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https://observatorio.fm.usp.br/handle/OPI/57413
Title: | P53 and VEGF are promising biomarkers for sorafenib efficacy in an experimental model of NASH-related HCC |
Authors: | NASSAR-REIS, Joao Pedro; UMETA, Pedro Fukui; STEFANO, Jose Tadeu; LONGATTO-FILHO, Adhemar; CARRILHO, Flair Jose; ALVES, Venancio Avancini Ferreira; COGLIATI, Bruno; OLIVEIRA, Claudia P. |
Citation: | JOURNAL OF MOLECULAR HISTOLOGY, v.54, n.5, p.473-488, 2023 |
Abstract: | The efficacy of systemic therapy for hepatocellular carcinoma (HCC) related to non-alcoholic steatohepatitis (NASH) is poorly understood. In this study we evaluated the effects of sorafenib based on the expression of molecular markers related to major hepatocarcinogenesis pathways and angiogenesis in a NASH-related HCC model. Forty male rats were submitted to NASH-HCC induction through the combination of a high-fat and choline deficient diet and diethylnitrosamine (100 mg/L) administration in the drinking water for 13 and 16 weeks. After the induction period, the rats received daily gavage administration of saline solution (control) or Sorafenib (5 mg/kg/day) for 3 weeks. Thereafter, the animals were euthanized and samples from liver nodules were collected for histopathological analysis and immunohistochemical assessment of HEP-PAR-1, glutamine-synthetase, VEGF, survivin, & beta;-catenin and p53. A semi-quantitative score was used for VEGF, survivin and & beta;-catenin analysis. For p53, the percentage of positive cells was determined. Results were processed by Wilcoxon's test or Student's t-test. Both protocols efficiently induced HCC, most of them being moderately to poorly differentiated. Sorafenib-treated animals showed a decreased expression of VEGF and p53 in HCCs generated at 13 weeks when compared to control animals (p = 0.03; p = 0.04, respectively). No significant difference in & beta;-catenin and survivin were observed. There was a significant decrease in VEGF and p53 expression when comparing the two control groups (13 vs. 16 weeks, p < 0.01). p53 and VEGF are promising biomarkers for assessment of efficacy of Sorafenib, whereas survivin and & beta;-catenin were not found useful. Decreased immunohistochemical expression of p53 and VEGF in the 16 week control group may indicate a different metabolic status of HCC. |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - FM/MGT Artigos e Materiais de Revistas Científicas - FM/MPT Artigos e Materiais de Revistas Científicas - HC/ICHC Artigos e Materiais de Revistas Científicas - LIM/07 Artigos e Materiais de Revistas Científicas - LIM/14 Artigos e Materiais de Revistas Científicas - ODS/03 |
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