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1.
Brain Pathol ; 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31733156

RESUMO

In the 2016, WHO classification of tumors of the central nervous system, isocitrate dehydrogenase (IDH) mutation is a main classifier for lower grade astrocytomas and IDH-mutated astrocytomas is now regarded as a single group with longer survival. However, the molecular and clinical heterogeneity among IDH mutant lower grade (WHO Grades II/III) astrocytomas have only rarely been investigated. In this study, we recruited 160 IDH mutant lower grade (WHO Grades II/III) astrocytomas, and examined PDGFRA amplification, CDKN2A deletion and CDK4 amplification by FISH analysis, TERT promoter mutation by Sanger sequencing and ATRX loss and p53 expression by immunohistochemistry. We identified PDGFRA amplification, CDKN2A homozygous deletion and CDK4 amplification in 18.8%, 15.0% and 18.1% of our cohort respectively, and these alterations occurred in a mutually exclusive fashion. PDGFRA amplification was associated with shorter PFS (P = 0.0003) and OS (P < 0.0001). In tumors without PDGFRA amplification, CDKN2A homozygous deletion or CDK4 amplification was associated with a shorter OS (P = 0.035). Tumors were divided into three risk groups based on the presence of molecular alterations: high risk (PDGFRA amplification), intermediate risk (CDKN2A deletion or CDK4 amplification) and low risk (neither CDKN2A deletion and CDK4 amplification nor PDGFRA amplification). These three risk groups were significantly different in overall survival with mean survivals of 40.5, 62.9 and 71.5 months. The high-risk group also demonstrated a shorter PFS compared to intermediate- (P = 0.036) and low-risk (P < 0.0001) groups. One limitation of this study is the relatively short follow-up period, a common confounding factor for studies on low-grade tumors. Our data illustrate that IDH mutant lower grade astrocytomas is not a homogeneous group and should be molecularly stratified for risk.

2.
Sci Rep ; 9(1): 13239, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519974

RESUMO

Inflammation and immunoreaction markers were correlated with the survival of patients in many tumors. However, there were no reports investigating the relationships between preoperative hematological markers and the prognosis of medulloblastoma (MB) patients based on the molecular subgroups (WNT, SHH, Group 3, and Group 4). A total 144 MB patients were enrolled in the study. The differences of preoperative hematological markers among molecular subgroups of MB were compared by One-way ANOVA method. Kaplan-Meier method was used to calculate the curves of progression free survival (PFS) and overall survival (OS). The comparison of survival rates in different groups were conducted by the Log-rank test. Multivariate analysis was used to evaluate independent prognostic factors. Increased preoperative NLR (neutrophil-to-lymphocyte ratio, PFS, P = 0.004, OS, P < 0.001) and PLR (platelet-to-lymphocyte ratio, PFS, P = 0.028, OS, P = 0.003) predicted poor prognosis in patients with MB, while preoperative MLR (monocyte-to-lymphocyte ratio), MPV (mean platelet volume), PDW (platelet distribution width), and AGR (albumin-to-globulin ratio) were revealed no predictive value on the prognosis of patients with MB. Furthermore, high preoperative NLR and PLR predicted unfavorable prognosis in childhood MB patients. However, preoperative NLR and PLR were not associated with the prognosis in adult MB patients. Multivariate analysis demonstrated preoperative NLR (PFS, P = 0.029, OS, P = 0.005) and PLR (PFS, P = 0.023, OS, P = 0.005) were the independent prognostic factors in MB patients. Emphatically, the levels of preoperative NLR and PLR in Group 3 MB were significantly higher than those in WNT MB. High preoperative NLR was associated with unfavorable OS in Group 3 (P = 0.032) and Group 4 (P = 0.027) tumors. Similarly, increased preoperative PLR predicted poor PFS (P = 0.012) and OS (P = 0.009) in Group 4 tumors. Preoperative NLR and PLR were the potential prognostic markers for MB patients. Preoperative NLR and PLR were significantly associated with the survival of Group 3 and Group 4 tumors.

