Fibrosis-associated hepatocarcinogenesis revisited: Establishing standard medium-term chemically-induced male and female models
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1371/journal.pone.0203879 http://hdl.handle.net/11449/176837 |
Resumo: | Hepatocellular carcinoma causes ~10% of all cancer-related deaths worldwide, usually emerging in a background of liver fibrosis/cirrhosis (70%-90% of cases). Chemically-induced mouse models for fibrosis-associated hepatocarcinogenesis are widely-applied, resembling the corresponding human disease. Nonetheless, a long time is necessary for the development of preneoplastic/neoplastic lesions. Thus, we proposed an early fibrosis-associated hepatocarcinogenesis model for male and female mice separately, focusing on reducing the experimental time for preneoplastic/neoplastic lesions development and establishing standard models for both sexes. Then, two-week old susceptible C3H/HeJ male and female mice (n = 8 animals/sex/group) received a single dose of diethylnitrosamine (DEN, 10 or 50 mg/Kg). During 2 months, mice received 3 weekly doses of carbon tetrachloride (CCl4, 10% corn oil solution, 0.25 to 1.50 μL/g b.wt.) and they were euthanized at week 17. DEN/CCl4 protocols for males and females displayed clear liver fibrosis, featuring collagen accumulation and hepatic stellate cell activation (α-SMA). In addition, liver from males displayed increased CD68+ macrophage number, COX-2 protein expression and IL-6 levels. The DEN/CCl4 models in both sexes impaired antioxidant defense as well as enhanced hepatocyte proliferation and apoptosis. Moreover, DEN/CCl4-treated male and female developed multiple preneoplastic altered hepatocyte foci and hepatocellular adenomas. As expected, the models showed clear male bias. Therefore, we established standard and suitable fibrosis-associated hepatocarcinogenesis models for male and female mice, shortening the experimental time for the development of hepatocellular preneoplastic/neoplastic lesions in comparison to other classical models. |
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Fibrosis-associated hepatocarcinogenesis revisited: Establishing standard medium-term chemically-induced male and female modelsHepatocellular carcinoma causes ~10% of all cancer-related deaths worldwide, usually emerging in a background of liver fibrosis/cirrhosis (70%-90% of cases). Chemically-induced mouse models for fibrosis-associated hepatocarcinogenesis are widely-applied, resembling the corresponding human disease. Nonetheless, a long time is necessary for the development of preneoplastic/neoplastic lesions. Thus, we proposed an early fibrosis-associated hepatocarcinogenesis model for male and female mice separately, focusing on reducing the experimental time for preneoplastic/neoplastic lesions development and establishing standard models for both sexes. Then, two-week old susceptible C3H/HeJ male and female mice (n = 8 animals/sex/group) received a single dose of diethylnitrosamine (DEN, 10 or 50 mg/Kg). During 2 months, mice received 3 weekly doses of carbon tetrachloride (CCl4, 10% corn oil solution, 0.25 to 1.50 μL/g b.wt.) and they were euthanized at week 17. DEN/CCl4 protocols for males and females displayed clear liver fibrosis, featuring collagen accumulation and hepatic stellate cell activation (α-SMA). In addition, liver from males displayed increased CD68+ macrophage number, COX-2 protein expression and IL-6 levels. The DEN/CCl4 models in both sexes impaired antioxidant defense as well as enhanced hepatocyte proliferation and apoptosis. Moreover, DEN/CCl4-treated male and female developed multiple preneoplastic altered hepatocyte foci and hepatocellular adenomas. As expected, the models showed clear male bias. Therefore, we established standard and suitable fibrosis-associated hepatocarcinogenesis models for male and female mice, shortening the experimental time for the development of hepatocellular preneoplastic/neoplastic lesions in comparison to other classical models.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Pathology Botucatu Medical School São Paulo State University (UNESP)Department of Morphology Biosciences Institute São Paulo State University (UNESP)Department of Pathology School of Veterinary Medicine and Animal Science University of São Paulo (USP)Department of Chemistry and Biochemistry Biosciences Institute São Paulo State University (UNESP)Department of Food and Experimental Nutrition Faculty of Pharmaceutical Sciences University of São Paulo (USP)Department of Pathology Botucatu Medical School São Paulo State University (UNESP)Department of Morphology Biosciences Institute São Paulo State University (UNESP)Department of Chemistry and Biochemistry Biosciences Institute São Paulo State University (UNESP)CNPq: #140251/2016-2FAPESP: #2016/ 12015-0FAPESP: #2016/14420-0Universidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Romualdo, Guilherme Ribeiro [UNESP]Prata, Gabriel Bacil [UNESP]da Silva, Tereza CristinaFernandes, Ana Angélica Henrique [UNESP]Moreno, Fernando SalvadorCogliati, BrunoBarbisan, Luís Fernando [UNESP]2018-12-11T17:22:42Z2018-12-11T17:22:42Z2018-09-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1371/journal.pone.0203879PLoS ONE, v. 13, n. 9, 2018.1932-6203http://hdl.handle.net/11449/17683710.1371/journal.pone.02038792-s2.0-850532398742-s2.0-85053239874.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPLoS ONE1,164info:eu-repo/semantics/openAccess2024-09-03T13:14:53Zoai:repositorio.unesp.br:11449/176837Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T13:14:53Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Fibrosis-associated hepatocarcinogenesis revisited: Establishing standard medium-term chemically-induced male and female models |
