Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 359
Filtrar
1.
Medicine (Baltimore) ; 100(25): e26437, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160435

RESUMO

ABSTRACT: Recent studies have shown that some inflammatory markers are associated with the prognosis of solid tumors. This study aims to evaluate the prognosis of glioma patients with or without adjuvant treatment using the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR).All patients who were diagnosed with gliomas at the first and second affiliated hospital of Guangxi Medical University between 2011 and 2020 were included in this study. The optimal cutoff value of SII, NLR, and PLR was determined by X-tile software program. We stratified patients into several groups and evaluated the progression-free survival (PFS) and overall survival (OS) of SII, NLR, and PLR during the period of pre-surgical, con-chemoradiotherapy, and post-treatments. Multivariate Cox regression analyses were performed to detect the relationships between OS, PFS, and prognostic variables.A total of 67 gliomas patients were enrolled in the study. The cutoff values of SII, NLR, and PLR were 781.5 × 109/L, 2.9 × 109/L, and 123.2 × 109/L, respectively. Patients who are pre-SII < 781.5 × 109/L had better PFS (P = .027), but no difference in OS. In addition, patients who had low pre-NLR (<2.9 × 109/L) meant better OS and PFS. PLR after adjuvant treatments (post-PLR) was significantly higher than pre-PLR (P = .035). Multivariate analyses revealed that pre-SII, pre-NLR were independent prognostic factors for OS (pre-SII: HR 1.002, 95% CI: 1.000-1.005, P = .030 and pre-PLR: HR 0.983, 95% CI: 0.973-0.994, P = .001), while pre-PLR was an independent factor for PFS (HR 0.989, 95% CI: 0.979-1.000, P = .041).High pre-SII or high pre-NLR could be prognostic markers to identify glioma patients who had a poor prognosis.


Assuntos
Plaquetas/imunologia , Neoplasias Encefálicas/terapia , Glioma/terapia , Linfócitos/imunologia , Procedimentos Neurocirúrgicos , Neutrófilos/imunologia , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/mortalidade , Quimiorradioterapia/métodos , Feminino , Glioma/sangue , Glioma/imunologia , Glioma/mortalidade , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Contagem de Plaquetas , Período Pré-Operatório , Prognóstico , Intervalo Livre de Progressão , Valores de Referência , Estudos Retrospectivos , Adulto Jovem
2.
Cancer Sci ; 112(9): 3491-3506, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34036683

RESUMO

Temozolomide (TMZ) resistance is the main challenge in the management of glioma patients. Heparanase can mediate the secretion and function of exosomes, which are considered to be a promising molecular delivery system for cancer therapy. Therefore, this study aimed to investigate whether heparanase-mediated delivery of exosomes was related to TMZ resistance of glioma. Heparanase was upregulated in TMZ-resistant glioma cells, and overexpression of heparanase led to increased resistance of U87 cells to TMZ. Knockdown of heparanase led to increased sensitivity of TMZ-resistant U251 cells (U251R) cells to TMZ. Heparanase promoted the secretion of exosomes from glioma cells, and coculture with exosomes derived from heparanase knockdown U251R cells partly restored the sensitivity of U251 cells to TMZ compared with exosomes derived from si-control transfected U251R cells. It was identified by circular RNA microarrays that hsa_circ_0042003 was upregulated in exosomes derived from U251R, which could be positively regulated by heparanase. U251R cell-derived exosomal hsa_circ_0042003 conferred the resistance of U251 cells to TMZ. In vivo studies also showed that U251R cell-derived exosomes induced resistance of U251 cells to TMZ, and the combination of tail-injected exosomal si-heparanase or exosomal si-hsa_circ_0042003 and intraperitoneal TMZ applied to nude mice abolished TMZ resistance. Heparanase mediated the transfer of exosomal hsa_circ_0042003 from TMZ-resistant glioma cells to drug-sensitive cells, which contributed to the chemoresistance of glioma to TMZ.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Exossomos/metabolismo , Glioma/tratamento farmacológico , Glucuronidase/metabolismo , RNA Circular/metabolismo , Via Secretória/genética , Temozolomida/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Glioma/sangue , Glioma/patologia , Glucuronidase/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Circular/genética , Transfecção , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Aging (Albany NY) ; 13(9): 13287-13299, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33982667

