Ductular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in rats
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.6/9024 |
Resumo: | Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is characterized by multistage formation. The presence of ductular reaction, cytokeratin 7 positivity (PCK7), and increased levels of gamma glutamyltransferase (γGT) has been observed during liver carcinogenesis and contribute to tumor progression. Our goal was to evaluate the ductular reaction in multistage carcinogenesis and to correlate PCK7 and γGT levels with tumor incidence, histological characteristics, liver DNA damage index, and the expression of oxidative stress proteins. HCC was induced in 24 male Wistar rats weighing 145-150 g by chronic and intermittent exposure to 50 or 100 mg/kg diethylnitrosamine (DEN). Six control animals received only vehicle. Blood was collected to determine hepatic enzyme levels. Animals were divided into three groups: control (CO), precancerous lesions (PL), and advanced HCC. Liver samples were obtained for immunohistochemical analyses and the measurement of protein expression. Statistical analyses included Tukey's test and Pearson's correlation analyses. We observed an extensive ductular reaction in advanced HCC and a strong correlation between PCK7 and levels of γGT and the poor prognosis and aggressiveness of HCC. The extent of PCK7 and high γGT levels were associated with overexpression of inducible nitric oxide synthase (iNOS) and heat shock factor protein 1 (HSF-1). However, PCK7 and γGT levels were negatively correlated with protein expression of nuclear factor erythroid 2-related factor 2 (NRF2) and inducible heat shock protein 70 (iHSP70). These findings suggest that ductular reaction is involved in the progression of multistage hepatocarcinogenesis. |
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Ductular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in ratsAnimalsBlotting - WesternCarcinogenesisCarcinoma - HepatocellularComet AssayKeratin-7LiverLiver Neoplasms - ExperimentalMaleNeoplasm ProteinsNeoplasm StagingRats - WistarGamma-GlutamyltransferaseHepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is characterized by multistage formation. The presence of ductular reaction, cytokeratin 7 positivity (PCK7), and increased levels of gamma glutamyltransferase (γGT) has been observed during liver carcinogenesis and contribute to tumor progression. Our goal was to evaluate the ductular reaction in multistage carcinogenesis and to correlate PCK7 and γGT levels with tumor incidence, histological characteristics, liver DNA damage index, and the expression of oxidative stress proteins. HCC was induced in 24 male Wistar rats weighing 145-150 g by chronic and intermittent exposure to 50 or 100 mg/kg diethylnitrosamine (DEN). Six control animals received only vehicle. Blood was collected to determine hepatic enzyme levels. Animals were divided into three groups: control (CO), precancerous lesions (PL), and advanced HCC. Liver samples were obtained for immunohistochemical analyses and the measurement of protein expression. Statistical analyses included Tukey's test and Pearson's correlation analyses. We observed an extensive ductular reaction in advanced HCC and a strong correlation between PCK7 and levels of γGT and the poor prognosis and aggressiveness of HCC. The extent of PCK7 and high γGT levels were associated with overexpression of inducible nitric oxide synthase (iNOS) and heat shock factor protein 1 (HSF-1). However, PCK7 and γGT levels were negatively correlated with protein expression of nuclear factor erythroid 2-related factor 2 (NRF2) and inducible heat shock protein 70 (iHSP70). These findings suggest that ductular reaction is involved in the progression of multistage hepatocarcinogenesis.uBibliorumMoreira, Andrea JanzRodrigues, Graziella RamosBona, SilviaFratta, Leila Xavier SinigagliaWeber, Giovana ReginaPicada, Jaqueline NascimentoSantos, Jorge Luiz dosCerski, Carlos ThadeuMarroni, Claudio AugustoMarroni, Norma Possa2020-02-05T12:18:12Z20162016-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.6/9024eng10.1007/s00709-016-1000-0info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-12-15T09:49:37Zoai:ubibliorum.ubi.pt:10400.6/9024Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:49:16.900172Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Ductular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in rats |
