CLAUDIA PINTO MARQUES SOUZA DE OLIVEIRA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Gastroenterologia, Faculdade de Medicina - Docente
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
34 resultados
Resultados de Busca
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conferenceObject Integrative Molecular Profiling of Non-Alcoholic Steatohepatitis-Related Hepatocellular Carcinoma(2018) TORRECILLA, Sara; PINYOL, Roser; WEI-QIANG, Leow; WANG, Huan; MOEINI, Agrin; MONTIRONI, Carla; BASSAGANYAS, Laia; ANDREU-OLLER, Carmen; OLIVEIRA, Claudia P. M. S.; ALVES, Venancio A. F.; LACHENMAYER, Anja; ROESSLER, Stephanie; MINGUEZ, Beatriz; SCHIRMACHER, Peter; BOFFETTA, Paolo; DUFOUR, Jean-Francois; THUNG, Swan N.; UZILOV, Andrew; CARRILHO, Flair Jose; CHANG, Charissa Y.; SIA, Daniela; LLOVET, Josep M.- Molecular characterisation of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis(2021) PINYOL, Roser; TORRECILLA, Sara; WANG, Huan; MONTIRONI, Carla; PIQUE-GILI, Marta; TORRES-MARTIN, Miguel; WEI-QIANG, Leow; WILLOUGHBY, Catherine E.; RAMADORI, Pierluigi; ANDREU-OLLER, Carmen; TAIK, Patricia; LEE, Youngmin A.; MOEINI, Agrin; PEIX, Judit; FAURE-DUPUY, Suzanne; RIEDL, Tobias; SCHUEHLE, Svenja; OLIVEIRA, Claudia P.; ALVES, Venancio A.; BOFFETTA, Paolo; LACHENMAYER, Anja; ROESSLER, Stephanie; MINGUEZ, Beatriz; SCHIRMACHER, Peter; DUFOUR, Jean-Francois; THUNG, Swan N.; REEVES, Helen L.; CARRILHO, Flair J.; CHANG, Charissa; V, Andrew Uzilov; HEIKENWALDER, Mathias; SANYAL, Arun; FRIEDMAN, Scott L.; SIA, Daniela; LLOVET, Josep M.Background and Aims: Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is increasing globally, but its molecular features are not well defined. We aimed to identify unique molecular traits characterising NASH-HCC compared to other HCC aetiologies. Methods: We collected 80 NASH-HCC and 125 NASH samples from 5 institutions. Expression array (n = 53 NASH-HCC; n = 74 NASH) and whole exome sequencing (n = 52 NASH-HCC) data were compared to HCCs of other aetiologies (n = 184). Three NASH-HCC mouse models were analysed by RNA-seq/expression-array (n = 20). Activin A receptor type 2A (ACVR2A) was silenced in HCC cells and proliferation assessed by colorimetric and colony formation assays. Results: Mutational profiling of NASH-HCC tumours revealed TERT promoter (56%), CTNNB1 (28%), TP53 (18%) and ACVR2A (10%) as the most frequently mutated genes. ACVR2A mutation rates were higher in NASH-HCC than in other HCC aetiologies (10% vs. 3%, p <0.05). In vitro, ACVR2A silencing prompted a significant increase in cell proliferation in HCC cells. We identified a novel mutational signature (MutSig-NASH-HCC) significantly associated with NASH-HCC (16% vs. 2% in viral/alcohol-HCC, p = 0.03). Tumour mutational burden was higher in non-cirrhotic than in cirrhotic NASH-HCCs (1.45 vs. 0.94 mutations/megabase; p <0.0017). Compared to other aetiologies of HCC, NASH-HCCs were enriched in bile and fatty acid signalling, oxidative stress and inflammation, and presented a higher fraction of Wnt/ TGF-beta proliferation subclass tumours (42% vs. 26%, p = 0.01) and a lower prevalence of the CTNNB1 subclass. Compared to other aetiologies, NASH-HCC showed a significantly higher prevalence of an immunosuppressive cancer field. In 3 murine models of NASH-HCC, key features of human NASH-HCC were preserved. Conclusions: NASH-HCCs display unique molecular features including higher rates of ACVR2A mutations and the presence of a newly identified mutational signature. Lay summary: The prevalence of hepatocellular carcinoma (HCC) associated with non-alcoholic steatohepatitis (NASH) is increasing globally, but its molecular traits are not well characterised. In this study, we uncovered higher rates of ACVR2A mutations (10%) - a potential tumour suppressor - and the presence of a novel mutational signature that characterises NASH-related HCC.
