MADSON QUEIROZ DE ALMEIDA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
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
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
19 resultados
Resultados de Busca
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- Amplification of the Insulin-Like Growth Factor 1 Receptor Gene Is a Rare Event in Adrenocortical Adenocarcinomas: Searching for Potential Mechanisms of Overexpression(2014) RIBEIRO, Tamaya Castro; JORGE, Alexander Augusto; ALMEIDA, Madson Q.; MARIANI, Beatriz Marinho de Paula; NISHI, Mirian Yumi; MENDONCA, Berenice Bilharinho; FRAGOSO, Maria Candida Barisson Villares; LATRONICO, Ana ClaudiaContext. IGF1R overexpression appears to be a prognostic biomarker of metastatic pediatric adrenocortical tumors. However, the molecular mechanisms that are implicated in its upregulation remain unknown. Aim. To investigate the potential mechanisms involved in IGF1R overexpression. Patients and Methods. We studied 64 adrenocortical tumors. IGF1R copy number variation was determined in all patients using MLPA and confirmed using real time PCR. In a subgroup of 32 patients, automatic sequencing was used to identify IGF1R allelic variants and the expression of microRNAs involved in IGF1R regulation by real time PCR. Results. IGF1R amplification was detected in an adrenocortical carcinoma that was diagnosed in a 46-year-old woman with Cushing's syndrome and virilization. IGF1R overexpression was demonstrated in this case. In addition, gene amplification of other loci was identified in this adrenocortical malignant tumor, but no IGF1R copy number variation was evidenced in the remaining cases. Automatic sequencing revealed three known polymorphisms but they did not correlate with its expression. Expression of miR-100, miR-145, miR-375, and miR-126 did not correlate with IGF1R expression. Conclusion. We demonstrated amplification and overexpression of IGF1R gene in only one adrenocortical carcinoma, suggesting that these combined events are uncommon. In addition, IGF1R polymorphisms and abnormal microRNA expression did not correlate with IGF1R upregulation in adrenocortical tumors.
- High 18F-FDG uptake in PMAH correlated with normal expression of Glut1, HK1, HK2, and HK3(2016) CAVALCANTE, Isadora Pontes; ZERBINI, Maria Claudia Nogueira; ALENCAR, Guilherme Asmar; MARIANI, Beatriz de Paula; BUCHPIGUEL, Carlos Alberto; ALMEIDA, Madson Queiroz; MENDONCA, Berenice Bilharinho; FRAGOSO, Maria Candida Barisson VillaresBackground Primary macronodular adrenal hyperplasia (PMAH) is a rare cause of Cushing's syndrome, characterized by functioning adrenal macronodules and variable cortisol production. Recently, we demonstrated a high 18F-FDG uptake in PMAH, an unexpected finding for a benign disorder. Purpose To investigate whether there is a correlation between 18F-FDG high uptake and the expression levels of the glycolytic pathway components GLUT1, HK1, HK2, and HK3 in PMAH. Material and Methods We selected 12 patients undergoing surgery for PMAH who had preoperatively undergone 18F-FDG PET/CT. mRNA and protein expression of the selected genes were evaluated in the adrenal nodules from patients who underwent surgery through quantitative RT-PCR and by immunohistochemistry, respectively. Results SUVmax in PMAH was in the range of 3.3-8.9 and the adrenal size was in the range of 3.5-15cm. A strong correlation between 18F-FDG uptake and largest adrenal diameter was observed in patients with PMAH. However, no correlation between 18F-FDG uptake and GLUT1, HK1, HK2, HK3 mRNA, and protein expression was observed. Conclusion High 18F-FDG uptake is observed in the majority of PMAH cases. However, 18F-FDG uptake in PMAH is independent of the expression levels of GLUT1, HK1, HK2, and HK3. Further investigation is required to elucidate the molecular mechanisms underlying increased 18F-FDG uptake in PMAH.
