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1.
Adv Exp Med Biol ; 1202: 203-222, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32034715

RESUMO

STAT (signal transducers and activators of transcription) are latent cytoplasmic transcription factors that function as downstream effectors of cytokine and growth factor receptor signaling. The canonical JAK/STAT signaling pathway involves the activation of Janus kinases (JAK) or growth factors receptor kinases, phosphorylation of STAT proteins, their dimerization and translocation into the nucleus where STATs act as transcription factors with pleiotropic downstream effects. STAT signaling is tightly controlled with restricted kinetics due to action of its negative regulators. While STAT1 is believed to play an important role in growth arrest and apoptosis, and to act as a tumor suppressor, STAT3 and 5 are involved in promoting cell cycle progression, cellular transformation, and preventing apoptosis. Aberrant activation of STATs, in particular STAT3 and STAT5, have been found in a large number of human tumors, including gliomas and may contribute to oncogenesis. In this chapter, we have (1) summarized the mechanisms of STAT activation in normal and malignant signaling; (2) discussed evidence for the critical role of constitutively activated STAT3 and STAT5 in glioma pathobiology; (3) disclosed molecular and pharmacological strategies to interfere with STAT signaling for potential therapeutic intervention in gliomas.


Assuntos
Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Glioma/metabolismo , Glioma/patologia , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Transformação Celular Neoplásica , Humanos , Janus Quinases/metabolismo , Fosforilação
2.
Adv Exp Med Biol ; 1202: 259-279, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32034718

RESUMO

Signal transduction pathways directly communicate and transform chromatin to change the epigenetic landscape and regulate gene expression. Chromatin acts as a dynamic platform of signal integration and storage. Histone modifications and alteration of chromatin structure play the main role in chromatin-based gene expression regulation. Alterations in genes coding for histone modifying enzymes and chromatin modifiers result in malfunction of proteins that regulate chromatin modification and remodeling. Such dysregulations culminate in profound changes in chromatin structure and distorted patterns of gene expression. Gliomagenesis is a multistep process, involving both genetic and epigenetic alterations. Recent applications of next generation sequencing have revealed that many chromatin regulation-related genes, including ATRX, ARID1A, SMARCA4, SMARCA2, SMARCC2, BAF155 and hSNF5 are mutated in gliomas. In this review we summarize newly identified mechanisms affecting expression or functions of selected histone modifying enzymes and chromatin modifiers in gliomas. We focus on selected examples of pathogenic mechanisms involving ATRX, histone methyltransferase G9a, histone acetylases/deacetylases and chromatin remodeling complexes SMARCA2/4. We discuss the impact of selected epigenetics alterations on glioma pathobiology, signaling and therapeutic responses. We assess the attempts of targeting defective pathways with new inhibitors.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Cromatina/metabolismo , Glioma/tratamento farmacológico , Glioma/patologia , Histonas/metabolismo , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/genética , Cromatina/genética , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Glioma/enzimologia , Glioma/genética , Código das Histonas/efeitos dos fármacos , Histonas/química , Humanos
3.
Adv Exp Med Biol ; 1202: 281-298, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32034719

RESUMO

In this chapter we describe the state of the art knowledge of the role played by myeloid cells in promoting and supporting the growth and the invasive properties of a deadly brain tumor, glioblastoma. We provide a review of the works describing the intercellular communication among glioma and associated microglia/macrophage cells (GAMs) using in vitro cellular models derived from mice, rats and human patients and in vivo animal models using syngeneic or xenogeneic experimental systems. Special emphasis will be given to 1) the timing alteration of brain microenvironment under the influence of glioma, 2) the bidirectional communication among tumor and GAMs, 3) possible approaches to interfere with or to guide these interactions, with the aim to identify molecular and cellular targets which could revert or delay the vicious cycle that favors tumor biology.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Macrófagos/patologia , Microglia/patologia , Microambiente Tumoral , Animais , Humanos
4.
Medicine (Baltimore) ; 99(5): e19017, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000446