3.
Aging (Albany NY) ; 11(16): 6252-6272, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444316

RESUMO

The prediction of clinical outcome for patients with infiltrative gliomas is challenging. Although preoperative hematological markers have been proposed as predictors of survival in glioma and other cancers, systematic investigations that combine these data with other relevant clinical variables are needed to improve prognostic accuracy and patient outcomes. We investigated the prognostic value of preoperative hematological markers, alone and in combination with molecular pathology, for the survival of 592 patients with Grade II-IV diffuse gliomas. On univariate analysis, increased neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), and decreased albumin-to-globulin ratio (AGR), all predicted poor prognosis in Grade II/III gliomas. Multivariate analysis incorporating tumor status based on the presence of IDH mutations, TERT promoter mutations, and 1p/19q codeletion showed that in lower-grade gliomas, high NLR predicted poorer survival for the triple-negative, IDH mutation only, TERT mutation only, and IDH and TERT mutation groups. NLR was an independent prognostic factor in Grade IV glioma. We therefore propose a prognostic model for diffuse gliomas based on the presence of IDH and TERT promoter mutations, 1p/19q codeletion, and NLR. This model classifies lower-grade gliomas into nine subgroups that can be combined into four main risk groups based on survival projections.

4.
J Clin Neurosci ; 67: 234-238, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31221576

RESUMO

During neurological surgery, neurosurgeons have to transform the two-dimensional (2D) sectional images into three-dimensional (3D) structures at the cognitive level. The complexity of the intracranial structures increases the difficulty and risk of neurosurgery. Mixed reality (MR) applications reduce the obstacles in the transformation from 2D images to 3D visualization of anatomical structures of central nervous system. In this study, the holographic image was established by MR using computed tomography (CT), computed tomography angiography (CTA) and magnetic resonance imaging (MRI) data of patients. The surgeon's field of vision was superimposed with the 3D model of the patient's intracranial structure displayed on the mixed reality head-mounted display (MR-HMD). The neurosurgeons practiced and evaluated the feasibility of this technique in neurosurgical cases. We developed the segmentation image masks and texture mapping including brain tissue, intracranial vessels, nerves, tumors, and their relative positions by MR technologies. The results showed that the three-dimensional imaging is in a stable state in the operating room with no significant flutter and blur. And the neurosurgeon's feedback on the comfort of the equipment and the practicality of the technology was satisfactory. In conclusion, MR technology can holographically construct a 3D digital model of patient's lesions and improve the anatomical perception of neurosurgeons during craniotomy. The feasibility of the MR-HMD application in neurosurgery is confirmed.


Assuntos
Craniotomia/métodos , Holografia/métodos , Cirurgia Assistida por Computador/métodos , Idoso , Neoplasias Encefálicas/cirurgia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos
5.
Medicine (Baltimore) ; 97(50): e13675, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30558073

RESUMO

Glioma is the most common malignant tumor in the central nervous system (CNS). Lower-grade gliomas (LGG) refer to Grade II and III gliomas. In LGG patients, seizure often appears as an initial symptom and play an important role in clinical performance and quality of life of the patients. To date, the relationship between the onset of seizures and the molecular pathology in gliomas is still poorly investigated. In this study, we investigate the potential relationship between isocitrate dehydrogenase (IDH)/telomerase reverse transcriptase promoter (TERTp) mutations and preoperative seizures in patients with LGG. 289 adult LGG patients were enrolled in this study. Data of clinical characteristics and molecular pathology were acquired. Sanger sequencing was used to detect IDH/TERTp mutations. Chi-square test was performed to determine if the IDH/TERTp mutations were associated with seizures and seizure types. In 289 LGG patients, preoperative seizures accounted for 25.3% (73/289), IDH mutations accounted for 34.3%(99/289), and TERTp mutations accounted for 44.3% (128/289). The correlation analysis demonstrated that IDH mutation is a significant factor influencing the occurrence of tumor-related epilepsy (P <.001, chi-square test). On the other hand, the statistical analysis revealed no significant correlation between TERTp mutations and seizure in LGG patients (P = .102, chi-square test). The tumor-related epilepsy rates vary among different subgroups according to IDH/TERTp mutations. However, there is no definite correlation between the IDH (P = 1.000, chi-square test)/TERTp (P = .613, chi-square test) mutations and the types of epileptic seizure. IDH mutations are more common in preoperative LGG patients with epileptic symptoms, suggesting that this mutation is positively correlated with seizures. However, there was no significant correlation between TERTp mutations and seizures. Different molecular pathologic types based on IDH/TERTp have different incidences of tumor-associated epilepsy in LGGs.


