Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.286
Filtrar
Mais filtros

Eixos temáticos
Intervalo de ano de publicação
1.
Genes Dev ; 36(15-16): 874-875, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36207139

RESUMO

Loss of the NF2 tumor suppressor gene is a common finding in meningiomas, and more recently YAP1 fusions have been found in a subset of pediatric NF2 wild-type meningiomas. In the previous issue of Genes & Development, Szulzewsky and colleagues (pp. 857-870) showed that TEAD-dependent YAP1 activity by either the loss of the NF2 gene or YAP1-MAML2 fusion is an oncogenic process promoting meningioma tumorigenesis. Furthermore, pharmacological inhibition of YAP1-TEAD resulted in antitumor activity in both YAP1 fusion-positive and NF2 mutant meningiomas. Together, these data indicate that disruption of the YAP1-TEAD interaction raises a potential therapeutic option for these tumors that requires future investigation.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Neoplasias Meníngeas , Meningioma , Fatores de Transcrição/metabolismo , Carcinogênese/genética , Criança , Humanos , Neoplasias Meníngeas/genética , Meningioma/genética , Meningioma/patologia , Oncogenes , Fatores de Transcrição/genética
2.
Proc Natl Acad Sci U S A ; 120(16): e2214997120, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37043537

RESUMO

While somatic variants of TRAF7 (Tumor necrosis factor receptor-associated factor 7) underlie anterior skull-base meningiomas, here we report the inherited mutations of TRAF7 that cause congenital heart defects. We show that TRAF7 mutants operate in a dominant manner, inhibiting protein function via heterodimerization with wild-type protein. Further, the shared genetics of the two disparate pathologies can be traced to the common origin of forebrain meninges and cardiac outflow tract from the TRAF7-expressing neural crest. Somatic and inherited mutations disrupt TRAF7-IFT57 interactions leading to cilia degradation. TRAF7-mutant meningioma primary cultures lack cilia, and TRAF7 knockdown causes cardiac, craniofacial, and ciliary defects in Xenopus and zebrafish, suggesting a mechanistic convergence for TRAF7-driven meningiomas and developmental heart defects.


Assuntos
Cardiopatias Congênitas , Neoplasias Meníngeas , Meningioma , Animais , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Cardiopatias Congênitas/genética , Neoplasias Meníngeas/genética , Meningioma/genética , Meningioma/patologia , Mutação , Crânio/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Humanos , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral
3.
FASEB J ; 38(13): e23737, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38953724

RESUMO

Meningiomas are the most common primary intracranial tumors and account for nearly 30% of all nervous system tumors. Approximately half of meningioma patients exhibit neurofibromin 2 (NF2) gene inactivation. Here, NF2 was shown to interact with the endoplasmic reticulum (ER) calcium (Ca2+) channel inositol 1,4,5-trisphosphate receptor 1 (IP3R1) in IOMM-Lee, a high-grade malignant meningioma cell line, and the F1 subdomain of NF2 plays a critical role in this interaction. Functional assays indicated that NF2 promotes the phosphorylation of IP3R (Ser 1756) and IP3R-mediated endoplasmic reticulum (ER) Ca2+ release by binding to IP3R1, which results in Ca2+-dependent apoptosis. Knockout of NF2 decreased Ca2+ release and promoted resistance to apoptosis, which was rescued by wild-type NF2 overexpression but not by F1 subdomain deletion truncation overexpression. The effects of NF2 defects on the development of tumors were further studied in mouse models. The decreased expression level of NF2 caused by NF2 gene knockout or mutation affects the activity of the IP3R channel, which reduces Ca2+-dependent apoptosis, thereby promoting the development of tumors. We elucidated the interaction patterns of NF2 and IP3R1, revealed the molecular mechanism through which NF2 regulates IP3R1-mediated Ca2+ release, and elucidated the new pathogenic mechanism of meningioma-related NF2 variants. Our study broadens the current understanding of the biological function of NF2 and provides ideas for drug screening of NF2-associated meningioma.


