P53 and VEGF are promising biomarkers for sorafenib efficacy in an experimental model of NASH-related HCC.

Autor: Nassar-Reis JP; Laboratory of Experimental and Comparative Liver Research (Liver Lab), Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, 05508-270, Brazil.; Laboratório de Gastroenterologia Clínica e Experimental (LIM-07), Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, 01246-903, Brazil., Umeta PF; Laboratório de Gastroenterologia Clínica e Experimental (LIM-07), Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, 01246-903, Brazil., Stefano JT; Laboratório de Gastroenterologia Clínica e Experimental (LIM-07), Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, 01246-903, Brazil., Longatto-Filho A; Department of Pathology (LIM-14), University of São Paulo School of Medicine, São Paulo, 05808-010, Brazil.; School of Medicine, Life and Health Sciences Research Institute (ICVS), University of Minho, 4704-553, Braga, Portugal.; ICVS/3B's-PT Government Associate Laboratory, 4710-057, Braga, Portugal.; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, 14784-400, Brazil., Carrilho FJ; Laboratório de Gastroenterologia Clínica e Experimental (LIM-07), Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, 01246-903, Brazil., Alves VAF; Department of Pathology (LIM-14), University of São Paulo School of Medicine, São Paulo, 05808-010, Brazil., Cogliati B; Laboratory of Experimental and Comparative Liver Research (Liver Lab), Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, 05508-270, Brazil., Oliveira CP; Laboratório de Gastroenterologia Clínica e Experimental (LIM-07), Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, 01246-903, Brazil. cpm@usp.br.
Jazyk: angličtina
Zdroj: Journal of molecular histology [J Mol Histol] 2023 Oct; Vol. 54 (5), pp. 473-488. Date of Electronic Publication: 2023 Aug 21.
DOI: 10.1007/s10735-023-10142-9
Abstrakt: 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, β-catenin and p53. A semi-quantitative score was used for VEGF, survivin and β-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 β-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 β-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.
(© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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