RESUMO

O-(2-[F]fluoroethyl)-L-tyrosine positron-emission tomography/computed tomography (F-FET PET/CT) is well known in brain tumor management. Our study aimed to identify the prognostic value of F-FET PET/CT in high-grade gliomas (HGG) according the current 2016 World Health Organization (WHO) classification.Patients with histologically proven WHO 2016 HGG were prospectively included. A dynamic F-FET PET/CT was performed allowing to obtain 2 static PET frames (static frame 1: 20-40 minutes and static frame 2: 2-22 minutes). We analyzed static parameters (standard uptake value [SUV]max, SUVmean, SUVpeak, TBRmax, TBRmean, tumoral lesion glycolysis, and metabolic tumoral volume) for various isocontours (from 10% to 90%). PET parameters, clinical features, and molecular biomarkers were compared with progression-free survival (PFS) and overall survival (OS) in univariate and multivariate analysis.Twenty-nine patients were included (grade III n = 3, grade IV n = 26). Mean PFS and OS were, respectively, 8.8 and 13.9 months. According to univariate analysis, SUVmean, SUVpeak, TBRmax, and TBRmean were significantly correlated with OS. In static 1 analysis, TBRmax seemed to be the best OS prognostic parameter (P = .004). In static 2 analysis, TBRmean was the best parameter (P = .01). In static 1 analysis, only SUVpeak was significant (P = .05) for PFS. Good performance status (PS < 2; P < .0001) and extent of resection (P = .019) identified the subgroup of patients with the best OS. Only TBRmax (P = .026) and extent of resection (P = .025) remained significant parameters in multivariate analysis.Our data suggested that high TBRmax seemed to be the most significant OS independent prognostic factor in patients with newly diagnosed HGG.


Assuntos
Glioma/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Meios de Contraste , Feminino , Glioma/patologia , Glioma/cirurgia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Estudos Prospectivos , Compostos Radiofarmacêuticos , Taxa de Sobrevida , Tirosina/análogos & derivados
5.
J Photochem Photobiol B ; 203: 111773, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31931385

RESUMO

Glioma is the prime cause of cancer allied mortality in adolescent people and it accounts about 80% of all malignant tumours. Eugenol is a major bioactive constituent present in the essential oils with numerous pharmacological benefits including nueroprotective activity. The major drawback of eugenol is its extreme volatile property and oxygen sensitivity therefore we increased the efficacy of drug; eugenol by encapsulating with chitosan polymer. Eugenol loaded chitosan polymer (EuCs) was characterized using FTIR, XRD, SEM, HR-TEM analysis and the encapsulation, drug release efficacy was assessed at in vitro condition. The induction of autophagy and anticancer efficacy of EuCs on glioma cells was evaluated with rat C6 glioma cells using MTT assay, acridine orange staining, immunocytochemical analysis of NFκß protein expression and FLOW cytometric analysis. The anti-metastatic property of Eu-CS was assessed by immunoblotting and RT-PCR analysis of epithelial mesenchymal transition protein expression in EuCs treated rat C6 glioma cells. Our characterization analysis proves that EuCs possess essential physical and functional properties of copolymer to be utilized as a drug. Further the MTT analysis and AO staining confirms even in the presence of oncogenic inducer and autophagic inhibitors, EuCs exhibits apoptotic potency on rat C6 glioma cells. The result of immunocytochemical studies depicts the inhibition of NFκß protein expression and flow cytometry studies confirm apoptosis induction by EuCs. The inhibition of metastasis by EuCs was proven by the decrease in epithelial mesenchymal transition protein expression in Eu-Cs treated rat C6 glioma cells. Over all our results authentically confirms eugenol loaded chitosan nanopolymer persuasively induces apoptosis and inhibits metastasis in rat C6 glioma cells.


Assuntos
Antineoplásicos/química , Apoptose/efeitos dos fármacos , Quitosana/química , Eugenol/química , Metaloproteinase 9 da Matriz/metabolismo , Nanoestruturas/química , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Portadores de Fármacos/química , Eugenol/farmacologia , Glioma/metabolismo , Glioma/patologia , NF-kappa B/metabolismo , Ratos , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
7.
World Neurosurg ; 133: 196-200, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31606508

