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1.
Comput Biol Med ; 187: 109730, 2025 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39889447

RESUMO

Adult-type diffuse gliomas arise from glial or progenitor cells. These tumors are currently classified as astrocytoma isocitrate dehydrogenase (IDH)-mutant or IDH-mutant oligodendroglioma with co-deletion of chromosomal arms 1p and 19q, both of which could be either slow-growing tumors, or glioblastoma (GBM), which is a more aggressive tumor. Despite advances in diagnosis and treatment, the median survival time after GBM diagnosis remains low at approximately 15 months, with a 5-year overall survival (OS) rate of 6.8 %. Therefore, new biomarker and therapeutic target discoveries are required to improve prognosis. Mucin 1 (MUC1) and MUC4 are membrane-bound mucins and potential biomarkers of several tumors. However, the role of these mucins in adult gliomas has not been well explored. In this retrospective study, in silico analysis of data from patients with adult-type diffuse glioma revealed differential methylation and expression patterns of MUC1 and MUC4 between GBM and non-GBM groups. In the GBM group, decreased methylation and elevated expression of MUC1 were observed (r = -0.25, p < 0.0001), whereas increased methylation and decreased expression of MUC4 were observed (r = -0.13, p = 0.1344). Conversely, in the non-GBM group, MUC1 exhibited higher methylation and lower expression (r = -0.27, p < 0.0001), whereas MUC4 showed lower methylation and higher expression (r = -0.32, p < 0.0001). The expression of these genes influenced OS in adult patients with glioma (p = 0.0344), with high MUC1 and low MUC4 expression associated with worse OS. MUC1 and MUC4 expression correlated with that of MUC20 in both GBM (r = 0.54) and non-GBM (r = 0.53) groups (p < 0.0001). Functional enrichment analysis identified the biological roles of MUC1-co-expressed genes as involvement in innate immunity, antigen processing, and proinflammatory responses in both the non-GBM and GBM groups, and integrin-based signaling pathways in the GBM group. MUC4-co-expressed genes are involved in ion transport in GBM patients. Using molecular docking, we observed that MUC1 domains physically interact with immune response-related proteins, such as receptors for advanced glycation end products (RAGE), major histocompatibility complex II (MHC-II), and extracellular matrix receptor integrin alpha 2 (ITGA2). To our knowledge, this is the first retrospective study and in silico analysis demonstrating the relevance and correlation of MUC1 and MUC4 in adult gliomas. These findings elucidate the molecular mechanisms underlying adult-type diffuse glioma progression and highlight MUC1 and MUC4 as potential prognostic markers and therapeutic targets for glioma management.


Assuntos
Glioma , Mucina-1 , Mucina-4 , Humanos , Mucina-1/genética , Mucina-1/metabolismo , Mucina-4/genética , Mucina-4/metabolismo , Glioma/metabolismo , Glioma/genética , Glioma/imunologia , Adulto , Masculino , Regulação Neoplásica da Expressão Gênica , Feminino , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Metilação de DNA
2.
J Clin Neurosci ; 133: 111052, 2025 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39827768

RESUMO

BACKGROUND: The Endoscopic Endonasal Approach (EEA) has revolutionized the treatment landscape for optic pathway-hypothalamic gliomas (OPHGs) by providing precise visualization of the lesion neuroanatomic and minimizing brain manipulation. Despite the variable clinical trajectories of OPHGs, the optimal management neurosurgical strategy continues to be a subject of debate. METHODS: We present a case of an 8-year-old female with an OPHG who underwent EEA and performed a systematic review search in English and Spanish case reports from January 2007 (date of first reported case) to June 2024, focusing on OPHG treated with EEA. Databases such as PubMed, Lilacs, and Embase. SEARCH RESULTS: Our systematic review encompassed 30 cases of OPHGs treated with EEA. Most patients (86.6%) presented with visual disturbance, 43.3% with headaches, and 30% with endocrine disturbances. Gross-total resection (GTR) was achieved in 20%, subtotal in 40%, and near-total in 20%. Histologically, pilocytic astrocytoma predominated (73.3%), with varied clinical presentations highlighting the need for tailored management approaches. CONCLUSIONS: The EEA offers safe access to the optic pathway and hypothalamic region. Despite limitations in achieving GTR compared to other approaches, EEA's benefits in clinical improvement and neuroanatomical preservation make it a valuable option for select cases of OPHGs.


Assuntos
Glioma , Neoplasias Hipotalâmicas , Humanos , Feminino , Criança , Neoplasias Hipotalâmicas/cirurgia , Neoplasias Hipotalâmicas/diagnóstico por imagem , Glioma/cirurgia , Glioma/patologia , Neuroendoscopia/métodos , Glioma do Nervo Óptico/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos
3.
Neurochem Res ; 50(1): 56, 2024 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-39671046

