore, expression of GLUT-1 mRNA did not correlate with disease etiological factors. In ESCC expression of HK2, PKM2 and GLUT-1 was seen in all tumors, and the expression of HIF1α and PKM1 was variable. We found that increased expression of HIF-1α correlates with lymph node invasion and differentiation, whereas the expression of HK2 is related to survival, and differentiation with PKM1. The clinical correlations found suggest that alterations in energy metabolism are an interesting subject of study for development of biomarkers that help clinical practice.O carcinoma epidermoide de esôfago (CEE) representa 90% dos casos de câncer de esôfago no Brasil. O CEE tem detecção tardia, um comportamento extremamente agressivo e baixa sobrevida, sendo, portanto, um alvo interessante para o estudo dos mecanismos envolvidos em sua carcinogênese, a fim de se identificar possíveis alvos terapêuticos ou marcadores moleculares que ajudem na prática clínica. Mudanças no metabolismo energético da célula tumoral parecem ter papel de destaque na transformação maligna. Sabe-se que células tumorais consomem glicose avidamente produzindo ácido lático, mesmo em condições de normóxia. Dentre os fatores que podem contribuir para o estímulo da glicólise em células tumorais destacam-se as alterações em enzimas da via glicolítica tais como: as piruvato-cinases M1 e M2 (PKM1 e PKM2), a hexocinase II (HKII), isofoma 1 do transportador de glicose, GLUT-1, e o fator de transcrição induzido por hipóxia (HIF1α), responsável pela transcrição das proteínas citadas. O objetivo do estudo é avaliar a relação entre a expressão de HIF1α, HK2, PKM2, PKM1 e GLUT-1 e dados clínico-patológicos no CEE. Para tal, foram avaliados tumores conservados em parafina de 44 pacientes com CEE matriculados no INCA e no Hospital das Clínicas de Porto Alegre. Além disso, foram coletadas amostras de biópsia de esôfago em 67 pacientes sem doença esofágica, que foram submetidos à endoscopia no Hospital Universitário Pedro Ernesto (HUPE). A expressão das proteínas foi avaliada nos tecidos por imuno-histoquímica, enquanto que a expressão do mRNA de GLUT-1 também foi avaliada nas amostras controle. Foi observado que as amostras controle expressam HK2, PKM1, PKM2, HIF1α nas camadas do epitélio esofágico. Já GLUT-1 e Ki-67 são vistos apenas na camada basal. Além disso, a expressão do mRNA de GLUT-1 não teve correlação com fatores etiológicos da doença. Em CEE a expressão de HK2, PKM2 e GLUT-1 foi vista em todos os tumores, já a expressão de HIF1α e PKM1 foi variável. Além disso, observou-se que maior expressão de HIF-1α apresenta correlação com invasão linfonodal e diferenciação, enquanto que a expressão de HK2 tem relação com sobrevida e PKM1 com diferenciação. As correlações clínicas encontradas sugerem que alterações no metabolismo energético é um alvo de estudo interessante para desenvolvimento de marcadores moleculares que auxiliem a prática clínica.Submitted by Boris INFORMAT (boris@uerj.br) on 2021-04-26T01:15:34Z No. of bitstreams: 1 DISSERTACAO_FINAL_Ester_de_Andrade_Barreto.pdf: 2787267 bytes, checksum: 14693f5574e6d46af7f6d274fc355270 (MD5)Made available in DSpace on 2021-04-26T01:15:34Z (GMT). No. of bitstreams: 1 DISSERTACAO_FINAL_Ester_de_Andrade_Barreto.pdf: 2787267 bytes, checksum: 14693f5574e6d46af7f6d274fc355270 (MD5) Previous issue date: 2013-03-07Conselho Nacional de Desenvolvimento Científico e Tecnológicoapplication/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em BiociênciasUERJBRCentro Biomédico::Instituto de Biologia Roberto Alcantara GomesWarburg effectEsophageal squamous cell carcinomaGLUT-1Pyruvate kinasesHexokinaseHIF-1αEfeito WarburgCarcinoma epidermoide de esôfagoGLUT-1Piruvato cinasesHexocinaseHIF-1αCarcinoma de células escamosasEsôfago CâncerCarcinogenesePiruvato QuinaseCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA::METABOLISMO E BIOENERGETICAAlterações em genes relacionados à via glicolítica em tumores de carcinoma epidermoide de esôfagoAlterations in genes involved in glycolysis in esophageal squamous cell carcinomainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALDISSERTACAO_FINAL_Ester_de_Andrade_Barreto.pdfapplication/pdf2787267http://www.bdtd.uerj.br/bitstream/1/16256/1/DISSERTACAO_FINAL_Ester_de_Andrade_Barreto.pdf14693f5574e6d46af7f6d274fc355270MD511/162562024-02-26 11:39:28.922oai:www.bdtd.uerj.br:1/16256Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032024-02-26T14:39:28Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false |
