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
52 resultados
Resultados de Busca
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- 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.
- Exercise training attenuates skeletal muscle fat infiltration and improves insulin pathway of patients with immune-mediated necrotizing myopathies and dermatomyositis(2023) OLIVEIRA, Diego Sales de; BORGES, Isabela Bruna Pires; MARIE, Suely Kazue Nagahashi; LERARIO, Antonio Marcondes; OBA-SHINJO, Sueli Mieko; SHINJO, Samuel KatsuyukiObjectives: This study aims to evaluate the effects of exercise training on intramuscular lipid content and genes related to insulin pathway in patients with systemic autoimmune myopathies (SAMs). Patients and methods: Between January 2016 and May 2019, a total of seven patients with dermatomyositis (DM; 3 males, 4 females; mean age: 49.8 & PLUSMN;2.3 years; range, 43 to 54 years), six with immune mediated necrotizing myopathy (IMNM; 3 males, 3 females; mean age: 58.5 & PLUSMN;10.6 years; range, 46 to 74 years), and 10 control individuals (CTRL group; 4 males, 6 females; mean age: 48.7 & PLUSMN;3.9 years; range, 41 to 56 years) were included. The muscle biopsy before and after the intervention was performed to evaluate the intramuscular lipid content. Patients underwent a combined exercise training program for 12 weeks. Skeletal muscle gene expression was analyzed and the DM versus CTRL group, DM pre-and post-, and IMNM pre-and post-intervention were compared. Results: The DM group had a higher intramuscular lipid content in type II muscle fibers compared to the CTRL group. After the intervention, there was a reduction of lipid content in type I and II fibers in DM and IMNM group. The CTRL group showed a significantly higher expression of genes related to insulin and lipid oxidation pathways (AMPK$2, AS160, INSR, PGC1-a, PI3K, and RAB14) compared to the DM group. After exercise training, there was an increase gene expression related to insulin pathway and lipid oxidation in DM group (AMPK$2, AS160, INSR, PGC1-a, PI3K, and RAB14) and in IMNM group (AKT2, AMPK$2, RAB10, RAB14, and PGC1-a). Conclusion: Exercise training attenuated the amount of fat in type I and II muscle fibers in patients with DM and IMNM and increased gene expression related to insulin pathways and lipid oxidation in DM and IMNM. These results suggest that exercise training can improve the quality and metabolic functions of skeletal muscle in these diseases.
- Changes in the expression of proteins associated with aerobic glycolysis and cell migration are involved in tumorigenic ability of two glioma cell lines(2012) RAMAO, Anelisa; GIMENEZ, Marcela; LAURE, Helen Julie; IZUMI, Clarice; VIDA, Rodrigo Cesar dos Santos; OBA-SHINJO, Sueli; MARIE, Suely Kazue Nagahashi; ROSA, Jose CesarBackground: The most frequent and malignant brain cancer is glioblastoma multiforme (GBM). In gliomas, tumor progression and poor prognosis are associated with the tumorigenic ability of the cells. U87MG cells (wild-type p53) are known to be tumorigenic in nude mice, but T98G cells (mutant p53) are not tumorigenic. We investigated the proteomic profiling of these two cell lines in order to gain new insights into the mechanisms that may be involved in tumorigenesis. Results: We found 24 differentially expressed proteins between T98G and U87MG cells. Gene Ontology supports the notion that over-representation of differentially expressed proteins is involved in glycolysis, cell migration and stress oxidative response. Among those associated with the glycolysis pathway, TPIS and LDHB are up-regulated in U87MG cells. Measurement of glucose consumption and lactate production suggests that glycolysis is more effective in U87MG cells. On the other hand, G6PD expression was 3-fold higher in T98G cells and this may indicate a shift to the pentose-phosphate pathway. Moreover, GRP78 expression was also three-fold higher in T98G than in U87MG cells. Under thapsigargin treatment both cell lines showed increased GRP78 expression and the effect of this agent was inversely correlated to cell migration. Quantitative RT-PCR and immunohistochemistry of GRP78 in patient samples indicated a higher level of expression of GRP78 in grade IV tumors compared to grade I and non-neoplastic tissues, respectively. Conclusions: Taken together, these results suggest an important role of proteins involved in key functions such as glycolysis and cell migration that may explain the difference in tumorigenic ability between these two glioma cell lines and that may be extrapolated to the differential aggressiveness of glioma tumors.
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- 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.
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, ShigeobookPart Sequenciamento em larga escala: impactos em oncologia(2017) OBA-SHINJO, Sueli Mieko; MARIE, Suely Kazue Nagahashi- 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.