Assuntos
Apoptose , Sinalização do Cálcio , Cálcio , Receptores de Inositol 1,4,5-Trifosfato , Neoplasias Meníngeas , Meningioma , Animais , Humanos , Camundongos , Cálcio/metabolismo , Linhagem Celular Tumoral , Retículo Endoplasmático/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/genética , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/genética , Meningioma/metabolismo , Meningioma/patologia , Meningioma/genética , Neurofibromina 2
4.
Genes Chromosomes Cancer ; 63(5): e23248, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38801095

RESUMO

Meningiomas are non-glial tumors that are the most common primary brain tumors in adults. Although meningioma can possibly be cured with surgical excision, variations in atypical/anaplastic meningioma have a high recurrence rate and a poor prognosis. As a result, it is critical to develop novel therapeutic options for high-grade meningiomas. This review highlights the current histology of meningiomas, prevalent genetic and molecular changes, and the most extensively researched signaling pathways and therapies in meningiomas. It also reviews current clinical studies and novel meningioma treatments, including immunotherapy, microRNAs, cancer stem cell methods, and targeted interventions within the glycolysis pathway. Through the examination of the complex landscape of meningioma biology and the highlighting of promising therapeutic pathways, this review opens the way for future research efforts aimed at improving patient outcomes in this prevalent intracranial tumor entity.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/genética , Meningioma/patologia , Meningioma/terapia , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/terapia , MicroRNAs/genética , Imunoterapia/métodos , Transdução de Sinais
5.
Cancer ; 130(15): 2586-2600, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38753473

RESUMO

Meningioma is the most common type of primary brain tumor. Surgical resection followed by surveillance is the first-line treatment for the majority of symptomatic meningiomas; however, recent advances in molecular sequencing, DNA methylation, proteomics, and single-cell sequencing provide insights into further characterizing this heterogeneous group of tumors with a wide range of prognoses. A subset of these tumors are highly aggressive and cause severe morbidity and mortality. Therefore, identifying those individuals with a poor prognosis and intervening are critical. This review aims to help readers interpret the molecular profiling of meningiomas to identify patients with worse prognoses and guide the management and strategy for surveillance.


Assuntos
Genômica , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/genética , Meningioma/terapia , Meningioma/patologia , Genômica/métodos , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/terapia , Prognóstico , Metilação de DNA , Biomarcadores Tumorais/genética
6.
J Neurooncol ; 166(3): 503-511, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38336917

RESUMO

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Idoso , Meningioma/patologia , Neoplasias Meníngeas/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Medição de Risco
7.
J Neurooncol ; 168(2): 187-196, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38530549

RESUMO

PURPOSE: Extraneural meningioma metastasis is a rare occurrence and may pose a clinical challenge due to its unclear prognosis. In this systematic review, we analyze patient demographics, clinical characteristics, management strategies, and outcomes. METHODS: PubMed, EMBASE, Scopus, Cochrane, and Web of Science databases were searched from inception to February 23, 2024 for cases of metastatic meningioma according to PRISMA guidelines. Descriptive statistics, Mann-Whitney U test, Fisher's exact tests, Kaplan-Meier curves, and log-rank tests were used for selected analyses. RESULTS: A total of 288 patients (52% male) were included with an average age of 49 years at meningioma diagnosis. Tumors were distributed across WHO grade 1 (38%), 2 (36%), and 3 (26%). Most patients experienced intracranial recurrence (79%) and mean time to first metastasis was approximately 8 years. No change in WHO grade between primary and metastasis was observed for most cases (65%). Treatment of the initial metastasis was most often with surgery (43%), chemotherapy (20%), or no treatment (14%). Half of the patients were alive (50%) with an average follow-up of 3 years following metastasis. Overall median survival was 36 months for the entire cohort. This differed significantly between WHO grade 1 versus 2/3 meningioma primaries (168 vs. 15 months, p < 0.005). CONCLUSION: Metastatic meningioma appears to be associated with more positive prognosis than other brain tumor types with extra-neural metastasis or metastasis in general. This is particularly true for cases arising from a WHO grade 1 meningioma.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/patologia , Meningioma/terapia , Neoplasias Meníngeas/secundário , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/terapia , Prognóstico , Pessoa de Meia-Idade , Masculino
8.
J Neurooncol ; 168(3): 527-535, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38656725