- A New Insight into the Surgical Treatment of Primary Macronodular Adrenal Hyperplasia(2020) TANNO, Fabio Yoshiaki; SROUGI, Victor; ALMEIDA, Madson Q.; YAMAUCHI, Fernando Ide; COELHO, Fernando Morbeck Almeida; NISHI, Mirian Yumie; ZERBINI, Maria Claudia Nogueira; SOARES, Iracy Silvia Correa; PEREIRA, Maria Adelaide Albergaria; CHARCHAR, Helaine Laiz Silva; LACOMBE, Amanda Meneses Ferreira; BRONDANI, Vania Balderrama; SROUGI, Miguel; NAHAS, Willian Carlos; MENDONCA, Berenice B.; CHAMBO, Jose Luis; FRAGOSO, Maria Candida Barisson VillaresPurpose: This prospective study presents the results of a new approach in the treatment of primary macronodular adrenal hyperplasia (PMAII), with simultaneous total adrenalectomy of the larger adrenal gland and partial adrenalectomy of the contralateral adrenal gland (adrenal-sparing surgery). Materials and Methods: We performed a prospective study including 17 patients with PMAH treated surgically with adrenal-sparing surgery in a tertiary referral hospital, with a median follow-up of 41 months. Clinical, hormonal, and genetic parameters were evaluated before surgery and during follow-up. All patients had at least 1 radiological examination before and after the procedure. Results: Among the 17 patients, all but 1 patient had complete hypercortisolism control, and 12 recovered normal adrenal function after surgery. Significant improvement in clinical parameters was observed: weight loss (P = .004); reduction of both systolic (P = .001) and diastolic (P = .001) blood pressure; and reduction in the number of antihypertensive drugs (P < .001). Intra-, peri-, and postoperative complications were not observed. Conclusion: Adrenal-sparing surgery is a safe and feasible procedure to treat patients with PMAH, providing a substantial chance of hypercortisolism control without the disadvantages of lifetime corticosteroid replacement. (C) Endocrine Society 2020.
- 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 VillaresAdrenocortical 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.
- Clinical spectrum of Li-Fraumeni syndrome/Li-Fraumeni-like syndrome in Brazilian individuals with the TP53 p.R337H mutation(2019) FERREIRA, Amanda Meneses; BRONDANI, Vania Balderrama; HELENA, Vanessa Petry; CHARCHAR, Helaine Laiz Silva; ZERBINI, Maria Claudia Nogueira; LEITE, Luiz Antonio Senna; HOFF, Ana Oliveira; LATRONICO, Ana Claudia; MENDONCA, Berenice Bilharinho; DIZ, Maria Del Pilar Estevez; ALMEIDA, Madson Queiroz de; FRAGOSO, Maria Candida Barisson VillaresBackground: The TP53 p.R337H germline mutation is highly prevalent among children with adrenocortical tumors (ACTs) from South and Southeast Brazil. However, the prevalence of other tumors of the Li-Fraumeni syndrome (LFS) and Li-Fraumeni-like syndrome (LFL) spectrum, the clinical outcomes and the potential tumor occurrence in relatives carrying this distinct TP53 mutation were not fully investigated. Patients and Methods: We investigated tumor profile data and outcomes of individuals and their close relatives with the TP53 p.R337H germline mutation. A questionnaire and the Toronto protocol were used for evaluation of asymptomatic carriers of this TP53 mutation. Results: The cohort of this study comprised 51 patients from 46 different families; 67% were female. All but one harbored the TP53 p.R337H mutation in heterozygous state; only one child was homozygous for this variant. Maternal allele inheritance occurred in 72% of the cases (p = 0,002). In pediatric group, ACT was the most common primary tumor at the diagnosis (55%; median age = 2 years). No patient of the pediatric group who initially presented with ACT developed a second primary tumor and 11% (n= 3) died due to complications related to the primary tumor (median follow-up time of 81.5 months, range = 3-378 months). In adult group, the main tumors at diagnosis were: adrenocortical carcinoma (ACC) (23%; median age= 29.5 years), breast cancer (12%; median age = 38.5 years), soft tissue sarcoma (8%; median age = 50.3 years) and choroid plexus carcinoma (CPC) (2%; median age= 18 years). Among adult patients who were diagnosed with ACC as the first primary tumor, all presented with aggressive disease as per histologic and clinical criteria at diagnosis, and 75% of patients died (median follow-up time of 19 months, range= 1-69 months). Five adult patients (22%) had a second primary tumor, including bronchoalveolar lung cancer (2 cases), ACC, uterine cervical carcinoma and fibrosarcoma. The diagnosis of these tumors was established from 8 to 36 months after the first primary tumor. Three families presented more than one case of ACT. Nine malignant neoplasms were diagnosed in asymptomatic carriers using Toronto protocol. Conclusions: This study confirms a high frequency of TP53 p.R337H mutation in pediatric group with ACT. In addition, we observed the occurrence of other tumors of LFS/LFL spectrum and a difference in the aggressiveness of ACTs depending on the age group in which they were diagnosed. The predominance of maternal mutated allele inheritance was first demonstrated in the affected Brazilian's families.