RESUMO

Among the spectrum of gliomas, glioblastoma stands out as the most aggressive brain tumor affecting the central nervous system. In addressing this urgent medical challenge, exploring therapeutic alternatives becomes imperative to enhance the patient's prognosis. In this regard, Butia odorata (BO) fruit emerges as a promising candidate due to its array of bioactive compounds, including flavonoids, phenolic acids, and carotenoids, known for their antioxidant, anti-inflammatory, and antitumor properties. Thus, this study aimed to investigate the impact of standardized hydroalcoholic extract of BO on rat C6 and human U87MG glioma cell lines. Cells were exposed to varying extract concentrations (125-2000 µg/mL) for intervals of 0, 2, 4, 6, 24, 48, or 72 h. Then, cell viability, proliferation, colony formation, redox equilibrium parameters, cell migration, and the relative mRNA expression of genes related to gliomagenesis were evaluated. Our findings revealed a reduction in viability, proliferation, colony formation, reactive oxygen species, and nitrite levels in both glioma cell lines upon exposure to the extract. Conversely, an increase in sulfhydryl content and the activity of superoxide dismutase and catalase were observed in both glioma cell lines. No significant changes in viability and proliferation were observed in astrocytes. Furthermore, in the C6 cells only, the BO extract reduced the migration and downregulated the relative mRNA expression of matrix metalloproteinase-2, O6-methylguanine-DNA methyltransferase, nuclear factor-kappa B, interleukin-6 genes, and upregulated caspase-3 gene. These results underscore the promising anti-glioma potential of BO extract, attributed to its diverse bioactive composition.


Assuntos
Sobrevivência Celular , Glioma , Oxirredução , Extratos Vegetais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Humanos , Glioma/tratamento farmacológico , Glioma/metabolismo , Glioma/patologia , Ratos , Linhagem Celular Tumoral , Animais , Sobrevivência Celular/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Proliferação de Células/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Movimento Celular/efeitos dos fármacos
4.
Sci Rep ; 14(1): 25435, 2024 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-39455622

RESUMO

Oncostreams are self-organized structures formed by spindle-like, elongated, self-propelled cells recently described in glioblastomas and especially in gliosarcomas. Cells within these structures either move as large clusters in one main direction, flocks, or as linear, intermingling collections of cells advancing in opposite directions, streams. Round, passive cells are also observed, either inside or segregated from the oncostreams. Here we generalize a recently formulated particle-field approach to investigate the genesis and evolution of these structures, first showing that, in systems consisting only of identical self-propelled cells, both flocks and streams emerge as self-organized dynamic configurations. Flocks are the more stable configurations, while streams are transient and usually originate in collisions between flocks. Stream degradation is easier at low self-propulsion speeds. In systems consisting of both motile and passive cells, the latter block stream formation and accelerate their degradation and flock stabilization. Since the flock appears to be the most effective invasive structure, we thus argue that a phenotype mixture (motile and passive cells) may favor glioblastoma invasion. hlBy relating cellular properties to the observed outcome, our model shows that oncostreams are self-organized structures that result from the interplay between speed, shape, and steric repulsion.


Assuntos
Glioma , Humanos , Glioma/patologia , Glioma/metabolismo , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Modelos Biológicos , Movimento Celular , Invasividade Neoplásica
5.
Arch. argent. pediatr ; 122(5): e202310244, oct. 2024. ilus
Artigo em Inglês, Espanhol | LILACS, BINACIS | ID: biblio-1571610

RESUMO

Los gliomas tectales representan un subtipo de tumores de bajo grado que se desarrollan en la región tectal, en la parte superior del tronco encefálico. Los síntomas incluyen los causados por el aumento de la presión intracraneal por hidrocefalia obstructiva. Son comunes la cefalea, la visión borrosa o doble, las náuseas y los vómitos. El tratamiento de la hidrocefalia es la ventriculostomía endoscópica del tercer ventrículo o la derivación ventrículo-peritoneal. Los gliomas tectales se diagnostican habitualmente en la infancia, pero son frecuentes también en adultos. En general son benignos y de progresión lenta; es suficiente el seguimiento ambulatorio clínico y radiológico. Se presentan dos pacientes pediátricos con tumores de la placa tectal mesencefálica. Un niño de 11 años y una niña de 15 años concurrieron al Departamento de Emergencias con diferentes síntomas. El niño fue tratado con derivación ventrículo-peritoneal por hidrocefalia aguda.


Tectal gliomas represent a subset of low-grade tumors that arise in the tectal region at the roof of the brainstem. Symptoms of tectal glioma include those caused by increased intracranial pressure due to obstructive hydrocephalus. Headache, blurred vision, double vision, nausea and vomiting are common symptoms. In the treatment, ETV (endoscopic third ventriculostomy) or VP-shunt (ventriculoperitoneal) can be applied to treat hydrocephalus. Tectal gliomas are usually diagnosed in childhood and often occur in adults. They are often benign, slowly progressing lesions; outpatient clinical and radiological followup is sufficient. We present two cases of pediatric patients with mesencephalic tectal plate tumors. An 11-year-old boy and a 15-year-old girl applied to the Emergency Department with different complaints. The 11 year-old-boy was treated with VP-shunt due to acute hydrocephalus.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Teto do Mesencéfalo , Glioma/complicações , Glioma/diagnóstico , Hidrocefalia/diagnóstico , Hidrocefalia/etiologia , Doença Aguda , Neoplasias do Tronco Encefálico/complicações , Neoplasias do Tronco Encefálico/diagnóstico
6.
Neurosurg Rev ; 47(1): 617, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39276262