RESUMO

BACKGROUND: Rosette-forming glioneuronal tumors (RGNTs) with multifocal growth throughout the ventricular system are extremely rare, and only 1 case of RGNT with dissemination limited to supratentorial ventricles has previously been reported. Recent evidence based on molecular data suggest that low-grade glioneuronal tumors (GNT) involving the septum pellucidum and the lateral ventricles, with either dysembryoplastic neuroepithelial tumor-like or RGNT-like features, may belong to a neuropathologic entity distinct from cortical dysembryoplastic neuroepithelial tumor and "typical" fourth ventricle RGNT, respectively. Given their rarity, the classification of these neoplasms is still uncertain and their clinicopathological and radiological aspects are only partially known. CASE DESCRIPTION: A 24-year-old male presented a GNT with RGNT-like morphological features centered in the septum pellucidum with multifocal masses occupying the lateral ventricles and the third ventricle with extraventricular infiltration of the frontal lobe. The patient underwent subtotal resection and 4 years follow-up. The clinicopathological and radiological features of the neoplasm are discussed. CONCLUSIONS: Advanced magnetic resonance imaging (magnetic resonance spectroscopy and perfusion-weighted imaging) may provide valuable information in the differential diagnosis between rare GNTs and other more frequent intraventricular neoplasms. In the present case, the enhancing remnant portion of the tumor showed remarkable contrast enhancement variability during the follow-up with slow in situ progression. However, available data suggest that spontaneous contrast enhancement "fluctuations" over time in RGNT may not represent a reliable indicator of tumor behavior.


Assuntos
Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Septo Pelúcido/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Craniotomia , Glioma/diagnóstico por imagem , Glioma/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Procedimentos Neurocirúrgicos , Septo Pelúcido/diagnóstico por imagem , Septo Pelúcido/patologia , Resultado do Tratamento , Adulto Jovem
8.
World Neurosurg ; 133: 192-195, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31574328

RESUMO

BACKGROUND: The frontal aslant tract (FAT) is a white matter fiber pathway connecting the superior frontal gyrus to the Broca area. This tract in the dominant hemisphere has been shown to play a role in speech initiation and production, and direct subcortical stimulation can induce stuttering and speech arrest in a patient. However, controversy remains as to whether disruption of this pathway will lead to a permanent language deficit and if it is even necessary to map this tract during tumor resections of the dominant frontal lobe. CASE DESCRIPTION: Here, we report a case of a patient with a lower-grade diffuse glioma invading the dominant FAT that was removed with an asleep craniotomy. In the immediate postoperative state, the patient had a transcortical motor dysphasia and was unable to initiate speech. These immediate language deficits quickly recovered, and the patient was neurologically intact at the time of discharge a few days after surgery. CONCLUSIONS: Given the high likelihood for a complete neurologic recovery including transient aphasia, we propose that awake mapping for the purpose of identifying the dominant FAT is unnecessary during tumor resection and that disruption of this tract is not associated with any long-term language deficits.


Assuntos
Afasia/etiologia , Craniotomia/efeitos adversos , Glioma/cirurgia , Substância Branca/cirurgia , Afasia/diagnóstico por imagem , Afasia/patologia , Feminino , Glioma/diagnóstico por imagem , Glioma/patologia , Humanos , Imagem por Ressonância Magnética , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto Jovem
9.
Gene ; 726: 144196, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31669648

RESUMO

Accumulating evidence has indicated the important roles of circular RNAs (circRNAs) in different tumors. However, their detailed regulatory mechanisms in glioma are not fully understood. In this study, the functional role of a novel circRNA, circ-EZH2, was investigated by cell counting kit-8 (CCK-8), colony formation, flow cytometry, and transwell experiments. The regulatory mechanism of circ-EZH2 was explored by bioinformatics analysis, quantitative real-time PCR (qRT-PCR), Western blot and dual-luciferase reporter assay. We identified that circ-EZH2 was overexpressed in glioma tissues and cell lines. Further studies revealed that ectopic expression of circ-EZH2 significantly promoted cell growth, migration and invasion but inhibited cell apoptosis. By contrast, silencing of circ-EZH2 induced the opposite effects. Additionally, we found circ-EZH2 served as a miRNA sponge for miR-1265 to release its suppression on DDAH1 and CBX3. Rescue assays further revealed that the oncogenic function of circ-EZH2 was partly dependent on its modulation of DDAH1 and CBX3. Our study unraveled a novel molecular pathway in glioma and may provide a new perspective for the treatment of glioma.


