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1.
Mol Carcinog ; 63(7): 1235-1247, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38517048

RESUMO

Glioblastoma (GBM) is the most aggressive brain tumor type with worse clinical outcome due to the hallmarks of strong invasiveness, high rate of recurrence, and therapeutic resistance to temozolomide (TMZ), the first-line drug for GBM, representing a major challenge for successful GBM therapeutics. Understanding the underlying mechanisms that drive GBM progression will shed novel insight into therapeutic strategies. Receptor-type tyrosine-protein phosphatase S (PTPRS) is a frequently mutated gene in human cancers, including GBM. Its role in GBM has not yet been clarified. Here, inactivating PTPRS mutation or deficiency was frequently found in GBM, and deficiency in PTPRS significantly induced defects in the G2M checkpoint and limited GBM cells proliferation, leading to potent resistance to TMZ treatment in vitro and in vivo. Surprisingly, loss of PTPRS triggered an unexpected mesenchymal phenotype that markedly enhances the migratory capabilities of GBM cells through upregulating numerous matrix metalloproteinases via MAPK-MEK-ERK signaling. Therefore, this work provides a therapeutic window for precisely excluding PTPRS-mutated patients who do not respond to TMZ.


Assuntos
Antineoplásicos Alquilantes , Neoplasias Encefálicas , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Glioblastoma , Temozolomida , Temozolomida/farmacologia , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Camundongos , Movimento Celular/efeitos dos fármacos , Mutação , Ensaios Antitumorais Modelo de Xenoenxerto , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo
2.
Exp Neurol ; 374: 114691, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38224942

RESUMO

Blood-brain barrier (BBB) impairment and glutamate release are two pathophysiological features of traumatic brain injury (TBI), contributing to secondary brain damage and neuroinflammation. However, our knowledge of BBB integrity damage and dysfunction are still limited due to the diverse and fluctuating expression of glutamate receptors after trauma. Here, we confirmed the downregulation of metabotropic glutamate receptor 5 (mGluR5) on microvascular endothelial cell within the acute phase of TBI, and the recovered mGluR5 levels on BBB was positively associated with blood perfusion and neurological recovery. In whole body mGluR5-knockout mice, BBB dysfunction and neurological deficiency were exacerbated after TBI compared with wild type mice. In terms of mechanism, the amino acid sequence 201-259 of cytoskeletal protein Alpha-actinin-1 (ACTN1) interacted with mGluR5, facilitating mGluR5 translocation from cytoplasmic compartment to plasma membrane in endothelial cells. Activation of plasma membrane mGluR5 triggers the PLC/PKCµ/c-Jun signaling pathway, leading to increased expression of the tight junction-actin cytoskeleton connecting protein zonula occludens-1 (ZO-1). Our findings uncover a novel mechanism mediated by membrane and cytoplasmic mGluR5 in endothelial cell integrity maintenance and repair, providing the potential therapeutic target for TBI treatment targeting at mGluR5 and mGluR5/ACTN1 complex in BBB.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Animais , Camundongos , Barreira Hematoencefálica/metabolismo , Lesões Encefálicas/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Células Endoteliais/metabolismo , Camundongos Knockout , Receptor de Glutamato Metabotrópico 5/metabolismo
3.
Neural Regen Res ; 19(5): 1072-1077, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37862210

RESUMO

MIcroglia/macrophage-mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage. Dynamic cytoskeletal changes accompany phagocytosis. However, whether and how these changes are associated with microglia/macrophage-mediated erythrophagocytosis remain unclear. In this study, we investigated the function of acetylated α-tubulin, a stabilized microtubule form, in microglia/macrophage erythrophagocytosis after intracerebral hemorrhage both in vitro and in vivo. We first assessed the function of acetylated α-tubulin in erythrophagocytosis using primary DiO GFP-labeled red blood cells co-cultured with the BV2 microglia or RAW264.7 macrophage cell lines. Acetylated α-tubulin expression was significantly decreased in BV2 and RAW264.7 cells during erythrophagocytosis. Moreover, silencing α-tubulin acetyltransferase 1 (ATAT1), a newly discovered α-tubulin acetyltransferase, decreased Ac-α-tub levels and enhanced the erythrophagocytosis by BV2 and RAW264.7 cells. Consistent with these findings, in ATAT1-/- mice, we observed increased ionized calcium binding adapter molecule 1 (Iba1) and Perls-positive microglia/macrophage phagocytes of red blood cells in peri-hematoma and reduced hematoma volume in mice with intracerebral hemorrhage. Additionally, knocking out ATAT1 alleviated neuronal apoptosis and pro-inflammatory cytokines and increased anti-inflammatory cytokines around the hematoma, ultimately improving neurological recovery of mice after intracerebral hemorrhage. These findings suggest that ATAT1 deficiency accelerates erythrophagocytosis by microglia/macrophages and hematoma absorption after intracerebral hemorrhage. These results provide novel insights into the mechanisms of hematoma clearance and suggest ATAT1 as a potential target for the treatment of intracerebral hemorrhage.