RESUMO

Stereotactic Brachytherapy Iodine-125 (SBT I-125) has been investigated by some studies for the treatment of lowgrade gliomas. We performed a meta-analysis to assess the efficacy and safety of SBT I-125 Brachytherapy for treatment of patients with Low-Grade Gliomas. PubMed, Cochrane, Web of Science, and EMBASE databases were searched for randomized and observational studies. This systematic review and meta-analysis was conducted according to the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. We used relative risk (RR) with 95% confidence intervals and random effects model to compare the effects of I-125 SBT treatment on the interest outcomes. We evaluated heterogeneity using I2 statistics; we considered heterogeneity to be significant if the p-value was less than 0.05 and I2 was higher than 35%. We performed statistical analysis using the software R (version 4.2.3). A total of 20 studies with a cohort of 988 patients with low grade gliomas who received SBT I-125 as a treatment option. The pooled analysis evidenced: (1) Complication rate of 10% (95% CI: 7-12%; I² = 60%); (2) 5-year PFS of 66% (99% CI: 45-86%; I²= 98%); (3) 10-year PFS was 66% (99% CI: 45-86%; I²= 98%); (4) Malignant transformation rate of 26% (95% CI: 8-45%; I²=0); (5) Mortality of 33% (95% CI: 15-51%; I² = 0%). Our systematic review and meta-analysis of SBT I-125 for low-grade gliomas have revealed significant concerns regarding its safety and efficacy. Despite a proportion of patients remaining progression-free, elevated rates of complications and mortality cast doubt on the intervention's reliability. Future research should prioritize long-term follow-up studies, standardized protocols, and comparative effectiveness research.


Assuntos
Braquiterapia , Neoplasias Encefálicas , Glioma , Radioisótopos do Iodo , Humanos , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Glioma/mortalidade , Glioma/patologia , Glioma/radioterapia , Radioisótopos do Iodo/efeitos adversos , Radioisótopos do Iodo/uso terapêutico , Resultado do Tratamento
7.
World Neurosurg ; 191: e652-e663, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39265939

RESUMO

OBJECTIVE: To describe our experience in the resection of gliomas involving the insula and analyze the variables implicated in the management and prognosis of these tumors. METHODS: This retrospective, single-center, analytic study included a cohort of 83 patients who underwent surgery for insular gliomas by the same surgeon in a third-level Argentine center, in the period between 2010 and 2023. We analyzed the population's demographic, clinical, and radiologic features and surgical variables associated with postoperative results and prognosis using multivariate regression analysis. RESULTS: A total of 53 patients (54% men) were included, with a mean follow-up of 40.7 months. The mean age at surgery was 41 years (range, 21-73) and 66.1% corresponded to low-grade gliomas (LGGs). Seizures were the initial symptom in most cases. There was evidence of tumor extension over the insula to the temporal or/and frontal lobe in 64.2% of patients. An extent of resection >90% was achieved in 62.3% of cases (27% of gross total resection), with an average resected volume of 89.4%. Awake craniotomy was indicated in 47% of patients and intraoperative magnetic resonance imaging was performed in 24%. Recurrence was observed in 44% of patients, with a mean progression-free survival of 31 months (42 months in LGG and 10 months in high-grade glioma [HGG]). Nine patients underwent reoperation. By the time of 2 years, survival was 100% for LGG and 46% for HGG, whereas 4-year overall survival was 92% for patients with LGG and 15.4% for those with HGG. CONCLUSIONS: Surgery for insular gliomas is a complex task that needs to be managed with adequate preoperative and intraoperative assessment to achieve maximum safe resection with low morbidity for better functional and oncologic outcomes. Adequate anatomic understanding, radiologic analysis, awake craniotomy, and cortical and subcortical mapping are paramount to pursue this aim.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Glioma/cirurgia , Glioma/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Adulto , Estudos Retrospectivos , Idoso , Prognóstico , Adulto Jovem , Córtex Cerebral/cirurgia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Procedimentos Neurocirúrgicos/métodos , Argentina/epidemiologia , Craniotomia/métodos , Imageamento por Ressonância Magnética , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia
8.
J Neurooncol ; 170(3): 483-493, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39230804

RESUMO

BACKGROUND: High-grade gliomas (HGG) are the most aggressive primary brain tumors with poor prognoses despite conventional treatments. Immunotherapy has emerged as a promising avenue due to its potential to elicit a targeted immune response against tumor cells. OBJECTIVE: This meta-analysis aimed to evaluate the efficacy and safety of various immunotherapeutic strategies, including immune checkpoint inhibitors (ICI), virotherapy, and dendritic cell vaccines (DCV) in treating HGG. METHODS: Following the PRISMA framework, we searched PubMed, Cochrane, and Embase for studies reporting outcomes of HGG patients treated with immunotherapy. Key metrics included overall survival, progression-free survival, and treatment-related adverse events. RESULTS: We reviewed 47 studies, analyzing data from 3674 HGG patients treated with immunotherapy. The mean overall survival for patients treated with ICI was 11.05 months, with virotherapy at 11.79 months and notably longer for DCV at 24.11 months. The mean progression-free survival (PFS) for ICIs was 3.65 months. Virotherapy demonstrated a PFS favoring the control group, indicating minimal impact, while DCV showed substantial PFS improvement with a median of 0.43 times lower hazard compared to controls (95% CI: 29-64%). Adverse events were primarily Grade 1 or 2 for ICI, included a Grade 5 event for virotherapy, and were predominantly Grade 1 or 2 for DCV, indicating a favorable safety profile. CONCLUSION: Immunotherapy holds potential as an effective treatment for HGG, especially DCV. However, results vary significantly with the type of therapy and individual patient profiles. Further randomized controlled trials are necessary to establish robust clinical guidelines and optimize treatment protocols.


