JOAO EVANGELISTA BEZERRA NETO

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Lattes
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Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina

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Agora exibindo 1 - 10 de 29
  • bookPart
    Câncer de Esôfago
    (2014) HOFF, Paulo M. G.; SABBAGA, Jorge; COSTA, Frederico P.; FERNANDES, Gustavo dos Santos; CAPARELI, Fernanda; SARAGIOTTO, Daniel; PEREIRA, Guilherme Stelko; PFIFFER, Tulio; BEZERRA NETO, João Evangelista
  • bookPart
    Câncer de Canal Anal
    (2014) HOFF, Paulo M. G.; SABBAGA, Jorge; COSTA, Frederico P.; FERNANDES, Gustavo dos Santos; CAPARELI, Fernanda; SARAGIOTTO, Daniel; PEREIRA, Guilherme Stelko; PFIFFER, Tulio; BEZERRA NETO, João Evangelista
  • article 4 Citação(ões) na Scopus
    SDHB large deletions are associated with absence of MIBG uptake in metastatic lesions of malignant paragangliomas
    (2021) PETENUCI, Janaina; FAGUNDES, Gustavo F. C.; BENEDETTI, Anna Flavia F.; GUIMARAES, Augusto G.; AFONSO, Ana Caroline F.; MOTA, Flavia T.; MAGALHAES, Aurea Luiza F.; COURA-FILHO, George B.; ZERBINI, Maria Claudia N.; SIQUEIRA, Sheila; MONTENEGRO, Fabio L. M.; SROUGI, Victor; TANNO, Fabio Y.; CHAMBO, Jose Luis; FERRARI, Marcela S. S.; BEZERRA NETO, Joao Evangelista; PEREIRA, Maria Adelaide A.; LATRONICO, Ana Claudia; FRAGOSO, Maria Candida B. V.; MENDONCA, Berenice B.; HOFF, Ana O.; ALMEIDA, Madson Q.
  • article 61 Citação(ões) na Scopus
    Phase 2 Trial of Metformin Combined With 5-Fluorouracil in Patients With Refractory Metastatic Colorectal Cancer
    (2016) MIRANDA, Vanessa C.; BRAGHIROLI, Maria Ignez; FARIA, Luiza Dib; BARIANI, Giovanni; ALEX, Alexandra; BEZERRA NETO, Joao Evangelista; CAPARELI, Fernanda C.; SABBAGA, Jorge; SANTOS, Juliana Ferreira Lobo dos; HOFF, Paulo M.; RIECHELMANN, Rachel P.
    Effects of metformin in colorectal cancer have not been tested in clinical trials. In this phase 2 trial with 50 patients, metformin and 5-fluorouracil (5-FU) showed median progression-free survival of 2 months and overall survival of 7.9 months. However, among patients who experienced stable disease at 8 weeks, disease stabilization lasted for 5.6 months and patients survived for 16 months. Obese patients and those with longer periods off 5-FU seemed to derive more benefit. Background: Observational and preclinical studies have suggested that metformin has antitumor effects in solid tumors, including colorectal cancer (CRC). However, the effects of metformin in CRC have not been tested in clinical trials. Patients and Methods: This was a single-center, single-arm phase 2 clinical trial where histologically confirmed CRC patients with measurable and progressing metastatic disease previously treated with 5-fluorouracil (5-FU), irinotecan, oxaliplatin, and an antieepidermal growth factor receptor (if the tumor was RAS wild type) were enrolled to receive metformin 850 mg orally continuously 2 times a day plus 5-FU 425 mg/m(2) and leucovorin 50 mg intravenously weekly until disease progression, unacceptable toxicity, or withdrawal of consent. The primary end point was disease control rate at 8 weeks. Results: Among 50 patients included, 11 (22%) met the primary end point. The median progression-free survival was 1.8 months and the median overall survival 7.9 months. Analyzing only the 11 patients who experienced disease control at 8 weeks, their median progression-free survival was 5.6 months and their median overall survival was 16.2 months. There was a trend for prolonged median survival for obese patients (12.4 vs. 5.8 months) and those longer off 5-FU. The treatment was well tolerated; the main adverse effects were diarrhea, nausea, vomiting, and myelotoxicity. Conclusion: Metformin and 5-FU showed an overall modest but intriguing activity in patients with refractory CRC in this phase 2 study. Some patients experienced long-term disease control. Further trials are needed to confirm these results, particularly in obese patients with CRC.
  • article 77 Citação(ões) na Scopus
    Exosomes from patients with septic shock convey miRNAs related to inflammation and cell cycle regulation: new signaling pathways in sepsis?