Assuntos
Amidoidrolases/genética , Proliferação de Células/genética , Proteínas Cromossômicas não Histona/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Glioma/genética , MicroRNAs/genética , Invasividade Neoplásica/genética , Apoptose/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Glioma/patologia , Humanos , Invasividade Neoplásica/patologia
10.
World Neurosurg ; 133: 366-380.e2, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31473344

RESUMO

BACKGROUND: With the 2016 update of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System incorporating molecular subtyping to histology, WHO grade II diffuse astrocytic and oligodendroglial tumors are subcategorized by distinct molecular markers. There are no reported systematic reviews quantifying differences in progression-free survival (PFS) and overall survival (OS) on the basis of molecular subtypes of WHO grade II diffuse gliomas, against the background of administered treatments. METHODS: Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the Cochrane Handbook of Systemic Reviews of Interventions, we conducted a systematic review through MEDLINE, Embase, and CENTRAL (Cochrane Central Register of Controlled Trails). RESULTS: For OS, the first quartile (25%), median (50%), third quartile (75%), and 95% confidence interval, respectively, were identified (in months): astrocytoma-wild-type WHO II (A-wt II): 22.8, 32.2, 40.7, and 21.6-61.2; astrocytoma-mutant WHO II (A-mt II): 69.85, 115.2, 128.4, and 55.4-164.0; oligodendroglioma WHO II (OD-II): 106.3, 163.7, 213.3, and 67.3-235.4 (P value = 0.0002). For PFS, the 25th, 50th, and 75th percentiles, and 95% confidence interval, respectively, are as follows (in months): A-wt II: 6.90, 17.45, 19.57, and 3.00-23.69; A-mt II: 37.20, 43.20, 55.63, and 35.7-60.0; OD-II: 47.42, 59.2, 88.28, and 46.3-91.2 (P value = 0.015). CONCLUSIONS: This seems to be the first systematic review of OS and PFS in patients with WHO grade II low-grade gliomas (LGGs), against treatment modalities, in molecularly stratified subsets introduced by the WHO 2016 classification of central nervous system tumors. Overall, A-wt II was confirmed to have a significantly shorter OS than did A-mt II; no significant difference was found between OS of OD-II with A-wt II and A-mt II. In addition, all 3 molecular subtypes were found to have statistically significant differences between PFS, with OD-II having a statistically better PFS than A-mt II. These data can provide valuable prognostic insight to patients and clinicians. In addition, assessing survival differences enhances understanding of treatment recommendations against molecular markers and may facilitate future clinical trial design.


Assuntos
Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Glioma/mortalidade , Glioma/terapia , Neoplasias Encefálicas/patologia , Glioma/patologia , Humanos , Gradação de Tumores , Intervalo Livre de Progressão , Taxa de Sobrevida
12.
Int J Cancer ; 146(1): 248-261, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31144303

RESUMO

Brain glioma is the most common malignant tumor of the central nervous system, and one of the leading causes of death in patients with intracranial tumors. The clinical outcome of glioma is usually poor due to abundant vascularity, fast growth and susceptibility of invasion to normal brain tissues. Our microarray study showed that lncRNA-LINC01116 was significantly upregulated in glioma tissues and played an important role in cell proliferation, cycle, migration, invasion and angiogenesis. In addition, vascular endothelial growth factor (VEGFA) may be the major target genes in the downstream of lncRNA-LINC01116. Dual luciferase assay showed that LINC01116 and VEGFA both contained a miR-31-5p binding site, and LINC01116 could regulate the expression of VEGFA through competitive absorption of miR-31-5p. RNA immunoprecipitation indicated that LINC01116 and VEGFA were present in the miR-31-5p-RISC complex, and biotinylated miR-31-5p pull-down assay suggested that there was a competitive relationship between LINC01116 and VEGFA to bind with miR-31-5p. Collectively, our study has identified a novel lncRNA-LINC01116 and clarified the role and mechanism of LINC01116 in the tumorigenesis of glioma. LINC01116 may prove to be a potential target for the clinical diagnosis and treatment of glioma.