Assuntos
Glioma/genética , Isocitrato Desidrogenase/genética , Convulsões/genética , Telomerase/genética , Neoplasias Encefálicas/patologia , Sistema Nervoso Central/patologia , Feminino , Glioma/classificação , Glioma/patologia , Glioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Convulsões/etiologia , Análise de Sequência de DNA/métodos
6.
Cell Physiol Biochem ; 48(4): 1755-1770, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30078018

RESUMO

BACKGROUND/AIMS: CDH18 (cadherin 18) is specifically expressed in the central nervous system and associated with various neuropsychiatric disorders. In this study, the role of CDH18 in glioma carcinogenesis and progression was investigated. METHODS: The expression of CDH18 and its prognostic value in patients with gliomas were analyzed in public database and validated by real-time PCR/immunohistochemical staining (IHC) in our cohort. CCK-8 assay, transwell migration assay, wound healing assay, clonogenic assay and tumorigenicity assay were used to compare the proliferation, invasion and migration ability of glioma cells with different expressions of CDH18. iTRAQ-based quantitative proteomic analysis were used to reveal the downstream target of CDH18. Rescue experiments were conducted to further validate the relationship between UQCRC2 and CDH18. RESULTS: The expression of CDH18 was depressed in a ladder-like pattern from normal tissues to WHO IV gliomas, and was an independent prognostic factor in TCGA (The Cancer Genome Atlas), CGGA (the Chinese glioma genome-atlas) and our glioma cohorts (n=453). Functional experiments in vitro and in vivo demonstrated that CDH18 inhibited invasion/migration, enhanced chemoresistance and suppressed tumorigenicity of glioma cells. UQCRC2 was identified as the downstream target of CDH18 by proteomic analysis. The expression of UQCRC2 was gradually absent as the WHO grades of gliomas escalated and was positively correlated with the expression of CDH18. Furthermore, in vitro assays demonstrated that down-regulation of UQCRC2 partly reversed the inhibition of invasion/migration ability and chemoresistance in CDH18 overexpressed glioma cell lines. Survival analysis demonstrated that combined CDH18/UQCRC2 biomarkers significantly influenced the prognosis of glioma patients. CONCLUSIONS: The present research demonstrated that CDH18 exerted its tumor-suppressor role via UQCRC2 in glioma cells and CDH18 might serve as a therapeutic target for treating gliomas.


Assuntos
Neoplasias Encefálicas/patologia , Caderinas/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Glioma/patologia , Idoso , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Caderinas/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dacarbazina/análogos & derivados , Dacarbazina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Complexo III da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Complexo III da Cadeia de Transporte de Elétrons/genética , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , Humanos , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Temozolomida
7.
Cell Death Dis ; 9(7): 767, 2018 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-29991742

RESUMO

Sirtuin-1 (SIRT1), the mammalian ortholog of yeast Sir2p, is well known to be a highly conserved NAD+-dependent protein deacetylase that has been emerging as a key cancer target. Autophagy, an evolutionarily conserved, multi-step lysosomal degradation process, has been implicated in cancer. Accumulating evidence has recently revealed that SIRT1 may act as a tumor suppressor in several types of cancer, and thus activating SIRT1 would represent a possible therapeutic strategy. Thus, in our study, we identified that SIRT1 was a key prognostic factor in brain cancer based upon The Cancer Genome Atlas and tissue microarray analyses. Subsequently, we screened a series of potential small-molecule activators of SIRT1 from Drugbank, and found the best candidate compound F0911-7667 (hereafter, named Comp 5), which showed a good deacetylase activity for SIRT1 rather than other Sirtuins. In addition, we demonstrated that Comp 5-induced autophagic cell death via the AMPK-mTOR-ULK complex in U87MG and T98G cells. Interestingly, Comp 5-induced mitophagy by the SIRT1-PINK1-Parkin pathway. Further iTRAQ-based proteomics analyses revealed that Comp 5 could induce autophagy/mitophagy by downregulating 14-3-3γ, catalase, profilin-1, and HSP90α. Moreover, we showed that Comp 5 had a therapeutic potential on glioblastoma (GBM) and induced autophagy/mitophagy by activating SIRT1 in vivo. Together, these results demonstrate a novel small-molecule activator of SIRT1 that induces autophagic cell death/mitophagy in GBM cells, which would be utilized to exploit this compound as a leading drug for future cancer therapy.


