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
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conferenceObject A Lower Ki 67 Labelling Index (LI) Cut-Point Improves the Prognostic Assessment and Might Aid in the Diagnosis of Adult Adrenocortical Tumors(2018) MARTINS FILHO, Sebastiao N.; ALMEIDA, Madson Q.; SOARES, Ibere C.; WAKAMATSU, Alda; ALVES, Venancio; FRAGOSO, Maria C.; ZERBINI, MariaconferenceObject A Lower Ki 67 Labelling Index (LI) Cut-Point Improves the Prognostic Assessment and Might Aid in the Diagnosis of Adult Adrenocortical Tumors(2018) MARTINS FILHO, Sebastiao N.; ALMEIDA, Madson Q.; SOARES, Ibere C.; WAKAMATSU, Alda; ALVES, Venancio; FRAGOSO, Maria C.; ZERBINI, Maria- The role of ARMC5 in human cell cultures from nodules of primary macronodular adrenocortical hyperplasia (PMAH)(2018) CAVALCANTE, Isadora P.; NISHI, Mirian; ZERBINI, Maria Claudia N.; ALMEIDA, Madson Q.; BRONDANI, Vania B.; BOTELHO, Maria Luiza Anhaia de Arruda; TANNO, Fabio Y.; SROUGI, Victor; CHAMBO, Jose Luis; MENDONCA, Berenice B.; BERTHERAT, Jerome; LOTFI, Claudimara F. P.; FRAGOSO, Maria Candida B. V.The participation of aberrant receptors and intra-adrenal ACTH in hyperplastic tissue are considered mechanisms that regulate hypercortisolism in PMAH. Additionally, germline ARMC5 mutations have been described as the most frequent genetic abnormality found in patients diagnosed with PMAH. Previous functional studies analyzed ARMC5 role using H295R cells. Therefore, we investigated the role of ARMC5 in cell cultures obtained from PMAH nodules containing steroidogenic cells, aberrant receptors and intra-adrenal ACTH. ARMC5 silencing in non-mutated PMAH cell cultures decreased steroidogenesis-related genes and increased CCNE1 mRNA expression and proliferative capacity without affecting cell viability. Additionally, ARMC5 overexpression induced cell death in PMAH mutated cell cultures, thereby decreasing cell viability. We confirmed the role of ARMC5 as an important pro-apoptotic protein involved in PMAH-related steroidogenesis. We also report for the first time the involvement of ARMC5 in controlling proliferation and regulating cell cycle in PMAH cell cultures; these effects need to be explored further.
conferenceObject A Simple Yet Powerful Algorithm Including Ki67 Labeling Index (LI) Helps Predict Outcome Pediatric Adrenocortical Tumors (ACT)(2018) MARTINS FILHO, Sebastiao N.; ALMEIDA, Madson Q.; WAKAMATSU, Alda; ALVES, Venancio; FRAGOSO, Maria C.; ZERBINI, MariaconferenceObject A Simple Yet Powerful Algorithm Including Ki67 Labeling Index (LI) Helps Predict Outcome in Pediatric Adrenocortical Tumors (ACT)(2018) MARTINS FILHO, Sebastiao N.; ALMEIDA, Madson Q.; WAKAMATSU, Alda; ALVES, Venancio; FRAGOSO, Maria C.; ZERBINI, Maria- Insulinoma: A retrospective study analyzing the differences between benign and malignant tumors(2018) CAMARA-DE-SOUZA, A. B.; TOYOSHIMA, M. T. K.; GIANNELLA, M. L.; FREIRE, D. S.; CAMACHO, C. P.; LOURENCO JR., D. M.; ROCHA, M. S.; BACCHELLA, T.; JUREIDINI, R.; MACHADO, M. C. C.; ALMEIDA, M. Q.; PEREIRA, M. A. A.Background/objectives: Insulinoma is a rare pancreatic tumor and, usually, a benign disease but can be a malignant one and, sometimes, a highly aggressive disease. The aim of this study was to determine differences between benign and malignant tumors. Methods: Retrospective study of 103 patients with insulinoma treated in a tertiary center. It was analyzed demographic, clinical, laboratory, localization and histologic analysis of tumor and follow up data of subjects in order to identify differences between individuals benign and malignant disease. Results: Almost all patients (87%) had a benign tumor and survival rates of 100% following pancreatic tumor surgery. Those with malignant tumors (13%) have a poor prognosis, 77% insulinoma-related deaths over a period of 1-300 months after the diagnosis with a survival rate of 24% in five years. The following factors are associated with an increased risk of malignant disease: duration of symptoms < 24 months, fasting time for the occurrence of hypoglycemia < 8 h, blood plasma insulin concentration > 28 mu U/mL and C-peptide >= 4.0 ng/mL at the glycemic nadir and tumor size >= 2.5 cm. Conclusions: Our data help to base the literature about these tumors, reinforcing that although insulinoma is usually a single benign and surgically treated neoplasia, the malignant one is difficult to treat. We highlight the data that help predict a malignancy behavior of tumor and suggest a long follow up after diagnosis in these cases.