    (2018) REAL, Juliana Monte; FERREIRA, Ludmila Rodrigues Pinto; ESTEVES, Gustavo Henrique; KOYAMA, Fernanda Christtanini; DIAS, Marcos Vincius Salles; BEZERRA-NETO, Joao Evangelista; CUNHA-NETO, Edecio; MACHADO, Flavia Ribeiro; SALOMAO, Reinaldo; AZEVEDO, Luciano Cesar Pontes
    Background: Exosomes isolated from plasma of patients with sepsis may induce vascular apoptosis and myocardial dysfunction by mechanisms related to inflammation and oxidative stress. Despite previous studies demonstrating that these vesicles contain genetic material related to cellular communication, their molecular cargo during sepsis is relatively unknown. In this study, we evaluated the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) related to inflammatory response and redox metabolism in exosomes of patients with septic shock. Methods: Blood samples were collected from 24 patients with septic shock at ICU admission and after 7 days of treatment. Twelve healthy volunteers were used as control subjects. Exosomes were isolated by ultracentrifugation, and their miRNA and mRNA content was evaluated by qRT-PCR array. Results: As compared with healthy volunteers, exosomes from patients with sepsis had significant changes in 65 exosomal miRNAs. Twenty-eight miRNAs were differentially expressed, both at enrollment and after 7 days, with similar kinetics (18 miRNAs upregulated and 10 downregulated). At enrollment, 35 differentially expressed miRNAs clustered patients with sepsis according to survival. The pathways enriched by the miRNAs of patients with sepsis compared with control subjects were related mostly to inflammatory response. The comparison of miRNAs from patients with sepsis according to hospital survival demonstrated pathways related mostly to cell cycle regulation. At enrollment, sepsis was associated with significant increases in the expression of mRNAs related to redox metabolism (myeloperoxidase, 64-fold; PRDX3, 2.6-fold; SOD2, 2.2-fold) and redox-responsive genes (FOXM1, 21-fold; SELS, 16-fold; GLRX2, 3.4-fold). The expression of myeloperoxidase mRNA remained elevated after 7 days (65-fold). Conclusions: Exosomes from patients with septic shock convey miRNAs and mRNAs related to pathogenic pathways, including inflammatory response, oxidative stress, and cell cycle regulation. Exosomes may represent a novel mechanism for intercellular communication during sepsis.
  • article 2 Citação(ões) na Scopus
    METNET: a phase II trial of metformin in patients with well-differentiated neuroendocrine tumours
    (2022) GLASBERG, Joao; TALANS, Aley; GIOLLO, Thomas Rivelli; RECCHIMUZZI, Debora Zachello; BEZERRA NETO, Joao Evangelista; LOPEZ, Rossana Veronica Mendonza; HOFF, Paulo Marcelo Gehm; RIECHELMANN, Rachel P.
    Background: Preclinical studies have suggested that metformin has anti-tumour effects, likely due to blockage of mammalian target of rapamycin pathway through adenosine monophosphate-activated protein kinase and decreased insulin levels. A retrospective study showed that metformin added to everolimus to treat type 2 diabetes mellitus offered longer progression-free survival (PFS) in patients with pancreatic neuroendocrine tumours (NET). Aim(s): To evaluate the efficacy and safety of metformin monotherapy in patients with advanced/metastatic well-differentiated NET (WD-NET) of gastroenteropancreatic (GEP) or pulmonary origin. Patients and methods: Single-arm phase II trial of metformin 850 mg PO twice daily until progression or intolerance for patients with progressive metastatic well-differentiated GEP or pulmonary NET. The primary endpoint was disease control rate (DCR) by RECIST 1.1 at 6 months. Secondary endpoints were response rate, PFS, toxicity and variations in glycaemic profiles (glycaemia, glycated haemoglobin and peptide C and insulin) at baseline, at 30 and 90 days. Results: From 2014 to 2019, 28 patients were enrolled: median age was 50 years; 84% had non-functional NET, 86% were of GEP origin and 62% had G2 NET. At the time of last follow-up, 26 patients had progression, with 13 (46%) presenting DCR at 6 months and a median PFS of 6.3 months (95% confidence interval: 3.2-9.3). There was no objective response, but one patient with refractory carcinoid syndrome had complete symptom relief, lasting for more than 5 years. Variations in glycaemic profiles were not associated with DCR at 6 months. Diarrhoea was the most common adverse event, being grade 3 or 4 in 10% of the cases. Conclusion: Metformin monotherapy offers modest anti-tumour activity in well-differentiated GEP or lung NET.
  • bookPart
    Câncer de Pâncreas e Vias Biliares
    (2014) HOFF, Paulo M. G.; SABBAGA, Jorge; COSTA, Frederico P.; FERNANDES, Gustavo dos Santos; CAPARELI, Fernanda; SARAGIOTTO, Daniel; PEREIRA, Guilherme Stelko; PFIFFER, Tulio; BEZERRA NETO, João Evangelista
  • article 27 Citação(ões) na Scopus
    Complete Resolution of Hypercortisolism with Sorafenib in a Patient with Advanced Medullary Thyroid Carcinoma and Ectopic ACTH (Adrenocorticotropic Hormone) Syndrome
    (2014) BARROSO-SOUSA, Romualdo; LERARIO, Antonio Marcondes; EVANGELISTA, Joao; PAPADIA, Carla; LOURENCO JR., Delmar M.; LIN, Chin Shien; KULCSAR, Marco Antonio; FRAGOSO, Maria Candida; HOFF, Ana O.