- Glutaminolysis dynamics during astrocytoma progression correlates with tumor aggressiveness(2021) FRANCO, Yollanda E. Moreira; ALVES, Maria Jose; UNO, Miyuki; MORETTI, Isabele Fattori; TROMBETTA-LIMA, Marina; SANTOS, Suzana de Siqueira; SANTOS, Ancely Ferreira dos; ARINI, Gabriel Santos; BAPTISTA, Mauricio S.; LERARIO, Antonio Marcondes; OBA-SHINJO, Sueli Mieko; MARIE, Suely Kazue NagahashiBackground Glioblastoma is the most frequent and high-grade adult malignant central nervous system tumor. The prognosis is still poor despite the use of combined therapy involving maximal surgical resection, radiotherapy, and chemotherapy. Metabolic reprogramming currently is recognized as one of the hallmarks of cancer. Glutamine metabolism through glutaminolysis has been associated with tumor cell maintenance and survival, and with antioxidative stress through glutathione (GSH) synthesis. Methods In the present study, we analyzed the glutaminolysis-related gene expression levels in our cohort of 153 astrocytomas of different malignant grades and 22 non-neoplastic brain samples through qRT-PCR. Additionally, we investigated the protein expression profile of the key regulator of glutaminolysis (GLS), glutamate dehydrogenase (GLUD1), and glutamate pyruvate transaminase (GPT2) in these samples. We also investigated the glutathione synthase (GS) protein profile and the GSH levels in different grades of astrocytomas. The differential gene expressions were validated in silico on the TCGA database. Results We found an increase of glutaminase isoform 2 gene (GLSiso2) expression in all grades of astrocytoma compared to non-neoplastic brain tissue, with a gradual expression increment in parallel to malignancy. Genes coding for GLUD1 and GPT2 expression levels varied according to the grade of malignancy, being downregulated in glioblastoma, and upregulated in lower grades of astrocytoma (AGII-AGIII). Significant low GLUD1 and GPT2 protein levels were observed in the mesenchymal subtype of GBM. Conclusions In glioblastoma, particularly in the mesenchymal subtype, the downregulation of both genes and proteins (GLUD1 and GPT2) increases the source of glutamate for GSH synthesis and enhances tumor cell fitness due to increased antioxidative capacity. In contrast, in lower-grade astrocytoma, mainly in those harboring the IDH1 mutation, the gene expression profile indicates that tumor cells might be sensitized to oxidative stress due to reduced GSH synthesis. The measurement of GLUD1 and GPT2 metabolic substrates, ammonia, and alanine, by noninvasive MR spectroscopy, may potentially allow the identification of IDH1(mut) AGII and AGIII progression towards secondary GBM.
- Comparison between treatment naive juvenile and adult dermatomyositis muscle biopsies: difference of inflammatory cells phenotyping(2018) SHINJO, Samuel Katsuyuki; SALLUM, Adriana Maluf Elias; OBA-SHINJO, Sueli Mieko; SILVA, Marilda Guimaraes; SILVA, Clovis Artur; MARIE, Suely Kazue NagahashiBackground: Different inflammatory cells (i.e., CD4, CD8, CD20 and CD68) are involved in pathogenesis of DM muscle. In this context, the aim of this study was to assess and compare these inflammatory cell phenotyping in muscle samples of treatment naive juvenile and adult patients with dermatomyositis. Methods: This is a cross-sectional study, in which 28 untreated juvenile and 28 adult untreated dermatomyositis patients were included. Immunohistochemical analysis was performed on serial frozen muscle sections. Inflammatory cell phenotyping was analyzed quantitatively in endomysium, perimysium, and perivascular (endomysium and perimysium) area. Results: Mean age at disease onset was 73 and 42.0 years in juvenile and adult dermatomyositis, respectively. Both groups had comparable time duration from symptom's onset to biopsy performance. CD4 and CD8 positive cells distributions were similar in both groups in all analyzed area, except for more predominance of CD4 in perimysium at juvenile muscle biopsies. The CD20 and CD68 positive cells were predominantly observed in adult muscle biopsy sections, when compared to juvenile samples, except for similar distribution of CD20 in perivascular endomysium, and CD68 in perimysium. Conclusions: These data show that the differences between juvenile and adult dermatomyositis may be restricted not only to patients' age, but also to different inflammatory cell distribution, particularly, in new-onset disease. Further studies are necessary to confirm the present study data and to analyze meaning of the different inflammatory cell phenotyping distribution finding in these both diseases.