RESUMO

BACKGROUND: Glioma is one of the most wide-spreading brain cancers worldwide. Exosomes have emerged as essential regulators in intercellular communication, and exosomal circular RNAs (circRNAs) are critical for cancer progression. In this study, we aimed to investigate the role of exosomal circRNAs in glioma progression and associated mechanisms. METHODS: Exosomes derived from glioma cells were isolated and identified by transmission electron microscopy and nanoparticle tracking analysis (NTA). CCK-8, wound healing assays, transwell invasion assays, and flow cytometry assays were performed to assess glioma progression. RNA sequencing, RT-qPCR, western blotting, fluorescence in situ hybridization assay, luciferase assays, and cell transfection assay were performed to investigate related molecular mechanisms. RESULTS: The results demonstrated that exosomes derived from glioma cells promoted glioma progression. Also, exosomal circRNA 0001445 was taken up and upregulated in glioma cells treated with exosomes. In addition, exosomal circRNA 0001445 acted as a sponge for miRNA-127-5p to upregulate the expression of sorting nexin 5 (SNX5). Lastly, the effect of exosomal circRNA 0001445 was mediated by miRNA-127-5p/ SNX5 signaling pathway. CONCLUSION: These results demonstrated that exosomal circRNA 0001445 promoted glioma progression through miRNA-127-5p/SNX5 signaling pathway. This study provides a novel understanding of the molecular mechanism of glioma progression.


Assuntos
Neoplasias Encefálicas/genética , Exossomos/metabolismo , Glioma/metabolismo , RNA Circular/sangue , Neoplasias Encefálicas/metabolismo , Movimento Celular/fisiologia , Glioma/sangue , Glioma/genética , Humanos , Análise de Sequência de RNA/métodos , Nexinas de Classificação/metabolismo
4.
Cancer Imaging ; 21(1): 27, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33691798

RESUMO

BACKGROUND: The purpose of this study was to develop a voxel-wise clustering method of multiparametric magnetic resonance imaging (MRI) and 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (FDOPA) positron emission tomography (PET) images using an unsupervised, two-level clustering approach followed by support vector machine in order to classify the isocitrate dehydrogenase (IDH) status of gliomas. METHODS: Sixty-two treatment-naïve glioma patients who underwent FDOPA PET and MRI were retrospectively included. Contrast enhanced T1-weighted images, T2-weighted images, fluid-attenuated inversion recovery images, apparent diffusion coefficient maps, and relative cerebral blood volume maps, and FDOPA PET images were used for voxel-wise feature extraction. An unsupervised two-level clustering approach, including a self-organizing map followed by the K-means algorithm was used, and each class label was applied to the original images. The logarithmic ratio of labels in each class within tumor regions was applied to a support vector machine to differentiate IDH mutation status. The area under the curve (AUC) of receiver operating characteristic curves, accuracy, and F1-socore were calculated and used as metrics for performance. RESULTS: The associations of multiparametric imaging values in each cluster were successfully visualized. Multiparametric images with 16-class clustering revealed the highest classification performance to differentiate IDH status with the AUC, accuracy, and F1-score of 0.81, 0.76, and 0.76, respectively. CONCLUSIONS: Machine learning using an unsupervised two-level clustering approach followed by a support vector machine classified the IDH mutation status of gliomas, and visualized voxel-wise features from multiparametric MRI and FDOPA PET images. Unsupervised clustered features may improve the understanding of prioritizing multiparametric imaging for classifying IDH status.


Assuntos
Neoplasias Encefálicas/sangue , Glioma/sangue , Isocitrato Desidrogenase/metabolismo , Aprendizado de Máquina/normas , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Neoplasias Encefálicas/patologia , Feminino , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
World Neurosurg ; 151: e37-e46, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33746099

RESUMO

BACKGROUND: Gliomas, particularly high-grade gliomas, are the most common primary brain tumors. From the Chinese Glioma Genome Atlas (CGGA) database, the relationships between the altered molecular pathways and gliomas could be easily observed. A close connection in the occurrence of the pathogenesis exists between the microenvironment, the glioma, and the associated genes. METHODS: Validation of the role of ZNF311 oncogene was confirmed by data from the CGGA dataset on glioblastoma and low-grade glioma. Furthermore, we used CIBERSORT to analyze the correlation between ZNF311 and cancer immune infiltrates. RESULTS: According to our analysis, ZNF311 was expressed higher in patients with grade-depended glioma with poor prognosis. In addition, we obtained valuable prognostic results between isocitrate dehydrogenase 1 (IDH1) and ZNF311 through the analysis of integrated correlations. Similarly, we simultaneously revealed the prognostic results between 1p/19q and ZNF311. In addition, we found that ZNF311 is correlated with a large number of tumor-infiltrating immune cells. CONCLUSIONS: Based on the study findings, we conclude that ZNF311 is potentially a novel biomarker for assessing prognosis and immune infiltration in glioblastoma and diffuse glioma cases.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/imunologia , Glioma/diagnóstico , Glioma/imunologia , Adulto , Idoso , Algoritmos , Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/sangue , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glioma/sangue , Humanos , Isocitrato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Análise de Sobrevida , Microambiente Tumoral
6.
Turk Neurosurg ; 31(3): 399-403, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33759165