Assuntos
Neoplasias Encefálicas/patologia , Carcinogênese , Glioma/patologia , RNA Longo não Codificante/fisiologia , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Sítios de Ligação , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Glioma/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
Medicine (Baltimore) ; 98(49): e18271, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804365

RESUMO

RATIONALE: Rosette-forming glioneuronal tumor (RGNT) is a rare tumor which has been first reported as the fourth ventricle tumor by Komori et al and is classified as a distinct clinicopathological entity by the WHO Classification of Tumors of the Central Nervous System as in 2007. Although RGNTs were reported to occur in both supratentorial and inflatentorial sites, only 4 case reports of spinal RGNT have been demonstrated. PATIENT CONCERNS: A 37-year-old female presenting with slowly progressing right-sided clumsiness. Cervical magnetic resonance imaging revealed a spinal intramedullary tumor between the C2 and C5 levels. DIAGNOSES: Pathological analysis showed unique biphasic cellular architecture consisting of perivascular pseudorosettes dominantly with few neurocytic rosettes and diffuse astrocytoma component. The tumor cells composed of perivascular pseudorosettes showed positivity for both synaptophysin and glial markers such as GFAP and Olig2. Therefore, the diagnosis of RGNT was made. INTERVENTIONS: Gross total resection of the tumor was achieved. No adjuvant chemotherapy nor radiotherapy was conducted after operation. OUTCOMES: At 2 years after the operation, no recurrence was observed. LESSONS: Although RGNT arising from the spinal cord is extremely rare, we need to consider the tumor as a differential diagnosis for intramedullary spinal cord tumors.


Assuntos
Glioma/diagnóstico por imagem , Imagem por Ressonância Magnética , Neoplasias da Medula Espinal/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Feminino , Glioma/patologia , Glioma/cirurgia , Humanos , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/cirurgia
14.
Adv Exp Med Biol ; 1190: 281-297, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760651

RESUMO

Gliomas are a heterogeneous group of tumors with evolving classification based on genotype. Isocitrate dehydrogenase (IDH) mutation is an early event in the formation of some diffuse gliomas, and is the best understood mechanism of their epigenetic dysregulation. Glioblastoma may evolve from lower-grade lesions with IDH mutations, or arise independently from copy number changes in platelet-derived growth factor receptor alpha (PDGFRA) and phosphatase and tensin homolog (PTEN). Several molecular subtypes of glioblastoma arise from a common proneural precursor with a tendency toward transition to a mesenchymal subtype. Following oncogenic transformation, gliomas escape growth arrest through a distinct step of aberrant telomere reverse transcriptase (TERT) expression, or mutations in either alpha thalassemia/mental retardation syndrome (ATRX) or death-domain associated protein (DAXX) genes. Metabolic reprogramming allows gliomas to thrive in harsh microenvironments such as hypoxia, acidity, and nutrient depletion, which contribute to tumor initiation, maintenance, and treatment resistance.


Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Glioma/patologia , Reprogramação Celular , Humanos , Isocitrato Desidrogenase/genética , Mutação , PTEN Fosfo-Hidrolase/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Telomerase/genética , Microambiente Tumoral , Proteína Nuclear Ligada ao X/genética
15.
Anticancer Res ; 39(11): 6007-6014, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704826

RESUMO

BACKGROUND/AIM: The histone demethylase NO66 regulates gene and protein expression. Epidermal growth factor receptor (EGFR) is a key oncogenic factor for glioblastoma. This study aimed to examine the role of NO66 in glioblastoma. MATERIALS AND METHODS: The prognostic value of NO66 expression in 263 human glioma tissues and 510 glioblastoma tissues was examined by Kaplan and Meier survival analysis. Immunoblot analysis of EGFR expression, cell proliferation assays and cell cycle analysis were performed in glioblastoma cells after NO66 knockdown. RESULTS: In 263 human glioma tissues, high levels of NO66 expression correlated with advanced disease stage and poor patient prognosis. In 510 glioblastoma tissues, high levels of NO66 expression also predicted poor patient prognosis. NO66 knockdown reduced EGFR expression and cell proliferation in glioblastoma cells. CONCLUSION: High levels of NO66 in glioma and glioblastoma tissues predict poor patient prognosis, and NO66 is required for EGFR expression and glioblastoma cell proliferation.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Proliferação de Células , Dioxigenases/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Histona Desmetilases/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Dioxigenases/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Seguimentos , Glioma/genética , Glioma/metabolismo , Histona Desmetilases/genética , Humanos , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas
16.
Medicine (Baltimore) ; 98(46): e17949, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725652