Assuntos
Neoplasias Encefálicas , Glioma , Imunoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Imunoterapia/métodos , Glioma/terapia , Glioma/imunologia , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Terapia Viral Oncolítica/métodos
9.
Childs Nerv Syst ; 40(10): 3099-3105, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39207527

RESUMO

Pediatric brain tumors, particularly those affecting the brainstem, present a significant challenge due to their intricate anatomical location and diverse classification. This review explores the classification, anatomical considerations, and surgical approaches for pediatric brainstem tumors, focusing on recent updates from the World Health Organization (WHO) classification. Brainstem tumors encompass a spectrum from diffuse gliomas to focal intrinsic and exophytic types, each presenting unique clinical and surgical challenges. Surgical strategies have evolved with advancements in neuroimaging and surgical techniques, emphasizing approaches such as neuroendoscopy and tailored incisions to minimize damage to critical structures. Despite the complexities involved, recent developments offer promising outcomes in tumor resection and patient management, highlighting ongoing advancements in neurosurgical care for pediatric brain tumors.


Assuntos
Neoplasias do Tronco Encefálico , Glioma , Neuroendoscopia , Humanos , Glioma/cirurgia , Glioma/patologia , Glioma/diagnóstico por imagem , Neoplasias do Tronco Encefálico/cirurgia , Neoplasias do Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Criança , Neuroendoscopia/métodos
10.
Biomedica ; 44(2): 191-206, 2024 05 30.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-39088535

RESUMO

Introduction: High-grade gliomas are the most common primary brain tumors in adults, and they usually have a quick fatal course. Average survival is 18 months, mainly, because of tumor resistance to Stupp protocol. Objective: To determine high-grade glioma patient survival and the effect of persuasion variables on survival. Materials and methods: We conducted a longitudinal descriptive study in which 80 untreated recently diagnosed high-grade glioma patients participated. A survey was conducted regarding their exposure to some risk factors, degree of genetic instability in peripheral blood using micronucleus quantification on binuclear lymphocytes, micronuclei in reticulocytes and sister-chromatid exchanges in lymphocytes. In the statistical analysis, this study constructed life tables, used the Kaplan-Meier, and the log-rank test, and in the multivariate analysis, a Cox proportional hazards model was constructed. Results: Eighty patients' clinical, demographic and lifestyle characteristics were analyzed, as well as their survival rates and the average survival time is 784 days (interquartile range: 928). Factors like age, exposure at work to polycyclic hydrocarbons and the number of sister-chromatid exchanges in lymphocytes in the first sampling was significantly survivalrelated in the multivariate analysis. Conclusion: We determined that only three of the analyzed variables have an important effect on survival time when it comes to high-grade glioma patients.


Introducción. Los gliomas de alto grado son los tumores cerebrales primarios más comunes en adultos y, por lo general, tienen un curso mortal rápido. La supervivencia media es de 18 meses, principalmente, como consecuencia de la resistencia del tumor al protocolo Stupp. Objetivo. Determinar la supervivencia de los pacientes con glioma de alto grado y el efecto de las variables de persuasión en la supervivencia. Materiales y métodos. Se llevó a cabo un estudio descriptivo longitudinal en el que participaron 80 pacientes con diagnóstico reciente de glioma de alto grado no tratados. Se hizo una encuesta sobre su exposición a algunos factores de riesgo, grado de inestabilidad genética en sangre periférica mediante cuantificación de micronúcleos en linfocitos binucleares, micronúcleos en reticulocitos e intercambios de cromátidas hermanas en linfocitos. En el análisis estadístico, se construyeron tablas de vida, se utilizó Kaplan-Meier y la prueba de rangos logarítmicos, y en el análisis multivariado, se construyó un modelo de riesgos proporcionales de Cox. Resultados. Se analizaron las características clínicas, demográficas y de estilo de vida de 80 pacientes, así como sus tasas de supervivencia y el tiempo medio de supervivencia fue de 784 días (rango intercuartílico: 928). Factores como la edad, la exposición laboral a hidrocarburos policíclicos y el número de intercambios de cromátidas hermanas en linfocitos en el primer muestreo se relacionaron significativamente con la supervivencia en el análisis multivariante. Conclusión. Según los resultados, el estudio determinó que solo tres de las variables analizadas tienen un efecto importante en el tiempo de supervivencia cuando se trata de pacientes con glioma de alto grado.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Glioma/mortalidade , Glioma/patologia , Glioma/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Longitudinais , Análise de Sobrevida , Fatores de Risco , Troca de Cromátide Irmã , Exposição Ocupacional/efeitos adversos , Idoso , Estimativa de Kaplan-Meier , Gradação de Tumores
11.
Childs Nerv Syst ; 40(12): 4259-4264, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39110187