- Survivin expression patterns could reflect different roles in hepatocarcinogenesis, especially in non-alcoholic fatty liver disease-related hepatocellular carcinoma(2011) STEFANO, Jose T.; OLIVEIRA, Claudia P.; CARRILHO, Flair J.; ALVES, Venancio A. F.
- S-nitroso-N-acetylcysteine attenuates liver fibrosis in experimental nonalcoholic steatohepatitis(2013) MAZO, Daniel F. C.; OLIVEIRA, Marcelo G. de; PEREIRA, Isabel V. A.; COGLIATI, Bruno; STEFANO, Jose T.; SOUZA, Gabriela F. P. de; RABELO, Fabiola; LIMA, Fabiana R.; ALVES, Venancio A. Ferreira; CARRILHO, Flair J.; OLIVEIRA, Claudia P. M. S. deS-Nitroso-N-acetylcysteine (SNAC) is a water soluble primary S-nitrosothiol capable of transferring and releasing nitric oxide and inducing several biochemical activities, including modulation of hepatic stellate cell activation. In this study, we evaluated the antifibrotic activity of SNAC in an animal model of nonalcoholic steatohepatitis (NASH) induced in Sprague-Dawley rats fed with a choline-deficient, high trans fat diet and exposed to diethylnitrosamine for 8 weeks. The rats were divided into three groups: SNAC, which received oral SNAC solution daily; NASH, which received the vehicle; and control, which received standard diet and vehicle. Genes related to fibrosis (matrix metalloproteinases [MMP]-13, -9, and -2), transforming growth factor beta-1 [TGF beta-1], collagen-1 alpha, and tissue inhibitors of metalloproteinase [TIMP-1 and -2] and oxidative stress (heat-shock proteins [HSP]-60 and -90) were evaluated. SNAC led to a 34.4% reduction in the collagen occupied area associated with upregulation of MMP-13 and -9 and downregulation of HSP-60, TIMP-2, TGF beta-1, and collagen-1 alpha. These results indicate that oral SNAC administration may represent a potential antifibrotic treatment for NASH.
conferenceObject NON-Invasive Biomarkers to Monitoring LIVER Disease Progression in Nash Patients(2018) MALTA, Fernanda; LIMA, Rodrigo V.; SALLES, Ana Paula M.; STEFANO, Jose Tadeu; MAZO, Daniel; ALVES, Venancio A. F.; CARRILHO, Flair Jose; PINHO, Joao Renato R.; OLIVEIRA, Claudia P. M. S.- Distinctive molecular traits of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis(2019) TORRECILLA, Sara; PINYOL, Roser; WANG, Huan; MONTIRONI, Carla; ANDREU-OLLER, Carmen; LEOW, Wei Qiang; MOEINI, Agrin; OLIVEIRA, Claudia; ALVES, Venancio Avancini Ferreira; LACHENMAYER, Anja; ROESSLER, Stephanie; MINGUEZ, Beatriz; SCHIRMACHER, Peter; BOFFETTA, Paolo; DUFOUR, Jean-Francois; THUNG, Swan N.; UZILOV, Andrew; CARRILHO, Flair Jose; CHANG, Charissa; SIA, Daniela; LLOVET, Josep M.
