SUELY KAZUE NAGAHASHI MARIE
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Neurologia, Faculdade de Medicina - Docente
LIM/15 - Laboratório de Investigação em Neurologia, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/15 - Laboratório de Investigação em Neurologia, Hospital das Clínicas, Faculdade de Medicina - Líder
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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.
- 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.
- Aquaporin-4 Expression in Meningioma Malignancy Progression(2023) PEREIRA, Benedito Jamilson Araujo; OBA-SHINJO, Sueli M.; AGUIAR, Paulo Henrique Pires de; ALMEIDA, Antonio Nogueira de; PAIVA, Wellingson da Silva; MARIE, Suely Kazue NagahashiObjectives The aim of the present study is to analyze if aquaporin-4 (AQP4 ) may also be a tumor progression marker for meningiomas. Methods This is an immunohistochemistry study realized at the Universidade de Sao Paulo, Sao Paulo, state of Sao Paulo, Brazil: frozen meningioma samples from 81 patients (57 females and 24 males, age range from 22 to 81 years old, average 56.5 +/- 14.1 years old), including 57 meningiomas World Health Organization (WHO) grade I (GI); 19 grade II (GII), and 5 grade III (GIII) were analyzed. The relative expression level of AQP4 was analyzed by quantitative polymerase chain reaction (qPCR), using the SYBR Green approach and for staining detection. Tissue sections were routinely processed and subjected to antigen retrieval. Results The expression of AQP4 in meningioma samples ranged from 0 to 10.26, with a median of 0.001 in GI cases, of 0.008 in GII cases, and of 0.006 in GIII cases. Although not statistically significant ( p = 0.942), GI meningiomas have a lower median AQP4 expression level than higher malignant grade cases. Conclusion The AQP4 gene and protein expressions presented no association with meningioma malignant progression.
- Impact of radiotherapy in atypical meningioma recurrence: literature review(2019) PEREIRA, Benedito Jamilson Araujo; ALMEIDA, Antonio Nogueira de; PAIVA, Wellingson Silva; TEIXEIRA, Manoel Jacobsen; MARIE, Suely Kazue NagahashiEvaluate whether radiotherapy (RT) after the neurosurgical treatment of atypical meningiomas (AM) has an impact on the reduction rate of recurrence. A Medline search through October 2017 using ""atypical meningioma"" returned 1277 papers for initial review. Inclusion criteria were as follows. We analyzed the database and included articles in which the anatomic pathological classification of atypical meningiomas was in accordance with WHO 2007 or WHO 2016 criteria, patients > 18 years of age, and there was postoperative external beam radiation to the tumor bed. Exclusion criteria were WHO grade I or III meningioma, patients who underwent whole-brain radiation, RT used as salvage therapy for recurrence, palliative dose of RT (< 45 Gy), recurrent AMs, and multiple AMs. Papers reporting outcomes in which atypical and anaplastic meningiomas were analyzed together were rejected, as were papers with small samples that may compromise evaluation. After filtering our initial selection, only 17 papers were selected. After reviewing the seventeen articles including a total of 1761 patients (972 female and 799 male; 1.21 female/1.0 male), the difference in proportion of tumor recurrence between patients with and without radiotherapy after neurosurgical procedure was 1.0448, 95% CI [0.8318 to 1.3125], p value = 0.7062. On the basis of this review, there is no evidence to suggest that RT decreases the rate of recurrence in patients with atypical meningiomas.