dc.title.por.fl_str_mv |
Alterações em genes relacionados à via glicolítica em tumores de carcinoma epidermoide de esôfago |
dc.title.alternative.eng.fl_str_mv |
Alterations in genes involved in glycolysis in esophageal squamous cell carcinoma |
title |
Alterações em genes relacionados à via glicolítica em tumores de carcinoma epidermoide de esôfago |
spellingShingle |
Alterações em genes relacionados à via glicolítica em tumores de carcinoma epidermoide de esôfago Barreto, Ester de Andrade Warburg effect Esophageal squamous cell carcinoma GLUT-1 Pyruvate kinases Hexokinase HIF-1α Efeito Warburg Carcinoma epidermoide de esôfago GLUT-1 Piruvato cinases Hexocinase HIF-1α Carcinoma de células escamosas Esôfago Câncer Carcinogenese Piruvato Quinase CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA::METABOLISMO E BIOENERGETICA |
title_short |
Alterações em genes relacionados à via glicolítica em tumores de carcinoma epidermoide de esôfago |
title_full |
Alterações em genes relacionados à via glicolítica em tumores de carcinoma epidermoide de esôfago |
title_fullStr |
Alterações em genes relacionados à via glicolítica em tumores de carcinoma epidermoide de esôfago |
title_full_unstemmed |
Alterações em genes relacionados à via glicolítica em tumores de carcinoma epidermoide de esôfago |
title_sort |
Alterações em genes relacionados à via glicolítica em tumores de carcinoma epidermoide de esôfago |
author |
Barreto, Ester de Andrade |
author_facet |
Barreto, Ester de Andrade |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Albano, Rodolpho Mattos |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/1268859650338952 |
dc.contributor.advisor-co1.fl_str_mv |
Pinto, Luis Felipe Ribeiro |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/0774809439237135 |
dc.contributor.referee1.fl_str_mv |
Teixeira, Ana Maria Rossini |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/0370020634398898 |
dc.contributor.referee2.fl_str_mv |
Viola, João Paulo de Biaso |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/7032301842334963 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/9174662235152595 |
dc.contributor.author.fl_str_mv |
Barreto, Ester de Andrade |
contributor_str_mv |
Albano, Rodolpho Mattos Pinto, Luis Felipe Ribeiro Teixeira, Ana Maria Rossini Viola, João Paulo de Biaso |
dc.subject.eng.fl_str_mv |
Warburg effect Esophageal squamous cell carcinoma GLUT-1 Pyruvate kinases Hexokinase HIF-1α |
topic |
Warburg effect Esophageal squamous cell carcinoma GLUT-1 Pyruvate kinases Hexokinase HIF-1α Efeito Warburg Carcinoma epidermoide de esôfago GLUT-1 Piruvato cinases Hexocinase HIF-1α Carcinoma de células escamosas Esôfago Câncer Carcinogenese Piruvato Quinase CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA::METABOLISMO E BIOENERGETICA |
dc.subject.por.fl_str_mv |
Efeito Warburg Carcinoma epidermoide de esôfago GLUT-1 Piruvato cinases Hexocinase HIF-1α Carcinoma de células escamosas Esôfago Câncer Carcinogenese Piruvato Quinase |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA::METABOLISMO E BIOENERGETICA |
description |