Assuntos
Antineoplásicos/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Sirtuína 1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Autofagia/efeitos dos fármacos , Autofagia/genética , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Profilinas/genética , Profilinas/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Proteômica , Sirtuína 1/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
8.
Acta Neuropathol ; 136(4): 641-655, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29948154

RESUMO

Pediatric low-grade gliomas (PLGGs) consist of a number of entities with overlapping histological features. PLGGs have much better prognosis than the adult counterparts, but a significant proportion of PLGGs suffers from tumor progression and recurrence. It has been shown that pediatric and adult low-grade gliomas are molecularly distinct. Yet the clinical significance of some of newer biomarkers discovered by genomic studies has not been fully investigated. In this study, we evaluated in a large cohort of 289 PLGGs a list of biomarkers and examined their clinical relevance. TERT promoter (TERTp), H3F3A and BRAF V600E mutations were detected by direct sequencing. ATRX nuclear loss was examined by immunohistochemistry. CDKN2A deletion, KIAA1549-BRAF fusion, and MYB amplification were determined by fluorescence in situ hybridization (FISH). TERTp, H3F3A, and BRAF V600E mutations were identified in 2.5, 6.4, and 7.4% of PLGGs, respectively. ATRX loss was found in 4.9% of PLGGs. CDKN2A deletion, KIAA1549-BRAF fusion and MYB amplification were detected in 8.8, 32.0 and 10.6% of PLGGs, respectively. Survival analysis revealed that TERTp mutation, H3F3A mutation, and ATRX loss were significantly associated with poor PFS (p < 0.0001, p < 0.0001, and p = 0.0002) and OS (p < 0.0001, p < 0.0001, and p < 0.0001). BRAF V600E was associated with shorter PFS (p = 0.011) and OS (p = 0.032) in a subset of PLGGs. KIAA1549-BRAF fusion was a good prognostic marker for longer PFS (p = 0.0017) and OS (p = 0.0029). MYB amplification was also a favorable marker for a longer PFS (p = 0.040). Importantly, we showed that these molecular biomarkers can be used to stratify PLGGs into low- (KIAA1549-BRAF fusion or MYB amplification), intermediate-I (BRAF V600E and/or CDKN2A deletion), intermediate-II (no biomarker), and high-risk (TERTp or H3F3A mutation or ATRX loss) groups with distinct PFS (p < 0.0001) and OS (p < 0.0001). This scheme should aid in clinical decision-making.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Gradação de Tumores/métodos , Adolescente , Biomarcadores Tumorais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino , Mutação/genética , Patologia Molecular , Pediatria , Prognóstico , Intervalo Livre de Progressão , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
9.
Int J Biochem Cell Biol ; 99: 133-139, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29608952

RESUMO

BACKGROUND: Both LncRNA UCA1 and miR-495 are crucial gene regulators in various disorders. This study aims to investigate their role in epilepsy and seizure-induced brain injury. METHODS: In this research, rat model of epilepsy was established by pilocarpine induction. The RNA and protein expression in hippocampal tissues and neurons were determined by qRT-PCR and western blot, respectively. The hippocampal neurons were isolated from hippocampal tissues, and treated with magnesium-free (MGF) physiological solution for epileptiform activity induction. The endogenous expression of related genes was modulated by recombinant plasmids and cell transfection. Flow cytometry was used to analyze the cell apoptosis. Dual luciferase reporter assay was performed to determine the interaction between miR-495 and Nrf2 in HEK-293 cells. RESULTS: The lncRNA UCA1 and Nrf2 were down-regulated in epileptiform hippocampal tissues and neurons, while the miR-495 was up-regulated. Over-expression of UCA1 inhibited apoptosis of hippocampal neurons by suppressing miR-495. MiR-495 negatively regulated Nrf2. UCA1 inhibited apoptosis of hippocampal neurons through miR-495/Nrf2-ARE pathway. UCA1 suppressed pilocarpine-induced epilepsy in rat. CONCLUSION: LncRNA UCA1 suppressed pilocarpine-induced epilepsy by inhibiting apoptosis of hippocampal neurons through miR-495/Nrf2-ARE pathway, and thereby inhibiting brain injury induced by seizure.


