5 results on '"Granato, Anna Maria"'
Search Results
2. Metformin and insulin impact on clinical outcome in patients with advanced hepatocellular carcinoma receiving sorafenib: Validation study and biological rationale.
- Author
-
Casadei Gardini, Andrea, Faloppi, Luca, De Matteis, Serena, Foschi, Francesco Giuseppe, Silvestris, Nicola, Tovoli, Francesco, Palmieri, Vincenzo, Marisi, Giorgia, Brunetti, Oronzo, Vespasiani-Gentilucci, Umberto, Perrone, Giuseppe, Valgiusti, Martina, Granato, Anna Maria, Ercolani, Giorgio, Negrini, Giulia, Tamburini, Emiliano, Aprile, Giuseppe, Passardi, Alessandro, Santini, Daniele, and Cascinu, Stefano
- Subjects
- *
PROTEIN metabolism , *SORAFENIB , *TUMOR suppressor genes , *PEOPLE with diabetes , *DRUG resistance in cancer cells , *GENE expression , *HEPATOCELLULAR carcinoma , *IMMUNOHISTOCHEMISTRY , *INSULIN , *TYPE 2 diabetes , *TRANSFERASES , *TREATMENT effectiveness , *METFORMIN , *THERAPEUTICS - Abstract
Purpose In 2015, we published a study on a small series of patients with hepatocellular carcinoma (HCC) treated chronically with metformin for type II diabetes mellitus (DM2) who showed a poorer response to sorafenib. The aim of the present study was to validate the prognostic significance of metformin in HCC patients treated with sorafenib, providing a biological rationale for the mechanism of resistance to sorafenib in patients on chronic metformin therapy, and to clarify the role of sirtuin-3 (SIRT-3), a protein involved in metabolic diseases and acknowledged as a tumour suppressor in HCC, in this resistance. Patients and methods We analysed 279 patients consecutively treated with sorafenib for the clinical analysis. Of the 86 (30%) patients with DM2, 52 (19%) were on chronic treatment with metformin and 34 (12%) with insulin. We included 43 patients with HCC for the biological study: 19 (44.1%) were diabetic and 14 (73.7%) of these received metformin for DM2. SIRT-3 expression was investigated by immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded (FFPE) samples. Results In HCC patients undergoing chronic treatment with metformin, the use of sorafenib was associated with poor progression-free survival (PFS) and overall survival (OS) (1.9 and 6.6 months, respectively) compared to 3.7 months and 10.8 months, respectively, for patients without DM2 and 8.4 months and 16.6 months, respectively, for patients on insulin ( P < .0001). We also observed that SIRT-3 protein expression was significantly higher in patients treated with metformin than in those not taking this medication (65% versus 25%, respectively) ( P = .013). Conclusions Our findings could be attributed to increased tumour aggressiveness and resistance to sorafenib caused by chronic treatment with metformin. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
3. Role of SIRT-3, p-mTOR and HIF-1α in Hepatocellular Carcinoma Patients Affected by Metabolic Dysfunctions and in Chronic Treatment with Metformin
- Author
-
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, 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, and Frassineti, Giovanni Luca
- Subjects
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 - Abstract
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.
- Published
- 2019
- Full Text
- View/download PDF
4. Metformin and insulin impact on clinical outcome in patients with advanced hepatocellular carcinoma receiving sorafenib. Validation study and biological rationale
- Author
-
Oronzo Brunetti, Serena De Matteis, Andrea Casadei Gardini, Giorgio Ercolani, Emiliano Tamburini, Daniele Santini, Mario Scartozzi, Giuseppe Perrone, Giovanni Luca Frassineti, Nicola Silvestris, Francesco Tovoli, Umberto Vespasiani-Gentilucci, Luca Faloppi, Giuseppe Aprile, Martina Valgiusti, Giulia Negrini, Stefano Cascinu, Alessandro Passardi, Giorgia Marisi, Francesco Giuseppe Foschi, Anna Maria Granato, Vincenzo Palmieri, Casadei Gardini, Andrea, Faloppi, Luca, De Matteis, Serena, Foschi, Francesco Giuseppe, Silvestris, Nicola, Tovoli, Francesco, Palmieri, Vincenzo, Marisi, Giorgia, Brunetti, Oronzo, Vespasiani-Gentilucci, Umberto, Perrone, Giuseppe, Valgiusti, Martina, Granato, Anna Maria, Ercolani, Giorgio, Negrini, Giulia, Tamburini, Emiliano, Aprile, Giuseppe, Passardi, Alessandro, Santini, Daniele, Cascinu, Stefano, Frassineti, Giovanni Luca, and Scartozzi, Mario
- Subjects