4.
Front Neurol ; 14: 1247549, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38313405

RESUMO

Background: Endovascular or surgical treatment of wide-neck, large basilar apex aneurysms is challenging. We present a novel concept for the treatment of complex basilar apex aneurysms using flow-diverter devices combined with the flow-T stenting-assisted coiling technique. Assess the efficacy and safety profile of the technique in this complex aneurysm. Case description: A patient with multiple unruptured intracranial aneurysms underwent staged treatment. A large basilar apex aneurysm was treated with a flow-diverter stent combined with a flow-T stenting-assisted coiling technique in the first stage, and a giant supraclinoid aneurysm was treated with a flow-diverter stent applied in the second stage. Clinical presentations, technical details, intra- and perioperative complications, and clinical and angiographic outcomes were recorded, with a 9-month follow-up. Results: The patient achieved full neurologic recovery postoperatively. Cerebral angiography performed postoperatively showed revascularization, good laminar flow, and no in-stent or adjacent stenosis. Conclusion: Flow-diverter stents combined with flow-T stenting-assisted coiling for the treatment of giant basilar apex aneurysms is a feasible technique with efficacy demonstrated at a 9-month follow-up. Staged endovascular treatment of multiple intracranial aneurysms may be a safe and viable option.

5.
Front Cell Infect Microbiol ; 13: 1296491, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38274731

RESUMO

Streptomyces, the largest genus in the Streptomycetaceae family and a prolific producer of antibacterial drugs, is a saprophytic soil organism that rarely causes invasive infections. Here we report a case of necrotic pneumonia caused by Streptomyces albireticuli in a 75-year-old man who presented with progressive chest tightness and dyspnea. Streptomyces albireticuli was isolated from his bronchoalveolar lavage fluid and identified through whole-genome sequencing (WGS) and phylogenetic analysis. The patient responded satisfactorily to clarithromycin therapy. The findings of this study may enhance our vigilance in identifying visceral infections caused by Streptomyces.


Assuntos
Cistos , Pneumopatias , Pneumonia , Streptomyces , Masculino , Humanos , Idoso , Filogenia , Streptomyces/genética , Pulmão
6.
Comput Math Methods Med ; 2022: 3436631, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912147

RESUMO

Objective: To develop and authenticate a risk stratification framework and nomogram for ascertaining cancer-specific survival (CSS) among the pediatric brainstem gliomas. Methods: For patients less than 12 years, according to Surveillance, Epidemiology, and End Results (SEER), information from 1998 to 2016 is found in their databases. The survival outcomes, treatments, and demographic clinicopathologic conditions are scrutinized per the database validation, and training cohorts are divided and validated using multivariate Cox regression analysis. A nomogram was designed, and predominantly, the risk stratification conceptualization engaged selected tenets according to the multivariate analysis. The model's authenticity was substantiated through C-index measure and calibration curves. Results: There are 806 pediatric concerns of histologically concluded brainstem glioma in the research. According to multivariate analysis, age, grade, radiotherapy, and race (with P value < 0.05) depicted independent prognostic variations of the pediatric gliomas. The nomogram's C-index was approximately 0.75 and an accompanied predictive capability for CSS. Conclusion: The nomogram constructed in this glioma's context is the primary predictor of using risk stratification. A combination of nomograms with the risk stratification mechanism assists clinicians in monitoring high-risk individuals and engage targeted accessory treatment.