Assuntos
Elementos de Resposta Antioxidante , Lesões Encefálicas/prevenção & controle , Epilepsia/complicações , MicroRNAs/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , RNA Longo não Codificante/genética , Convulsões/complicações , Animais , Apoptose , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Células Cultivadas , Epilepsia/induzido quimicamente , Epilepsia/patologia , Regulação da Expressão Gênica , Hipocampo/metabolismo , Hipocampo/patologia , MicroRNAs/genética , Agonistas Muscarínicos/toxicidade , Fator 2 Relacionado a NF-E2/genética , Neurônios/metabolismo , Neurônios/patologia , Pilocarpina/toxicidade , Ratos , Ratos Sprague-Dawley , Convulsões/induzido quimicamente , Convulsões/patologia
10.
Oncol Res ; 26(2): 307-313, 2018 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-29089067

RESUMO

Recently, long noncoding RNAs (lncRNAs) have emerged as new gene regulators and prognostic markers in several cancers, including glioma. Here we focused on lncRNA LUCAT1 on the progression of glioma. qRT-PCR was used to determine the expression of LUCAT1 and miR-375 in glioma tissues and cells. MTT and Transwell invasion assays were performed to determine the function of LUCAT1 in glioma progression. The bioinformatics tool DIANA was used to predict the targets of LUCAT1. Pearson's correlation analysis was performed to explore the correlation between LUCAT1 and miR-375. In the present study, we showed that LUCAT1 was substantially upregulated in glioma tissues and cells. LUCAT1 inhibition significantly suppressed the proliferation and invasion of glioma cells. Subsequently, DIANA showed that miR-375 was predicted to contain the complementary binding sites to LUCAT1. Luciferase reporter assay showed that miR-375 directly targeted LUCAT1. In addition, we found that miR-375 was downregulated in glioma tissues and negatively correlated with LUCAT1 expression in glioma tissues. Furthermore, the results showed that miR-375 could rescue the function of LUCAT1 in glioma progression. The lncRNA LUCAT1 was critical for the proliferation and invasion of glioma cells by regulating miR-375. Our findings indicated that LUCAT1 might offer a potential novel therapeutic target for the treatment of glioma.


Assuntos
Regulação Neoplásica da Expressão Gênica , Glioma/genética , MicroRNAs/genética , Interferência de RNA , RNA Longo não Codificante/genética , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Feminino , Humanos , Masculino , Gradação de Tumores
11.
Oncol Rep ; 38(5): 3078-3084, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28901497

RESUMO

A previous study revealed that ubiquitin-like with PHD and RING finger domains 1 (UHRF1) promoted cell proliferation and was a potential biomarker in medulloblastoma (MB). In the present study, we reported that miR-378 inhibited the expression of UHRF1 to affect the proliferation of MB through competitive binding to the same region of its 3'-UTR. We found that the expression of miR-378 was significantly downregulated in MB tissues and inversely correlated with the expression of UHRF1. Western blot analysis revealed that overexpression of miR-378 led to the suppression of UHRF1. Moreover, a dual-luciferase assay demonstrated that miR-378 negatively regulated the activity of target gene UHRF1 by binding to its 3'-UTR. An in vitro assay revealed that overexpression of miR-378 suppressed MB cell proliferation and promoted cell apoptosis. Ectopic expression of UHRF1 rescued miR-378-suppressed cell proliferation and miR-378-promoted cell apoptosis. Collectively, the present study demonstrated that miR-378 could inhibit the proliferation of MB by downregulation of UHRF1 and act as a potential therapeutic target against MB.


Assuntos
Proteínas Estimuladoras de Ligação a CCAAT/genética , Neoplasias Cerebelares/genética , Meduloblastoma/genética , MicroRNAs/genética , Regiões 3' não Traduzidas , Apoptose , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Cerebelares/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Meduloblastoma/metabolismo
12.
Oncotarget ; 8(70): 115657-115666, 2017 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-29383189

