正、反义β-1,4-半乳糖基转移酶V表达质粒在星形胶质细胞瘤细胞中的转染与鉴定

目的：构建β-1，4-半乳糖基转移酶-V(β-1，4-GalTV)正、反义表达质粒，并将其转染到人脑星形胶质细胞瘤细胞SHG-44中，为探讨神经胶质瘤细胞表达β-1，4-GalTV的生物学意义提供研究基础。方法：构建β-1，4-GalTV表达质粒，并将其转染到人脑星形胶质细胞瘤细胞SHG-44中；用Western印迹和Northern印迹鉴定转染情况。结果：通过酶切鉴定和测序分析，实验成功构建β-1，4-GalTV表达质粒。将构建的表达质粒转染到胶质细胞瘤细胞SHG-44中，经鉴定表明，转染的正义表达质粒能增加胶质细胞瘤细胞SHG-44中的β-1，4-GalTV表达量，而转染反义质粒则能降低细胞中β-1，4-GalTV表达量。结论：正、反义β-1，4-GalTV表达质粒在人脑星形胶质细胞瘤细胞SHG-44中的稳定转染和表达，对分析胶质瘤细胞表达β-1，4-GalTV的意义如对肿瘤细胞的增殖、迁移和黏附等的影响提供了研究基础。     

星形细胞瘤FLI-1蛋白表达及其与病人预后的关系

目的 探讨星形细胞瘤Friend白血病整合素1转录因子（FLI-1）表达水平及其与病人预后的关系。方法 选取2015年6月~2018年6月手术切除的术后病理检查确诊的星形细胞瘤标本112例和颅脑损伤内减压术获得非肿瘤脑组织59例（对照组）,采用免疫组织化学染色法检测FLI-1表达情况。术后随访3年,记录无进展生存、总生存情况,其中无进展生存为预后良好,肿瘤进展或病人死亡为预后不良。结果 112例星形细胞瘤中,预后良好62例,预后不良50例。星形细胞瘤FLI-1表达阳性率[66.96%（75/112）]明显高于对照组[16.95%（10/59）;P<0.05]。星形细胞瘤FLI-1表达与IDH1表达呈明显负相关（r=-0.682,P<0.001）,与p53表达呈正明显相关（r=0.711,P<0.001）。多因素logistic回归分析显示FLI-1表达阳性是星形细胞瘤预后不良的独立危险因素（OR=3.758 ;95% CI 1.439~9.814 ;P=0.009）。生存曲线分析显示,FLI-1表达阴性病人3年累积无进展生存率（75.68%）、3年累积总生存率（81.08%）均明显高于FLI-1表达阳性的病人（分别为45.33%、49.33%;P<0.05）。结论 星形细胞瘤FLI-1呈高表达,与病人的不良预后有关。     

术中超声在脊髓髓内室管膜瘤和星形细胞瘤外科治疗中的应用

目的探讨术中超声在脊髓髓内室管膜瘤和星形细胞瘤显微外科手术中的应用价值。方法回顾性分析2010年1月至2018年5月华中科技大学同济医学院附属同济医院神经外科收治的78例脊髓髓内室管膜瘤和34例脊髓髓内星形细胞瘤患者的临床资料。根据术中是否使用超声辅助,分别将室管膜瘤和星形细胞瘤患者分为超声组(前者44例,后者18例)和对照组(前者34例,后者16例)。对所有患者行门诊或电话随访,通过影像学复查和改良McCormick量表(MMS)分级评估肿瘤复发和脊髓功能恢复情况。分别比较室管膜瘤和星形细胞瘤两组患者的疗效,并评价术中超声对肿瘤完全切除率的评估准确率。结果两组室管膜瘤和星形细胞瘤患者的性别、年龄、首诊症状、MMS分级及肿瘤累及脊髓节段的差异均无统计学意义(均P>0.05),基线资料均基本一致。室管膜瘤的超声组和对照组患者肿瘤完全切除率[分别为97.7%(43/44)、91.2%(31/34)]、术后并发症发生率[分别为8.8%(3/44)、11.8%(4/34)]及术后3个月脊髓功能恢复良好率[分别为36.4%(16/44)、32.4%(11/34)]的差异均无统计学意义(均P>0.05)。超声组和对照组的星形细胞瘤患者术后并发症发生比例(分别为:0/18、2/16)和术后3个月脊髓功能恢复良好比例(分别为:3/18、2/16)的差异均无统计学意义(均P>0.05);但与对照组比较,超声组的肿瘤完全切除比例高[分别为16/18、9/16,P<0.05]、无进展生存期(PFS)长[中位PFS分别为84.0(67.5~100.5)个月、75.0(52.0~98.0)个月,P<0.05]。以增强MRI为标准,术中超声判断室管膜瘤和星形细胞瘤全切除的准确比率分别为97.7%(42/43)、14/16。结论术中超声有助于实时、准确地判断脊髓髓内室管膜瘤和星形细胞瘤的肿瘤切除程度,且对星形细胞瘤的应用价值较大。     

Review of Forty Years of Rehabilitation Issues in Spinal Cord Injury

Abstract

Context

Childhood laminectomy can lead to spinal deformity. This is a report of a case of paraplegia caused by rotokyphoscoliosis, a late complication of laminectomy.