RESUMO

PURPOSE: Unresectable pediatric low-grade gliomas (LGG) usually need adjuvant therapy, and carboplatin hypersensitivity reaction (HR) commonly leads to premature treatment cessation of a standard chemotherapy regimen. In the molecular era, advances in understanding tumor genetic characteristics allowed the development of targeted therapies for this group of tumors; however, cost-effectiveness assessment of treatments, especially in low-income countries, is crucial. The aim is to describe the results of carboplatin desensitization protocol in a single center in a middle-income country. METHOD: Prospective analysis of children with LGG submitted to carboplatin desensitization from December 2017 to June 2020 with follow-up until April 2024. RESULTS: Nine patients were included. The mean age was 11 years. Five patients were male. Seven had optic pathway and two cervicomedullary location. Six had histologic diagnosis and four molecular analyses. The incidence of carboplatin reactions during the study period was 39.1%. Six patients underwent skin prick test, three with positive results. The first HR occurred, on average, around the 9th cycle of treatment. All patients had cutaneous symptoms, and five out of nine had anaphylaxis as the first reaction. 77.7% of the patients completed the protocol, and the clinical benefit rate (stable disease and partial response) was 88.8%. Six patients further required other lines of therapy. Monthly, the total cost for carboplatin was $409.09, and for target therapies (dabrafenib plus trametinib), $4929.28 to $5548.57. CONCLUSION: Our study presented an interesting and cost-effective option where desensitization allowed children with HR to be treated with first-line therapy, avoiding the discontinuation of an effective treatment.


Assuntos
Antineoplásicos , Carboplatina , Dessensibilização Imunológica , Glioma , Humanos , Carboplatina/efeitos adversos , Masculino , Criança , Feminino , Antineoplásicos/efeitos adversos , Adolescente , Dessensibilização Imunológica/métodos , Estudos Prospectivos , Glioma/tratamento farmacológico , Hipersensibilidade a Drogas/terapia , Neoplasias Encefálicas/tratamento farmacológico , Pré-Escolar
12.
Medicina (B Aires) ; 84(3): 592-596, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-38907981

RESUMO

The frontal aslant tract (FAT) connects the supplementary motor area (SMA) with the pars opercularis. Its role in language and its implications in glioma surgery remain under discussion. We present an anatomosurgical study of three cases with surgical resolution. Three patients with gliomas in the left frontal lobe were operated on using an awake patient protocol with cortical and subcortical mapping techniques, conducting motor and language evaluations. Tractography was performed using DSI Studio software. All three patients showed intraoperative language inhibition through subcortical stimulation of the FAT. Resection involving the FAT correlated with language deficits in all cases and movement initiation deficits in two cases. All patients recovered from their deficits at six months postoperatively. In conclusion, the tract has been successfully reconstructed, showing both anatomical and functional complexity, supporting the idea of its mapping and preservation in glioma surgery. Future interdisciplinary studies are necessary to determine the transient or permanent nature of the deficits.


El tracto oblicuo frontal (TOF) conecta el área motora suplementaria (AMS) con la pars opercularis. Su rol en el lenguaje y su implicancia en la cirugía de gliomas siguen en discusión. Presentamos un estudio anatomoquirúrgico de tres casos con resolución quirúrgica. Se operaron tres pacientes con gliomas en el lóbulo frontal izquierdo utilizando protocolo de paciente despierto con técnicas de mapeo cortical y subcortical realizando evaluación motora y del lenguaje. Las tractografías fueron realizadas con el software DSI Studio. Los tres pacientes presentaron inhibición intraoperatoria del lenguaje mediante la estimulación subcortical de TOF. La resección en contacto con el TOF se correlacionó con déficits del lenguaje en todos los casos y en dos casos déficits en la iniciación del movimiento. Todos los pacientes recuperaron su déficit a los seis meses postoperatorios. En conclusión, se ha logrado reconstruir al tracto. Éste presenta una complejidad anatómica y funcional, que apoya la idea de su mapeo y preservación en la cirugía de gliomas. Futuros estudios interdisciplinarios son necesarios para determinar el carácter transitorio o permanente de los déficits.


Assuntos
Neoplasias Encefálicas , Lobo Frontal , Glioma , Humanos , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Glioma/cirurgia , Glioma/diagnóstico por imagem , Glioma/patologia , Masculino , Lobo Frontal/cirurgia , Lobo Frontal/diagnóstico por imagem , Pessoa de Meia-Idade , Feminino , Adulto , Procedimentos Neurocirúrgicos/métodos , Mapeamento Encefálico/métodos , Córtex Motor/diagnóstico por imagem , Córtex Motor/cirurgia , Córtex Motor/anatomia & histologia , Imagem de Tensor de Difusão
13.
Biomédica (Bogotá) ; Biomédica (Bogotá);44(2): 191-206, ene.-jun. 2024. tab, graf
Artigo em Inglês | LILACS, COLNAL | ID: biblio-1574085

RESUMO

Introduction. High-grade gliomas are the most common primary brain tumors in adults, and they usually have a quick fatal course. Average survival is 18 months, mainly, because of tumor resistance to Stupp protocol. Objective. To determine high-grade glioma patient survival and the effect of persuasion variables on survival. Materials and methods. We conducted a longitudinal descriptive study in which 80 untreated recently diagnosed high-grade glioma patients participated. A survey was conducted regarding their exposure to some risk factors, degree of genetic instability in peripheral blood using micronucleus quantification on binuclear lymphocytes, micronuclei in reticulocytes and sister-chromatid exchanges in lymphocytes. In the statistical analysis, this study constructed life tables, used the Kaplan-Meier, and the log-rank test, and in the multivariate analysis, a Cox proportional hazards model was constructed. Results. Eighty patients' clinical, demographic and lifestyle characteristics were analyzed, as well as their survival rates and the average survival time is 784 days (interquartile range: 928). Factors like age, exposure at work to polycyclic hydrocarbons and the number of sister-chromatid exchanges in lymphocytes in the first sampling was significantly survival-related in the multivariate analysis. Conclusion. We determined that only three of the analyzed variables have an important effect on survival time when it comes to high-grade glioma patients.


