dc.contributor | Universidade Estadual Paulista (Unesp) | |
dc.contributor | Barretos Cancer Hospital | |
dc.contributor | Barretos School of Health Sciences | |
dc.contributor | Universidade de São Paulo (USP) | |
dc.date.accessioned | 2018-12-11T17:15:00Z | |
dc.date.available | 2018-12-11T17:15:00Z | |
dc.date.created | 2018-12-11T17:15:00Z | |
dc.date.issued | 2017-11-05 | |
dc.identifier | Toxicology Letters, v. 281, p. 84-94. | |
dc.identifier | 1879-3169 | |
dc.identifier | 0378-4274 | |
dc.identifier | http://hdl.handle.net/11449/175252 | |
dc.identifier | 10.1016/j.toxlet.2017.09.015 | |
dc.identifier | 2-s2.0-85029846477 | |
dc.identifier | 2-s2.0-85029846477.pdf | |
dc.description.abstract | This study aimed the integrative characterization of morphological, biochemical and molecular features of chemically-induced cirrhosis-associated hepatocarcinogenesis. Thus, male Wistar rats were submitted to a diethylnitrosamine (DEN)/thioacetamide (TAA)-induced model. Liver tissue was processed for global gene expression, histopathological and collagen evaluations; as well as immunohistochemical and oxidative stress analysis. Gene Ontology and functional analysis showed the upregulation of extracellular matrix deposition genes, such as collagen type I alpha 1 and 2 (Col1α1 and Col1α2) and tissue inhibitor of metalloproteinase 1 and 2 genes (Timp1 and Timp2). In agreement these findings, animals presented extensive liver cirrhosis with increased collagen deposition (Sirius red). Besides, the animals developed many glutathione S-transferase pi (GST-P)-positive preneoplastic lesions showing high cell proliferation (Ki-67), in keeping with the Gstp1 and Gstp2 increased gene expression. DEN/TAA-treated rats also showed the upregulation of tumorigenesis-related annexin A2 gene (Anxa2) and few neoplastic lesions (hepatocellular adenomas, carcinomas, and cholangiocarcinoma). In contrast, gene expression and activity of antioxidant enzymes were decreased (glutathione peroxidase, total glutathione-S-transferase, and catalase). The model featured remarkable similarities to human hepatocarcinogenesis. Our findings could bring up new molecular insights into cirrhosis-associated hepatocarcinogenesis, and provide a suitable animal model for the establishment of further diagnostic, preventive and therapeutic approaches. | |
dc.language | eng | |
dc.relation | Toxicology Letters | |
dc.relation | 1,103 | |
dc.rights | Acesso aberto | |
dc.source | Scopus | |
dc.subject | Diethylnitrosamine | |
dc.subject | Hepatocarcinogenesis | |
dc.subject | Liver cirrhosis | |
dc.subject | Oligo microarray | |
dc.subject | Thioacetamide | |
dc.subject | Wistar rats | |
dc.title | An integrative analysis of chemically-induced cirrhosis-associated hepatocarcinogenesis: Histological, biochemical and molecular features | |
dc.type | Artículos de revistas | |