- Clinical Outcome, Tumor Recurrence, and Causes of Death: A Long-Term Follow-Up of Surgically Treated Meningiomas(2017) ALMEIDA, Antonio Nogueira de; PEREIRA, Benedito Jamilson Araujo; AGUIAR, Paulo Henrique Pires; PAIVA, Wellingson Silva; CABRERA, Hector Navarro; SILVA, Clemar Correa da; TEIXEIRA, Manoel Jacobsen; MARIE, Suely Kazue NagahashiOBJECTIVE: The medical literature still lacks information about the impact of surgery and adjuvant treatment on the life of patients with meningioma. The clinical outcome, timing of tumor recurrence, and causes of death are often overlooked. This study evaluates these data taking into account tumor localization and histologic grade. METHODS: The article is a cross-sectional study of patients operated on between 2000 and 2014 in a single institution. The series has 593 adult patients (442 females and 151 males) and follow-up of 68.8 +/- 48.9 months. Imaging of 434 patients was reviewed and 379 patients/families interviewed. RESULTS: Sixty-eight deaths were related to tumor treatment/progression and 36 to other causes. After 2 years of surgery, deaths not related to tumor were 7 times more frequent than were tumor-related deaths (odds ratio, 7.1; 95% confidence interval, 2.8e19.5; P < 0.0001). Ten-year survival was expected in 85% of patients with grade I (GI) meningioma, 35% of patients with atypic (GII) meningioma, and 0% of patients with anaplastic (GIII) meningioma. Convexity tumors had about half the risk of recurrence compared with other localizations (odds ratio, 0.4; 95% confidence interval, 0.27-0.67; P = 0.0002). In GI meningioma, recurrence was neither related to death nor to impairment of independent life. All patients with GII and GIII meningioma who had recurrence died. 96.3% of interviewees reported neurologic improvement or stability after the surgery. CONCLUSIONS: Histologic grade is the most important factor for long-term survival. Complete resection has to be pursued in GII and GIII meningioma but must be carefully weighed against morbidities in GI meningioma.
- Assessment of hemorrhagic onset on meningiomas: Systematic review(2020) PEREIRA, Benedito Jamilson Araujo; ALMEIDA, Antonio Nogueira de; PAIVA, Wellingson Silva; AGUIAR, Paulo Henrique Pires de; TEIXEIRA, Manoel Jacobsen; MARIE, Suely Kazue NagahashiObjective: To review the data published on the subject to create a more comprehensive natural history of the haemorrhagic onset of meningiomas (IVMs). Patients and methods: A Medline search up to June 2020, using the search term ""bleeding meningioma,"" returned 136 papers. As a first selection step, we adopted the following inclusion criteria: series and case reports about bleeding meningioma. Papers written in other languages but with abstracts written in English were also evaluated. Results: A total of 190 tumours were evaluated, specifically 109 tumours from female patients and 81 tumours from male patients with a ratio of 1.34 female to 1.0 male (mean age of 54.86 16.1years old). The majority were located in the convexity (129-67.9 %). Among the 190 tumours evaluated, 171 patients (90 %) presented with GI tumours, with a predominance of the meningothelial subtype (32.6 %). Nine patients (4.7 %) presented with grade GII tumours, and 10 (5.3 %) presented with GIII tumours. The most prevalent type was intracerebral haemorrhage (ICH) at 50 %, followed by subdural at 27.36 %; the mortality rate was 13.1 % (25 deaths), the distribution of both location (prevalence of convexity: 18-72 %) and histopathology (grade 1: 22-88 %). Conclusion: These tumours follow the histopathological distribution of meningiomas, in general. The age distribution shows prevalence among the adult population but with a greater proportion in the elderly. The fact that the overwhelming majority of cases involve meningiomas with a benign histological subtype is noteworthy. Another relevant factor observed is that most reports are from Asian origin.
- Neuroinflammatory responses to traumatic brain injury(2015) PAIVA, Wellingson Silva; CORREIA, Angelica Duarte; MARIE, Suely Kazue
- Natural history and neuro-oncological approach in spinal gangliogliomas: a systematic review(2024) PEREIRA, Benedito Jamilson Araujo; ALMEIDA, Antonio Nogueira de; PAIVA, Wellingson Silva; TZU, Wen Hung; MARIE, Suely Kazue NagahashiTo describe the natural history of spinal gangliogliomas (GG) in order to determine the most appropriate neuro-oncological management. A Medline search for relevant publications up to July 2023 using the key phrase ""ganglioglioma spinal"" and ""ganglioglioma posterior fossa"" led to the retrieval of 178 studies. This corpus provided the basis for the present review. As an initial selection step, the following inclusion criteria were adopted: (i) series and case reports on spinal GG; (ii) clinical outcomes were reported specifically for GG; (iii) GG was the only pathological diagnosis for the evaluation of the tumor; (iv) papers written only in English was evaluated; and (v) papers describing each case in the series were included. The World Health Organization (WHO) 2021 grading criteria for gangliogliomas were applied. A total of 107 tumors were evaluated (63 from male patients and 44 from female patients; 1.43 male/1.0 female ratio, mean age 18.34 +/- 15.84 years). The most common site was the cervical spine, accounting for 43 cases (40.18%); GTR was performed in 35 cases (32.71%) and STR in 71 cases (66.35%), while this information was not reported in 1 case (0.94%). 8 deaths were reported (7.47%) involving 2 males (25%) and 6 females (75%) aged 4-78 years (mean 34.27 +/- 18.22) years. GGs located on the spine displayed the same gender ratio as these tumors in general. The most frequent symptom was pain and motor impairment, while the most prevalent location was the cervical spinal cord. GTR of the tumor posed a challenge for neurosurgeons, due to the difficulty of resecting the lesion without damaging the spinal eloquent area, explaining the lower rate of cure for this tumor type.