Introducción. Los gliomas de alto grado son los tumores cerebrales primarios más comunes en adultos y, por lo general, tienen un curso mortal rápido. La supervivencia media es de 18 meses, principalmente, como consecuencia de la resistencia del tumor al protocolo Stupp. Objetivo. Determinar la supervivencia de los pacientes con glioma de alto grado y el efecto de las variables de persuasión en la supervivencia. Materiales y métodos. Se llevó a cabo un estudio descriptivo longitudinal en el que participaron 80 pacientes con diagnóstico reciente de glioma de alto grado no tratados. Se hizo una encuesta sobre su exposición a algunos factores de riesgo, grado de inestabilidad genética en sangre periférica mediante cuantificación de micronúcleos en linfocitos binucleares, micronúcleos en reticulocitos e intercambios de cromátidas hermanas en linfocitos. En el análisis estadístico, se construyeron tablas de vida, se utilizó Kaplan-Meier y la prueba de rangos logarítmicos, y en el análisis multivariado, se construyó un modelo de riesgos proporcionales de Cox. Resultados. Se analizaron las características clínicas, demográficas y de estilo de vida de 80 pacientes, así como sus tasas de supervivencia y el tiempo medio de supervivencia fue de 784 días (rango intercuartílico: 928). Factores como la edad, la exposición laboral a hidrocarburos policíclicos y el número de intercambios de cromátidas hermanas en linfocitos en el primer muestreo se relacionaron significativamente con la supervivencia en el análisis multivariante. Conclusión. Según los resultados, el estudio determinó que solo tres de las variables analizadas tienen un efecto importante en el tiempo de supervivencia cuando se trata de pacientes con glioma de alto grado.


Assuntos
Humanos , Fatores de Risco , Genética , Glioma , Prognóstico , Estimativa de Kaplan-Meier , Sobrevivência
14.
Biol Res ; 57(1): 30, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760850

RESUMO

BACKGROUND: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), are present in most gliomas. IDH1 mutation is an important prognostic marker in glioma. However, its regulatory mechanism in glioma remains incompletely understood. RESULTS: miR-182-5p expression was increased within IDH1-mutant glioma specimens according to TCGA, CGGA, and online dataset GSE119740, as well as collected clinical samples. (R)-2-hydroxyglutarate ((R)-2HG) treatment up-regulated the expression of miR-182-5p, enhanced glioma cell proliferation, and suppressed apoptosis; miR-182-5p inhibition partially eliminated the oncogenic effects of R-2HG upon glioma cells. By direct binding to Cyclin Dependent Kinase Inhibitor 2 C (CDKN2C) 3'UTR, miR-182-5p inhibited CDKN2C expression. Regarding cellular functions, CDKN2C knockdown promoted R-2HG-treated glioma cell viability, suppressed apoptosis, and relieved cell cycle arrest. Furthermore, CDKN2C knockdown partially attenuated the effects of miR-182-5p inhibition on cell phenotypes. Moreover, CDKN2C knockdown exerted opposite effects on cell cycle check point and apoptosis markers to those of miR-182-5p inhibition; also, CDKN2C knockdown partially attenuated the functions of miR-182-5p inhibition in cell cycle check point and apoptosis markers. The engineered CS-NPs (antagomir-182-5p) effectively encapsulated and delivered antagomir-182-5p, enhancing anti-tumor efficacy in vivo, indicating the therapeutic potential of CS-NPs(antagomir-182-5p) in targeting the miR-182-5p/CDKN2C axis against R-2HG-driven oncogenesis in mice models. CONCLUSIONS: These insights highlight the potential of CS-NPs(antagomir-182-5p) to target the miR-182-5p/CDKN2C axis, offering a promising therapeutic avenue against R-2HG's oncogenic influence to glioma.


Assuntos
Neoplasias Encefálicas , Glioma , Isocitrato Desidrogenase , MicroRNAs , Humanos , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Glioma/genética , Glioma/metabolismo , Animais , Camundongos , Xenoenxertos , Transplante de Neoplasias , Neoplasias Encefálicas/genética , MicroRNAs/metabolismo
15.
Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167248, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38777100

RESUMO

Recent studies in Diffuse Midline Gliomas (DMG) demonstrated a strong connection between epigenome dysregulation and metabolic rewiring. Here, we evaluated the value of targeting a glycolytic protein named Phosphofructo-2-kinase/Fructose-2,6-bisphosphatase 3 (PFKFB3) in H3.3K27M DMG. We observed that the viability of H3.3K27M cells is dramatically reduced by PFK15, a potent inhibitor of PFKFB3. Furthermore, PFKFB3 inhibition induced apoptosis and G2/M arrest. Interestingly, CRISPR-Knockout of the K27M mutant allele has a synergistic effect on the observed phenotype. Altogether, we identified PFKFB3 as a new target for H3.3K27M DMG, making PFK15 a potential candidate for future animal studies and clinical trials.