Assuntos
Neoplasias Encefálicas/mortalidade , Tronco Encefálico/patologia , Glioma/mortalidade , Neoplasias Encefálicas/terapia , Criança , Pré-Escolar , Estudos de Coortes , Glioma/terapia , Humanos , Lactente , Análise Multivariada , Nomogramas , Prognóstico , Análise de Regressão , Medição de Risco/métodos , Programa de SEER
7.
Cell Biol Int ; 46(11): 1927-1936, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35971755

RESUMO

Microglia is the major cellular component of glioma mass that promotes glioma growth, invasion, and chemoresistance by releasing inflammatory factors. Sterile alpha and HEAT/Armadillo motif (SARM), a member of the Toll-interleukin-1 receptor (TIR) domain-containing adaptor family, is primarily expressed in the central nervous system. However, the role of SARM in glioma is still undefined. In the present work, we examined the function of SARM in microglial polarization and glioma progression. Our results showed that forced the expression of SARM in GL261 glioma cells inhibited tumor growth, and reduced interleukin (IL)-6 secretion in conditioned media. Silencing of SARM in microglia cells inhibited IL-4-induced M2 polarization, enhanced lipopolysaccharide -induced M1 microglial polarization. Furthermore, overexpression of SARM increased the migration of microglia cells upon TGFß stimulation. These data suggested that SARM is involved in neuro-inflammation and microglia activation. In summary, this study provides novel insight into the mechanisms of microglial polarization.


Assuntos
Glioma , Microglia , Meios de Cultivo Condicionados , Glioma/metabolismo , Humanos , Interleucina-4/metabolismo , Lipopolissacarídeos/farmacologia , Microglia/metabolismo , Receptores de Interleucina-1/metabolismo , Fator de Crescimento Transformador beta/metabolismo
9.
Neurosci Bull ; 38(10): 1199-1214, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35819574

RESUMO

The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b+ pericytes after TBI. These CD11b+ pericyte subsets are characterized by increased permeability and pro-inflammatory profiles compared to CD11b- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinflammation and BBB dysfunction after TBI. These data indicate that neutrophil-NET-pericyte and histone-Dectin-1-CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.


Assuntos
Lesões Encefálicas Traumáticas , Armadilhas Extracelulares , Barreira Hematoencefálica/metabolismo , Encéfalo/patologia , Lesões Encefálicas Traumáticas/metabolismo , Armadilhas Extracelulares/metabolismo , Histonas , Humanos , Lectinas Tipo C , Pericitos/patologia
10.
Front Aging Neurosci ; 14: 835373, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250548

RESUMO

OBJECTIVE: The treatment of unruptured small intracranial aneurysms remains controversial. A distinguishing characteristic of A1 segment aneurysms is that they tend to rupture when they are small, which may be related to their distinctive morphology and hemodynamics. Our study sought to investigate the rupture risk factors of A1 segment aneurysms by analyzing the clinical risk factors, morphology, and hemodynamic characteristics of A1 segment aneurysms. METHODS: We retrospectively enrolled 49 (23 ruptured, 26 unruptured) consecutive patients presenting to our institute with A1 segment aneurysms between January 2010 and March 2020. Independent risk factors associated with the rupture of A1 segment aneurysms were analyzed by multivariate regression analysis in the ruptured group and unruptured group. RESULTS: Clinical risk factors, including age, sex, hypertension, smoking history, and SAH family history revealed no difference between the ruptured and unruptured groups. The ruptured group presented a significantly larger size (Size, P = 0.007), aspect ratio (AR, P = 0.002), size ratio (SR, P = 0.001), bottleneck index (BN, P = 0.016), dome-to-neck ratio (DN, P = 0.001), and oscillatory shear index (OSI) (P = 0.001) than the unruptured group. The normalized wall shear stress (NWSS) of the ruptured aneurysms was lower than the unruptured group (P = 0.001). In the multivariate regression analysis, only SR (OR = 3.672, P = 0.003) and NWSS (OR = 0.474, P = 0.01) were independent risk factors in the A1 segment aneurysm rupture. CONCLUSION: A higher SR and lower NWSS revealed a close connection with the rupture of A1 segment aneurysms in our study, thus providing a reference for clinical decision-making in treating A1 segment unruptured aneurysms.