RESUMO

Recently, we have proposed a theoretical modified tri-exponential model for multi-b-value diffusion-weighted imaging (DWI) to measure the cytoplasmic organelle water fraction (COWF). This study aims to investigate whether COWF maps are effective in evaluating the malignant degree of gliomas and distinguishing primary central nervous system lymphomas (PCNSL) from gliomas.We performed this retrospective study based on our prospectively collected data. All patients underwent preoperative multi-b-value DWI. Parametric maps were derived from multi-b-value DWI maps using the modified tri-exponential model. Receiver operating characteristic analyses were used to assess the diagnostic accuracy of the parameter maps. Pearson correlation coefficients were calculated to investigate the correlations between the parameters and the Ki-67 proliferation index.A total of 66 patients were enrolled, including 16 low-grade gliomas (LGG), 45 high-grade gliomas (HGG), and 5 PCNSL. The mean COWF values were significantly different among LGG (3.1 ±â€Š1.4%), HGG (6.9 ±â€Š2.8%), and PCNSL (14.0 ±â€Š2.2%) (P < .001). The areas under the curves of the mean COWF value in distinguishing HGG from LGG and distinguishing PCNSL from gliomas were 0.899 and 0.980, respectively. The mean COWF value had a moderate correlation with the Ki-67 proliferation index (r = 0.647).The COWF map is useful in malignant grading of gliomas, and may be helpful in distinguishing PCNSL from gliomas.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Glioma/diagnóstico por imagem , Glioma/patologia , Organelas/patologia , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/diagnóstico , Diagnóstico Diferencial , Feminino , Glioma/diagnóstico , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade
17.
Anal Bioanal Chem ; 411(30): 7929-7933, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31754769

RESUMO

Knowledge of the isocitrate dehydrogenase (IDH) mutation status of glioma patients could provide insights for decision-making during brain surgery. However, pathology is not able to provide such information intraoperatively. Here we describe the first application of a miniature mass spectrometer (MS) to the determination of IDH mutation status in gliomas intraoperatively. The instrumentation was modified to be compatible with use in the operating room. Tandem MS was performed on the oncometabolite, 2-hydroxyglutarate, and a reference metabolite, glutamate, which is not involved in the IDH mutation. Ratios of fragment ion intensities were measured to calculate an IDH mutation score, which was used to differentiate IDH mutant and wild-type tissues. The results of analyzing 25 biopsies from 13 patients indicate that reliable determination of IDH mutation status was achieved (p = 0.0001, using the Kruskal-Wallis non-parametric test). With its small footprint and low power consumption and noise level, this application of miniature mass spectrometers represents a simple and cost-effective platform for an important intraoperative measurement. Graphical abstract.


Assuntos
Neoplasias Encefálicas/enzimologia , Glioma/enzimologia , Isocitrato Desidrogenase/genética , Mutação , Espectrometria de Massas por Ionização por Electrospray/instrumentação , Espectrometria de Massas em Tandem/instrumentação , Biópsia , Neoplasias Encefálicas/patologia , Estudos de Coortes , Glioma/patologia , Humanos , Período Intraoperatório
18.
Medicine (Baltimore) ; 98(45): e17583, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702614