    Background: The treatment of advanced medullary thyroid carcinoma (MTC) has evolved significantly over the past decade. The discovery of genetic abnormalities in MTC has led to the development of targeted therapies such as vandetanib and cabozantinib. Other kinase inhibitors (KI), such as sorafenib, have been investigated in this setting and are an alternative therapeutic option. The lack of specificity of these KIs to a single target may result in additional, unexpected effects. In this report, we describe a patient with metastatic MTC and Ectopic ACTH (adrenocorticotropic hormone) Syndrome in whom treatment with sorafenib resulted in complete resolution of hypercortisolism. Summary: A 45-year-old male with progressive metastatic MTC presented with clinical manifestations suspicious for Cushing's syndrome. Investigation revealed ACTH-dependent hypercortisolism suggestive of Ectopic ACTH Syndrome. Treatment with sorafenib 400 mg twice a day was initiated resulting in a rapid and significant reduction of cortisol and ACTH levels associated with dramatic clinical improvement. The rapid and effective control of hypercortisolism in the absence of a significant tumor reduction raises the question of whether sorafenib may have a direct effect on ACTH or cortisol hypersecretion. Conclusions: This report suggests a previously unknown potential effect of sorafenib on the pituitary-adrenal axis. Further studies will be necessary to investigate the role of sorafenib in other cases of ACTH excess and to understand the mechanisms by which it alters steroid synthesis, action, or secretion.
  • bookPart
    Câncer do Intestino Delgado
    (2014) HOFF, Paulo M. G.; SABBAGA, Jorge; COSTA, Frederico P.; FERNANDES, Gustavo dos Santos; CAPARELI, Fernanda; SARAGIOTTO, Daniel; PEREIRA, Guilherme Stelko; PFIFFER, Tulio; BEZERRA NETO, João Evangelista
  • article 19 Citação(ões) na Scopus
    Sterol O-Acyl Transferase 1 as a Prognostic Marker of Adrenocortical Carcinoma
    (2020) LACOMBE, Amanda Meneses Ferreira; SOARES, Ibere Cauduro; MARIANI, Beatriz Marinho de Paula; NISHI, Mirian Yumie; BEZERRA-NETO, Joao Evangelista; CHARCHAR, Helaine da Silva; BRONDANI, Vania Balderrama; TANNO, Fabio; SROUGI, Victor; CHAMBO, Jose Luiz; FREITAS, Ricardo Miguel Costa de; MENDONCA, Berenice Bilharinho; HOFF, Ana O.; ALMEIDA, Madson Q.; WEIGAND, Isabel; KROISS, Matthias; ZERBINI, Maria Claudia Nogueira; FRAGOSO, Maria Candida Barisson Villares
    Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis. Despite the poor prognosis in the majority of patients, no improvements in treatment strategies have been achieved. Therefore, the discovery of new prognostic biomarkers is of enormous interest. Sterol-O-acyl transferase 1 (SOAT1) is involved in cholesterol esterification and lipid droplet formation. Recently, it was demonstrated that SOAT1 inhibition leads to impaired steroidogenesis and cell viability in ACC. To date, no studies have addressed the impact of SOAT1 expression on ACC prognosis and clinical outcomes. We evaluated SOAT1 expression by quantitative real-time polymerase chain reaction and immunohistochemistry in a tissue microarray of 112 ACCs (Weiss score >= 3) from adults treated in a single tertiary center in Brazil. Two independent pathologists evaluated the immunohistochemistry results through a semiquantitative approach (0-4). We aimed to evaluate the correlation between SOAT1 expression and clinical, biochemical and anatomopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). SOAT1 protein expression was heterogeneous in this cohort, 37.5% of the ACCs demonstrated a strong SOAT1 protein expression (score > 2), while 62.5% demonstrated a weak or absent protein expression (score <= 2). Strong SOAT1 protein expression correlated with features of high aggressiveness in ACC, such as excessive tumor cortisol secretion (p = 0.01), an advanced disease stage [European Network for the Study of Adrenal Tumors (ENSAT) staging system 3 and 4 (p = 0.011)] and a high Ki67 index (p = 0.002). In multivariate analysis, strong SOAT1 protein expression was an independent predictor of a reduced OS (hazard ratio (HR) 2.15, confidence interval (CI) 95% 1.26-3.66; p = 0.005) in all patients (n = 112), and a reduced RFS (HR 2.1, CI 95% 1.09-4.06; p = 0.027) in patients with localized disease at diagnosis (n = 83). Our findings demonstrated that SOAT1 protein expression has prognostic value in ACC and reinforced the importance of investigating SOAT1 as a possible therapeutic target for patients with ACC.