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Ductular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in rats

2016Journal article Open access
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dc.contributor.authorMoreira, Andrea Janz
dc.contributor.authorRodrigues, Graziella Ramos
dc.contributor.authorBona, Silvia
dc.contributor.authorFratta, Leila Xavier Sinigaglia
dc.contributor.authorWeber, Giovana Regina
dc.contributor.authorPicada, Jaqueline Nascimento
dc.contributor.authorSantos, Jorge Luiz dos
dc.contributor.authorCerski, Carlos Thadeu
dc.contributor.authorMarroni, Claudio Augusto
dc.contributor.authorMarroni, Norma Possa
dc.date.accessioned2020-02-05T12:18:12Z
dc.date.available2020-02-05T12:18:12Z
dc.date.issued2016
dc.description.abstractHepatocellular 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1007/s00709-016-1000-0pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/9024
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectAnimalspt_PT
dc.subjectBlotting - Westernpt_PT
dc.subjectCarcinogenesispt_PT
dc.subjectCarcinoma - Hepatocellularpt_PT
dc.subjectComet Assaypt_PT
dc.subjectKeratin-7pt_PT
dc.subjectLiverpt_PT
dc.subjectLiver Neoplasms - Experimentalpt_PT
dc.subjectMalept_PT
dc.subjectNeoplasm Proteinspt_PT
dc.subjectNeoplasm Stagingpt_PT
dc.subjectRats - Wistarpt_PT
dc.subjectGamma-Glutamyltransferasept_PT
dc.titleDuctular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in ratspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage920pt_PT
oaire.citation.issue2pt_PT
oaire.citation.startPage911pt_PT
oaire.citation.titleProtoplasmapt_PT
oaire.citation.volume254pt_PT
person.familyNameMoreira
person.familyNamedos Santos
person.givenNameAndrea Janz
person.givenNameJorge Luiz
person.identifier.orcid0000-0001-6361-9693
person.identifier.orcid0000-0002-3839-0222
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationb400965f-7737-4a67-a57d-f84ef5d0c67c
relation.isAuthorOfPublicatione2e81f33-a7b7-448c-a479-81afd7ca3378
relation.isAuthorOfPublication.latestForDiscoveryb400965f-7737-4a67-a57d-f84ef5d0c67c

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