RESUMO

AIM: To measure serum levels of thrombospondin-1 (TSP-1) and thrombospondin-2 (TSP-2) in patients with common brain tumors, namely high-grade glioma (HGG), low-grade glioma (LGG), and meningioma. MATERIAL AND METHODS: For this prospective study, a total of 56 patients were operated on for supratentorial gliomas and meningiomas, and 18 healthy subjects were evaluated. Serum levels of angiostatic molecules were measured with enzyme-linked immunosorbent assay. The results of patients were compared with those of healthy subjects. RESULTS: High serum levels of TSP-1 were seen in HGG, followed by LGG, meningioma groups, and controls. The only significant difference was found between HGGs and controls (p=0.004). There was a trend to decrease from HGG to controls. High serum levels of TSP-2 were seen in controls, followed by meningioma, LGG, and HGG. None of the patient groups showed significant differences compared with controls. Among the patient groups, TSP-2 was significantly higher in the meningioma group than the HGG group (p=0.01). No correlation was found with any of the molecules and the clinical parameters, including the presence of peritumoral edema or seizure, the anterior-posterior diameter of the tumor, and, more importantly, the grade of glioma. CONCLUSION: Our results indicate that TSP-2 might be more important than TSP-1 in preventing angiogenesis and a major angiostatic factor in glioma cells.


Assuntos
Neoplasias Encefálicas/sangue , Glioma/sangue , Neoplasias Meníngeas/sangue , Meningioma/sangue , Trombospondina 1/sangue , Trombospondinas/sangue , Adulto , Idoso , Neoplasias Encefálicas/patologia , Feminino , Glioma/patologia , Humanos , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Pessoa de Meia-Idade , Estudos Prospectivos
7.
Cancer Causes Control ; 32(4): 347-355, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33484419

RESUMO

PURPOSE: Evidence is mixed on whether cholesterol plays a role in the pathogenesis of glioma. We explored the associations between circulating lipids and glioma risk in three prospective cohorts. METHODS: Using prospective data from the UK Biobank, we examined the associations of total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), and triglycerides (TG) with glioma risk in multivariable (MV)-adjusted Cox proportional hazards models. Within the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS), we carried out a matched, nested case-control study to examine these same associations. RESULTS: In the UK Biobank, 490 gliomas accrued over 2,358,964 person-years. TC was not significantly associated with glioma risk (MV HR = 1.20, 95% CI 0.89-1.61 for highest quartile vs. lowest, p-trend = 0.24). In 4-year lagged analyses (n = 229), higher TC was associated with significantly higher risk of glioma in men (MV HR = 2.26, 95% CI 1.32-3.89, p-trend = 0.002) but not women (MV HR = 1.28, 95% CI 0.61-2.68, p-trend = 0.72); similar findings emerged for HDL-C and, to a lesser extent, LDL-C. In the NHS/HPFS, no significant associations were found between cholesterol and glioma risk. No significant associations were identified for TG. CONCLUSION: In the UK Biobank, higher prediagnostic TC and HDL-C levels were associated with higher risk of glioma in 4-year lagged analyses, but not in non-lagged analyses, in men only. These findings merit further investigation, given that there are few risk factors and no reliable biomarkers of risk identified for glioma.


Assuntos
Neoplasias Encefálicas/sangue , Colesterol/sangue , Glioma/sangue , Triglicerídeos/sangue , Idoso , Neoplasias Encefálicas/epidemiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Glioma/epidemiologia , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Reino Unido/epidemiologia
8.
Neurosurgery ; 88(3): E221-E230, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33442748

RESUMO

Accurate circulating biomarkers have potential clinical applications in population screening, tumor subclassification, monitoring tumor status, and the delivery of individualized treatments resulting from tumor genotyping. Recently, significant progress has been made within this field in several cancer types, but despite the many potential benefits, currently there is no validated circulating biomarker test for patients with glioma. A number of circulating factors have been examined, including circulating tumor cells, cell-free DNA, microRNA, exosomes, and proteins from both peripheral blood and cerebrospinal fluid with variable results. In the following article, we provide a narrative review of the current evidence pertaining to circulating biomarkers in patients with glioma, including discussion of the advantages and challenges encountered with the current methods used for discovery. Additionally, the potential clinical applications are described with reference to the literature.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/sangue , Glioma/sangue , Células Neoplásicas Circulantes/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Exossomos/metabolismo , Exossomos/patologia , Glioma/patologia , Humanos , MicroRNAs/sangue , MicroRNAs/metabolismo , Células Neoplásicas Circulantes/patologia
9.
Medicine (Baltimore) ; 99(51): e23840, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371165