RESUMO

Backgrounds: HOX (homologous box) is known as the dominant gene of vertebrate growth and cell differentiation. Abnormal expression of HOX gene in various tumors has attracted the attention of scholars. As a component of HOX clusters, HOXD4 plays a controversial role in the tumorigenesis of central nervous system. Results: The data demonstrated that and the results demonstrated that HOXD4 was overexpressed in glioma tissues compared to that of normal brain tissues. patients with high HOXD4 expression had a significant shorter survival than those with low HOXD4 expression in total glioma cohort (p<0.001), WHO Grade II cohort (p=0.003) and Grade III cohort (p<0.001), but not in Grade IV cohort when OS (overall survival) was analyzed (p=0.216). The findings were confirmed by the large-scale omics data analysis including lower-grade glioma (LGG) and glioblastoma multiforme (GBM) in TCGA (the cancer genome atlas) and CGGA (Chinese glioma genome atlas). Moreover, it was revealed that the expression of HOXD4 have a significant impact on the OS of Grade IV glioma with IDH wild-type and 1p/19q intact according to TCGA data. Methods: Clinicopathological analysis of HOXD4 expression in 453 glioma patients was performed in the current study. Expression of HOXD4 was evaluated by qPCR and immunohistochemical (IHC) staining. Univariate and multivariate analysis were conducted to investigate the prognostic role of HOXD4 in glioma patients. Conclusions: Expression of HOXD4 was closely related to the clinical outcomes of patients with gliomas, and HOXD4 may be a potential prognostic biomarker of gliomas.

13.
Exp Ther Med ; 12(5): 3275-3281, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27882149

RESUMO

As there are multiple factors causing hydrocephalus subsequent to intraventricular hemorrhage (IVH), it is difficult to achieve the best treatment effect using a single drug alone. In the present study, the protective effect of combination treatment with granulocyte-colony stimulating factor (G-CSF) and lithium chloride against hydrocephalus after IVH was investigated. A total of 130 adult male Sprague-Dawley rats were divided into five groups, including the IVH control, G-CSF treatment, lithium chloride treatment, combination treatment and sham surgery groups. An IVH rat model was established in order to examine the effect of combination treatment on hydrocephalus incidence. A TUNEL assay was performed to detect neuronal apoptosis in the five groups. In addition, the protein expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected by western blot analysis. The differentiation of nerve cells in the brain tissue obtained from the five rat groups was also determined with double immunofluorescence staining. The results demonstrated that administration of G-CSF or lithium chloride alone was able to only partly relieve the incidence of hydrocephalus after IVH. By contrast, combination treatment with G-CSF and lithium chloride significantly attenuated the development of hydrocephalus following IVH. TUNEL assay showed that neuronal apoptosis was significantly reduced by the combination treatment with G-CSF and lithium chloride. Furthermore, the expression of Bcl-2 was upregulated, whereas Bax expression was downregulated in the combination treatment group. The results also detected the highest expression of BrdU/GFAP, BrdU/NeuN and BrdU/PSA-NCAM in the combination treatment group. In conclusion, the combination of endogenous neural stem cell mobilization (using G-CSF) and lithium chloride treatment resulted in highly reduced incidence of hydrocephalus after IVH by inhibiting neuronal apoptosis.

14.
Oncol Lett ; 11(2): 1057-1060, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26893690

RESUMO

Solitary fibrous tumors (SFTs) are uncommon, with the pleura as a site of predilection. Central nervous system SFTs, particularly intracranial SFTs, are extremely rare. The lesions are generally benign and localized, and surgery is the main therapeutic solution. The current study reports the cases of a patient who presented with right haunch pain, right leg weakness and paresthesias for several months, and a patient with a history of unexpected loss of consciousness. Magnetic resonance imaging revealed the presence of lesions, with a spindle cell morphology evident on pathological examination. The immunohistochemical examination demonstrated a strong immunoreaction for cluster of differentiation 34, which supported the diagnosis of an SFT. Following a near-total resection, the patients had a good neural prognosis. The present study also provides a literature review, discussing the imageological and pathological characteristics of SFT, and the diagnostic methods that aid in distinguishing the entity from other spindle-cell central nervous system tumors.