title |
Fibrosis-associated hepatocarcinogenesis revisited: Establishing standard medium-term chemically-induced male and female models |
spellingShingle |
Fibrosis-associated hepatocarcinogenesis revisited: Establishing standard medium-term chemically-induced male and female models Romualdo, Guilherme Ribeiro [UNESP] |
title_short |
Fibrosis-associated hepatocarcinogenesis revisited: Establishing standard medium-term chemically-induced male and female models |
title_full |
Fibrosis-associated hepatocarcinogenesis revisited: Establishing standard medium-term chemically-induced male and female models |
title_fullStr |
Fibrosis-associated hepatocarcinogenesis revisited: Establishing standard medium-term chemically-induced male and female models |
title_full_unstemmed |
Fibrosis-associated hepatocarcinogenesis revisited: Establishing standard medium-term chemically-induced male and female models |
title_sort |
Fibrosis-associated hepatocarcinogenesis revisited: Establishing standard medium-term chemically-induced male and female models |
author |
Romualdo, Guilherme Ribeiro [UNESP] |
author_facet |
Romualdo, Guilherme Ribeiro [UNESP] Prata, Gabriel Bacil [UNESP] da Silva, Tereza Cristina Fernandes, Ana Angélica Henrique [UNESP] Moreno, Fernando Salvador Cogliati, Bruno Barbisan, Luís Fernando [UNESP] |
author_role |
author |
author2 |
Prata, Gabriel Bacil [UNESP] da Silva, Tereza Cristina Fernandes, Ana Angélica Henrique [UNESP] Moreno, Fernando Salvador Cogliati, Bruno Barbisan, Luís Fernando [UNESP] |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Romualdo, Guilherme Ribeiro [UNESP] Prata, Gabriel Bacil [UNESP] da Silva, Tereza Cristina Fernandes, Ana Angélica Henrique [UNESP] Moreno, Fernando Salvador Cogliati, Bruno Barbisan, Luís Fernando [UNESP] |
description |
Hepatocellular carcinoma causes ~10% of all cancer-related deaths worldwide, usually emerging in a background of liver fibrosis/cirrhosis (70%-90% of cases). Chemically-induced mouse models for fibrosis-associated hepatocarcinogenesis are widely-applied, resembling the corresponding human disease. Nonetheless, a long time is necessary for the development of preneoplastic/neoplastic lesions. Thus, we proposed an early fibrosis-associated hepatocarcinogenesis model for male and female mice separately, focusing on reducing the experimental time for preneoplastic/neoplastic lesions development and establishing standard models for both sexes. Then, two-week old susceptible C3H/HeJ male and female mice (n = 8 animals/sex/group) received a single dose of diethylnitrosamine (DEN, 10 or 50 mg/Kg). During 2 months, mice received 3 weekly doses of carbon tetrachloride (CCl4, 10% corn oil solution, 0.25 to 1.50 μL/g b.wt.) and they were euthanized at week 17. DEN/CCl4 protocols for males and females displayed clear liver fibrosis, featuring collagen accumulation and hepatic stellate cell activation (α-SMA). In addition, liver from males displayed increased CD68+ macrophage number, COX-2 protein expression and IL-6 levels. The DEN/CCl4 models in both sexes impaired antioxidant defense as well as enhanced hepatocyte proliferation and apoptosis. Moreover, DEN/CCl4-treated male and female developed multiple preneoplastic altered hepatocyte foci and hepatocellular adenomas. As expected, the models showed clear male bias. Therefore, we established standard and suitable fibrosis-associated hepatocarcinogenesis models for male and female mice, shortening the experimental time for the development of hepatocellular preneoplastic/neoplastic lesions in comparison to other classical models. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12-11T17:22:42Z 2018-12-11T17:22:42Z 2018-09-01 |
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://dx.doi.org/10.1371/journal.pone.0203879 PLoS ONE, v. 13, n. 9, 2018. 1932-6203 http://hdl.handle.net/11449/176837 10.1371/journal.pone.0203879 2-s2.0-85053239874 2-s2.0-85053239874.pdf |
url |
http://dx.doi.org/10.1371/journal.pone.0203879 http://hdl.handle.net/11449/176837 |
identifier_str_mv |
PLoS ONE, v. 13, n. 9, 2018. 1932-6203 10.1371/journal.pone.0203879 2-s2.0-85053239874 2-s2.0-85053239874.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
PLoS ONE 1,164 |
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 |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
repositoriounesp@unesp.br |
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1810021376284688384 |