RESUMO

ABSTRACT: Tumor-associated macrophages (TAMs) play a crucial role in the immune response to many malignancies, but the signaling pathways by which the glioma microenvironment cross-talk with TAMs are poorly understood. The aim of this study was to uncover the potential signaling pathways of the regulation of TAMs and identify candidate targets for therapeutic intervention of glioma through bioinformatics analysis.Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) datasets were used to download RNA-Seq data and microarray data of human glioma specimen. Differentially expressed genes (DEGs) between CD68-high samples and CD68-low samples were sorted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs was conducted. Protein-protein interaction (PPI) network were formed to identify the hub genes.The prognostic value of TAMs in glioma patients was confirmed. A total of 477 specific DEGs were sorted. The signaling pathway was identified in pathway enrichment and the DEGs showed prominent representations of immune response networks in glioma. The hub genes including C3, IL6, ITGB2, PTAFR, TIMP1 and VAMP8 were identified form the PPI network and they were all correlated positively with the expression of CD68 and showed the excellent prognostic value in glioma patients.TAMs can be used as a good prognostic indicator in glioma patients. By analyzing comprehensive bioinformatics data, we uncovered the underlying signaling pathway of the DEGs between glioma patients with high and low expression level of CD68. Furthermore, the 6 hub genes identified were closely associated with TAMs in glioma microenvironment and need further investigation.


Assuntos
Glioma/sangue , Glioma/genética , Macrófagos Associados a Tumor/imunologia , Antígenos CD/análise , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/análise , Antígenos de Diferenciação Mielomonocítica/sangue , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Glioma/patologia , Humanos , Prognóstico , Transdução de Sinais/genética , Microambiente Tumoral/imunologia
10.
Cancer Chemother Pharmacol ; 86(6): 793-801, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33089408

RESUMO

BACKGROUND: Temozolomide is an alkylating agent approved by the U.S. Food and Drug Administration in 1999 for the treatment of patients with primary brain tumors. The aim of this study was to confirm the bioequivalence and safety of two strengths (20-100 mg) of generic temozolomide in the form of TOZ039 and Temodal® capsules administered to brain tumor patients. STUDY DESIGN: An open-label, randomized, two-phase, two-period, crossover pharmacokinetic study was performed in a single institution. The reference and test drugs were prescribed at a dose of 150 mg/m2 daily from days 1 to 5 of a 28-day cycle in the first phase; in the second phase, either a 150- or 200-mg/m2 dose was prescribed, depending on patient tolerance. On days 1 and 2 of each phase, a fixed 200-mg dose was administered either as ten 20-mg capsules in the first cycle or two 100-mg capsules in the second cycle. Drug administration in the first two days was randomized, i.e., if TOZ309 was administered on day 1, Temodal® was administered on day 2, and vice versa. The rest of the prescribed dose was administered in the form of Temodal® and spread equally over days 3-5. Blood samples were obtained for pharmacokinetic evaluation on days 1 and 2. Bioequivalence was demonstrated if the geometric means ratio of the three main pharmacokinetic parameters (mean maximum plasma concentration (Cmax), area under the concentration-time curve (AUC) 0-t, AUC 0-∞) fell within the equivalence boundary of 80-125%. RESULTS: Twenty-nine glioblastoma multiforme or anaplastic astrocytoma patients were enrolled and dosed with the test and reference formulations under fasting conditions. The 90% confidence interval of the geometric means ratio for Cmax (91.08%, 106.18%), AUC0-t (98.62%,102.18%), and AUC0-∞ (98.65%, 102.21%) was well within the 80%-125% range for the 20-mg capsule, as was the Cmax (90.49%, 113.32%), AUC0-t (99.89%, 104.63%) and AUC0-∞ (99.99%, 104.67%) for the 100-mg capsule drug product. Additionally, all the secondary pharmacokinetic parameters were not significantly different. After two cycles of treatment, there was no mortality among the 29 patients, treatment-related severe adverse events, or events that would require study discontinuation; however, one significant adverse effect (life-threatening seizures) occurred and was related to disease progression. Adverse events were reported in 82.8% (24/29) patients, and treatment emergent adverse events were reported in 72.4% (21/29) patients. CONCLUSION: It can be concluded that 20-mg and 100-mg capsules of TOZ309 are bioequivalent to Temodal® capsules of the same strength under fasting conditions. TRIAL REGISTRATION: https://www.chinadrugtrials.org.cn/index.html , CTR2017 0122.


Assuntos
Antineoplásicos Alquilantes/farmacocinética , Neoplasias Encefálicas/tratamento farmacológico , Medicamentos Genéricos/farmacocinética , Glioma/tratamento farmacológico , Temozolomida/farmacocinética , Administração Oral , Adolescente , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Área Sob a Curva , Disponibilidade Biológica , Neoplasias Encefálicas/sangue , Cápsulas , China , Estudos Cross-Over , Relação Dose-Resposta a Droga , Medicamentos Genéricos/administração & dosagem , Jejum , Glioma/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Temozolomida/administração & dosagem , Equivalência Terapêutica , Adulto Jovem
11.
J Vis Exp ; (163)2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32986022