RESUMO

PURPOSE: To identify the risk factors and management of the multiple recurrences and reoperations for intracranial meningiomas. METHODS: Data of a neurosurgical series of 35 patients reoperated on for recurrent intracranial meningiomas were reviewed. Analyzed factors include patient age and sex, tumor location, extent of resection, WHO grade, Ki67-MIB1 and PR expression at initial diagnosis, time to recurrence; pattern of regrowth, extent of resection, WHO grade and Ki67-MIB1 at first recurrence were also analyzed. All these factors were stratified into two groups based on single (Group A) and multiple reoperations (Group B). RESULTS: Twenty-four patients (69%) belonged to group A and 11 (31%) to group B. The age < 65 years, male sex, incomplete resection at both initial surgery and first reoperation, and multicentric-diffuse pattern of regrowth at first recurrence are risk factors for multiple recurrences and reoperations. In group B, the WHO grade and Ki67-MIB1 increased in further recurrences in 54% and 64%, respectively. The time to recurrence was short in 7 cases (64%), whereas 4 patients (36%) further recurred after many years. Eight patients (73%) are still alive after 7 to 22 years and 2 to 4 reoperations. CONCLUSION: The extent of resection and the multicentric-diffuse pattern of regrowth at first recurrence are the main risk factors for multiple recurrences and reoperations. Repeated reoperations might be considered even in patients with extensive recurrent tumors before the anaplastic transformation occurs. In such cases, even partial tumor resections followed by radiation therapy may allow long survival in good clinical conditions.


Assuntos
Neoplasias Meníngeas , Meningioma , Recidiva Local de Neoplasia , Reoperação , Humanos , Meningioma/cirurgia , Meningioma/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Reoperação/estatística & dados numéricos , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Antígeno Ki-67/metabolismo , Fatores de Risco , Estudos Retrospectivos , Seguimentos , Adulto Jovem
9.
J Neurooncol ; 167(3): 427-436, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38451361

RESUMO

PURPOSE: Several retrospective studies and meta-analyses of Peptide Radionuclide Radiation Therapy in meningiomas suggest six-month progression-free survival improvement for WHO grade 1 and 2 meningiomas. In the present study, we aimed to evaluate the impact of such treatment on three-dimensional volume growth rate (3DVGR) in nonanaplastic meningiomas. METHODS: The authors performed a retrospective study including eight patients treated with Lutathera®. Millimetric 3D T1-weighted with gadolinium enhancement magnetic resonance imaging sequences were requested for volume measurement. Then, tumor growth rate was classified following a previously described 3DVGR classification (Graillon et al.). RESULTS: Patients harbored seven WHO grade 2 meningiomas and one aggressive WHO grade 1. All patients, except one, underwent four treatment cycles. 3DVGR significantly decreased at 3, 6, and 12 months after treatment initiation analyzing each lesion separately. Mean and median 3DVGR from all patients were respectively at 29.5% and 44.5%/6 months before treatment initiation, then at 16.5% and 25%/6 months at three months post-treatment initiation, 9.5% and 4.5%/6 months after 6 months, as well as 9.5% and 10.5%/6 months after 12 months. At 3, 6, and 12 months after treatment initiation, 4/8, 6/7, and 5/6 patients were class 2 (stabilization or severe 3DVGR slowdown), respectively. No patient was class 1 at 6 and 12 months, suggesting a lack of drug response. CONCLUSION: In nonanaplastic meningiomas, Lutathera®'s antitumoral activity appeared delayed and more likely observed at six months, while no major response was observed under treatment. Moreover, its antitumoral activity persisted for 12-18 months following treatment initiation.


