Role of SIRT-3, p-mTOR and HIF-1α in Hepatocellular Carcinoma Patients Affected by Metabolic Dysfunctions and in Chronic Treatment with Metformin
| العنوان: | Role of SIRT-3, p-mTOR and HIF-1α in Hepatocellular Carcinoma Patients Affected by Metabolic Dysfunctions and in Chronic Treatment with Metformin |
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| المؤلفون: | Francesco Giuseppe Foschi, Andrea Casadei-Gardini, Alessandro Cucchetti, Giorgia Marisi, Paola Cravero, Laura Gramantieri, Emanuela Scarpi, Giovanni Luca Frassineti, Anna Maria Granato, Erika Bandini, Giorgio Ercolani, Daniele Santini, Umberto Vespasiani-Gentilucci, Stefano Cascinu, Luca Faloppi, Giuliano La Barba, Serena De Matteis, Mario Scartozzi, Martina Ghetti |
| المساهمون: | De Matteis, Serena, Scarpi, Emanuela, Granato, Anna, Vespasiani-Gentilucci, Umberto, La Barba, Giuliano, Foschi, Francesco, Bandini, Erika, Ghetti, Martina, Marisi, Giorgia, Cravero, Paola, Gramantieri, Laura, Cucchetti, Alessandro, Ercolani, Giorgio, Santini, Daniele, Frassineti, Giovanni, Faloppi, Luca, Scartozzi, Mario, Cascinu, Stefano, Casadei-Gardini, Andrea, Granato, Anna Maria, Foschi, Francesco Giuseppe, Frassineti, Giovanni Luca |
| المصدر: | International Journal of Molecular Sciences Volume 20 Issue 6 International Journal of Molecular Sciences, Vol 20, Iss 6, p 1503 (2019) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Male, Drug resistance, lcsh:Chemistry, 0302 clinical medicine, Sirtuin 3, lcsh:QH301-705.5, Spectroscopy, Aged, 80 and over, biology, diabetes, TOR Serine-Threonine Kinases, Liver Neoplasms, General Medicine, Middle Aged, Computer Science Applications, Metformin, metformin, non-alcoholic steatohepatitis, Liver, Liver Neoplasm, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Sirtuin, Female, medicine.drug, Human, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Article, Catalysis, metabolic syndrome, Inorganic Chemistry, 03 medical and health sciences, Internal medicine, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Physical and Theoretical Chemistry, Molecular Biology, Aged, Hypoglycemic Agent, business.industry, Diabetes, Metabolic syndrome, Non-alcoholic steatohepatitis, Organic Chemistry, Cancer, medicine.disease, Hypoxia-Inducible Factor 1, alpha Subunit, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Diabetes Mellitus, Type 2, diabete, Etiology, biology.protein, business, non-alcoholic steatohepatiti |
| الوصف: | The incidence of hepatocellular carcinoma deriving from metabolic dysfunctions has increased in the last years. Sirtuin- (SIRT-3), phospho-mammalian target of rapamycin (p-mTOR) and hypoxia-inducible factor- (HIF-1&alpha ) are involved in metabolism and cancer. However, their role in hepatocellular carcinoma (HCC) metabolism, drug resistance and progression remains unclear. This study aimed to better clarify the biological and clinical function of these markers in HCC patients, in relation to the presence of metabolic alterations, metformin therapy and clinical outcome. A total of 70 HCC patients were enrolled: 48 and 22 of whom were in early stage and advanced stage, respectively. The expression levels of the three markers were assessed by immunohistochemistry and summarized using descriptive statistics. SIRT-3 expression was higher in diabetic than non-diabetic patients, and in metformin-treated than insulin-treated patients. Interestingly, p-mTOR was higher in patients with metabolic syndrome than those with different etiology, and, similar to SIRT-3, in metformin-treated than insulin-treated patients. Moreover, our results describe a slight, albeit not significant, benefit of high SIRT-3 and a significant benefit of high nuclear HIF-1&alpha expression in early-stage patients, whereas high levels of p-mTOR correlated with worse prognosis in advanced-stage patients. Our study highlighted the involvement of SIRT-3 and p-mTOR in metabolic dysfunctions that occur in HCC patients, and suggested SIRT-3 and HIF-1&alpha as predictors of prognosis in early-stage HCC patients, and p-mTOR as target for the treatment of advanced-stage HCC. |
| وصف الملف: | application/pdf; ELETTRONICO |
| اللغة: | English |
| تدمد: | 1422-0067 |
| DOI: | 10.3390/ijms20061503 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24373c28ef0e8c6a42072a4811aea9aeTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....24373c28ef0e8c6a42072a4811aea9ae |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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| DOI: | 10.3390/ijms20061503 |