RESUMO

Identifying mutations in tumors of cancer patients is a very important step in disease management. These mutations serve as biomarkers for tumor diagnosis as well as for the treatment selection and its response in cancer patients. The current gold standard method for detecting tumor mutations involves a genetic test of tumor DNA by means of tumor biopsies. However, this invasive method is difficult to be performed repeatedly as a follow-up test of the tumor mutational repertoire. Liquid biopsy is a new and emerging technique for detecting tumor mutations as an easy-to-use and non-invasive biopsy approach. Cancer cells multiply rapidly. In parallel, numerous cancer cells undergo apoptosis. Debris from these cells are released into a patient's circulatory system, together with finely fragmented DNA pieces, called cell-free DNA (cfDNA) fragments, which carry tumor DNA mutations. Therefore, for identifying cfDNA based biomarkers using liquid biopsy technique, blood samples are collected from the cancer patients, followed by the separation of plasma and buffy coat. Next, plasma is processed for the isolation of cfDNA, and the respective buffy coat is processed for the isolation of a patient's genomic DNA. Both nucleic acid samples are then checked for their quantity and quality; and analyzed for mutations using next-generation sequencing (NGS) techniques. In this manuscript, we present a detailed protocol for liquid biopsy, including blood collection, plasma, and buffy coat separation, cfDNA and germline DNA extraction, quantification of cfDNA or germline DNA, and cfDNA fragment enrichment analysis.


Assuntos
Ácidos Nucleicos Livres/sangue , Neoplasias/sangue , Neoplasias/genética , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , Fluorometria , Genoma Humano , Glioma/sangue , Glioma/genética , Humanos , Biópsia Líquida
12.
Biosci Rep ; 40(7)2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32639004

RESUMO

We enrolled 122 patients with glioma who received surgery treatment in our hospital from June 2010 to May 2012, and 60 healthy individuals. We found that the plasma miR-720 in the glioma group was significantly higher than that in the healthy control group (3.19 ± 1.26 vs 0.98 ± 0.65, P<0.001). The sensitivity and specificity were 71.3% (95%CI: 62.4-79.1%) and 83.3% (71.5-91.7%), respectively. The results indicated that the plasma miR-720 level was associated with tumor grade (t = 104.418, P<0.001). The advanced tumor tended to have higher miR-720 expression level. No significant association was found between miR-720 and age, sex, tumor size, KPS and tumor position (P=0.438, 0.514, 0.518, 0.058, 0.226). The multivariate cox analysis indicated that the high expression of miR-720 (HR = 1.48, 95%CI: 1.12-2.97, P=0.023) was independently predictors of adverse prognosis in patients with glioma. The high expression of miR-720 was also associated with recurrence or development in patients with glioma (HR = 1.47, 95%CI: 1.18-3.14, P=0.012). Plasma miR-720 has a moderate diagnostic ability in early diagnostic of glioma and may be a potential tumor biomarker. The high plasma miR-720 was related to adverse prognosis in patients with glioma and could be a prognosis predictor of glioma patients.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/diagnóstico , Glioma/diagnóstico , MicroRNAs/sangue , Adulto , Biomarcadores Tumorais/metabolismo , Encéfalo/patologia , Encéfalo/cirurgia , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Estudos de Casos e Controles , Intervalo Livre de Doença , Feminino , Seguimentos , Glioma/sangue , Glioma/mortalidade , Glioma/cirurgia , Voluntários Saudáveis , Humanos , Estimativa de Kaplan-Meier , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Procedimentos Neurocirúrgicos , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Taxa de Sobrevida
13.
Medicine (Baltimore) ; 99(27): e20927, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629692

RESUMO

BACKGROUND: The serum albumin, albumin-to-globulin ratio (AGR), and prognostic nutritional index (PNI) have been recommended to represent the nutritional and inflammatory status. Thus, they may be potential prognostic biomarkers for cancer. However, contradictory results were reported in different studies on glioma. The goal of this study was to perform a meta-analysis to re-evaluate their prognostic potential for glioma. METHODS: Databases of PubMed, EMBASE, and Cochrane Library were systematically searched to enroll all the studies investigating the prognostic significance of albumin, AGR, and PNI for glioma. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using STATA 13.0 software to indicate the intensity of association. RESULTS: Eleven studies with 2928 cases were included. Overall meta-analysis showed that the prognostic values of albumin, AGR, and PNI were limited for glioma (P > .05). However, subgroup analysis demonstrated a high preoperative serum albumin was significantly related with excellent OS of patients with GBM (HR = 0.95, 95% CI: 0.91-0.99, P = .018), while high PNI (HR = 0.56, 95% CI: 0.43-0.73, P < .001) and AGR (HR = 0.57, 95% CI: 0.34-0.96, P = .034) may be a protective factor of favorable OS for patients with high-grade gliomas. Furthermore, integration of all studies with multivariate analysis and clear cut-off also proved reduced preoperative serum albumin, AGR, and PNI were predictors of poor prognosis for patients with gliomas. CONCLUSION: Preoperative serum albumin, AGR, and PNI may represent promising biomarkers to predict the prognosis in patients with glioma, especially for high-grade.


