SUELI MIEKO OBA SHINJO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Neurologia, Faculdade de Medicina
LIM/15 - Laboratório de Investigação em Neurologia, Hospital das Clínicas, Faculdade de Medicina
LIM/15 - Laboratório de Investigação em Neurologia, Hospital das Clínicas, Faculdade de Medicina
94 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 94
- Impact of a cell cycle and an extracellular matrix remodeling transcriptional signature on tumor progression and correlation with EZH2 expression in meningioma(2022) PEREIRA, Benedito Jamilson Araujo; LERARIO, Antonio Marcondes; SOLA, Paula Rodrigues; LAURENTINO, Talita de Sousa; MOHAN, Dipika R.; ALMEIDA, Antonio Nogueira de; AGUIAR, Paulo Henrique Pires de; PAIVA, Wellingson da Silva; WAKAMATSU, Alda; TEIXEIRA, Manoel Jacobsen; OBA-SHINJO, Sueli Mieko; MARIE, Suely Kazue NagahashiOBJECTIVE The authors searched for genetic and transcriptional signatures associated with tumor progression and recurrence in their cohort of patients with meningiomas, combining the analysis of targeted exome, NF2-LOH, transcrip-tome, and protein expressions. METHODS The authors included 91 patients who underwent resection of intracranial meningioma at their institution between June 2000 and November 2007. The search of somatic mutations was performed by Next Generation Sequenc-ing through a customized panel and multiplex ligation-dependent probe amplification for NF2 loss of heterozygosity. The transcriptomic profile was analyzed by QuantSeq 3 ' mRNA-Seq. The differentially expressed genes of interest were validated at the protein level analysis by immunohistochemistry.RESULTS The transcriptomic analysis identified an upregulated set of genes related to metabolism and cell cycle and downregulated genes related to immune response and extracellular matrix remodeling in grade 2 (atypical) meningio-mas, with a significant difference in recurrent compared with nonrecurrent cases. EZH2 nuclear positivity associated with grade 2, particularly with recurrent tumors and EZH2 gene expression level, correlated positively with the expres-sion of genes related to cell cycle and negatively to genes related to immune response and regulation of cell motility. CONCLUSIONS The authors identified modules of dysregulated genes in grade 2 meningiomas related to the activation of oxidative metabolism, cell division, cell motility due to extracellular remodeling, and immune evasion that were predic-tive of survival and exhibited significant correlations with EZH2 expression.
conferenceObject CD99 role in glioblastoma cell migration(2018) CARDOSO, Cavalca; LERARIO, Antonio Marcondes; BRANTIS, Carlos Eduardo de Carvalho; FREITAS, Vanessa Galdeno; SOARES, Roseli da Silva; MARIE, Suely Kazue Nagahashi; OBA-SHINJO, Sueli Mieko- Melatonergic system-based two-gene index is prognostic in human gliomas(2016) KINKER, Gabriela S.; OBA-SHINJO, Sueli M.; CARVALHO-SOUSA, Claudia E.; MUXEL, Sandra M.; MARIE, Suely K. N.; MARKUS, Regina P.; FERNANDES, Pedro A.Gliomas, the most common primary brain tumors in adults, are classified into four malignancy grades according to morphological features. Recent studies have shown that melatonin treatment induces cytotoxicity in glioma-initiating cells and reduces the invasion and migration of glioma cell lines, inhibiting the nuclear factor kappa B (NF kappa B) oncopathway. Given that C6 rat glioma cells produce melatonin, we investigated the correlation between the capacity of gliomas to synthesize/metabolize melatonin and their overall malignancy. We first characterized the melatonergic system of human gliomas cell lines with different grades of aggressiveness (HOG, T98G, and U87MG) and demonstrated that glioma-synthesized melatonin exerts an autocrine antiproliferative effect. Accordingly, the sensitivity to exogenous melatonin was higher for the most aggressive cell line, U87MG, which synthesized/accumulated less melatonin. Using The Cancer Genome Atlas RNAseq data of 351 glioma patients, we designed a predictive model of the content of melatonin in the tumor microenvironment, the ASMT:CYP1B1 index, combining the gene expression levels of melatonin synthesis and metabolism enzymes. The ASMT: CYP1B1 index negatively correlated with tumor grade, as well as with the expression of pro-proliferation and anti-apoptotic NF kappa B target genes. More importantly, the index was a grade-and histological type-independent prognostic factor. Even when considering only high-grade glioma patients, a low ASMT: CYP1B1 value, which suggests decreased melatonin and enhanced aggressiveness, was strongly associated with poor survival. Overall, our data reveal the prognostic value of the melatonergic system of gliomas and provide insights into the therapeutic role of melatonin.