11.
Front Pediatr ; 9: 564991, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34386463

RESUMO

Background: Nosocomial meningitis with multidrug-resistant (MDR) or extensively drug-resistant (XDR) Acinetobacter baumannii is a life-threatening complication in neurosurgery. Treatment of these infections is challenging because of poor penetration of the available antibiotics into the cerebrospinal fluid (CSF). Intrathecal (ITH) or intraventricular (IVT) administration of antibiotics is increasingly used as the last treatment option against MDR/XDR Gram-negative bacteria meningitis not responding to intravenous (IV) regimens. However, pertinent data in pediatric patients is scarce. Case Presentation: A 14-year-old male patient developed meningitis from an MDR strain of A. baumannii following endoscopic endonasal resection of craniopharyngioma. Despite a combination therapy involving IV tigecycline, we observed clinical and bacteriologic failure. The patient was then successfully treated with an ITH and IV polymyxin B-based combination. Quantification of tigecycline and polymyxin B in CSF was performed with two-dimensional high-performance liquid chromatography (2D-HPLC) and HDLC coupled with tandem mass spectrometry (HPLC-MS/MS), respectively. Adverse drug reactions (neurotoxicity and skin hyperpigmentation), probably induced by polymyxin B, were acceptable and reversible. Conclusions: The case illustrates ITH and IV Polymyxin B-based combination is an optimal therapeutic option against MDR A. baumannii meningitis in this pediatric patient. In the future, real-time PK/PD data obtained from patients during ITH/IVT polymyxin B therapy should be required to optimize polymyxin use with maximal efficacy and minimal adverse effects.

12.
Comput Struct Biotechnol J ; 19: 3077-3086, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34136106

RESUMO

The secreting function of pituitary adenomas (PAs) plays a critical role in making the treatment strategies. However, Magnetic Resonance Imaging (MRI) analysis for pituitary adenomas is labor intensive and highly variable among radiologists. In this work, by applying convolutional neural network (CNN), we built a segmentation and classification model to help distinguish functioning pituitary adenomas from non-functioning subtypes with 3D MRI images from 185 patients with PAs (two centers). Specifically, the classification model adopts the concept of transfer learning and uses the pre-trained segmentation model to extract deep features from conventional MRI images. As a result, both segmentation and classification models obtained high performance in two internal validation datasets and an external testing dataset (for segmentation model: Dice score = 0.8188, 0.8091 and 0.8093 respectively; for classification model: AUROC = 0.8063, 0.7881 and 0.8478, respectively). In addition, the classification model considers the attention mechanism for better model interpretation. Taken together, this work provides the first deep learning-based tumor region segmentation and classification models of PAs, which enables early diagnosis and subtyping PAs from MRI images.

13.
Sci Rep ; 10(1): 14151, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843668

RESUMO

The invasion ability of glioblastoma (GBM) causes tumor cells to infiltrate the surrounding brain parenchyma and leads to poor outcomes. Transient receptor potential vanilloid 4 (TRPV4) exhibits a remarkable role in cancer cell motility, but the contribution of TRPV4 to glioblastoma metastasis is not fully understood. Here, we reported that TRPV4 expression was significantly elevated in malignant glioma compared to normal brain and low-grade glioma, and TRPV4 expression was negatively correlated with the prognosis of glioma patients. Functionally, stimulation of TRPV4 promoted glioblastoma cell migration and invasion, and repression of TRPV4 hindered the migration and invasion of glioblastoma cells in vitro. Molecularly, TRPV4 strongly colocalized and interacted with skeletal protein-F-actin at cellular protrusions, and TRPV4 regulated the formation of invadopodia and filopodia in glioblastoma cells. Furthermore, the Cdc42/N-wasp axis mediated the effect of TRPV4-regulated cellular protrusions and invasion. Foremost, TRPV4 inhibitor treatment or downregulation of TRPV4 significantly reduced the invasion-growth of subcutaneously and intracranially transplanted glioblastoma in mice. In conclusion, the TRPV4/Cdc42/wasp signaling axis regulates cellular protrusion formation in glioblastoma cells and influences the invasion-growth phenotype of glioblastoma in vivo. TRPV4 may serve as a prognostic factor and specific therapeutic target for GBM patients.


Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Invasividade Neoplásica/fisiopatologia , Proteínas de Neoplasias/fisiologia , Transdução de Sinais/fisiologia , Canais de Cátion TRPV/fisiologia , Proteína Neuronal da Síndrome de Wiskott-Aldrich/fisiologia , Proteína cdc42 de Ligação ao GTP/fisiologia , Actinas/metabolismo , Animais , Linhagem Celular Tumoral , Feminino , Células HEK293 , Xenoenxertos , Humanos , Estimativa de Kaplan-Meier , Camundongos , Camundongos Nus , Prognóstico , Pseudópodes/ultraestrutura , Ratos
14.
Brain Res ; 1736: 146781, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32184164

RESUMO

Glioblastoma (GBM) has been regarded as the most aggressive disease in the nervous system. Accumulating literatures have illustrated the crucial role of competing endogenous RNAs (ceRNAs) network in the pathogenesis and progression of various tumors. The promoting effect of LEF1-AS1 on GBM development has been previously identified. This study attempted to explore the underlying mechanism of LEF1-AS1 in GBM. Data of clinical GBM patients was downloaded from TCGA and GEO databases. The proliferative ability, clonogenic vitality, invasive, and migratory capabilities of GBM cells were measured using Cell counting kit-8 (CCK-8), colony formation and transwell assays. Luciferase reporter gene analysis was performed to verify the correlations between LEF1-AS1/EN2 and miR-543. qRT-PCR and western blotting were implemented to evaluate the mRNA and protein levels, respectively. Our results consolidated that LEF1-AS1 was highly expressed in GBM tissue specimens and its up-regulation induced unfavorable prognosis. The loss/gain-of-function analyses verified that LEF1-AS1 promoted the GBM cell malignant behaviors. Mechanically, LEF1-AS1 acted as a ceRNA for miR-543 and positively regulated engrailed homeobox 2 (EN2) expression. Down-regulation of miR-543 elevated GBM cell malignant behaviors, which was reversed by LEF1-AS1 knockdown. Meanwhile, the LEF1-AS1 inhibition could arrest the promoting effect of high-regulated EN2 on GBM cell aggressiveness and vice versa. In conclusion, our findings identified LEF1-AS1 as a ceRNA for miR-543 and showed that EN2 was positively regulated by LEF1-AS1. The LEF1-AS1/miR-543/EN2, as a novel ceRNA network, was implicated in the progression of GBM, which provided a novel insight for GBM treatment.


Assuntos
Glioblastoma/genética , Fator 1 de Ligação ao Facilitador Linfoide/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Bases de Dados Genéticas , Progressão da Doença , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Glioblastoma/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , RNA Antissenso/genética , RNA Longo não Codificante/genética , Transcriptoma/genética
15.
Cell Commun Signal ; 18(1): 22, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046730

RESUMO

BACKGROUND: Glioblastoma and Alzheimer's disease (AD) are the most common and devastating diseases in the central nervous system. The dysfunction of Presenilin1 is the main reason for AD pathogenesis. However, the molecular function of Presenilin1 and its relative mechanism in glioblastoma remain unclear. METHODS: Expression of presenilin1 in glioma was determined by IHC. CCK-8, colony formation, Flow cytometry, Edu staining were utilized to evaluate functions of presenilin1 on glioblastoma proliferation. The mechanism of above process was assessed by Western blotting and cell immunofluorescence. Mouse transplanting glioblastoma model and micro-MRI detection were used to verified presenilin1 function in vivo. RESULTS: In this study, we found that all grades of glioma maintained relatively low Presenilin1 expression and that the expression of Presenilin1 in high-grade glioma was significantly lower than that in low-grade glioma. Moreover, the Presenilin1 level had a positive correlation with glioma and glioblastoma patient prognosis. Next, we determined that Presenilin1 inhibited the growth and proliferation of glioblastoma cells by downregulating CDK6, C-myc and Cyclin D1 to arrest the cell cycle at the G1/S phase. Mechanistically, Presenilin1 promoted the direct phosphorylation of ß-catenin at the 45 site and indirect phosphorylation at the 33/37/41 site, then decreased the stabilized part of ß-catenin and hindered its translocation from the cytoplasm to the nucleus. Furthermore, we found that Presenilin1 downregulation clearly accelerated the growth of subcutaneous glioblastoma, and Presenilin1 overexpression significantly repressed the subcutaneous and intracranial transplantation of glioblastoma by hindering ß-catenin-dependent cell proliferation. CONCLUSION: Our data implicate the antiproliferative effect of Presenilin1 in glioblastoma by suppressing Wnt/ß-catenin signaling, which may provide a novel therapeutic agent for glioblastoma. Video Abstract.