Assuntos
Neoplasias do Sistema Nervoso Central/sangue , Glioma/sangue , Globulinas/metabolismo , Avaliação Nutricional , Albumina Sérica/metabolismo , Feminino , Humanos , Masculino , Prognóstico
14.
Int J Mol Sci ; 21(13)2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32635403

RESUMO

Improving outcomes for diffuse glioma patients requires methods that can accurately and sensitively monitor tumour activity and treatment response. Extracellular vesicles (EV) are membranous nanoparticles that can traverse the blood-brain-barrier, carrying oncogenic molecules into the circulation. Measuring clinically relevant glioma biomarkers cargoed in circulating EVs could revolutionise how glioma patients are managed. Despite their suitability for biomarker discovery, the co-isolation of highly abundant complex blood proteins has hindered comprehensive proteomic studies of circulating-EVs. Plasma-EVs isolated from pre-operative glioma grade II-IV patients (n = 41) and controls (n = 11) were sequenced by Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) and data extraction was performed by aligning against a custom 8662-protein library. Overall, 4054 proteins were measured in plasma-EVs. Differentially expressed proteins and putative circulating-EV markers were identified (adj. p-value < 0.05), including those reported in previous in-vitro and ex-vivo glioma-EV studies. Principal component analysis showed that plasma-EV protein profiles clustered according to glioma histological-subtype and grade, and plasma-EVs resampled from patients with recurrent tumour progression grouped with more aggressive glioma samples. The extensive plasma-EV proteome profiles achieved here highlight the potential for SWATH-MS to define circulating-EV biomarkers for objective blood-based measurements of glioma activity that could serve as ideal surrogate endpoints to assess tumour progression and allow more dynamic, patient-centred treatment protocols.


Assuntos
Neoplasias Encefálicas/sangue , Vesículas Extracelulares/metabolismo , Glioma/sangue , Proteômica/métodos , Adulto , Idoso , Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/patologia , Estudos de Casos e Controles , Micropartículas Derivadas de Células/metabolismo , Micropartículas Derivadas de Células/ultraestrutura , Estudos de Coortes , Vesículas Extracelulares/ultraestrutura , Feminino , Glioma/classificação , Glioma/patologia , Humanos , Biópsia Líquida/métodos , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem/métodos , Fluxo de Trabalho
15.
Mediators Inflamm ; 2020: 1798147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32684831

RESUMO

Objective: In recent years, the role of the modern inflammatory markers TREM-1 (triggering receptors expressed on myeloid cells) and HMGB1 (high mobility group box 1 protein) in tumorigenesis has begun to be studied. Their role in gliomas is not clear. The aim of our study was to find the role of inflammation in gliomas. Patients and Methods. In 63 adult patients with gliomas and 31 healthy controls, the expressions of TREM-1 and TREM-2 on CD14+ blood cells (method: flow cytometry) and the levels of soluble sTREM-1, HMGB1, IL-6, and IL-10 (Elisa tests) were analyzed. Results: Cox proportional hazard analysis showed that a TREM-1/TREM-2 ratio was associated with reduced overall survival (HR = 1.001, P = 0.023). Patients with a TREM-1/TREM-2 ratio above 125 survived significantly shorter than patients with a TREM-1/TREM-2 ratio below 125. The percentage of CD14+ TREM-1+ cells was strongly associated with a plasma IL-6/IL-10 ratio (positively) and with IL-10 (negatively). Conversely, we found a higher percentage of CD14+ TREM-2+ monocytes in better surviving patients; these cells could downregulate the exaggerated inflammation and potentiate the phagocytosis in the tumor. The serum levels of HMGB1 negatively correlated with the percentage of CD14+ TREM-1+ cells and with the TREM-1/TREM-2 ratio. The positive correlation between the serum levels of a late proinflammatory cytokine HMGB1 with the percentage of TREM2+ CD14+ monocytes can be explained as an effort for suppression of systemic inflammation by anti-inflammatory acting CD14+ TREM-2+ cells. Conclusion: We showed that the TREM-1/TREM-2 ratio (expression on the surface of blood monocytes) could help predict prognosis in patients with gliomas, especially in high-grade gliomas, and that systemic inflammation has an impact on the patient's overall survival. This is the first study that showed that TREM expression on monocytes in peripheral blood could help predict prognosis in patients with gliomas.