- 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.
- Primary malignant tumors of the adrenal glands(2018) ALMEIDA, Madson Q.; BEZERRA-NETO, Joao Evangelista; MENDONCA, Berenice B.; LATRONICO, Ana Claudia; V, Maria Candida B. FragosoMalignancy must be considered in the management of adrenal lesions, including those incidentally identified on imaging studies. Adrenocortical carcinomas (ACCs) are rare tumors with an estimated annual incidence of 0.7-2 cases per year and a worldwide prevalence of 4-12 cases per million/year. However, a much higher incidence of these tumors (415 times) has been demonstrated in south and southeastern Brazil. Most ACCs cause hypersecretion of steroids including glucocorticoids and androgens. ACC patients have a very poor prognosis with a 5-year overall survival (OS) below 30% in most series. Pheochromocytoma or paraganglioma (PPGL) is a metabolically active tumor originating from the chromaffin cells of the adrenal medulla. The incidence of PPGL is 0.2 to 0.9 cases per 100,000 individuals per year. Pheochromocytomas are present in approximately 4-7% of patients with adrenal incidentalomas. Classically, PPGL manifests as paroxysmal attacks of the following 4 symptoms: headaches, diaphoresis, palpitations, and severe hypertensive episodes. The diagnosis of malignant PPGL relies on the presence of local invasion or metastasis. In this review, we present the clinical and biochemical characteristics and pathogenesis of malignant primary lesions that affect the cortex and medulla of human adrenal glands.
- Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors(2018) KRAUSS, Tobias; FERRARA, Alfonso Massimiliano; LINKS, Thera P.; WELLNER, Ulrich; BANCOSS, Irina; KVACHENYUK, Andrey; HERAS, Karim Villar Gomez de las; YUKINA, Marina Y.; PETROV, Roman; BULLIVANT, Garrett; DUECKER, Laura von; JADHAV, Swati; PLOECKINGER, Ursula; WELIN, Staffan; SCHALIN-JANTTI, Camilla; GIMM, Oliver; PFEIFER, Marija; NGEOW, Joanne; HASSE-LAZAR, Kornelia; SANSO, Gabriela; QI, Xiaoping; UGURLU, M. Umit; DIAZ, Rene E.; WOHLLK, Nelson; PECZKOWSKA, Mariola; ABERLE, Jens; JR, Delmar M. Lourenco; PEREIRA, Maria A. A.; V, Maria C. B. Fragoso; HOFF, Ana O.; ALMEIDA, Madson Q.; VIOLANTE, Alice H. D.; OUIDUTE, Ana R. P.; ZHANG, Zhewei; RECASENS, Monica; DIAZ, Luis Robles; KUNAVISARUT, Tada; WANNACHALEE, Taweesak; SIRINVARAVONG, Sirinart; JONASCH, Eric; GROZINSKY-GLASBERG, Simona; FRAENKEL, Merav; BELTSEVICH, Dmitry; I, Viacheslav Egorov; BAUSCH, Dirk; SCHOTT, Matthias; TILING, Nikolaus; PENNELLI, Gianmaria; ZSCHIEDRICH, Stefan; DAERR, Roland; RUF, Juri; DENECKE, Timm; LINK, Karl-Heinrich; ZOVATO, Stefania; DOBSCHUETZ, Ernst von; YAREMCHUK, Svetlana; AMTHAUER, Holger; MAKAY, Ozer; PATOCS, Attila; WALZ, Martin K.; HUBER, Tobias B.; SEUFERT, Jochen; HELLMAN, Per; EKATERINA, Raymond H.; KUCHINSKAYA, Ekaterina; SCHIAVI, Francesca; MALINOC, Angelica; REISCH, Nicole; JARZAB, Barbara; BARONTINI, Marta; JANUSZEWICZ, Andrzej; SHAH, Nalini; YOUNG JR., William F.; OPOCHER, Giuseppe; ENG, Charis; NEUMANN, Hartmut P. H.; BAUSCH, BirkePancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P < 0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P = 0.001). All metastatic tumors were >= 2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off >= 2.8 cm, 44% and 91% for TVDT cut-off of <= 24 months). In 117 of 273 patients, PanNETs > 1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs < 2.8 cm vs >= 2.8 cm (94% vs 85% by 10 years; P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.