Assuntos
Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Glioblastoma/metabolismo , Glioblastoma/patologia , Presenilina-1/metabolismo , Via de Sinalização Wnt , Animais , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/metabolismo , Regulação para Baixo , Fase G1 , Humanos , Camundongos Nus , Fosforilação , Prognóstico , Proteólise , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fase S , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismo
16.
Oncol Lett ; 18(6): 6108-6116, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788085

RESUMO

Intra-tumor heterogeneity (ITH) is one of the most important causes of therapy resistance, which eventually leads to the poor outcomes observed in patients with glioma. Mutant-allele tumor heterogeneity (MATH) values are based on whole-exon sequencing and precisely reflect genetic ITH. However, the significance of MATH values in predicting glioma recurrence remains unclear. Information of patients with glioma was obtained from The Cancer Genome Atlas database. The present study calculated the MATH value for each patient, analyzed the distributions of MATH values in different subtypes and investigated the rates of clinical recurrence in patients with different MATH values. Gene enrichment and Cox regression analyses were performed to determine which factors influenced recurrence. A nomogram table was established to predict 1-, 2- and 5-year recurrence probabilities. MATH values were increased in patients with glioma with the wild-type isocitrate dehydrogenase (NADP(+)) (IDH)1/2 (IDH-wt) gene (P=0.001) and glioblastoma (GBM; P=0.001). MATH values were negatively associated with the 2- and 5-year recurrence-free survival (RFS) rates in patients with glioma, particularly in the IDH1/2-wt and GBM cohorts (P=0.001 and P=0.017, respectively). Furthermore, glioma cases with different MATH levels had distinct patterns of gene mutation frequencies and gene expression enrichment. Finally, a nomogram table that contained MATH values could be used to accurately predict the probabilities of the 1-, 2- and 5-year RFS of patients with glioma. In conclusion, the MATH value of a patient may be an independent predictor that influences glioma recurrence. The nomogram model presented in the current study was an appropriate method to predict 1-, 2- and 5-year RFS probabilities in patients with glioma.

17.
Future Oncol ; 15(32): 3723-3738, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31650850

RESUMO

Aim: Apocynum venetum polyphenol (AVP) was used in in vitro glioma cells culture to prove the growth inhibitory effect of AVP on human U87 glioma cells via NF-κB pathway. Materials & methods: The MTT assay, DAPI morphology, quantitative PCR and western blot experiments were used for determination in vitro. Results & conclusion: AVP can also induce U87 cancer cells apoptosis illustrated by DAPI morphology. AVP could enhance the mRNA and protein expression of IκB-α, TNF-α, TRAIL, caspase-3 and caspase-9 in U87 cancer cells and reduce those of NF-κBp65, cIAP-1, cIAP-2, TGF-ß2, CyclinD1, VEGF and IL-8. After ammonium pyrrolidine dithiocarbamate (PDTC) treatment, the NF-κBp65 expression was reduced in U87 cells, and AVP could raise these effects. The results of HPLC indicate that AVP mainly contains six constituents. The growth inhibitory effects of AVP on U87 glioma cells are predominantly from these natural active constituents.