title |
Ductular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in rats |
spellingShingle |
Ductular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in rats Moreira, Andrea Janz Animals Blotting - Western Carcinogenesis Carcinoma - Hepatocellular Comet Assay Keratin-7 Liver Liver Neoplasms - Experimental Male Neoplasm Proteins Neoplasm Staging Rats - Wistar Gamma-Glutamyltransferase |
title_short |
Ductular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in rats |
title_full |
Ductular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in rats |
title_fullStr |
Ductular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in rats |
title_full_unstemmed |
Ductular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in rats |
title_sort |
Ductular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in rats |
author |
Moreira, Andrea Janz |
author_facet |
Moreira, Andrea Janz Rodrigues, Graziella Ramos Bona, Silvia Fratta, Leila Xavier Sinigaglia Weber, Giovana Regina Picada, Jaqueline Nascimento Santos, Jorge Luiz dos Cerski, Carlos Thadeu Marroni, Claudio Augusto Marroni, Norma Possa |
author_role |
author |
author2 |
Rodrigues, Graziella Ramos Bona, Silvia Fratta, Leila Xavier Sinigaglia Weber, Giovana Regina Picada, Jaqueline Nascimento Santos, Jorge Luiz dos Cerski, Carlos Thadeu Marroni, Claudio Augusto Marroni, Norma Possa |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
uBibliorum |
dc.contributor.author.fl_str_mv |
Moreira, Andrea Janz Rodrigues, Graziella Ramos Bona, Silvia Fratta, Leila Xavier Sinigaglia Weber, Giovana Regina Picada, Jaqueline Nascimento Santos, Jorge Luiz dos Cerski, Carlos Thadeu Marroni, Claudio Augusto Marroni, Norma Possa |
dc.subject.por.fl_str_mv |
Animals Blotting - Western Carcinogenesis Carcinoma - Hepatocellular Comet Assay Keratin-7 Liver Liver Neoplasms - Experimental Male Neoplasm Proteins Neoplasm Staging Rats - Wistar Gamma-Glutamyltransferase |
topic |
Animals Blotting - Western Carcinogenesis Carcinoma - Hepatocellular Comet Assay Keratin-7 Liver Liver Neoplasms - Experimental Male Neoplasm Proteins Neoplasm Staging Rats - Wistar Gamma-Glutamyltransferase |
description |
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is characterized by multistage formation. The presence of ductular reaction, cytokeratin 7 positivity (PCK7), and increased levels of gamma glutamyltransferase (γGT) has been observed during liver carcinogenesis and contribute to tumor progression. Our goal was to evaluate the ductular reaction in multistage carcinogenesis and to correlate PCK7 and γGT levels with tumor incidence, histological characteristics, liver DNA damage index, and the expression of oxidative stress proteins. HCC was induced in 24 male Wistar rats weighing 145-150 g by chronic and intermittent exposure to 50 or 100 mg/kg diethylnitrosamine (DEN). Six control animals received only vehicle. Blood was collected to determine hepatic enzyme levels. Animals were divided into three groups: control (CO), precancerous lesions (PL), and advanced HCC. Liver samples were obtained for immunohistochemical analyses and the measurement of protein expression. Statistical analyses included Tukey's test and Pearson's correlation analyses. We observed an extensive ductular reaction in advanced HCC and a strong correlation between PCK7 and levels of γGT and the poor prognosis and aggressiveness of HCC. The extent of PCK7 and high γGT levels were associated with overexpression of inducible nitric oxide synthase (iNOS) and heat shock factor protein 1 (HSF-1). However, PCK7 and γGT levels were negatively correlated with protein expression of nuclear factor erythroid 2-related factor 2 (NRF2) and inducible heat shock protein 70 (iHSP70). These findings suggest that ductular reaction is involved in the progression of multistage hepatocarcinogenesis. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016 2016-01-01T00:00:00Z 2020-02-05T12:18:12Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.6/9024 |
url |
http://hdl.handle.net/10400.6/9024 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1007/s00709-016-1000-0 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799136385271070720 |