Assuntos
Neoplasias Meníngeas , Meningioma , Recidiva Local de Neoplasia , Humanos , Meningioma/radioterapia , Meningioma/patologia , Meningioma/diagnóstico por imagem , Estudos Retrospectivos , Feminino , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Idoso , Recidiva Local de Neoplasia/radioterapia , Adulto , Imageamento por Ressonância Magnética , Seguimentos , Peptídeos/uso terapêutico
10.
J Neurooncol ; 168(3): 515-524, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38811523

RESUMO

PURPOSE: Accurate classification of cancer subgroups is essential for precision medicine, tailoring treatments to individual patients based on their cancer subtypes. In recent years, advances in high-throughput sequencing technologies have enabled the generation of large-scale transcriptomic data from cancer samples. These data have provided opportunities for developing computational methods that can improve cancer subtyping and enable better personalized treatment strategies. METHODS: Here in this study, we evaluated different feature selection schemes in the context of meningioma classification. To integrate interpretable features from the bulk (n = 77 samples) and single-cell profiling (∼ 10 K cells), we developed an algorithm named CLIPPR which combines the top-performing single-cell models, RNA-inferred copy number variation (CNV) signals, and the initial bulk model to create a meta-model. RESULTS: While the scheme relying solely on bulk transcriptomic data showed good classification accuracy, it exhibited confusion between malignant and benign molecular classes in approximately ∼ 8% of meningioma samples. In contrast, models trained on features learned from meningioma single-cell data accurately resolved the sub-groups confused by bulk-transcriptomic data but showed limited overall accuracy. CLIPPR showed superior overall accuracy and resolved benign-malignant confusion as validated on n = 789 bulk meningioma samples gathered from multiple institutions. Finally, we showed the generalizability of our algorithm using our in-house single-cell (∼ 200 K cells) and bulk TCGA glioma data (n = 711 samples). CONCLUSION: Overall, our algorithm CLIPPR synergizes the resolution of single-cell data with the depth of bulk sequencing and enables improved cancer sub-group diagnoses and insights into their biology.


Assuntos
Algoritmos , Neoplasias Meníngeas , Meningioma , Análise de Sequência de RNA , Análise de Célula Única , Humanos , Análise de Célula Única/métodos , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/classificação , Meningioma/genética , Meningioma/patologia , Meningioma/classificação , Análise de Sequência de RNA/métodos , Variações do Número de Cópias de DNA , Biomarcadores Tumorais/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Transcriptoma , Perfilação da Expressão Gênica/métodos
11.
J Neurooncol ; 169(2): 369-378, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38814405

RESUMO

PURPOSE: This study aimed to examine the effect of postoperative radiotherapy on survival outcomes in patients with malignant meningiomas. METHODS: We identified patients with malignant meningioma diagnosed between 2007 and 2018 using the Taiwan Cancer Registry and followed them up using the death registry. Survival was compared between patients with and without adjuvant radiotherapy. The potential confounding factors evaluated in this study included age, sex, comorbidities, and the Charlson Comorbidity Index (CCI). RESULTS: The analysis included 204 patients; 94 (46%) received adjuvant radiotherapy. The two groups had similar sex distributions (p = 0.53), mean age (p = 0.33), histologic subtype (p = 0.13), and CCI (p = 0.62). The prognosis of malignant meningioma was poor, with a median overall survival (OS) of 2.4 years. The median OS was 3.0 years (interquartile range (IQR) [1.4-6.1], and 2.0 years (IQR [0.5-3.9]) in the radiotherapy and non-radiotherapy groups, respectively (p = 0.001). However, Kaplan-Meier curves with the log-rank test showed no significant difference in OS between the two groups (p = 0.999). Controlling for age group, sex, histologic subtype, treatment, comorbidities, and CCI, adjuvant radiotherapy did not impart a survival benefit (hazard ratio [HR] = 0.87; 95% confidence interval [CI]: 0.6‒1.26); however, only factor of higher comorbidity score (HR = 2.03, 95%CI: 1.04‒3.94) was associated with unfavorable survival. CONCLUSION: This population-based retrospective analysis suggests that the role of radiotherapy remains unclear and underscores the need for randomized clinical trials to assess the usefulness of adjuvant radiotherapy in malignant meningioma.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/radioterapia , Meningioma/mortalidade , Meningioma/patologia , Meningioma/cirurgia , Masculino , Feminino , Radioterapia Adjuvante , Pessoa de Meia-Idade , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/cirurgia , Idoso , Taiwan/epidemiologia , Taxa de Sobrevida , Bases de Dados Factuais , Adulto , Prognóstico , Estudos Retrospectivos , Sistema de Registros/estatística & dados numéricos , Seguimentos
12.
J Neurooncol ; 169(3): 683-692, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38918319