conferenceObject ASSOCIATION BETWEEN PNPLA3 AND TM6SF2 GENE POLYMORPHISMS AND GENETIC ANCESTRY IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE FROM A HIGHLY ADMIXED BRAZILIAN POPULATION(2021) CAVALCANTE, Lourianne Nascimento; LYRA, Andre; STEFANO, Jose Tadeu; MAZO, Daniel; PORTO, Jun; REIS, Rui Manuel; LONGATTO FILHO, Adhemar; CARRILHO, Flair Jose; ALVES, Venancio A. F.; OLIVEIRA, Claudia P. M. S.conferenceObject MOLECULAR AND MUTATIONAL LANDSCAPE OF HEPATOCELLULAR CARCINOMA (HCC) RELATED TO NONALCOHOLIC STEATOHEPATITIS (NASH)(2020) PIQUE-GILI, Marta; PINYOL, Roser; TORRECILLA, Sara; WANG, Huan; MONTIRONI, Carla; RAMADORI, Pierluigi; WILLOUGHBY, Catherine E.; ANDREU-OLLER, Carmen; TORRES-MARTIN, Miguel; LEOW, Wei-Qiang; MOEINI, Agrin; TAIK, Patricia; GALLOFRE, Judit Peix; OLIVEIRA, Claudia P. M. S.; ALVES, Venancio A. F.; LACHENMAYER, Anja; ROESSLER, Stephanie; MINGUEZ, Beatriz; SCHIRMACHER, Peter; BOFFETTA, Paolo; DUFOUR, Jean-Francois; THUNG, Swan N.; REEVES, Helen; UZILOV, Andrew; CARRILHO, Flair J.; CHANG, Charissa Y.; HEIKENWAELDER, Mathias; SANYAL, Arun J.; FRIEDMAN, Scott L.; SIA, Daniela; LLOVET, Josep M.- Hepatocellular Carcinoma Management in Nonalcoholic Fatty Liver Disease Patients Applicability of the BCLC Staging System(2016) KIKUCHI, Luciana; OLIVEIRA, Claudia P.; ALVARES-DA-SILVA, Mario R.; TANI, Claudia M.; DINIZ, Marcio A.; STEFANO, Jose T.; CHAGAS, Aline L.; ALENCAR, Regiane S. S. M.; VEZOZZO, Denise C. P.; SANTOS, Gilmar R.; CAMPOS, Priscila B.; ALVES, Venancio A. F.; RATZIU, Vlad; CARRILHO, Flair J.Background/Aims: Nonalcoholic fatty liver disease (NAFLD) has emerged as an important cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). The Barcelona Clinic Liver Cancer (BCLC) system is the preferred staging system to evaluate patients with HCC and links prognosis assessment with treatment recommendation. The aim of this retrospective study was to evaluate whether the BCLC staging system and its treatment algorithm are suitable for,patients with HCC arising from NAFLD. Methods: Forty-two patients with HCC related to either to NAFLD or cryptogenic cirrhosis were retrieved retrospectively from 2 centers in Brazil. Patients were classified according to BCLC staging system. If the proposed HCC therapy could not be applied, the case was considered to represent deviations from the recommended BCLC guideline. Causes of treatment deviations were investigated. Results: There were 4 patients without evidence of cirrhosis according to liver biopsy and/or clinical evaluation. One (2%), 21 (50%), 10 (24%), 5 (12%), and 5 patients (12%) were classified initially to the very early (0), early (A), intermediate (B), advanced (C), and terminal (D) BCLC stages, respectively. Thirty-five patients (83%) were treated according to BCLC recommendations. There were 3 cases (of 5) of protocol deviation in BCLC C patients. The 1- and 2-year overall survival rates were 81% and 66%, respectively. Conclusions: The BCLC system is applied in most cases of NAFLD-related HCC cases. Deviation of BCLC is found more frequently in BCLC C stage patients.
conferenceObject Hepatocellular carcinoma in non-alchoolic steatohepatitis (NASH): Clinical, histopathological aspects and immunohistochemical of metabolic and proliferative related-markers(2017) CAMPOS, Priscila B.; OLIVEIRA, Claudia P.; STEFANO, Jose Tadeu; CHAGAS, Aline; HERMAN, Paulo; D'ALBUQUERQUE, Luiz C.; ALVARES-DA-SILVA, Mario R.; LONGATTO-FILHO, Adhemar; BALTAZAR, Ftima; GRANJA, Sara; CARRILHO, Flair J.; ALVES, Venancio Avancini F.