0301 basic medicine ,Oncology ,Male ,Cancer Research ,Time Factors ,Type II diabetes mellitus ,Databases, Factual ,Hepatocellular carcinoma ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Antineoplastic Agent ,0302 clinical medicine ,Retrospective Studie ,Sirtuin 3 ,Insulin ,Drug Interactions ,Aged, 80 and over ,Clinical pathology ,SIRT-3 ,Liver Neoplasms ,NASH ,hepatocellular carcinoma ,Sorafenib ,Middle Aged ,Immunohistochemistry ,Metformin ,Treatment Outcome ,Drug Interaction ,Italy ,Liver Neoplasm ,030220 oncology & carcinogenesis ,Female ,Liver cancer ,medicine.drug ,Human ,Phenylurea Compound ,Adult ,Niacinamide ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Time Factor ,Type II diabetes mellitu ,Protein Kinase Inhibitor ,Antineoplastic Agents ,Disease-Free Survival ,03 medical and health sciences ,Internal medicine ,NAFLD ,medicine ,Humans ,Hypoglycemic Agents ,In patient ,neoplasms ,Protein Kinase Inhibitors ,Aged ,Retrospective Studies ,Hypoglycemic Agent ,business.industry ,Phenylurea Compounds ,sorafenib ,metformin ,medicine.disease ,digestive system diseases ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,Drug Resistance, Neoplasm ,business - Abstract
Purpose In 2015, we published a study on a small series of patients with hepatocellular carcinoma (HCC) treated chronically with metformin for type II diabetes mellitus (DM2) who showed a poorer response to sorafenib. The aim of the present study was to validate the prognostic significance of metformin in HCC patients treated with sorafenib, providing a biological rationale for the mechanism of resistance to sorafenib in patients on chronic metformin therapy, and to clarify the role of sirtuin-3 (SIRT-3), a protein involved in metabolic diseases and acknowledged as a tumour suppressor in HCC, in this resistance. Patients and methods We analysed 279 patients consecutively treated with sorafenib for the clinical analysis. Of the 86 (30%) patients with DM2, 52 (19%) were on chronic treatment with metformin and 34 (12%) with insulin. We included 43 patients with HCC for the biological study: 19 (44.1%) were diabetic and 14 (73.7%) of these received metformin for DM2. SIRT-3 expression was investigated by immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded (FFPE) samples. Results In HCC patients undergoing chronic treatment with metformin, the use of sorafenib was associated with poor progression-free survival (PFS) and overall survival (OS) (1.9 and 6.6 months, respectively) compared to 3.7 months and 10.8 months, respectively, for patients without DM2 and 8.4 months and 16.6 months, respectively, for patients on insulin (P
- Published
- 2017
5. Interplay Between SIRT-3, Metabolism and Its Tumor Suppressor Role in Hepatocellular Carcinoma
- Author
-
Luca Faloppi, Martina Valgiusti, Giovanni Luca Frassineti, Mario Scartozzi, Roberta Napolitano, Francesco Giuseppe Foschi, Umberto Vespasiani Gentilucci, Giorgio Ercolani, Daniele Santini, Serena De Matteis, Andrea Casadei Gardini, Anna Maria Granato, Chiara Molinari, De Matteis, S, Granato, Am, Napolitano, R, Molinari, C, Valgiusti, M, Santini, D, Foschi, Fg, Ercolani, G, Vespasiani Gentilucci, U, Faloppi, L, Scartozzi, M, Frassineti, Gl, Casadei Gardini, A4., De Matteis, Serena, Granato, Anna Maria, Napolitano, Roberta, Molinari, Chiara, Valgiusti, Martina, Santini, Daniele, Foschi, Francesco Giuseppe, Ercolani, Giorgio, Vespasiani Gentilucci, Umberto, Faloppi, Luca, Scartozzi, Mario, Frassineti, Giovanni Luca, and Casadei Gardini, Andrea
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,tumor suppressor ,Hepatocellular carcinoma ,Physiology ,Nicotinamide adenine dinucleotide ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,Metabolic Diseases ,law ,Metabolism ,SIRT-3 ,Tumor suppressor ,Gastroenterology ,Neoplasms ,Sirtuin 3 ,Internal medicine ,hepatocellular carcinoma ,medicine ,Humans ,Chronic stress ,biology ,Tumor Suppressor Proteins ,Liver Neoplasms ,Neurodegeneration ,Cancer ,medicine.disease ,030104 developmental biology ,Histone ,Endocrinology ,chemistry ,biology.protein ,Cancer research ,Suppressor ,NAD+ kinase - Abstract
Sirtuins (SIRT), first described as nicotinamide adenine dinucleotide (NAD + )-dependent type III histone deacetylases, are produced by cells to support in the defense against chronic stress conditions such as metabolic syndromes, neurodegeneration, and cancer. SIRT-3 is one of the most studied members of the mitochondrial sirtuins family. In particular, its involvement in metabolic diseases and its dual role in cancer have been described. In the present review, based on the evidence of SIRT-3 involvement in metabolic dysfunctions, we aimed to provide an insight into the multifaceted role of SIRT-3 in many solid and hematological tumors with a particular focus on hepatocellular carcinoma (HCC). SIRT-3 regulatory effect and involvement in metabolism dysfunctions may have strong implications in HCC development and treatment. Research literature widely reports the relationship between metabolic disorders and HCC development. This evidence suggests a putative bridge role of SIRT-3 between metabolic diseases and HCC. However, further studies are necessary to demonstrate such interconnection.
- Published
- 2017
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.