- Natural history of intraventricular meningiomas: systematic review(2020) PEREIRA, Benedito Jamilson Araujo; ALMEIDA, Antonio Nogueira de; PAIVA, Wellingson Silva; AGUIAR, Paulo Henrique Pires de; TEIXEIRA, Manoel Jacobsen; MARIE, Suely Kazue NagahashiReview the data published on the subject to create a more comprehensive natural history of intraventricular meningiomas (IVMs). A Medline search up to March 2018 using ""intraventricular meningioma"" returned 98 papers. As a first selection step, we adopted the following inclusion criteria: series and case reports about IVMs, as well as papers written in other languages, but abstracts written in English were evaluated. Six hundred eighty-one tumors were evaluated from 98 papers. The majority of the tumors were located in the lateral ventricles (602-88.4%), fourth ventricle (59-8.7%), and third ventricle (20-2.9%). These tumors accounted for a mortality rate of 4.0% (25 deaths) and a recurrence rate of 5.3% (26 recurrences). The majority of the tumors were grade I (89.8%) and consisted of the following subtypes: fibrous, 39.7% (n = 171); transitional, 22.0% (n = 95); meningothelial, 18.6% (n = 80); angiomatosus, 3.2% (n = 14); psammomatous, 2.6% (n = 11); and others, 13.9% (n = 60). Forty-five patients (7.4%) presented with grade II (GII) tumors, and 17 patients (2.8%) presented with grade III (GIII) tumors. These tumors follow the histopathological distribution of meningiomas in general, with the exception of the higher prevalence of the fibrous subtype, possibly due to its embryonic origin. Recurrence and mortality were lower than in other localizations likely due to a complete surgical resection rate than in the convexity and skull base, which suggests that GTR is the gold standard for the management of IVMs.
- Comprehensive analysis of meningioma in the first two decades of life: A systematic review(2020) PEREIRA, B. Jamilson Araujo; ALMEIDA, A. Nogueira de; AGUIAR, P. Henrique Pires de; PAIVA, W. Silva; TEIXEIRA, M. Jacobsen; MARIE, S. Kazue NagahashiPurpose. - To evaluate the relationship between meningioma histological subtype and tumor site in under-20 year-olds. Methods. - A review of the literature on meningioma during the first 2 decades of life was carried out through a Medline search up to February 2019. To evaluate the adult population, a cross-sectional study was conducted on patients operated on between 2000 and 2014 in a single institution. Exclusion criteria comprised: series reports and papers that lacked detailed description of clinical findings, neuroimaging confirmation of tumor location, and/or at least 5 years' follow-up. Results. - One hundred and seven manuscripts were included, for 365 under-20 year-old patients: 200 male, and 164 female. Histopathology found 197 cases (53.9%) of WHO grade I meningioma, with predominance of meningothelial (41.1%) and transitional (30.9%) subtypes; 123 (33.7%) grade II, and 45 (12.3%) grade III. For 65 (18.25%) of the 356 cases, recurrence was documented, with only 24 deaths (6.7%). Conclusion. - Meningioma in this population presented 2 differences compared to the adult population: male predominance, and high incidence of atypical meningioma. Surgery was the primary treatment. Adjuvant radiotherapy is controversial in the literature.