RESUMO

PURPOSE: To report the outcomes of a large series of intracranial meningiomas (IMs) submitted to proton therapy (PT) with curative intent. METHODS: We conducted a retrospective analysis on all consecutive IM patients treated between 2014 and 2021. The median PT prescription dose was 55.8 Gy relative biological effectiveness (RBE) and 66 GyRBE for benign/radiologically diagnosed and atypical/anaplastic IMs, respectively. Local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), overall survival (OS), and radionecrosis-free survival (RNFS) were evaluated with the Kaplan-Meier method. Univariable analysis was performed to identify potential prognostic factors for clinical outcomes. Toxicity was reported according to the latest Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: Overall, 167 patients were included. With a median follow-up of 41 months (range, 6-99), twelve patients (7%) developed tumor local recurrence after a median time of 39 months. The 5-year LRFS was 88% for the entire cohort, with a significant difference between benign/radiologically diagnosed and atypical/anaplastic IMs (98% vs. 47%, p < 0.001); this significant difference was maintained also for the 5-year OS and the 5-year DRFS rates. Patients aged ≤ 56 years reported significantly better outcomes, whereas lower prescription doses and skull base location were associated with better RNFS rates. Two patients experienced G3 acute toxicities (1.2%), and three patients G3 late toxicities (1.8%). There were no G4-G5 adverse events. CONCLUSION: PT proved to be effective with an acceptable toxicity profile. To the best of our knowledge this is one of the largest series including IM patients submitted to PT.


Assuntos
Neoplasias Meníngeas , Meningioma , Terapia com Prótons , Humanos , Meningioma/radioterapia , Meningioma/mortalidade , Meningioma/patologia , Estudos Retrospectivos , Feminino , Masculino , Terapia com Prótons/efeitos adversos , Terapia com Prótons/métodos , Pessoa de Meia-Idade , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Seguimentos , Resultado do Tratamento , Taxa de Sobrevida , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/patologia , Prognóstico
13.
J Neurooncol ; 168(1): 27-33, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38689116

RESUMO

INTRODUCTION: Meningiomas with bone involvement account for 4.5-17% of all intracranial meningiomas. Little is known about whether these meningiomas (WHO grade I) behave differently than meningiomas without bone involvement. We sought to study the relatively uncommon imaging manifestations of meningioma and to evaluate their clinical significance. METHODS: A single-institution retrospective cohort study of surgically treated superficial meningioma patients between 2011 and 2022 was conducted. Age, sex, preoperative imaging, operative data, and surgical outcomes were reviewed. Imaging variables and outcomes were reported for patients with bone-invading meningiomas and compared with those with nonbone-invading meningiomas. Univariate analyses were also conducted. RESULTS: Of 577 total superficial meningiomas treated surgically, 47 (8.1%) exhibited bone invasion. Most bone-invading meningiomas were parasagittal (n = 29, 61.7%). A total of 12.7% (n = 6) of patients with bone-invading meningioma had recurrence, whereas 9.1% (n = 48) of patients with non-bone-invading meningioma had recurrence (p = 0.426). No significant difference in the median time to recurrence was observed between patients with bone-invading meningiomas and patients with nonbone-invading meningiomas (69.8 months, Q1:53.1; Q3:81.4 months vs. 69.7 months, Q1:47.5; Q3:96.7; p = 0.638). CONCLUSIONS: Superficial meningioma with bone involvement had similar outcomes compared to those of superficial meningioma without bone involvement. Hyperostosis in meningioma (WHO grade I) may not be a surrogate for aggressive meningioma behavior.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/cirurgia , Meningioma/patologia , Meningioma/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/diagnóstico por imagem , Estudos Retrospectivos , Idoso , Adulto , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , Resultado do Tratamento , Adulto Jovem , Idoso de 80 Anos ou mais , Seguimentos , Procedimentos Neurocirúrgicos , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/patologia , Adolescente , Invasividade Neoplásica
14.
J Neurooncol ; 168(3): 405-413, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38630387

