VEGF及CTGF的表达与脑胶质瘤分级的相关性研究

目的通过检测脑胶质瘤患者肿瘤组织中血管内皮生长因子和结缔组织生长因子的表达水平,探讨其和肿瘤级别的关系及作用机制。方法应用免疫组化SP法检测49例胶质瘤手术标本中的VEGF和CTGF的表达水平,统计分析表达水平和肿瘤级别之间的关系。结果VEGF和CTGF在胶质瘤高级别组（Ⅲ-Ⅳ级）中的表达均明显高于低级别组（Ⅰ-Ⅱ级）,说明随着肿瘤级别的升高VEGF和CTGF表达也增强。结论VEGF和CTGF在胶质瘤组织中高表达,而且表达水平和恶性程度有密切联系。VEGF和CTGF的检测可作为胶质瘤恶性程度判断的参考,为从基因水平上探讨胶质瘤的生物学行为、预后及治疗提供新的思路。     

CD44s和MT1—MMP mRNA在人脑胶质瘤中的表达及其意义

目的分析MT1-MMPmRNA和CD44蛋白的表达与脑胶质瘤恶性程度的关系。方法采用原位杂交和免疫组化方法检测42例人脑胶质瘤和8例正常脑组织中,CD44s蛋白和MT1-MMPmRNA的表达。结果①CD44s蛋白表达在Ⅲ-Ⅳ级脑胶质瘤与在正常脑组织、Ⅰ～Ⅱ级脑胶质瘤之间有显著的差异(P<0.01);②MT1-MMPmRNA的表达水平与肿瘤的级别呈正相关(P<0.01);在Ⅲ-Ⅳ级脑胶质瘤与在正常脑组织、Ⅰ～Ⅱ级脑胶质瘤之间其表达均有显著性差异(P<0.01)。③CD44s蛋白表达与MT1-MMPmRNA表达呈正相关(r=0.895,P<0.01),二者均与肿瘤的恶性程度呈正相关(P<0.01)。结论CD44s和MT1-MMP与脑胶质瘤的发生发展密切相关。     

人脑胶质瘤中ING4和CTGF的表达及其意义

目的 探讨人脑胶质瘤中生长抑制因子4(ING4)及结缔组织生长因子(CTGF)的mRNA的表达及其意义.方法 采用荧光实时定量聚合酶链式反应法检测ING4和CTGF mRNA在30例脑胶质瘤组织和5例正常脑组织中的表达水平,统计分析表达水平和肿瘤级别之间的关系以及二者表达水平的相天性.结果 ING4 mRNA在Ⅰ～Ⅱ级...     

端粒结合蛋白-1在脑胶质瘤中的表达及临床意义

目的探讨端粒结合蛋白-1(TRF-1)在不同级别脑胶质瘤及正常脑组织中的表达及其临床意义。方法选取58例脑胶质瘤和10例脑外伤内减压脑组织石蜡切片标本作为研究对象,应用免疫组化技术检测各组TRF1的表达水平,应用半定量法计算不同标本肿瘤细胞免疫标记的频率和强度积分。结果共58例不同级别胶质细胞瘤,其中低度恶性组(WHOⅠ、Ⅱ级)27例,高度恶性组(WHOⅢ、Ⅳ级)31例,10例脑外伤病人内减压脑组织作为正常对照。在所有胶质瘤组织及正常脑组织中均检测到TRF1表达,其中正常脑组织中TRF1表达高积分构成比90.00%,低度恶性胶质瘤组(WHOⅠ、Ⅱ级)的TRF1表达高积分构成比62.96%,高度恶性胶质瘤组(WHOⅢ、Ⅳ级)29.03%。统计分析发现,TRF1在不同级别胶质瘤中的表达与其恶性程度成负相关。结论在人脑胶质瘤和正常脑组织均有TRF1的广泛表达,其在不同级别脑胶质瘤中的表达水平与其恶性程度负相关,即随肿瘤的恶性程度的增高出现表达下调,TRF1可作为脑胶质瘤临床病理分级和恶性程度判断的参考指标。     