RESUMO

BACKGROUND: Long noncoding RNA paternally expressed 10 (lncRNA PEG10) is highly expressed in a variety of human cancers and related to the clinical prognosis of patients. However, to date there has been no previous study evaluating the prognostic significance of lncRNA PEG10 in gliomas. In the present study, we investigated the expression levels of lncRNA PEG10 to determine the prognostic value of this oncogene in human gliomas. METHODS: Expression levels of lncRNA PEG10 were detected by real-time polymerase chain reaction in a hospital-based study cohort of 147 glioma patients and 23 cases of patients with craniocerebral trauma tissues. Associations of lncRNA PEG10 expression with clinicopathological variables and clinical outcome of glioma patients were investigated. RESULTS: The results indicated that expression levels of lncRNA PEG10 were significantly increased in human gliomas compared to normal control brain tissues. In addition, lncRNA PEG10 expression was progressively increased from pathologic grade I to IV (P = .009) and correlated with the Karnofsky performance status (P = .018) in glioma patients. Furthermore, we also found that glioma patients with increased expression of lncRNA PEG10 had a higher risk to relapse and a statistically significant shorter overall survival (OS) than patients with reduced expression of lncRNA PEG10. In multivariate analysis, expression level of lncRNA PEG10 was found to be an independent prognostic factor for both progression-free survival and OS in glioma patients. CONCLUSIONS: LncRNA PEG10 served as an oncogene and played crucial roles in the progression of glioma. Molecular therapy targeted on lncRNA PEG10 might bring significant benefits to the clinical outcome of malignant glioma.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , RNA Longo não Codificante/genética , Regulação para Cima , Adulto , Idoso , Neoplasias Encefálicas/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Análise de Sobrevida , Adulto Jovem
19.
Chem Commun (Camb) ; 55(93): 13955-13958, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31617510

RESUMO

In this study, we designed and synthesized organelle-targeted cell-penetrating peptide (CPP)-conjugated boron compounds to increase their cellular uptake and to control the intracellular locations for the induction of sophisticated anticancer biological activity in boron neutron capture therapy (BNCT), leading to anticancer effects with ATP reduction and apoptosis when irradiated with neutrons in an in vitro BNCT assay.


Assuntos
Antineoplásicos/farmacologia , Compostos de Boro/química , Terapia por Captura de Nêutron de Boro , Peptídeos Penetradores de Células/química , Sistemas de Liberação de Medicamentos , Glioma/tratamento farmacológico , Trifosfato de Adenosina/antagonistas & inibidores , Trifosfato de Adenosina/metabolismo , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Glioma/patologia , Humanos , Organelas/química
20.
World Neurosurg ; 131: 346-355, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31658577

RESUMO

BACKGROUND: Erythropoietin (EPO) is a cytokine primarily involved in the regulation of erythropoiesis. In response to hypoxia-ischemia, hypoxia-inducible factor 1 induces EPO production, which, in turn, inhibits apoptosis of erythroid progenitor cells. By the same mechanism and acting through other signaling pathways, EPO exerts neuroprotective effects. Increased resistance to hypoxia and decreased apoptosis are thought to be important mechanisms for tumor progression, including malignant glioma. Because recent studies have demonstrated that EPO and its receptor (EPOR) are expressed in several tumors and can promote tumor growth, in the present study, we investigated EPO and EPOR expression in human glioma and the effect of EPO administration in a rat model of glioma implantation. METHODS: Using Western blotting and immunohistochemical analysis, we examined the expression of EPO, EPOR, platelet endothelial cell adhesion molecule, and Ki-67 in human glioma specimens and experimentally induced glioma in rats. In the experimental setting, a daily dose of recombinant human EPO (rHuEPO) or saline solution were administered for 21 days in Fischer rats subjected to 9L cell line implantation. RESULTS: In both human and animal specimens, we found an increase in EPOR expression as long as the lesion presented with an increasing malignant pattern. A significant direct correlation was found between the expression of EPOR and Ki-67 and EPOR and platelet endothelial cell adhesion molecule in low- and high-grade gliomas. The rats treated with rHuEPO presented with significantly larger tumor spread compared with the saline-treated rats. CONCLUSIONS: The results of our study have shown that the EPO/EPOR complex might play a significant role in the aggressive behavior of high-grade gliomas. The larger tumor spread in rHuEPO-treated rats suggests a feasible role for EPO in the aggressiveness and progression of malignant glioma.


Assuntos
Neoplasias Encefálicas/metabolismo , Eritropoetina/metabolismo , Glioma/metabolismo , Receptores da Eritropoetina/metabolismo , Adulto , Idoso , Animais , Western Blotting , Neoplasias Encefálicas/etiologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Eritropoetina/farmacologia , Eritropoetina/fisiologia , Feminino , Glioma/etiologia , Glioma/patologia , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Transplante de Neoplasias , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Ratos Endogâmicos F344 , Receptores da Eritropoetina/fisiologia , Proteínas Recombinantes/farmacologia , Carga Tumoral/efeitos dos fármacos
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