Assuntos
Glioma , Histonas , Fosfofrutoquinase-2 , Humanos , Glioma/metabolismo , Glioma/patologia , Glioma/genética , Fosfofrutoquinase-2/metabolismo , Fosfofrutoquinase-2/genética , Histonas/metabolismo , Histonas/genética , Linhagem Celular Tumoral , Criança , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamento farmacológico , Apoptose , Mutação , Glicólise/efeitos dos fármacos
16.
Rev Assoc Med Bras (1992) ; 70(5): e20231337, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38775506

RESUMO

OBJECTIVE: It has been previously shown that brain-derived neurotrophic factor is linked with various types of cancer. Brain-derived neurotrophic factor is found to be highly expressed in multiple human cancers and associated with tumor growth, invasion, and metastasis. Adipokinetic hormones are functionally related to the vertebrate glucagon, as they have similar functionalities that manage the nutrient-dependent secretion of these two hormones. Migrasomes are new organelles that contain numerous small vesicles, which aid in transmitting signals between the migrating cells. Therefore, the aim of this study was to investigate the effects of Anax imperator adipokinetic hormone on brain-derived neurotrophic factor expression and ultrastructure of cells in the C6 glioma cell line. METHODS: The rat C6 glioma cells were treated with concentrations of 5 and 10 Anax imperator adipokinetic hormone for 24 h. The effects of the Anax imperator adipokinetic hormone on the migrasome formation and brain-derived neurotrophic factor expression were analyzed using immunocytochemistry and transmission electron microscope. RESULTS: The rat C6 glioma cells of the 5 and 10 µM Anax imperator adipokinetic hormone groups showed significantly high expressions of brain-derived neurotrophic factor and migrasomes numbers, compared with the control group. CONCLUSION: A positive correlation was found between the brain-derived neurotrophic factor expression level and the formation of migrasome, which indicates that the increased expression of brain-derived neurotrophic factor and the number of migrasomes may be involved to metastasis of the rat C6 glioma cell line induced by the Anax imperator adipokinetic hormone. Therefore, the expression of brain-derived neurotrophic factor and migrasome formation may be promising targets for preventing tumor proliferation, invasion, and metastasis in glioma.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Glioma , Oligopeptídeos , Ácido Pirrolidonocarboxílico , Glioma/metabolismo , Glioma/patologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ratos , Linhagem Celular Tumoral , Ácido Pirrolidonocarboxílico/análogos & derivados , Ácido Pirrolidonocarboxílico/metabolismo , Oligopeptídeos/farmacologia , Hormônios de Inseto/metabolismo , Movimento Celular/efeitos dos fármacos , Imuno-Histoquímica , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Organelas/metabolismo , Organelas/efeitos dos fármacos , Organelas/ultraestrutura
17.
Clinics (Sao Paulo) ; 79: 100367, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38692010

RESUMO

OBJECTIVE: This study investigated the relationship between PDZK1 expression and Dynamic Contrast-Enhanced MRI (DCE-MRI) perfusion parameters in High-Grade Glioma (HGG). METHODS: Preoperative DCE-MRI scanning was performed on 80 patients with HGG to obtain DCE perfusion transfer coefficient (Ktrans), vascular plasma volume fraction (vp), extracellular volume fraction (ve), and reverse transfer constant (kep). PDZK1 in HGG patients was detected, and its correlation with DCE-MRI perfusion parameters was assessed by the Pearson method. An analysis of Cox regression was performed to determine the risk factors affecting survival, while Kaplan-Meier and log-rank tests to evaluate PDZK1's prognostic significance, and ROC curve analysis to assess its diagnostic value. RESULTS: PDZK1 was upregulated in HGG patients and predicted poor overall survival and progression-free survival. Moreover, PDZK1 expression distinguished grade III from grade IV HGG. PDZK1 expression was positively correlated with Ktrans 90, and ve_90, and negatively correlated with kep_max, and kep_90. CONCLUSION: PDZK1 is upregulated in HGG, predicts poor survival, and differentiates tumor grading in HGG patients. PDZK1 expression is correlated with DCE-MRI perfusion parameters.


Assuntos
Neoplasias Encefálicas , Meios de Contraste , Glioma , Imageamento por Ressonância Magnética , Gradação de Tumores , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/irrigação sanguínea , Glioma/diagnóstico por imagem , Glioma/patologia , Glioma/irrigação sanguínea , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética/métodos , Prognóstico , Curva ROC
18.
Childs Nerv Syst ; 40(8): 2321-2332, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38607550