内皮抑素和血管内皮生长因子在脑胶质瘤中的表达及意义

目的探讨内皮抑素(ES)和血管内皮生长因子(VEGF)在人脑胶质瘤中的表达和意义。方法采用免疫组织化学方法,对45例脑胶质瘤和5例正常脑组织标本中ES和VEGF的表达进行测定。结果Ⅲ-Ⅳ级胶质瘤中ES和VEGF表达水平明显高于Ⅰ-Ⅱ级胶质瘤和正常脑组织,差异有显著性意义(P<0.01);Ⅰ-Ⅱ级胶质瘤中VEGF表达水平显著高于正常脑组织(P<0.05);胶质瘤中ES与VEGF的比值和胶质瘤的分级呈负相关。结论ES和VEGF的协同作用可能在人脑胶质瘤细胞侵袭性生长及恶性发展中起重要作用,且有可能与胶质瘤的恶性程度及预后有关。     

MMP-2、TIMP-2在脑胶质瘤中的表达及其意义

目的 分析MMP-2、TIMP-2的表达与脑胶质瘤恶性程度和侵袭性之间的关系。方法 采用免疫组化和原位杂交的方法,检测42例人脑胶质瘤和8例正常脑组织中,MMP-2 mRNA、MMP-2和TIMP-2蛋白表达。结果 MMP-2蛋白表达水平(LI)与肿瘤的分级呈正相关(r=0.872,P<0.01);Ⅲ、Ⅳ级与正常脑组织、Ⅰ～Ⅱ级之间均有显著的差异(P<0.01)。MMP-2mRNA表达与肿瘤的分级同样呈正相关(P<0.01);Ⅲ、Ⅳ级与正常脑组织、Ⅰ～Ⅱ级之间均有显著的差异(P<0.01)。MMP-2蛋白表达增高时TIMP-2蛋白表达也增高;但随着肿瘤恶性程度的增加,TIMP-2表达强度增加的幅度较MMP-2明显减缓。结论 MMP-2的高表达与脑胶质瘤恶性程度呈正相关;TIMP-2与MMP-2间的平衡失调与脑胶质瘤的侵袭性和恶性程度密切相关。     

钙粘素、Ki67和p16在人脑胶质瘤中的表达及意义

目的探讨钙粘素(E-cd)、p16和Ki67在人脑胶质瘤中的表达及意义。方法采用免疫组织化学方法检测53例胶质瘤和12例正常脑组织中的E-cd、p16蛋白和Ki67的表达。结果E-cd和p16在正常脑组织中的阳性表达率均为100%;E-cd在Ⅰ-Ⅱ级和Ⅲ-Ⅳ级胶质瘤中阳性表达率分别为53.6%、20.0%,p16在Ⅰ-Ⅱ级和Ⅲ-Ⅳ级胶质瘤中阳性表达率分别为57.1%、24.0%,E-cd和p16在Ⅰ-Ⅱ级胶质瘤中的表达明显高于在Ⅲ-Ⅳ级胶质瘤中的表达(P<0.05),而低于正常脑组织中的表达(P<0.01);E-cd和p16二者在胶质瘤中的表达呈正相关(P<0.05);Ki67在正常脑组织中无表达。Ki67在Ⅰ-Ⅱ级胶质瘤中阳性率(3.15%±1.67%)明显低于Ⅲ-Ⅳ级胶质瘤中的阳性率(14.37%±4.89%),两胶质瘤组与对照组之间的阳性细胞率差异非常显著(P<0.01)。结论E-cd、p16和Ki67在胶质瘤的发生发展过程中可能起重要作用,并且对评估胶质瘤的恶性度及预后有重要意义。     

SYBR Green实时定量PCR检测人原发脑胶质瘤中REV3和REV7基因的表达

目的 运用实时定量PCR检测跨损伤修复基因REV3和REV7在人脑原发脑胶质瘤组织中的表达水平,探讨其和肿瘤级别之间的关系.方法 采用SYBR Green实时定量聚合酶链式反应(RT-PCR)法检测跨损伤修复基因REV3和REV7的mRNA在85例原发胶质瘤(Ⅱ级20例、Ⅲ级20例和Ⅳ级45例)和14例正常脑组织中的表达水平,统计学分析表达水平和肿瘤级别之间的关系.结果 与正常组织相比,REV3和REV7在各病理级别胶质瘤中均表达上调(P＜0.05);并且REV3在Ⅳ级胶质瘤中的表达比在Ⅱ级和Ⅲ级中都要高(P＜0.05).秩相关分析表明:REV3的表达量与胶质瘤病理分级呈正相关性(r=0.454,P＜0.001).结论 REV3和REV7在胶质瘤组织中均高表达,而且REV3表达水平和恶性程度有密切联系.     