- High Prevalence of Alterations in DNA Mismatch Repair Genes of Lynch Syndrome in Pediatric Patients with Adrenocortical Tumors Carrying a Germline Mutation on TP53(2020) BRONDANI, Vania Balderrama; MONTENEGRO, Luciana; LACOMBE, Amanda Meneses Ferreira; MAGALHAES, Breno Marchiori; NISHI, Mirian Yumie; FUNARI, Mariana Ferreira de Assis; NARCIZO, Amanda de Moraes; CARDOSO, Lais Cavalca; SIQUEIRA, Sheila Aparecida Coelho; ZERBINI, Maria Claudia Nogueira; DENES, Francisco Tibor; LATRONICO, Ana Claudia; MENDONCA, Berenice Bilharinho; ALMEIDA, Madson Queiroz; LERARIO, Antonio Marcondes; SOARES, Ibere Cauduro; FRAGOSO, Maria Candida Barisson VillaresAdrenocortical cancer is a rare malignant neoplasm associated with a dismal prognosis. Identification of the molecular pathways involved in adrenal tumorigenesis is essential for a better understanding of the disease mechanism and improvement of its treatment. The aim of this study is to define the prevalence of alterations in DNA mismatch repair (MMR) genes in Lynch syndrome among pediatric patients with adrenocortical neoplasia from southern Brazil, where the prevalence of a specific TP53 germline mutation (p.Arg337His) is quite high. Thirty-six pediatric patients were retrospectively evaluated. Immunohistochemistry (IHC) for theMMR enzymes MLH1, MSH2, MSH6, and PMS2, as well as next-generation sequencing (NGS) were performed. For IHC, 36 pediatric tumors were tested. In all of them, the expression of all evaluated MMR proteins was well-preserved. For NGS, 35 patients with pediatric tumor were tested. Three patients (8.57%) with the TP53 p.Arg337His germline mutation presented pathogenic and likely pathogenic variants in the MMR genes (two in MLH1 and one in MSH6). The prevalence of alteredMMR genes among pediatric patients was elevated (8.57%) and higher than in colorectal and endometrial cancer cohorts. Pediatric patients with adrenocortical tumors should, thus, be strongly considered as at genetic risk for Lynch syndrome.
- Allelic Variants of ARMC5 in Patients With Adrenal Incidentalomas and in Patients With Cushing's Syndrome Associated With Bilateral Adrenal Nodules(2020) MARIANI, Beatriz Marinho de Paula; NISHI, Mirian Yumie; WANICHI, Ingrid Quevedo; BRONDANI, Vania Balderrama; LACOMBE, Amanda Meneses Ferreira; CHARCHAR, Helaine; PEREIRA, Maria Adelaide Albergaria; SROUGI, Victor; TANNO, Fabio Yoshiaki; CECCATO, Filippo; REGAZZO, Daniela; BARBOT, Mattia; OCCHI, Gianluca; ALBIGER, Nora Maria Elvira; VIEIRA-CORREA, Marcelo; KATER, Claudio Elias; SCARONI, Carla; CHAMBO, Jose Luis; ZERBINI, Maria Claudia Nogueira; MENDONCA, Berenice B.; ALMEIDA, Madson Q.; FRAGOSO, Maria Candida Barisson VillaresObjective: Germline ARMC5 mutations are considered to be the main genetic cause of primary macronodular adrenal hyperplasia (PMAH). PMAH is associated with high variability of cortisol secretion caused from subclinical hypercortisolism to overt Cushing's syndrome (CS), in general due to bilateral adrenal nodules and rarely could also be due to non-synchronic unilateral adrenal nodules. The frequency of adrenal incidentalomas (AI) associated with PMAH is unknown. This study evaluated germline allelic variants of ARMC5 in patients with bilateral and unilateral AI and in patients with overt CS associated with bilateral adrenal nodules. Methods: We performed a retrospective multicenter study involving 123 patients with AI (64 bilateral; 59 unilateral). We also analyzed 20 patients with ACTH pituitary independent overt CS associated with bilateral adrenal nodules. All patients underwent germline genotyping analysis of ARMC5; abdominal CT and were classified as normal, possible or autonomous cortisol secretion, according to the low doses of dexamethasone suppression test. Results: We identified only one pathogenic allelic variant among the patients with bilateral AI. We did not identify any pathogenic allelic variants of ARMC5 in patients with unilateral AI. Thirteen out of 20 patients (65%) with overt CS and bilateral adrenal nodules were carriers of pathogenic germline ARMC5 allelic variants, all previously described. The germline ARMC5 mutation was observed in only one patient with bilateral AI; it was associated with autonomous cortisol secretion and showed to be a familial form. Conclusion: The rarity of germline ARMC5 mutations in AI points to other molecular mechanisms involved in this common adrenal disorder and should be investigated. In contrast, patients with overt Cushing's syndrome and bilateral adrenal nodules had the presence of ARMC5 mutations that were with high prevalence and similar to the literature. Therefore, we recommend the genetic analysis of ARMC5 for patients with established Cushing's syndrome and bilateral adrenal nodules rather than patients with unilateral AI.