RESUMO

INTRODUCTION: Meningiomas are the most common primary brain and central nervous system tumors, accounting for approximately 40% of these tumors. The most important exams for the radiological study of meningiomas are computed tomography (CT) and magnetic resonance imaging (MRI). We aimed to analyze the radiological features of patients with meningioma related to the simultaneous presence of bilateral macronodular adrenocortical disease (BMAD), with or without pathogenic variants of ARMC5. METHODS: This study included 10 patients who were diagnosed with BMAD. All of them had a radiological diagnosis of expansive brain lesions suggestive of meningioma. All patients underwent brain MRI and a neuroradiolgist analyzed the following parameters: number, site and size of lesions; presence of calcification, edema and bone involvement. RESULTS AND DISCUSSION: Eight patients presented with germline variants of ARMC5; the other 2, did not. The most significant result was the incidence of multiple meningiomas, which was 50% in BMAD patients, whereas the average incidence described thus far is lower than 10%. Considering location, the 22 tumors in the BMAD patients were 5 convexity tumors (22.7%), and 17 skull base tumors (77.2%), the opposite proportion of patients without BMAD. A total of 40.9% of the tumors had calcification, 9% had cerebral edema and 40.9% had bone invasion due to hyperostosis. The literature describes meningioma calcification in 25% of patients, bone invasion by tumor hyperostosis in 20%, and cerebral edema in approximately 60%. CONCLUSION: Relevant results were found considering the rate of multiple meningiomas and tumor location. This finding reinforces the need for further research into the neurological effects caused by genetic variants of ARMC5 in patients with BMAD.


Assuntos
Imageamento por Ressonância Magnética , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/genética , Meningioma/diagnóstico por imagem , Meningioma/patologia , Feminino , Masculino , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Pessoa de Meia-Idade , Adulto , Idoso , Tomografia Computadorizada por Raios X , Proteínas do Domínio Armadillo
15.
J Neurooncol ; 166(2): 303-307, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38194196

RESUMO

PURPOSE: The expression of PD-L1 in high-grade meningiomas made it a potential target for immunotherapy research in refractory cases. Several prospective studies in this field are still on going. We sought to retrospectively investigate the effects of check-point inhibitors (CI) on meningiomas that had been naïve to either surgical or radiation approaches by following incidental meningiomas found during treatment with CI for various primary metastatic cancers. METHODS: We used the NYU Perlmutter Cancer Center Data Hub to find patients treated by CI for various cancers, who also had serial computerized-tomography (CT) or magnetic-resonance imaging (MRI) reports of intracranial meningiomas. Meningioma volumetric measurements were compared between the beginning and end of the CI treatment period. Patients treated with chemotherapy during this period were excluded. RESULTS: Twenty-five patients were included in our study, of which 14 (56%) were on CI for melanoma, 5 (20%) for non-small-cell lung cancer and others. CI therapies included nivolumab (n = 15, 60%), ipilimumab (n = 11, 44%) and pembrolizumab (n = 9, %36), while 9 (36%) were on ipilimumab/nivolumab combination. We did not find any significant difference between tumor volumes before and after treatment with CI (1.31 ± 0.46 vs. 1.34 ± 0.46, p=0.8, respectively). Among patients beyond 1 year of follow-up (n = 13), annual growth was 0.011 ± 0.011 cm3/year. Five patients showed minor volume reduction of 0.12 ± 0.10 cm3 (21 ± 6% from baseline). We did not find significant predictors of tumor volume reduction. CONCLUSION: Check-point inhibitors may impact the natural history of meningiomas. Additional research is needed to define potential clinical indications and treatment goals.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/diagnóstico por imagem , Meningioma/terapia , Meningioma/patologia , Nivolumabe/uso terapêutico , Ipilimumab , Estudos Retrospectivos , Estudos Prospectivos , Imunoterapia , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/terapia , Neoplasias Meníngeas/patologia
16.
J Neurooncol ; 167(3): 455-465, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38446374