Ephrin-B2在人胶质瘤中的表达及意义

目的探讨Ephrin-B2基因在人胶质瘤中的表达规律及意义。方法分别用免疫组织化学和Western印迹法检测4例正常脑组织和21例人脑胶质瘤中Ephrin-B2基因的表达。结果Western印迹法检测显示,人正常脑组织中未见Ephrin-B2基因明显表达不同病理级别胶质瘤组织均有不同程度,Ephrin-B2蛋白表达,Ⅲ级、Ⅳ级表达较强,分别与Ⅰ、Ⅱ级比较,差异均有显著性(P<0.01),Ⅲ级与Ⅳ级之间以及Ⅰ与Ⅱ级之间比较,差异无显著性(P>0.05)。免疫组化检测显示,Ephrin-B2蛋白除在肿瘤细胞中有表达外在各级别胶质瘤中血管内皮细胞表达呈强阳性结论。Ephrin-B2在胶质瘤发生、发展和血管生成中可能有重要作用。     

TGF-β1和bFGF在人脑胶质瘤的表达及意义

目的观察转化生长因子β1(TGF-β1)和碱性成纤维生长因子(bFGF)在人脑胶质瘤中的表达和分布,加深对它们在胶质瘤恶性转化中作用的认识。方法采用免疫组化方法,对临床经过石蜡包埋的35例胶质瘤和7例正常脑组织标本中TGF-β1和bFGF的表达进行定位和定性检测,并分析二者的相关性。结果TGF-β1和bFGF在高级别胶质瘤(Ⅲ-Ⅳ级)中表达较多,在低级别胶质瘤(Ⅰ-Ⅱ级)中表达较少,在正常脑组织中几乎不表达,两两比较差异有显著性(P<0.05),且二者在胶质瘤中的表达呈显著正相关(r=0.79,P<0.01)。结论TGF-β1和bFGF的协同作用可能在人脑胶质瘤细胞的恶性转化中具有重要意义。     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.     

Anticonvulsant Drugs and Cognitive Function: A Review of the Literature

Summary: Alterations of cognitive function are separate from disturbances of behavior seen in association with epilepsy. The nature of the cognitive disability may to a certain extent depend on the seizure type. Partial seizures, mainly derived from a temporal lobe focus, impair memory tasks, while generalized seizures seem to have more effect on attentional abilities. A number of studies, reviewed in this paper, suggest that anticonvulsant drugs further impair cognitive function. Maximal impairments are seen in patients receiving polytherapy: rationalization of polytherapy improves cognitive abilities. Studies in children and adults have allowed differentiation of the effects of various commonly used antiepileptic agents. Maximal cognitive deficits are seen with. phenytoin, while phenobarbital and sodium valproate induce moderate disturbances, and carbamazepine seems relatively free from such toxicity. Further research is needed on the interrelationship between types of seizure disorders, types of anticonvulsant medications, and cognitive function.     

Dextromethorphan: Cellular Effects Reducing Neuronal Hyperactivity

Summary: Dextromethorphan is a dextrorotary morphinan without affinity for opioid receptors, commonly used as an antitussive medication. During the past 5 years, interest in the compound and its demethylated derivative, dextrorphan, has been revived because additional neuroprotective and an-tiepileptic properties were found in in vitro studies, animal experiments, and a few clinical cases. Both morphinans are able to inhibit N -methyl-D-aspartate (NMDA) receptor channels and voltage-operated calcium and sodium channels with different potencies. The inhibition of the NMDA receptor is believed to be the predominant mechanism of action responsible for the anticonvulsant and neuroprotective properties of the compounds.