The esophageal squamous cell carcinoma (ESCC) represents 90% of cases of esophageal cancer in Brazil. The ESCC has late diagnosis, highly aggressive behavior and poor survival. ESCC is an interesting target to the study of mechanism involved in its carcinogenesis, in order to identify potential drug targets or biomarkers to help clinical practice. Changes in tumor cell energy metabolism appear to have a prominent role in malignant transformation. Tumor cells consume glucose avidly and produce lactic acid, even under normoxia. Among the factors that may contribute to the stimulation of glycolysis in tumor cells, there are changes in the glycolytic pathway enzymes such as: pyruvate kinase M1 and M2 (PKM2 and PKM1), hexokinase II (HKII), glucose transporter isoform 1, GLUT-1, and transcription factor induced by hypoxia (HIF1α), responsible for the transcription of proteins cited. The goal of the study is to evaluate the relationship between the expression of HIF1α, HK2, PKM2, PKM1 and GLUT-1 and clinicopathological data in ESCC. Biopsy of the esophagus in patients without esophageal disease were collected, who underwent endoscopy at University Hospital Pedro Ernesto (HUPE). Tissue samples were collected from 44 patients with a histologically confirmed diagnosis of ESCC recruted from Hospital Universitário Pedro Ernesto (HUPE-UERJ), and Instituto Nacional de Câncer (INCA). Tissue samples from healthy individuals submitted to endoscopic routine examination, not related to cancer or esophageal disorders, at HUPE-UERJ were also included in this study. The expression of proteins in tissues was evaluated by immunohistochemistry, while mRNA expression of GLUT-1 was also evaluated in the control samples. It was observed that the control samples express HK2, PKM1, PKM2, HIF1α layers of the esophageal epithelium. GLUT-1 and Ki-67 are seen only in the basal layer. Furthermore, expression of GLUT-1 mRNA did not correlate with disease etiological factors. In ESCC expression of HK2, PKM2 and GLUT-1 was seen in all tumors, and the expression of HIF1α and PKM1 was variable. We found that increased expression of HIF-1α correlates with lymph node invasion and differentiation, whereas the expression of HK2 is related to survival, and differentiation with PKM1. The clinical correlations found suggest that alterations in energy metabolism are an interesting subject of study for development of biomarkers that help clinical practice. |
publishDate |
2013 |
dc.date.available.fl_str_mv |
2013-10-18 |
dc.date.issued.fl_str_mv |
2013-03-07 |
dc.date.accessioned.fl_str_mv |
2021-04-26T01:15:34Z |
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 |
BARRETO, Ester de Andrade. Alterações em genes relacionados à via glicolítica em tumores de carcinoma epidermoide de esôfago. 2013. 140 f. Dissertação (Mestrado em Biociências Nucleares; Ecologia) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2013. |
dc.identifier.uri.fl_str_mv |
http://www.bdtd.uerj.br/handle/1/16256 |
identifier_str_mv |
BARRETO, Ester de Andrade. Alterações em genes relacionados à via glicolítica em tumores de carcinoma epidermoide de esôfago. 2013. 140 f. Dissertação (Mestrado em Biociências Nucleares; Ecologia) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2013. |
url |
http://www.bdtd.uerj.br/handle/1/16256 |
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por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Universidade do Estado do Rio de Janeiro |
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Programa de Pós-Graduação em Biociências |
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UERJ |
dc.publisher.country.fl_str_mv |
BR |
dc.publisher.department.fl_str_mv |
Centro Biomédico::Instituto de Biologia Roberto Alcantara Gomes |
publisher.none.fl_str_mv |
Universidade do Estado do Rio de Janeiro |
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reponame:Biblioteca Digital de Teses e Dissertações da UERJ instname:Universidade do Estado do Rio de Janeiro (UERJ) instacron:UERJ |
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Biblioteca Digital de Teses e Dissertações da UERJ |
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Biblioteca Digital de Teses e Dissertações da UERJ |
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Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ) |
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