- Triple A Syndrome: Preliminary Response to the Antioxidant N-Acetylcysteine Treatment in a Child(2017) FRAGOSO, Maria Candida Barisson Villares; ALBUQUERQUE, Edoarda Vasco de Albuquerque; CARDOSO, Ana Luiza de Almeida; ROSA, Paula Waki Lopes da; PAULO, Rodrigo Bomeny de; SCHIMIZU, Maria Heloisa Massola; SEGURO, Antonio Carlos; PASSARELLI, Marisa; KOEHLER, Katrin; HUEBNER, Angela; ALMEIDA, Madson Q.; LATRONICO, Ana Claudia; ARNHOLD, Ivo Jorge Prado; MENDONCA, Berenice BilharinhoIntroduction: Triple A syndrome (AAAS) is a rare autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency, autonomic dysfunction, and progressive neurodegeneration. Increased oxidative stress, demonstrated in patients' fibroblasts in vitro, may be a central disease mechanism. N-acetylcysteine protects renal function in patients with kidney injuries associated with increased oxidative stress and improves viability of AAAS-knockdown adrenal cells in vitro. Patient and Results: A boy diagnosed with AAAS presented with short stature and increased oxidative stress in vivo assessed by increased thiobarbituric acid reactive substances (TBARS), which are markers of lipid peroxidation, and by the susceptibility of LDL to oxidation and the capacity of HDL to prevent it. A homozygous missense germline mutation (c.523G>T, p.Val175Phe) in AAAS was identified. N-acetylcysteine (600 mg orally, twice daily) decreased oxidative stress but did not change the patient's growth pattern. Conclusions: An increase in oxidative stress is reported for the first time in vivo in an AAAS patient. N-acetylcysteine was capable of decreasing TBARS levels, reducing the susceptibility of LDL to oxidation and improving the antioxidant role of HDL. The long-term effect of antioxidant treatment should be evaluated to determine the real benefit for the prevention of the degenerative process in AAAS. (C) 2017 S. Karger AG, Basel
bookPart Insuficiência primária da suprarrenal(2022) FRAGOSO, Maria Candida Barisson Villares; ALMEIDA, Madson Queiroz de- TCF21/POD-1, a Transcritional Regulator of SF-1/NR5A1, as a Potential Prognosis Marker in Adult and Pediatric Adrenocortical Tumors(2018) PASSAIA, Barbara dos Santos; DIAS, Matheus Henrique; KREMER, Jean Lucas; ANTONINI, Sonir Roberto Rauber; ALMEIDA, Madson Queiroz de; FRAGOSO, Maria Candida Barisson Villares; LOTFI, Claudimara Ferini PaciccoWith recent progress in understanding the pathogenesis of adrenocortical tumors (ACTs), identification of molecular markers to predict their prognosis has become possible. Transcription factor 21 (TCF21)/podocyte-expressed 1 (POD1) is a transcriptional regulatory protein expressed in mesenchymal cells at sites of epithelial-mesenchymal transition during the development of different systems. Adult carcinomas express less TCF21 than adenomas, in addition, the KEGG pathway analysis has shown that BUB1B, among others genes, is negatively correlated with TCF21 expression. The difference between BUB1B and PTEN-induced putative kinase 1 (PINK1) expression has been described previously to be associated with survival in adult but not in pediatric carcinomas. Here, we analyzed the gene expression of TCF21, BUB1B, PINK1, and NR5A1 in adult and pediatric ACTs. We found a negative correlation between the relative expression levels of TCF21 and BUB1B in adult ACTs, but the relative expression levels of TCF21, BUB1B, PINK1, and NR5A1 were similar in childhood ACTs. In addition, we propose using the subtracted expression levels of the TCF21/POD-1 genes as a predictor of overall survival (OS) in adult carcinomas and TCF21-NR5A1 as a predictor of malignancy for pediatric tumors in patients aged <5 years. These results require further validation in different cohorts of both adult and pediatric samples. Finally, we observed that the OS for patients aged <5 years was markedly favorable compared with that for patients >5 years as well as adult patients with carcinoma. In summary, we propose TCF21/POD-1 as a new prognostic marker in adult and pediatric ACTs.