Assuntos
Glioma/metabolismo , Glioma/mortalidade , Glicoproteínas de Membrana/metabolismo , Monócitos/metabolismo , Receptores Imunológicos/metabolismo , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Adulto , Idoso , Feminino , Glioma/sangue , Proteína HMGB1/sangue , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais
16.
Nat Commun ; 11(1): 3169, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576825

RESUMO

Understanding tumor metabolism holds the promise of new insights into cancer biology, diagnosis and treatment. To assess human cancer metabolism, here we report a method to collect intra-operative samples of blood from an artery directly upstream and a vein directly downstream of a brain tumor, as well as samples from dorsal pedal veins of the same patients. After performing targeted metabolomic analysis, we characterize the metabolites consumed and produced by gliomas in vivo by comparing the arterial supply and venous drainage. N-acetylornithine, D-glucose, putrescine, and L-acetylcarnitine are consumed in relatively large amounts by gliomas. Conversely, L-glutamine, agmatine, and uridine 5-monophosphate are produced in relatively large amounts by gliomas. Further we verify that D-2-hydroxyglutarate (D-2HG) is high in venous plasma from patients with isocitrate dehydrogenases1 (IDH1) mutations. Through these paired comparisons, we can exclude the interpatient variation that is present in plasma samples usually taken from the cubital vein.


Assuntos
Biomarcadores Tumorais/sangue , Vasos Sanguíneos/metabolismo , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/metabolismo , Glioma/sangue , Glioma/metabolismo , Metabolômica , Acetilcarnitina/sangue , Adulto , Idoso , Agmatina/sangue , Sangue , Análise Química do Sangue , Glicemia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Feminino , Glioma/diagnóstico por imagem , Glioma/genética , Glucose , Glutamina/sangue , Glutaratos/sangue , Humanos , Isocitrato Desidrogenase/sangue , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Masculino , Pessoa de Meia-Idade , Ornitina/análogos & derivados , Ornitina/sangue , Putrescina/sangue , Uridina Monofosfato/sangue , Adulto Jovem
17.
PLoS One ; 15(4): e0226444, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32240177

RESUMO

Glioblastoma, the most aggressive form of glioma, has a 5-year survival rate of <5%. While radiation and immunotherapies are routinely studied in the murine Gl261 glioma model, little is known about its inherent immune response. This study quantifies the temporal and spatial localization of immune cell populations and mediators during glioma development. Eight-week old male C57Bl/6 mice were orthotopically inoculated with 1x106 Gl261 cells and tumor morphology, local and systemic immune cell populations, and plasma cytokines/chemokines assessed at day 0, 1, 3, 7, 14, and 21 post-inoculation by magnetic resonance imaging, chromogenic immunohistochemistry, multiplex immunofluorescent immunohistochemistry, flow cytometry and multiplex immunoassay respectively. From day 3 tumors were distinguishable with >30% Ki67 and increased tissue vascularization (p<0.05). Increasing tumor proliferation/malignancy and vascularization were associated with significant temporal changes in immune cell populations within the tumor (p<0.05) and systemic compartments (p = 0.02 to p<0.0001). Of note, at day 14 16/24 plasma cytokine/chemokines levels decreased coinciding with an increase in tumor cytotoxic T cells, natural killer and natural killer/T cells. Data derived provide baseline characterization of the local and systemic immune response during glioma development. They reveal that type II macrophages and myeloid-derived suppressor cells are more prevalent in tumors than regulatory T cells, highlighting these cell types for further therapeutic exploration.


Assuntos
Glioma/imunologia , Imunidade Inata , Células Matadoras Naturais/imunologia , Linfócitos T Citotóxicos/imunologia , Animais , Linhagem da Célula/imunologia , Proliferação de Células/genética , Quimiocinas/sangue , Quimiocinas/imunologia , Citocinas/sangue , Citocinas/imunologia , Progressão da Doença , Citometria de Fluxo , Glioma/sangue , Glioma/patologia , Humanos , Células Matadoras Naturais/metabolismo , Camundongos , Linfócitos T Citotóxicos/metabolismo
18.
Magn Reson Imaging ; 70: 50-56, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32302735

RESUMO

INTRODUCTION: The presence of peritumorally impaired blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) has been unequivocally demonstrated in patients with diffuse glioma, and may have value to better identify tumor infiltration zone. Since BOLD-CVR does not measure hemodynamic changes directly, we performed additional MR perfusion studies to better characterize the peritumoral hemodynamic environment. METHODS: Seventeen patients with WHO grade III and IV diffuse glioma underwent high resolution advanced hemodynamic MR imaging including BOLD-CVR and MR perfusion. The obtained multiparametric hemodynamic factors (i.e., regional cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), mean transit time (MTT), time-to-peak (TTP) and BOLD-CVR, were analyzed within 10 concentric expanding 3 mm volumes of interest (VOIs) up to 30 mm from the tumor tissue mask. RESULTS: BOLD-CVR impairment was found within the tumor tissue mask and the peritumoral VOIs up to 21 mm as compared to the contralateral flipped CVR analysis (p<0.05). In the affected hemisphere, we observed positive spatial correlations including all VOIs between BOLD-CVR and rCBV values (r=0.27; p<0.001), rCBF (r=0.42; p<0.001) and a negative correlation between BOLD-CVR and TTP (r=-0.47; p<0.001). CONCLUSIONS: Peritumorally impaired BOLD-CVR is associated with concomitant hemodynamic alterations with severity correlating to tumor volume. The distribution of these multiparametric hemodynamic MRI patterns may be considered for future studies characterizing the hemodynamic peritumoral environment, thereby better identifying the extent of tumor infiltration.