- Cyclin E1 expression and malignancy in meningiomas(2020) PEREIRA, Benedito Jamilson Araujo; SANTANA JUNIOR, Pedro Augustto de; ALMEIDA, Antonio Nogueira de; CAVALCANTE, Stella Goncalves; MELO, Keyde Cristina Martins de; AGUIAR, Paulo Henrique Pires de; PAIVA, Wellingson da Silva; OBA-SHINJO, Sueli Mieko; MARIE, Suely Kazue NagahashiObjective: The aim of the present study was to analyze if the pathway Skp2-p27-cyclin El could also be a tumor progression marker for meningiomas. Patients and methods: We used quantitative real-time PCR to assess the relative expression levels of the genes coding for cyclin El (CCNE1), Skp2 (SKP2), and p27 (P27). The expression levels were compared in grades Ito III meningiomas and among different histological subtypes of grade I meningiomas. Results: Anaplastic meningiomas accounted for 4.9%, atypical meningiomas for 23.5% and grade I meningiomas for 71.6%.CCNE1 expression level was significantly higher in grade II compared to grade I meningiomas (p = 0.0027), and its expression level reliably predicts grade II meningiomas (ROC AUC = 0.731, p = 0.003). CCNE1 expression also correlated with SKP2 and P27 expression levels in grade I meningiomas (r = 0.539, p < 0.0001 and r = 0.687, p = < 0.0001, respectively for CCNE1/SKP2 and CCNE1/P27, Spearman's test). Fibrous subtype among grade I meningiomas presented the highest expression levels of CCNE1, SKP2 and P27. Higher expression of cyclin El protein was detected in the nuclei of atypical meningiomas compared to grade I meningiomas. Conclusions: CCNE1 expression level predicts meningioma malignancy, and the fibrous subtype presents the highest gene expression levels among grade I meningiomas.
- Transcriptomic analysis of purified human cortical microglia reveals age-associated changes(2017) GALATRO, Thais F.; HOLTMAN, Inge R.; LERARIO, Antonio M.; VAINCHTEIN, Ilia D.; BROUWER, Nieske; SOLA, Paula R.; VERAS, Mariana M.; PEREIRA, Tulio F.; LEITE, Renata E. P.; MOLLER, Thomas; WES, Paul D.; SOGAYAR, Mari C.; LAMAN, Jon D.; DUNNEN, Wilfred den; PASQUALUCCI, Carlos A.; OBA-SHINJO, Sueli M.; BODDEKE, Erik W. G. M.; MARIE, Suely K. N.; EGGEN, Bart J. L.Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes CX3CR1, P2RY12 and ITGAM (CD11B). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including TLR, F-c gamma and SIGLEC receptors, as well as TAL1 and IFI16, regulators of proliferation and cell cycle. Age-associated changes in human microglia were enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression and actin (dis)assembly. Limited overlap was observed in microglial genes regulated during aging between mice and humans, indicating that human and mouse microglia age differently.
- OTX1 and OTX2 Genes in Medulloblastoma (vol 127, pg e58, 2019)(2019) MUOIO, Valeria Marques Figueira; UNO, Miyuki; OBA-SHINJO, Sueli; SILVA, Roseli da; PEREIRA, Benedito Jamilson Araujo; CLARA, Carlos; MATUSHITA, Hamilton; MARIE, Suely K. N.