RESUMO

PURPOSE: Meningiomas are the most common type of brain tumors and are generally benign, but malignant atypical meningiomas and anaplastic meningiomas frequently recur with poor prognosis. The metabolism of meningiomas is little known, so few effective treatment options other than surgery and radiation are available, and the targets for treatment of recurrence are not well defined. The Aim of this paper is to find the therapeutic target. METHODS: The effects of bone morphogenetic protein (BMP) signal inhibitor (K02288) and upstream regulator Gremlin2 (GREM2) on meningioma's growth and senescence were examined. In brief, we examined as follows: 1) Proliferation assay by inhibiting BMP signaling. 2) Comprehensive analysis of forced expression GREM2.3) Correlation between GREM2 mRNA expression and proliferation marker in 87 of our clinical samples. 4) Enrichment analysis between GREM2 high/low expressed groups using RNA-seq data (42 cases) from the public database GREIN. 5) Changes in metabolites and senescence markers associated with BMP signal suppression. RESULTS: Inhibitors of BMP receptor (BMPR1A) and forced expression of GREM2 shifted tryptophan metabolism from kynurenine/quinolinic acid production to serotonin production in malignant meningiomas, reduced NAD + /NADH production, decreased gene cluster expression involved in oxidative phosphorylation, and caused decrease in ATP. Finally, malignant meningiomas underwent cellular senescence, decreased proliferation, and eventually formed psammoma bodies. Reanalyzed RNA-seq data of clinical samples obtained from GREIN showed that increased expression of GREM2 decreased the expression of genes involved in oxidative phosphorylation, similar to our experimental results. CONCLUSIONS: The GREM2-BMPR1A-tryptophan metabolic pathway in meningiomas is a potential new therapeutic target.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo I , Proteínas Morfogenéticas Ósseas , Calcinose , Neoplasias Meníngeas , Meningioma , Transdução de Sinais , Humanos , Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Proteínas Morfogenéticas Ósseas/metabolismo , Calcinose/patologia , Calcinose/metabolismo , Calcinose/genética , Proliferação de Células , Senescência Celular , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/genética , Meningioma/metabolismo , Meningioma/patologia , Meningioma/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/antagonistas & inibidores , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Citocinas/efeitos dos fármacos , Citocinas/metabolismo
17.
Semin Neurol ; 44(1): 1-15, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38052237

RESUMO

Meningiomas are the most frequent nonmalignant tumors of the central nervous system (CNS). Despite their benign nature and slow-growing pattern, if not diagnosed early, these tumors may reach relatively large sizes causing significant morbidity and mortality. Some variants are located in hard-to-access locations, compressing critical neurovascular structures, and making the surgical management even more challenging. Although most meningiomas have a good long-term prognosis after treatment, there are still controversies over their management in a subset of cases. While surgery is the first-line treatment, the use of fractionated radiotherapy or stereotactic radiosurgery is indicated for residual or recurrent tumors, small lesions, and tumors in challenging locations. Advances in molecular genetics and ongoing clinical trial results have recently helped both to refine the diagnosis and provide hope for effective biomolecular target-based medications for treatment. This article reviews the natural history and current therapeutic options for CNS meningiomas.


Assuntos
Neoplasias Meníngeas , Meningioma , Radiocirurgia , Humanos , Meningioma/diagnóstico , Meningioma/terapia , Meningioma/patologia , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/terapia , Neoplasias Meníngeas/patologia , Recidiva Local de Neoplasia/cirurgia , Radiocirurgia/métodos , Resultado do Tratamento
18.
Neuroradiology ; 66(8): 1301-1310, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38902484

RESUMO

PURPOSE: Meningioma is the most common intracranial tumor, graded on pathology using WHO criteria to predict tumor course and treatment. However, pathological grading via biopsy may not be possible in cases with poor surgical access due to tumor location. Therefore, our systematic review aims to evaluate whether diagnostic imaging features can differentiate high grade (HG) from low grade (LG) meningiomas as an alternative to pathological grading. METHODS: Three databases were searched for primary studies that either use routine magnetic resonance imaging (MRI) or computed tomography (CT) to assess pathologically WHO-graded meningiomas. Two investigators independently screened and extracted data from included studies. RESULTS: 24 studies met our inclusion criteria with 12 significant (p < 0.05) CT and MRI features identified for differentiating HG from LG meningiomas. Cystic changes in the tumor had the highest specificity (93.4%) and irregular tumor-brain interface had the highest positive predictive value (65.0%). Mass effect had the highest sensitivity (81.0%) and negative predictive value (90.7%) of all imaging features. Imaging feature with the highest accuracy for identifying HG disease was irregular tumor-brain interface (79.7%). Irregular tumor-brain interface and heterogenous tumor enhancement had the highest AUC values of 0.788 and 0.703, respectively. CONCLUSION: Our systematic review highlight imaging features that can help differentiate HG from LG meningiomas.