Assuntos
Glioma/patologia , Glioma/fisiopatologia , Hemodinâmica , Imageamento por Ressonância Magnética , Oxigênio/sangue , Adulto , Idoso , Circulação Cerebrovascular , Difusão , Feminino , Glioma/sangue , Glioma/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Artigo em Inglês | MEDLINE | ID: mdl-32132974

RESUMO

Purpose: To detect the presence of antipituitary (APA) and antihypothalamus antibodies (AHA) in subjects treated for brain cancers, and to evaluate their potential association with pituitary dysfunction. Methods: We evaluated 63 patients with craniopharyngioma, glioma, and germinoma treated with surgery and/or radiotherapy and/or chemotherapy at a median age of 13 years. Forty-one had multiple pituitary hormone deficiencies (MPHD), six had a single pituitary defect. GH was the most common defect (65.1%), followed by AVP (61.9%), TSH (57.1%), ACTH (49.2%), and gonadotropin (38.1%). APA and AHA were evaluated by simple indirect immunofluorescence method indirect immunofluorescence in patients and in 50 healthy controls. Results: Circulating APA and/or AHA were found in 31 subjects (49.2%) and in none of the healthy controls. In particular, 25 subjects out of 31 were APA (80.6%), 26 were AHA (83.90%), and 20 were both APA and AHA (64.5%). Nine patients APA and/or AHA have craniopharyngioma (29%), seven (22.6%) have glioma, and 15 (48.4%) have germinoma. Patients with craniopharyngioma were positive for at least one antibody in 39.1% compared to 33.3% of patients with glioma and to 78.9% of those with germinoma with an analogous distribution for APA and AHA between the three tumors. The presence of APA or AHA and of both APA and AHA was significantly increased in patients with germinoma. The presence of APA (P = 0.001) and their titers (P = 0.001) was significantly associated with the type of tumor in the following order: germinomas, craniopharyngiomas, and gliomas; an analogous distribution was observed for the presence of AHA (P = 0.002) and their titers (P = 0.012). In addition, we found a significant association between radiotherapy and APA (P = 0.03). Conclusions: Brain tumors especially germinoma are associated with the development of hypothalamic-pituitary antibodies and pituitary defects. The correct interpretation of APA/AHA antibodies is essential to avoid a misdiagnosis of an autoimmune infundibulo-neurohypophysitis or pituitary hypophysitis in patients with germinoma.


Assuntos
Autoanticorpos/sangue , Neoplasias Encefálicas/epidemiologia , Sobreviventes de Câncer/estatística & dados numéricos , Hipotálamo/imunologia , Doenças da Hipófise/epidemiologia , Hipófise/imunologia , Adolescente , Adulto , Idade de Início , Doenças Autoimunes/sangue , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/etiologia , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Estudos de Casos e Controles , Criança , Pré-Escolar , Craniofaringioma/sangue , Craniofaringioma/epidemiologia , Craniofaringioma/imunologia , Craniofaringioma/terapia , Feminino , Seguimentos , Germinoma/sangue , Germinoma/epidemiologia , Germinoma/imunologia , Germinoma/terapia , Glioma/sangue , Glioma/epidemiologia , Glioma/imunologia , Glioma/terapia , Humanos , Masculino , Doenças da Hipófise/sangue , Doenças da Hipófise/imunologia , Doenças da Hipófise/terapia , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/imunologia , Neoplasias Hipofisárias/terapia , Adulto Jovem
20.
Br J Cancer ; 122(10): 1441-1444, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32203223

RESUMO

Elevated levels of serum ferritin (SF) are observed in several types of cancer; however, little is known on the association between ferritin and glioma, the most frequent type of human primary brain tumour. Here we report that GBM patients show significantly increased pre-surgical SF levels (i.e. ferritinaemia) within the SF reference range and a marked ferritin immunoreactivity of resected tumour tissue. Our findings account for an indirect association between ferritin synthesis in glioma-tissue and altered SF levels, which limits the clinical value of SF as a tumour marker in glioma. Importantly, we show for the first time that GBM-derived glioma cells release ferritin in vitro, which exerts an apoptosis-stimulating activity. Albeit the pathophysiologic context of apoptosis induction by a tumour-derived ferritin remains to be defined, our findings account for a distinct growth-regulatory role of these ferritin species in tumour biology.


Assuntos
Biomarcadores Tumorais/sangue , Ferritinas/sangue , Glioblastoma/sangue , Glioma/sangue , Apoptose/genética , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Ferritinas/genética , Regulação Neoplásica da Expressão Gênica/genética , Glioblastoma/genética , Glioblastoma/patologia , Glioma/genética , Glioma/patologia , Humanos , Masculino , Inclusão em Parafina , Transdução de Sinais/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...