Assuntos
Antineoplásicos/farmacologia , Apocynum/química , Apoptose/efeitos dos fármacos , Glioma/patologia , Polifenóis/farmacologia , Fator de Transcrição RelA/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/metabolismo , Humanos , Polifenóis/química , Polifenóis/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/genética
18.
Medicine (Baltimore) ; 98(39): e17151, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574820

RESUMO

RATIONALE: Persistent primitive hypoglossal artery (PPHA) is often associated with intracranial anomalies such as aneurysms. Surgical treatment of aneurysms on the PPHA is challenging due to that the posterior circulation depends solely on PPHA. PATIENT CONCERNS: A case of an 83-year-old woman with a large aneurysm on PPHA presented with vertigo was reported. DIAGNOSIS: Three-dimensional angiogram revealed a wide-neck aneurysm on the PPHA. INTERVENTIONS: The aneurysm was successfully treated using a novel low-profile visualized intraluminal support stent-assisted coiling technique. OUTCOMES: No complications occurred during the procedure. The final angiogram confirmed the patency of the posterior inferior cerebellar artery and the parent artery and its distal branches. LESSONS: Our case suggests that stent-assisted coil embolization is safe and effective for the treatment of aneurysms on the PPHA.


Assuntos
Embolização Terapêutica/métodos , Aneurisma Intracraniano/cirurgia , Artéria Cerebral Posterior/cirurgia , Stents , Idoso de 80 Anos ou mais , Embolização Terapêutica/instrumentação , Feminino , Humanos , Resultado do Tratamento
19.
Oncol Lett ; 18(5): 5591-5599, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612066

RESUMO

The transcriptional coactivator tafazzin (TAZ) serves pivotal roles in organ development, tumor initiation and tumor progression. However, to the best of our knowledge, the expression of TAZ and its clinical significance in human medulloblastoma have not been defined. The present study aimed to clarify the clinical and biological significance of TAZ expression in human medulloblastoma. Immunohistochemical staining for TAZ was performed with 72 medulloblastoma and three normal brain tissue samples. A high expression level of TAZ was detected in 65.28% of medulloblastoma tissues, whereas low expression was identified in the normal brain tissues. TAZ expression was significantly associated with medulloblastoma recurrence. However, the expression of TAZ was not associated with sex, age, tumor location, tumor maximal diameter and tumor histology. Furthermore, both the overall survival and tumor-free survival rate of patients with high levels of expression of TAZ were shorter compared with those of patients with tumors expressing low levels of TAZ. In univariate and multivariate Cox regression analyses, TAZ expression was identified as a significant prognostic factor for patients with medulloblastoma. Functionally, downregulation of TAZ inhibited the proliferation and tumor formation of medulloblastoma cells and the expression of cell-cycle associated proteins in Daoy cells. In conclusion, high expression of TAZ may serve as a prognostic marker for patients with medulloblastoma and TAZ may be a potential target for medulloblastoma therapy.

20.
Med Sci Monit ; 25: 7652-7659, 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31604907

RESUMO

BACKGROUND As a kind of benign tumor, pituitary adenomas have attracted increasing attention from researchers. The plasmacytoma variant translocation 1 (PVT1) is a molecule in the lncRNA family protein that has been proven to play critical roles in many cancers; however, no study has explored the special biological roles of PVT1 in pituitary adenoma. MATERIAL AND METHODS The qRT-PCR assay was conducted to evaluate PVT1 expressions in various cell lines and tissues. Loss of function assays were carried out to detect the influence of silenced PVT1 on the proliferation, migration, and epithelial-mesenchymal transition (EMT) of pituitary adenoma cells. Western blotting was used to identify correlation between ß-catenin and PVT1. RESULTS The PVT1 expressions were significantly enhanced in tissues of pituitary adenoma and cancer cells. Cell migration and proliferation were inhibited when the PVT1 gene was knocked down. Knockdown of PVT1 repressed the migration and EMT of pituitary adenoma cells. The PVT1 downregulation obviously blocked Wnt/ß-catenin signaling pathway activity. PVT1 aggravated progression of pituitary adenoma through initiating the Wnt/ß-catenin signaling pathway. CONCLUSIONS PVT1 exerts an oncogenic role through activating Wnt/ß-catenin signaling in pituitary adenoma cells. The present results may provide a potential therapeutic target or approach for treating pituitary adenomas.


Assuntos
Adenoma/genética , Movimento Celular/genética , Ciclina D1/metabolismo , Transição Epitelial-Mesenquimal/genética , Neoplasias Hipofisárias/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Longo não Codificante/metabolismo , beta Catenina/metabolismo , Adenoma/patologia , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hipofisárias/patologia , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Via de Sinalização Wnt
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