- CD99 Expression in Glioblastoma Molecular Subtypes and Role in Migration and Invasion(2019) CARDOSO, Lais C.; SOARES, Roseli da S.; LAURENTINO, Talita de S.; LERARIO, Antonio M.; MARIE, Suely K. N.; OBA-SHINJO, Sueli MiekoGlioblastoma (GBM) is the most aggressive type of brain tumor, with an overall survival of 17 months under the current standard of care therapy. CD99, an over-expressed transmembrane protein in several malignancies, has been considered a potential target for immunotherapy. To further understand this potentiality, we analyzed the differential expression of its two isoforms in human astrocytoma specimens, and the CD99 involved signaling pathways in glioma model U87MG cell line. CD99 was also analyzed in GBM molecular subtypes. Whole transcriptomes by RNA-Seq of CD99-siRNA, and functional in vitro assays in CD99-shRNA, that are found in U87MG cells, were performed. Astrocytoma of different malignant grades and U87MG cells only expressed CD99 isoform 1, which was higher in mesenchymal and classical than in proneural GBM subtypes. Genes related to actin dynamics, predominantly to focal adhesion, and lamellipodia/filopodia formation were down-regulated in the transcriptome analysis, when CD99 was silenced. A decrease in tumor cell migration/invasion, and dysfunction of focal adhesion, were observed in functional assays. In addition, a striking morphological change was detected in CD99-silenced U87MG cells, further corroborating CD99 involvement in actin cytoskeleton rearrangement. Inhibiting the overexpressed CD99 may improve resectability and decrease the recurrence rate of GBM by decreasing tumor cells migration and invasion.
conferenceObject Brain transcriptome analysis of Japanese population living in Brazil(2019) MARIE, Suely Kazue Nagahashi; LERARIO, Antonio Marcondes; SHINJO, Sueli Mieko Oba; NASCIMENTO, Camila; LEITE, Renata; SUEMOTO, Claudia; PASQUALUCCI, Carlos Augusto; MURAYAMA, Shigeo- Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies(2014) BETTEGOWDA, Chetan; SAUSEN, Mark; LEARY, Rebecca J.; KINDE, Isaac; WANG, Yuxuan; AGRAWAL, Nishant; BARTLETT, Bjarne R.; WANG, Hao; LUBER, Brandon; ALANI, Rhoda M.; ANTONARAKIS, Emmanuel S.; AZAD, Nilofer S.; BARDELLI, Alberto; BREM, Henry; CAMERON, John L.; LEE, Clarence C.; FECHER, Leslie A.; GALLIA, Gary L.; GIBBS, Peter; LE, Dung; GIUNTOLI, Robert L.; GOGGINS, Michael; HOGARTY, Michael D.; HOLDHOFF, Matthias; HONG, Seung-Mo; JIAO, Yuchen; JUHL, Hartmut H.; KIM, Jenny J.; SIRAVEGNA, Giulia; LAHERU, Daniel A.; LAURICELLA, Calogero; LIM, Michael; LIPSON, Evan J.; MARIE, Suely Kazue Nagahashi; NETTO, George J.; OLINER, Kelly S.; OLIVI, Alessandro; OLSSON, Louise; RIGGINS, Gregory J.; SARTORE-BIANCHI, Andrea; SCHMIDT, Kerstin; SHIH, Ie-Ming; OBA-SHINJO, Sueli Mieko; SIENA, Salvatore; THEODORESCU, Dan; TIE, Jeanne; HARKINS, Timothy T.; VERONESE, Silvio; WANG, Tian-Li; WEINGART, Jon D.; WOLFGANG, Christopher L.; WOOD, Laura D.; XING, Dongmei; HRUBAN, Ralph H.; WU, Jian; ALLEN, Peter J.; SCHMIDT, C. Max; CHOTI, Michael A.; VELCULESCU, Victor E.; KINZLER, Kenneth W.; VOGELSTEIN, Bert; PAPADOPOULOS, Nickolas; DIAZ JR., Luis A.The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in > 75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.
- LOXL3 knock out affects pathways which involve cytoskeleton regulation, proliferation and apoptosis in glioblastoma cells(2023) LAURENTINO, Talita S.; SOARES, Roseli S.; LERARIO, Antonio M.; MARIE, Suely K.; OBA-SHINJO, Sueli Mieko