RESUMO

PURPOSE: This study aims to provide an exhaustive analysis of pediatric low-grade gliomas (pLGGs) in the cerebellar hemispheres, focusing on incidence, clinical characteristics, surgical outcomes, and prognosis. It seeks to enhance understanding and management of pLGGs in the pediatric population. METHODS: We conducted an observational, descriptive, retrospective, and cross-sectional study at a pediatric hospital, reviewing medical records of 30 patients with cerebellar hemispheric pLGGs treated from December 2014 to January 2023. Data collection included demographics, clinical presentation, imaging findings, surgical approach, postoperative complications, histopathological diagnosis, hydrocephalus management, and follow-up. Molecular markers and adjuvant therapies were also analyzed. RESULTS: The cohort predominantly presented with cerebellar symptoms, with 60% showing hydrocephalus at diagnosis. MRI with gadolinium was crucial for diagnosis. Surgical focus was on achieving gross total resection (GTR), accomplished in 70% of cases. Postsurgical hydrocephalus was less common, and cerebellar mutism was not reported. While a complete molecular analysis was not performed in all cases, available data suggest significant influence of molecular markers on prognosis and therapeutic options of pLGGs. CONCLUSIONS: This study highlights the unique clinical and molecular characteristics of cerebellar hemispheric pLGGs in children. The lower incidence of postoperative hydrocephalus and absence of cerebellar mutism are notable findings. Emphasizing a multidisciplinary approach, our findings contribute to a deeper understanding of pediatric pLGGs, underscoring the need for personalized treatment strategies and vigilant follow-up.


Assuntos
Neoplasias Cerebelares , Glioma , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neoplasias Cerebelares/cirurgia , Neoplasias Cerebelares/terapia , Estudos Transversais , Glioma/cirurgia , Glioma/terapia , Glioma/diagnóstico , Hospitais Pediátricos , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Procedimentos Neurocirúrgicos/métodos , Estudos Retrospectivos , Centros de Atenção Terciária
19.
Neurosurg Rev ; 47(1): 160, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625548

RESUMO

The right hemisphere has been underestimated by being considered as the non-dominant hemisphere. However, it is involved in many functions, including movement, language, cognition, and emotion. Therefore, because lesions on this side are usually not resected under awake mapping, there is a risk of unfavorable neurological outcomes. The goal of this study is to compare the functional and oncological outcomes of awake surgery (AwS) versus surgery under general anesthesia (GA) in supratentorial right-sided gliomas. A systematic review of the literature according to PRISMA guidelines was performed up to March 2023. Four databases were screened. Primary outcome to assess was return to work (RTW). Secondary outcomes included the rate of postoperative neurological deficit, postoperative Karnofsky Performance Status (KPS) score and the extent of resection (EOR). A total of 32 articles were included with 543 patients who underwent right hemisphere tumor resection under awake surgery and 294 under general anesthesia. There were no significant differences between groups regarding age, gender, handedness, perioperative KPS, tumor location or preoperative seizures. Preoperative and long-term postoperative neurological deficits were statistically lower after AwS (p = 0.03 and p < 0.01, respectively), even though no difference was found regarding early postoperative course (p = 0.32). A subsequent analysis regarding type of postoperative impairment was performed. Severe postoperative language deficits were not different (p = 0.74), but there were fewer long-term mild motor and high-order cognitive deficits (p < 0.05) in AwS group. A higher rate of RTW (p < 0.05) was documented after AwS. The EOR was similar in both groups. Glioma resection of the right hemisphere under awake mapping is a safer procedure with a better preservation of high-order cognitive functions and a higher rate of RTW than resection under general anesthesia, despite similar EOR.


Assuntos
Neoplasias Encefálicas , Glioma , Vigília , Humanos , Glioma/cirurgia , Vigília/fisiologia , Neoplasias Encefálicas/cirurgia , Procedimentos Neurocirúrgicos/métodos , Anestesia Geral/métodos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia
20.
World Neurosurg ; 186: 204-218.e2, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38580093

RESUMO

BACKGROUND: Classifying brain tumors accurately is crucial for treatment and prognosis. Machine learning (ML) shows great promise in improving tumor classification accuracy. This study evaluates ML algorithms for differentiating various brain tumor types. METHODS: A systematic review and meta-analysis were conducted, searching PubMed, Embase, and Web of Science up to March 14, 2023. Studies that only investigated image segmentation accuracy or brain tumor detection instead of classification were excluded. We extracted binary diagnostic accuracy data, constructing contingency tables to derive sensitivity and specificity. RESULTS: Fifty-one studies were included. The pooled area under the curve for glioblastoma versus lymphoma and low-grade versus high-grade gliomas were 0.99 (95% confidence interval [CI]: 0.98-1.00) and 0.89, respectively. The pooled sensitivity and specificity for benign versus malignant tumors were 0.90 (95% CI: 0.85-0.93) and 0.93 (95% CI: 0.90-0.95), respectively. The pooled sensitivity and specificity for low-grade versus high-grade gliomas were 0.99 (95% CI: 0.97-1.00) and 0.94, (95% CI: 0.79-0.99), respectively. Primary versus metastatic tumor identification yields sensitivity and specificity of 0.89, (95% CI: 0.83-0.93) and 0.87 (95% CI: 0.82-0.91), correspondingly. The differentiation of gliomas from pituitary tumors yielded the highest results among primary brain tumor classifications: sensitivity of 0.99 (95% CI: 0.99-1.00) and specificity of 0.99 (95% CI: 0.98-1.00). CONCLUSIONS: ML demonstrated excellent performance in classifying brain tumor images, with near-maximum area under the curves, sensitivity, and specificity.


Assuntos
Neoplasias Encefálicas , Aprendizado de Máquina , Humanos , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Glioblastoma/classificação , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Glioma/classificação , Glioma/diagnóstico por imagem , Glioma/patologia , Sensibilidade e Especificidade
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