Findings

A 55-year-old woman developed paraplegia due to post-laminectomy kyphoscoliosis. She had surgery for a spinal tumor at age 13 years. She developed kyphosis 2 years after the laminectomy, which has been gradually progressing over the years. She experienced weakness of lower limbs that progressed to paraplegia. There was no evidence for tumor recurrence. To our knowledge, this is the first reported case of post-laminectomy kyphoscoliosis causing late-onset paraplegia.

Conclusions/clinical relevance

This case highlights a possible long-term complication of laminectomy without stabilization or untreated kyphoscoliosis. Children should be followed closely after laminectomy because development of spinal deformity is very common. Without intervention, the kyphosis might progress and in the long term, serious neurological complications may result, including paraplegia.     

Increased expression in human astrocytomas of a 100 kDa protein with sequence homology to the ros tyrosine kinase domain

Abstract

A monoclonal antibody against the v-ros synthetic peptide VWETLTLGQQPYPCLSN IEVL (amino acid residues 455-475 of v-ros), which is in the conserved region of the c-ros tyrosine kinase domain, was used for Western blotting of human astrocytoma specimens. High levels of a 100 kDa protein were detected in many of these primary brain tumours. In contrast, low levels of this 100 kDa protein were consistently found in the nontumour brain control samples. This 100 kDa protein is however, probably not the c-ros protein, but may be a novel cytosolic protein-tyrosine kinase and a marker for early transformation of astrocytomas. [Neurol Res 1993; 15: 316-320].     

Skeletal spread of an anaplastic astrocytoma (WHO grade III) and preservation of histopathological properties within metastases

Background

The incidence of extraneural metastases of glioma is low. Metastases occur at different sites and, infrequently, as diffuse bone marrow infiltration. Direct contact of a glioma with extrameningeal tissues might be a reason for extraneural metastases. However, the role of haematogenous spread remains unclear.

Methods

We report on a young patient who suffered from a left frontal anaplastic WHO grade III astrocytoma, which was treated with gross total resection and irradiation (60 Gy). No local relapse occurred during the following course, but a diffuse infiltration of the bone marrow was diagnosed 12 months after the initial diagnosis. The patient died 6 months later, as a result of hypercalcaemia and pancytopenia.The histopathological properties of the tumour and its bone metastases were analysed, as well as the mutations of the isocitrate dehydrogenase 1 gene (IDH1). To study the route of tumour dissemination, the peripheral blood of the patient was analysed for circulating tumour cells (CTCs).

Results

This study describes a rare case of an extraneurally metastasised WHO grade III anaplastic astrocytoma. The occurrence of bone marrow infiltration coinciding with the finding of a stable intracranial tumour is a notably unusual situation. The properties of the primary tumour were maintained within the metastases in our patient. No CTCs were found in the peripheral blood at one random time point after the diagnosis of bone metastases.

Conclusions

Despite young patient age, a stable intracranial course with a single location and mutations in the IDH1 gene, the patient's overall survival was short at 18 months after diagnosis. This finding illustrates the therapeutic dilemma in patients with bone marrow involvement complicating the use of alkylating agents, such as temozolomide. Repeated and systematic blood sampling in a large cohort of patients is needed for the detection of CTCs in glioma patients with systemic tumour spread. Future studies investigating how intrinsic factors in glioma cell biology cause rare metastases in these tumours are needed.     

Expression of hypoxia-related tissue factors in astrocytic gliomas. A multivariate survival study with emphasis upon carbonic anhydrase IX

Carbonic anhydrase IX (CAIX) is a transmembrane enzyme involved in the reversible metabolism of carbon dioxide to carbonic acid and, hence, in physiological pH regulation. It also participates in cellular differentiation and proliferation, its expression being absent in most normal tissues. It has been recently postulated that the hypoxia-inducible factor (HIF-1) pathway up-regulated by hypoxia accounts for CAIX overexpression in most human tumors. In the present study, we examined the expression of this enzyme in diffuse gliomas of astrocytic origin in relation to vascular endothelial growth factor (VEGF) and HIF-1alpha expression, proliferation rate (as assessed with Ki-67 antigen), microvessel morphology, and survival. Of 84 cases analyzed, 61 cases (72.6%) displayed strong membrane and/or cytoplasmic expression of CAIX and were grouped as positive. Immunoreactivity tended to have a perinecrotic distribution and increased in parallel with the extent of necrosis (P < .001) and histologic grade (P < .001). A positive correlation was also noted with HIF-1alpha and VEGF expression (P < .001), proliferation rate (P = .010), microvessel density (P = .004), and microvessel caliber parameters (P = .014-.038). In univariate survival analysis, increased CAIX expression was associated with shortened survival in the entire cohort (P < .0001), along with VEGF (P = .0205) and HIF-1alpha levels (P = .0190). Multivariate analysis selected the interaction model of CAIX, with grade and age as the only parameters independently affecting survival. CAIX expression was also the only significant parameter for the survival of patients with grades II/III. We conclude that CAIX may be used as a prognostic indicator in diffuse astrocytomas to refine the information provided by grade. Given the role of CAIX in the acidification of tumor environment and its up-regulation by hypoxia, it is thought that CAIX expression may be linked to resistance of tumor cells to radiotherapy by allowing them to acclimatize to a hypoxic and acidic microenvironment.     

Prognostic significance of astrocyte elevated gene-1 in human astrocytomas

Astrocyte Elevated Gene-1 (AEG-1) has been proposed as a biomarker for a variety of cancers. This study aimed to investigate the expression of AEG-1 in human astrocytomas and the correlation between AEG-1 expression and clinicopathologic variables of astrocytomas. AEG-1 expression in four pairs of matched astrocytomas tissues and 5 cell lines was detected by immunohistochemical and Western blot analysis. In addition, AEG-1 protein expression was examined by immunohistochemical staining in 204 cases, including 32 normal brain tissues, 80 Low-malignant astrocytomas (LMAs) and 92 High-Malignant astrocytomas (HMAs). AEG-1 expression in 31 LMAs and 29 HMAs samples was detected by RT-PCR and Western blot analysis. We detected AEG-1 expression in normal neurons and glioma cell lines U87, U251 and M059K, but not in normal glial cells. Immunohistochemical analysis showed that 128 of 172 (74.4%) paraffin-embedded archival astrocytomas samples exhibited positive AEG-1 expression. Statistical analysis suggested that higher AEG-1 level was significantly correlated with histological grade of astrocytomas. In addition, AEG-1 mRNA and protein expression was higher in HMAs than in LMAs. AEG-1 expression had no correlation with the gender or age of astrocytoma patients. In summary, our data suggest that AEG-1 may represent a novel prognostic marker for astrocytomas.     

Ependymoma and pilocytic astrocytoma: Differentiation using radiomics approach based on machine learning

Mandatory accurate and specific diagnosis demands have brought about increased challenges for radiologists in pediatric posterior fossa tumor prediction and prognosis. With the development of high-performance computing and machine learning technologies, radiomics provides increasing opportunities for clinical decision-making. Several studies have applied radiomics as a decision support tool in intracranial tumors differentiation. Here we seek to achieve preoperative differentiation between ependymoma (EP) and pilocytic astrocytoma (PA) using radiomics analysis method based on machine learning. A total of 135 Magnetic Resonance Imaging (MRI) slices are divided into training sets and validation sets. Three kinds of radiomics features, including Gabor transform, texture and wavelet transform based ones are used to obtain 300 multimodal features. Kruskal–Wallis test score (KWT) and support vector machines (SVM) are applied for feature selection and tumor differentiation. The performance is investigated via accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) analysis. Results show that the accuracy, sensitivity, specificity, and AUC of the selected feature set are 0.8775, 0.9292, 0.8000, and 0.8646 respectively, having no significant differences compared with the overall feature set. For different types of features, texture features yield the best differentiation performance and the significance analysis results are consistent with this. Our study demonstrates texture features perform better than the other features. The radiomics approach based on machine learning is efficient for pediatric posterior fossa tumors differentiation and could enhance the application of radiomics methods for assisted clinical diagnosis.     

NF-κB、CDK4在脑星形细胞瘤中的表达及意义

目的 研究核因子-κB(NF-κB)及细胞周期依赖性激酶(CDK)在脑星形细胞瘤中表达的相互关系及意义.方法 对54例已获确诊的脑星形细胞瘤组织(星形细胞瘤Ⅰ级13例,星形细胞瘤Ⅱ级16例,星形细胞瘤Ⅲ级14例,星形细胞瘤Ⅳ级11例)及10例正常脑组织标本作免疫组化SP法染色,检测NF-κBp65及CDK4的表达水平,并对两者间关系进行统计学分析.结果 脑星形细胞瘤NF-κBp65、CDK4的表达在不同分级脑星形细胞瘤之间存在显著性差异(P<0.05),NF-κBp65与CDK4的表达有相关性(r=.5694,P<0.05).结论 NF-κBp65、CDK4在脑星形细胞瘤中的表达与其恶性程度相关,NF-κBp65、CDK4表达情况可作为考察脑星形细胞瘤患者的独立指标,对NF-κBp65、CDK4在脑星形细胞瘤中的作用进一步深入研究,可能获得基因治疗脑星形细胞瘤的有效途径.