Assuntos
Neoplasias Meníngeas , Meningioma , Gradação de Tumores , Tomografia Computadorizada por Raios X , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Meningioma/diagnóstico por imagem , Meningioma/patologia , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos
19.
Neurol Sci ; 45(5): 2311-2319, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38151626

RESUMO

INTRODUCTION: Meningiomas are usually slow-growing tumours, constituting about one third of all primary intracranial tumours. They occur more frequently in women. Clinical manifestation of meningiomas depends on their location, tumour size and growth rate. In most cases, surgical treatment is the procedure of choice. The success of this treatment is, however, associated with the radicality of the resection. Radiotherapy represents an additional or alternative treatment modality. Gamma knife surgery is another notable treatment method, especially in small and/or slow-growing tumours in eloquent areas or in elderly patients. MATERIAL AND METHODS: Authors describe their experience with the diagnosis, treatment and outcome of the patients with meningioma (n = 857). Furthermore, they also assess the postoperative morbidity/mortality and recurrence rate. RESULTS AND CONCLUSIONS: In view of the benign histology of meningiomas, the success of the treatment largely depends (besides the tumour grading) on the radicality of the resection. The emphasis is also put on appropriate follow-up of the patients. In certain patients, the watch and wait strategy should be also considered as a suitable treatment method.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Feminino , Idoso , Meningioma/cirurgia , Meningioma/patologia , Neoplasias Meníngeas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Microcirurgia , Resultado do Tratamento , Estudos Retrospectivos , Procedimentos Neurocirúrgicos/métodos
20.
Med Sci Monit ; 30: e944724, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990791

RESUMO

BACKGROUND The BrainLab VectorVision neuronavigation system is an image-guided, frameless localization system used intraoperatively, which includes a computer workstation for viewing and analyzing operative microscopic images. This retrospective study aimed to evaluate the use of the BrainLab VectorVision infrared-based neuronavigation imaging system in 80 patients with intracranial meningioma removed surgically between 2013 and 2023. MATERIAL AND METHODS Data were retrospectively collected from 36 patients with convexity meningioma and 44 patients with parasagittal meningioma between 2013 and 2023. The surgical operation of 40 of these patients was performed with the help of neuronavigation, while the other 40 were performed without neuronavigation. Demographic data, preoperative and postoperative radiologic images, craniotomy measurements, surgical complications, and operative times of patients with and without neuronavigation were analyzed. RESULTS Using neuronavigation significantly increased surgery duration (P=0.023). In 6 patients without the use of neuronavigation, the craniotomy had to be enlarged and this resulted in superior sagittal sinus (SSS) damage (P=0.77, P=0.107). Patients for whom neuronavigation was used did not experience any sinus damage and did not require craniotomy enlargement. Postoperative epidural hematoma (EH) developed in 9 patients without navigation, whereas it developed in only 1 patient with navigation (P=0.104). Residual tumors were less common in patients using navigation (P=0.237). CONCLUSIONS The use of neuronavigation allows the incision and craniotomy to be reduced in size. Intraoperatively, it allows the surgeon to master the boundaries of the tumor and surrounding vascular structures, reducing the risk of complications. These results suggest that neuronavigation systems are an effective ancillary in meningioma surgery.


Assuntos
Neoplasias Meníngeas , Meningioma , Neuronavegação , Humanos , Meningioma/cirurgia , Meningioma/patologia , Meningioma/diagnóstico por imagem , Neuronavegação/métodos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Meníngeas/cirurgia , Adulto , Idoso , Resultado do Tratamento , Craniotomia/métodos , Cirurgia Assistida por Computador/métodos , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/etiologia
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa