星形细胞肿瘤组织COX-2的表达及其与病理分级关系的研究

目的:检测星形细胞肿瘤组织中COX-2的表达,分析其与病理分级之间的关系。方法:应用免疫组化技术并用图像分析系统检测各级别星形细胞肿瘤组织及非肿瘤(脑)组织中COX-2的表达水平。结果:各组免疫组化染色阳性率分别为:肿瘤组织80.0%(36/45),其中毛细胞型星形细胞瘤60.0%(6/10),弥漫性星形细胞瘤76.9%(10/13),间变性星形细胞瘤90.0%(9/10),胶质母细胞瘤91.7%(11/12),非肿瘤(脑)组织28.6%(2/7);免疫组化染色强度(IODA值)分别为:肿瘤组织(6.38±3.68),其中毛细胞型星形细胞瘤(3.54±1.29),弥漫性星形细胞瘤(5.58±2.78),间变性星形细胞瘤(6.88±2.70),胶质母细胞瘤(9.19±4.62),非肿瘤(脑)组织(2.18±0.94)。COX-2在肿瘤组织中的表达显著高于其在非肿瘤(脑)组织中的表达(P=0.017)。结论:COX-2的过表达与星形细胞肿瘤的发生密切相关,并且与肿瘤的病理分级也密切相关;毛细胞型星形细胞瘤与弥漫性浸润性星形细胞肿瘤的遗传基础不同,是一种在生物学和形态学上所发生的基因改变不同于其它胶质瘤的星形细胞肿瘤;COX-2表达改变,为星形细胞肿瘤临床诊断、治疗和预后判断提供了新思路。     

高分级胶质瘤的放化综合治疗

胶质瘤是起源于神经胶质细胞的肿瘤，主要包括星形细胞肿瘤、少突胶质细胞肿瘤和混合性胶质细胞肿瘤。星形细胞瘤是胶质瘤中最常见的类型，其中的间变性星形细胞瘤又称恶性星形细胞瘤，属WHOⅢ级。临床常将恶性星形细胞瘤和胶质母细胞瘤统称为恶性胶质瘤，而将Ⅲ级胶质瘤（如间变性星形细胞瘤，间变性少突胶质细胞瘤）、胶质母细胞瘤、胶质肉瘤等统称为高分级胶质瘤。     

内向整流性钾通道4.1在人星形细胞瘤中的表达变化研究

目的：研究内向整流性钾通道4.1（kir4.1）在人星形细胞瘤和正常脑组织的表达差异,探讨星形细胞瘤增殖、生长的分子机制。方法：选取50例星形细胞瘤患者的肿瘤组织,其中胶质母细胞瘤21例,间变性星形细胞瘤15例,星形胶质细胞瘤14例。以肿瘤周围相对正常脑组织作为对照。利用免疫组化与蛋白印迹（Western-blot）方法检测肿瘤组织与对照组织的kir4.1表达。结果：不同星形细胞瘤组织与对照组相比较,kir4.1表达增强（P〈0.05）;其中,恶性程度较高的胶质母细胞瘤相对于恶性程度较低的星形胶质细胞瘤、间变性星形细胞瘤,kir4.1表达更为强烈（P〈0.05）。结论：kir4.1表达的变化与肿瘤的恶性程度有关。kir4.1在人星形细胞瘤组织表达增强。     

多形性胶质母细胞瘤放疗临床靶区范围及治疗的讨论

间变性星形细胞瘤为WHO Ⅲ级，多形性胶质母细胞瘤为WHO Ⅳ级，美国NCCN2007指引中建议，对于高级别胶质瘤应最大范围切除肿瘤，术后病理为间变性星形细胞瘤者，应予放疗±同期化疗±辅助化疗；而若证实为多形性胶质母细胞瘤者，则应予放疗＋同期化疗＋辅助化疗。关于高级别脑胶质瘤靶区的勾画尚无定论。我们收治一例右侧额叶混合性胶质瘤（部分为间变性星形细胞瘤，部分为多形性胶质母细胞瘤），于外院行肿瘤全切术，术后经多学科讨论后认为应予放疗加替莫唑胺同期化疗及辅助化疗。本文就此病例的放疗靶区勾画及治疗进行讨论。     

DEK蛋白在星形细胞肿瘤组织中的表达及意义

目的:探讨DEK蛋白表达与星形细胞肿瘤发生、发展的关系。方法:免疫印迹杂交法检测DEK蛋白在星形细胞肿瘤组织及正常脑组织中的表达水平。结果:DEK蛋白表达阳性率在肿瘤组织中为93.75%,DEK蛋白相对含量分别为:低级别肿瘤组织0.55±0.11,高级别肿瘤组织0.85±0.07;DEK蛋白在肿瘤组织中的表达显著高于其在正常脑组织中的表达（P<0.05）。结论:DEK蛋白表达与星形细胞肿瘤的发生、发展呈显著正相关,是评估星形细胞肿瘤恶性生物学行为的可靠指标。DEK作为凋亡抑制基因为星形细胞肿瘤的治疗提供了一个新靶点。     

GFAP、Vim、MDR-1与EGFR在颅内星形细胞肿瘤中的表达及意义

目的探讨颅内星形细胞肿瘤的GFAP、Vim和MDR-1、EGFR的表达及意义.方法采用S-P法对101例颅内星形细胞肿瘤进行GFAP、Vim、和MDR-1、EGFR免疫组化标记,并对临床和病理资料及免疫组化结果进行统计分析.结果免疫组化标记能帮助区别星形细胞肿瘤的组织类型和分化程度.间变性星形细胞瘤和胶质母细胞瘤GFAP表达减弱,而Vim、MDR-1、EGFR的表达增强,恶性程度增加,术后生存率低(P＜0.005).结论免疫组化标记对星形细胞肿瘤术后化疗方案的制定及预后估计具有重要意义.间变性和肥胖细胞性星形细胞瘤更具恶性,易复发.胶质母细胞瘤恶性程度最高,预后差.     

胶质瘤中MKK7与c-Jun磷酸化的表达及其相关性

目的 探讨胶质瘤中MKK7和c-Jun磷酸化（p-c-Jun）的表达及意义，分析两者表达的相关性。方法 选取弥漫型星形细胞瘤（15例）、少突胶质细胞瘤（5例）、间变性星形细胞瘤（11例）、间变性少突胶质细胞瘤（8例）、胶质母细胞瘤（53例）及其瘤旁正常脑组织（25例）共117例，采用免疫组织化学法检测MKK7、c-Jun及p-c-Jun的表达。体外培养神经胶质瘤细胞株U87，用脂质体转染MKK4-siRNA、MKK7-siRNA和对照siRNA，48 h后Western blot检测MKK7、c-Jun及p-c-Jun的表达水平。结果 胶质母细胞瘤中p-c-Jun及MKK7的表达均明显高于其他组织学类型胶质瘤及胶质母细胞瘤瘤旁正常脑组织中的表达（P=0.000, P=0.000）。随着胶质瘤WHO分级的升高，p-c-Jun及MKK7的表达增高，且与WHO分级呈明显正相关（r=0.494, P=0.000; r=0.606, P=0.000）。胶质瘤及胶质母细胞瘤瘤旁正常脑组织中MKK7与p-c-Jun的表达存在正相关关系（r=0.387, P=0.000）。沉默神经胶质瘤细胞株U87 MKK7表达抑制了c-Jun磷酸化水平。结论 MKK7可以通过调控JNK/c-Jun活性进而促进胶质母细胞瘤的发生。     

间变性星形细胞瘤中DR4及DR5的表达

目的研究肿瘤坏死因子相关凋亡诱导配体(TRAIL)的死亡受体(death receptor,DR)DR4和DR5在间变性星形细胞瘤中的表达,并探讨其临床意义.方法联合采用免疫组化和原位杂交方法检测24间变性星形细胞瘤和16例正常脑组织中DR的表达.结果免疫组化染色显示,24例间变性星形细胞瘤均大量表达死亡受体DR4和DR5,而16例正常脑组织中7例(43.8%)表达DR4,5例(31.3%)表达DR5.间变性星形细胞瘤组织中DR蛋白的表达显著高于正常脑组织中DR蛋白的表达,两者差异有显著性(P<0.01).原位杂交显示,DR在全部24例间变性星形细胞瘤组织和大部分正常脑组织中均呈强阳性表达,二者差异无显著性(P>0.05).结论间变性星形细胞瘤细胞中普遍存在DR的高表达,这可能为间变性星形细胞瘤的凋亡诱导治疗提供新的靶点.DR蛋白在正常脑组织和间变性星形细胞瘤中的表达差异,可能是TRAIL选择性诱导凋亡的机制之一.     

脑瘤WHO分类及影像学表现

长期以来脑瘤分类混乱 ,临床、病理、影像学研究结果不一 ,经过多年众多专家努力对其认识逐渐深入 ,在 1 993年 WHO对中枢神经系统组织的肿瘤分类 ,又于 2 0 0 0年再次对神经系统肿瘤分类 ,使分类趋于一致。本文介绍 1 993、2 0 0 0年 WHO分类和其中部分新分类脑瘤的影像学表现。1　 1 993年中枢神经系统肿瘤的 WHO分类1 .1　神经上皮组织肿瘤1 .1 .1　星形细胞肿瘤 :(1 )星形细胞瘤 ,变型 :纤维型、原浆型、肥胖细胞型 ;(2 )间变性 (恶性 )星形细胞瘤 ;(3 )胶质母细胞瘤 ,变型 :巨细胞胶质母细胞瘤、胶质肉瘤 ;(4)毛细胞型星形细胞瘤 ;…     

胶质瘤影像研究进展

Virshow最早应用胶质瘤 ( gliomas)一词来描述脑内原发性肿瘤 ,系指整个神经上皮组织来源的、包括各型胶质细胞和神经元的肿瘤。目前 ,这些肿瘤在神经影像学统称为胶质瘤 ,即广义上所称的胶质瘤。表 1　中枢神经系统肿瘤的 WHO恶性程度分级系统肿瘤组别肿瘤类型 级 级 级 级星形细胞肿瘤室管膜下巨细胞型 毛细胞型 低级别 多形性黄色瘤性星形细胞肿瘤 间变性 胶质母细胞瘤 少枝胶质瘤低级别 间变性 少枝 -星形细胞瘤低级别 间变性 室管膜肿瘤室管膜下室管膜瘤 黏液乳头状 低级别 间变性 脉络丛肿瘤乳头瘤癌 神经元…     

Preferential expression of alpha B-crystallin in astrocytic elements of neuroectodermal tumors.

Recently the authors have identified a major component of Rosenthal fibers as alpha B-crystallin, a major lens protein. In the current study the authors investigated the expression of alpha B-crystallin in four cultured glioma cell lines and in 115 human neuroectodermal tumors. alpha B-crystallin was expressed differentially by those glioma cell lines, but not by neuroblastoma cell lines. Northern blot analysis revealed two distinct messages for alpha B-crystallin in C-6, whereas only a single message in U-373MG and G26-24. In human surgical specimens positive immunostaining was frequently observed in the following brain tumors: pilocytic astrocytoma of the juvenile type, anaplastic astrocytoma, glioblastoma multiforme, and subependymal giant cell astrocytoma. The astrocytic elements of mixed oligoastrocytomas, glioblastomas with sarcomatous components, and gangliogliomas were likewise strongly stained. In contrast, little immunoreactivity was observed in ependymal and choroid plexus tumors. Thus, alpha B-crystallin is mainly expressed by astrocytic tumors among neuroectodermal neoplasms, without regard to the presence of Rosenthal fibers.     

Hemorrhagic onset of pilocytic astrocytoma and pilomyxoid astrocytoma

The incidence of hemorrhagic onset in pilocytic astrocytoma and pilomyxoid astrocytoma, and the clinical and histological characteristics, were compared to other types of neuroepithelial tumors or nonhemorrhagic pilocytic astrocytoma by retrospective review of 445 consecutive neuroepithelial tumors treated at our institute. Hemorrhagic onset was observed in 4 of 35 (11.4%) patients with pilocytic astrocytoma and pilomyxoid astrocytoma, with higher incidence than in glioblastoma (3.9%), anaplastic oligodendroglioma (7.7%), and anaplastic ependymoma (7.1%). The hemorrhagic onset occurred in 2 patients with sporadic pilocytic astrocytoma, 1 with pilocytic astrocytoma associated with neurofibromatosis type 1, and 1 with pilomyxoid astrocytoma. There was no correlation between hemorrhagic onset and clinical features, including age, sex, tumor location, proliferative activity, or microvascular proliferation. Hemorrhagic onset of pilocytic astrocytoma and pilomyxoid astrocytoma is not as uncommon as was previously thought, so pilocytic astrocytoma or pilomyxoid astrocytoma should be considered in the differential diagnosis of patients with brain tumors manifesting as hemorrhagic onset.     

Lack of Prognostic Significance of C-erbB-2 Expression in Low- and High- grade Astrocytomas

Background: Astrocytic tumors, the most common primary glial tumors of the central nervous system, areclassified from low to high grade according to the degree of anaplasia and presence of necrosis. Despite advancesin therapeutic management of high grade astrocytic tumors, prognosis remains poor. In the present study, thefrequency and prognostic significance of c-erb-B2 in astrocytic tumors was investigated. Materials and Methods:Records of 72 patients with low- and high-grade astrocytic tumors were evaluated. The expression of C-erbB-2was determined immunohistochemically and intensity was recorded as 0 to 3+. Tumors with weak staining (1+)or no staining (0) were considered Her-2 negative, while tumors with moderate (2+) and strong (3+) stainingwere considered Her-2 positive. Results: Of the 72 patients, 41 (56.9%) had glioblastoma (GBM), 10 (13.9%)had diffuse astrocytoma, 15 (20.8%) had anaplastic astrocytoma, 6 (8.3%) had pilocytic astrocytoma. C-erbB-2overexpression was detected in the tumor specimens of 17 patients (23.6%). Six (8.3%) tumors, all GBMs,exhibited strong staining, 2 (2.7%) specimens, both GBMs, exhibited moderate staining, and 9 specimens, 5 ofthem GBMs (12.5%), exhibited weak staining. No staining was observed in diffuse astrocytoma and pilocyticastrocytoma specimens. Median overall survival of patients with C-erbB-2 negative and C-erbB-2 positive tumorswere 30 months (95%CI: 22.5-37.4 months) and 16.9 months (95%CI: 4.3-29.5 months), respectively (p=0.244).Conclusions: Although there was no difference in survival, C-erbB-2 overexpression was observed only in theGBM subtype.     

Geminin: a good prognostic factor in high-grade astrocytic brain tumors

BACKGROUND: Geminin is a nuclear protein that belongs to the DNA replication inhibitor group. It inhibits DNA replication by preventing Cdt1 from loading minichromosome maintenance protein onto chromatin, as is required for DNA replication. For this study, the authors investigated geminin expression in high-grade astrocytic tumors, including anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM), with a view to predicting clinical outcomes on this basis in patients with these malignant brain tumors. METHODS: Immunohistochemistry was used to detect geminin expression in 51 patients with high-grade astrocytic tumors (19 AA and 32 GBM). Samples were categorized by taking the median value as the cut-off point for constructing Kaplan-Meier curves. The relation of geminin expression to clinical outcome in these malignant brain tumors was analyzed by using the Kaplan-Meier method and a Cox proportional hazards regression model. RESULTS: Geminin was expressed in all high-grade astrocytomas (mean geminin labeling index [LI], 24.90%). Kaplan-Meier curves showed that the group with higher geminin LI (>or=22.50%) had a better prognosis than the group with lower LI (<22.50%; P = .0296). Similarly, the Cox regression analysis showed that geminin expression has a significant correlation with survival in patients with high-grade astrocytoma (P = .0278), especially in an early stage. CONCLUSIONS: Although it is an inhibitor of DNA proliferation and, thus, is a cell cycle inhibitor, geminin expression was found in all malignant astrocytic tumors. The geminin LI was a significant predictive factor of outcomes in patients with high-grade astrocytoma, with higher expression indicating a good prognosis.     

Expression of phosphoprotein enriched in astrocytes 15 kDa (PEA-15) in astrocytic tumors: a novel approach of correlating malignancy grade and prognosis

Phosphoprotein enriched in astrocytes 15 kDa (PEA-15) is a multifunctional protein that was first identified in brain astrocytes and that has subsequently been shown to be expressed in different tissues. Despite its many important roles, the clinical significance of PEA-15 expression levels in astrocytic tumors has yet to be properly defined. We studied the PEA-15 expression pattern of 65 patients [diagnosed according to World Health Organization (WHO) criteria] with diffuse astrocytoma (WHO grade II), anaplastic astrocytoma (grade III), and glioblastoma (grade IV). PEA-15 expression levels were immunohistochemically measured and categorized as no, low, or high expression. All tumors expressed PEA-15 in our study. Twenty-three (35.4%) and 42 (64.6%) tumors expressed low and high PEA-15 levels, respectively. In grade II astrocytoma (diffuse astrocytoma) and grade III astrocytoma (anaplastic astrocytoma), 100% and 88.9% of patients expressed high PEA-15 levels, respectively, while a smaller number (50%) of patients with grade IV astrocytoma (glioblastoma) expressed high PEA-15 levels. PEA-15 expression level was inversely associated with WHO grade (P = 0.0006). Next, we evaluated prognosis and PEA-15 expression levels in 43 patients with high-grade astrocytomas based on the following parameters: age, gender, WHO grade, surgical resection extent, MIB-1 labeling index (LI), and PEA-15 expression level. Multivariable analyses revealed that high PEA-15 expression level displayed a significant correlation with longer overall survival (OS) in high-grade astrocytomas (P = 0.0024). Patients with total resection survived significantly longer (P = 0.0044) than those with lower resection extent, while patients with MIB-1 labeling index ≤25% indicated significant (P = 0.0434) correlation with OS as well. In conclusion, PEA-15 expression level was inversely associated with WHO grade and may serve as an important prognostic factor for high-grade astrocytomas.     

Measurement of fractional anisotropy using diffusion tensor MRI in supratentorial astrocytic tumors

In vivo, water diffusion displays directionality due to presence of complex microstructural barriers in tissue. The extent of directionality of water diffusion can be expressed as a fractional anisotropy (FA) value, using diffusion tensor MR imaging (DTI). The aim of this study was to determine whether FA values indicate microstructures in astrocytic tumors. We performed DTI in 31 patients with astrocytic tumor, and measured the FA values of tumor and normal brain regions prior to CT-guided stereotactic biopsy. After biopsy, FA values were compared to assess the cellularity and vascularity of tumor tissue. Although mean FA values trended to differ among histological types, all mean tumor FA values were lower than those of normal brain regions. Positive correlation was observed between FA values and both cellularity (r = 0.65, p < 0.05) and vascularity (r = 0.45, p < 0.05). We had hypothesized that the FA value of an astrocytic tumor would be determined by a balance between factors increasing the directionality of water diffusion, such as high cellularity and/or vascularity, and factors decreasing the directionality of water diffusion, such as fiber destruction. However, our results suggest that the FA values of glioblastoma, anaplastic astrocytoma, diffuse astrocytoma and pilocytic astrocytoma are largely affected by cellularity and/or vascularity, whereas that of gliomatosis cerebri are largely affected by the preservation of nerve fibers. Measurement of FA value using DTI will allow prediction of histological characteristics such as cellularity, vascularity and/or fiber structure in astrocytic tumors.     

Downregulation of putative tumor suppressor gene TSC-22 in human brain tumors

BACKGROUND AND OBJECTIVES: Our objective was to identify differentially expressed genes involved in the pathogenesis of glioblastoma multiforme (GBM). METHODS: Screening of arrayed human fetal brain and human postnatal brain cDNA libraries was performed by differential hybridization with glioblastoma multiforme and human normal brain cDNAs. RESULTS: Repeated differential hybridization of more than 100 cDNA clones selected by primary screening and analysis of RNA from adult normal brain and glial tumors showed 16 nucleotide sequences differentially expressed between normal brain and brain tumors. Among others, decreased content in astrocytic tumors was determined for TSC-22 mRNA corresponding to cDNA in the ICRFp507J1041 clone from human fetal brain cDNA library. Northern blot hybridization of RNA from different human brain tumors showed very low amounts of TSC-22 mRNA in most investigated samples of GBM, anaplastic astrocytoma, and some other tumors. Complete lack of expression of TSC-22 occurred in one sample of anaplastic astrocytoma, as well as in meningioma, brain sarcoma, sarcomatous meningioma, and oligodendroglioma. The differential expression of TSC-22 gene was confirmed by semiquantitative RT-PCR in 15 samples of astrocytomas WHO grade II-IV and three samples of normal brain. CONCLUSIONS: Significantly decreased levels of TSC-22 mRNA in human brain and salivary gland tumors and antiproliferative role of TSC-22 strongly suggest a tumor suppressor role for TSC-22. J.     

胆碱激酶α在不同级别胶质瘤中的表达差异及临床意义

背景与目的：胶质瘤是颅内中枢神经系统最常见的恶性肿瘤，常规治疗效果往往不理想。胆碱激酶α（choline kinase alpha，CHKα）与肿瘤的发生、发展密切相关。探讨CHKα在胶质瘤中的表达及与患者预后的关系。方法：回顾并分析宁夏医科大学总医院神经外科2017年1月—2019年12月收治的120例胶质瘤患者的临床病理学资料。患者根据世界卫生组织（World Health Organization，WHO）分级标准分为Ⅰ~Ⅳ级。采用免疫组织化学染色法检测CHKα在不同级别胶质瘤中的表达，分析CHKα的表达与患者的临床病理学特征之间的关系。采用Kaplan-Meier法对患者的生存情况进行分析。采用生物信息学数据库中的相关临床数据对CHKα表达与脑胶质瘤患者的生存关系进行进一步验证。结果：脑胶质瘤患者120例中，男性62例，女性58例。病理学类型包括毛细胞型星形细胞瘤32例，弥漫性星形细胞瘤26例，间变型星形细胞瘤30例，多形性胶质母细胞瘤32例。CHKα表达阳性率分别为9.77%、7.81%、95.03%和92.90%。CHKα蛋白在不同级别的胶质瘤组织中表达差异有统计学意义（P＜0.01）。截至2021年6月30日，有60例患者死亡，10例失访，随访率为91.67%。采用Kaplan-Meier法分析CHKα蛋白在不同级别胶质瘤中的表达差异与患者预后的关系，结果发现，CHKα低表达患者的总生存期比高表达者长，预后佳，并发症发生率显著低于CHKα高表达组，差异有统计学意义（P＜0.01）。这一结果与生物信息学分析结果相符（P＜0.05）。结论：CHKα在不同级别胶质瘤中的表达差异显著，且与患者预后密切相关。CHKα的表达情况可作为胶质瘤患者的诊断和判断患者预后的指标。     

Diffusion MRI in Evaluation of Pediatric Posterior Fossa Tumors

Background: To evaluate the role of diffusion MRI in differentiating pediatric posterior fossa tumors and determine the cut-off values of ADC ratio to distinguish medulloblastoma from other common tumors. Methods: We retrospectively reviewed MRI of 90 patients (7.5-year median age) with pathologically proven posterior fossa tumors (24 medulloblastoma, 7 ependymoma, 4 anaplastic ependymoma, 13 pilocytic astrocytoma, 30 diffuse intrinsic pontine glioma (DIPG), 4 ATRT, 3 diffuse astrocytoma, 2 high grade astrocytoma, 2 glioblastoma, and 1 low grade glioma). The conventional MRI characteristics were evaluated. Two readers reviewed DWI visual scale and measured ADC values by consensus.  ADC measurement was performed at the solid component of tumors. ADC ratio between the tumors to cerebellar white matter were calculated. Results: The ADC ratio of medulloblastoma was significantly lower than ependymoma, pilocytic astrocytoma and DIPG. The ADC cut-off ratio of ≤ 1.115 allowed discrimination medulloblastoma from other posterior fossa tumors with sensitivity, specificity, PPV and NPV of 95.8%, 81%, 67.6% and 97.9%, respectively. ADC ratio cut-off level to differentiate medulloblastoma from ependymoma was ≤ 0.995 with area under the curve (AUC)= 0.8693. ADC ratio cut-off level for differentiate medulloblastoma from pilocytic astrocytoma at ≤ 1.17 with AUC = 0.9936. ADC cut-off level for differentiate medulloblastoma from DIPG at ≤ 1.195 with AUC = 0.9681. The ADC ratio was correlated with WHO grading by the lower ADC ratio associated with the higher grade. Furthermore, High DWI visual scale was associated with high grade tumor. Conclusion: Diffusion MRI has a significant role in diagnosis of pediatric posterior fossa tumors. ADC ratio can be used to distinguish medulloblastoma from other posterior fossa tumor with good level of diagnostic performance.