15.
Trials ; 16: 528, 2015 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-26581842

RESUMO

BACKGROUND: Chronic subdural hematoma (CSDH) is a common disease that is more prevalent in older people. Surgical intervention is a safe treatment of choice. However, the recurrence rate is relatively high and the outcome is not always satisfactory among surgically treated patients. It is believed that aberrant angiogenesis and intracapsular inflammation contribute to the development of CSDH. Atorvastatin is reported to promote angiogenesis and suppress inflammation. We have recently shown that atorvastatin is effective to non-surgically reduce and eliminate CSDH with minimal side effects. Here, we report a clinical research trial protocol that is designed to evaluate the therapeutic effects of atorvastatin on CSDH. METHODS/DESIGN: We have designed a multi-center, randomized, placebo-controlled, double blind clinical trial for evaluating the efficacy of oral atorvastatin in reducing CSDH. We have so far recruited 96 patients with CT-confirmed or MRI-confirmed CSDHs from 16 medical centers in China. These patients were originally recruited for the Oriental Neurosurgical Evidence-based Study Team (ONET) study. After informed consent is provided, patients are randomized to receive either atorvastatin (oral 20 mg/night for 8 weeks) or placebo (dextrin for 8 weeks); and followed for 16 weeks after the treatment. The primary outcome is the change in hematoma volume at the end of 8-week treatment. Secondary outcomes include: changes in 1) the hematoma volume at the 4(th), 12(th), and 24(th) weeks; 2) Markwalder's Grading Scale and Glasgow Coma Scale (MGS-GCS); 3) Glasgow Outcome Score (GOS) and 4) Activities of Daily Life-the Barthel Index scale (ADL-BI). Safety will be assessed during the study by monitoring adverse events, laboratory tests, electrocardiography (ECG), measurements of vital signs (temperature, pulse, and blood pressure) and body weight. DISCUSSION: Results of this trial will provide critical information regarding whether atorvastatin is an effective and safe alternative to surgical treatment of CSDH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier--NCT02024373 The date of trial registration: 7 August 2013.


Assuntos
Atorvastatina/uso terapêutico , Hematoma Subdural Crônico/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Atividades Cotidianas , Administração Oral , Atorvastatina/administração & dosagem , Atorvastatina/efeitos adversos , China , Protocolos Clínicos , Método Duplo-Cego , Escala de Coma de Glasgow , Hematoma Subdural Crônico/diagnóstico , Hematoma Subdural Crônico/fisiopatologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Imagem por Ressonância Magnética , Estudos Prospectivos , Projetos de Pesquisa , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
Neurol Res ; 37(1): 77-83, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24965894

RESUMO

OBJECTIVES: Postconditioning with sevoflurane has been shown to protect against focal cerebral ischemia and reperfusion injury. However, the mechanism remains elusive. In this study, we tested the hypothesis that mitochondrial ATP-sensitive potassium (mitoKATP) and mitochondrial permeability transition pore (mPTP) play roles in the neuroprotection of postconditioning with sevoflurane. METHODS: Adult male Sprague-Dawley rats were subjected to MCAO for 90 minutes and then treated with sevoflurane at the beginning of reperfusion. The infarct volume, neurological deficit score, and brain edema were evaluated at 24 hours. Apoptosis were studied by TUNEL. The neuroprotective effect with or without 5-hydroxydecanoate (5-HD), a selective mitoKATP channel blocker or atractyloside (ATR), and an mPTP opener were analyzed. RESULTS: Postconditioning with sevoflurane significantly decreased neurological deficit scores, infarct volume, and brain edema and also reduced apoptotic cells. 5-HD and ATR abolished the neuroprotective effect, respectively. 5-HD or ATR alone had no effect on ischemia and reperfusion injury. DISCUSSION: Our data suggest that mitoKATP and mPTP play crucial roles in the neuroprotection of postconditioning with sevoflurane.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Éteres Metílicos/farmacologia , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Fármacos Neuroprotetores/farmacologia , Canais de Potássio/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Edema Encefálico/tratamento farmacológico , Edema Encefálico/patologia , Edema Encefálico/fisiopatologia , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Distribuição Aleatória , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Sevoflurano
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 16(11): 1118-21, 2014 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-25406555

RESUMO

OBJECTIVE: To investigate the characteristics of immune function in newborn infants of different gestational ages. METHODS: A total of 115 premature infants free of infection between June 1, 2012 and June 1, 2013 were divided into two groups according to their gestational age at birth: early preterm infant group (28-33+6 weeks, n=57) and late preterm infant group (34-36+6 weeks, n=58). Meanwhile, 88 full-term infants (37-41+6 week) were recruited to the control group. Venous blood samples were collected within 24 hours after birth. The percentages of lymphocyte subsets, such as CD3+, CD4+, CD8+, and CD19+ T cells and natural killer (NK) cells were measured by flow cytometry, and the absolute count of each population was calculated using the results from routine blood work. Concentrations of serum IgG, IgA, and IgM were measured by immunoturbidimetry. RESULTS: Both preterm infant groups had significantly higher percentages of CD3+ and CD4+ T cells and CD4+/CD8+ ratio (P<0.05) and significantly lower percentages of CD8+ and CD19+ T cells and NK cells (P<0.05), as compared with the full-term infant group. The absolute counts of total lymphocytes, CD3+, CD4+, CD8+, and CD19+ T cells, and NK cells in both preterm infant groups were significantly lower than those in the full-term infant group (P<0.05), and the above parameters in the late preterm infant group were significantly higher than those in the early preterm infant group (P<0.05). Both preterm infant groups showed significantly lower concentrations of serum IgG than the full-term infant group (P<0.05), while no significant differences in concentrations of serum IgA and IgM were observed between the three groups (P>0.05). CONCLUSIONS: Neonatal gestational age has an effect on cellular and humoral immunity. The immune function gradually improves with increasing gestational age.


Assuntos
Imunidade Celular , Imunidade Humoral , Recém-Nascido Prematuro/imunologia , Relação CD4-CD8 , Idade Gestacional , Humanos , Imunoglobulinas/sangue , Recém-Nascido , Contagem de Linfócitos
19.
Zhongguo Dang Dai Er Ke Za Zhi ; 16(8): 805-9, 2014 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-25140772

RESUMO

OBJECTIVE: To investigate the safety and efficacy of low-concentration inhaled nitric oxide (NO) in the treatment of hypoxic respiratory failure (HRF) among premature infants. METHODS: Sixty premature infants (gestational age ≤ 34 weeks) with HRF were randomized into NO and control groups between 2012 and 2013, with 30 cases in each group. Both groups received nasal continuous positive airway pressure (nCPAP) or mechanical ventilation. NO inhalation was continued for at least 7 days or until weaning in the NO group. The general conditions, blood gas results, complications, and clinical outcomes of the two groups were analyzed. RESULTS: The NO group showed significantly more improvement in blood gas results than the control group after 12 hours of treatment (P<0.05). After that, the change in oxygenation status over time showed no significant difference between the two groups (P>0.05). There were no significant differences in total time of assisted ventilation and duration of oxygen therapy between the two groups (P>0.05). The incidence of bronchopulmonary dysplasia (BPD), patent ductus arteriosus, necrotizing enterocolitis, retinopathy of prematurity, and pneumothorax in infants showed no significant differences between the NO and control groups (P>0.05), but the incidence of IVH and mortality were significantly lower in the NO group than in the control group (7% vs 17%, P<0.05; 3% vs 13%, P<0.05). CONCLUSIONS: NO inhalation may improve oxygenation status and reduce the mortality in premature infants with HRF, but it cannot reduce the incidence of BPD and the total time of mechanical ventilation or nCPAP and duration of oxygen therapy. NO therapy may have a brain-protective effect for premature infants with HRF and does not increase clinical complications.


Assuntos
Hipóxia/complicações , Óxido Nítrico/administração & dosagem , Insuficiência Respiratória/tratamento farmacológico , Administração por Inalação , Gasometria , Displasia Broncopulmonar/epidemiologia , Humanos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Insuficiência Respiratória/sangue , Insuficiência Respiratória/complicações
20.
Asian Pac J Trop Med ; 7(5): 386-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-25063066

RESUMO

OBJECTIVE: To investigate the effect of acute renal ischemia reperfusion on brain tissue. METHODS: Fourty eight rats were randomly divided into four groups (n=12): sham operation group, 30 min ischemia 60 min reperfusion group, 60 min ischemia 60 min reperfusion group, and 120 min ischemia 60 min reperfusion group. The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors. RESULTS: Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time. The detection at the molecular level showed decreased Bcl-2 expression, increased Bax expression, upregulated expression of NF-κB and its downstream factor COX-2/PGE2. CONCLUSIONS: Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation.


Assuntos
Lesão Renal Aguda/metabolismo , Encéfalo/metabolismo , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Proteínas Reguladoras de Apoptose/análise , Proteínas Reguladoras de Apoptose/metabolismo , Encéfalo/citologia , Química Encefálica , Citocinas/análise , Citocinas/metabolismo , Masculino , NF-kappa B/análise , Proteínas Proto-Oncogênicas c-bcl-2/análise , Ratos , Ratos Sprague-Dawley
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