胰岛素样生长因子结合蛋白-3在白藜芦醇抑制脑胶质瘤C6细胞增殖中的作用

目的探讨胰岛素样生长因子结合蛋白-3(insulin like growth factor binding protein-3,IGFBP-3)在白藜芦醇(resveratrol,Res)抑制脑胶质瘤C6细胞增殖中的作用。方法将脑胶质细胞和脑胶质瘤C6细胞分为脑胶质细胞组、Res+脑胶质细胞组、脑胶质瘤C6细胞组及Res+脑胶质瘤C6细胞组,采用MTT和Western blot法分别检测Res对各组细胞增殖及细胞中IGFBP-3和ERK蛋白表达水平的影响。将脑胶质瘤C6细胞分为空白对照组、Res组、si RNA-IGFBP-3组和Res+si RNA-IGFBP-3组,采用MTT法、流式细胞术、Transwell试验及Western blot法分别检测Res联合si RNA-IGFBP-3对脑胶质瘤C6细胞增殖、凋亡、侵袭能力及细胞中IGFBP-3和ERK蛋白表达水平的影响。结果各组细胞培养48 h后,Res+脑胶质细胞组与脑胶质细胞组的细胞增殖抑制率及细胞中IGFBP-3和ERK蛋白的表达水平均无明显变化(P0.05);Res+脑胶质瘤C6细胞组与脑胶质瘤C6细胞组比较,细胞增殖抑制率和细胞中ERK蛋白的表达水平均明显降低(P0.05),而IGFBP-3蛋白的表达水平明显升高(P0.05)。与空白对照组比较,Res组细胞增殖抑制率、凋亡率、IGFBP-3蛋白表达水平明显升高(P0.05),侵袭能力、ERK蛋白表达水平明显降低(P0.05);而si RNA-IGFBP-3组和Res+si RNA-IGFBP-3组细胞增殖抑制率、凋亡率、IGFBP-3蛋白表达水平明显降低(P0.05),侵袭能力、ERK蛋白表达水平明显升高(P0.05)。结论 Res可能是通过增强IGFBP-3的表达来抑制ERK信号通路的活性,进而发挥促进脑胶质瘤细胞凋亡的作用。     

替莫唑胺在脑胶质瘤治疗中的研究进展

脑胶质瘤是中枢神经系统中最常见和最具侵袭性的原发性脑肿瘤,具有恶性程度高、生长快、病程短、术后易复发、预后差等特点。目前标准治疗方法包括手术、放疗和化疗。替莫唑胺是是一种口服安全有效的咪唑并四嗪类抗肿瘤药物,可自由通过血脑屏障,是神经胶质瘤的标准化疗药物,效果良好。它具有巧妙地阻止胶质瘤细胞增殖和诱导细胞凋亡的能力。本文详细介绍替莫唑胺在脑胶质瘤治疗中的研究进展。     

小脑神经节细胞胶质瘤1例

脑神经节细胞胶质瘤(ganglioglioma)是发生于中枢神经系统中罕见的神经元和胶质细胞混合性肿瘤,其发生率占中枢神经系统肿瘤的0.4%,占脑肿瘤的1.3%。肿瘤好发于儿童和青年,60.0%在30岁以内。本文是对一患者小脑神经节细胞胶质瘤的诊断与治疗的观察。     

脑胶质瘤靶向递药系统研究现状

由于血脑屏障的存在,严重影响了化疗药物进入脑组织发挥疗效治疗脑胶质瘤,进年来随着对脑胶质瘤的不断认知以及科学技术手段的不断发展,越来越多的脑胶质瘤递送系统已经逐步建立起来,并可以达到有效治疗脑胶质瘤的目的。本文将主要综述治疗脑胶质瘤的纳米载体递送系统及脑靶向及肿瘤靶向纳米递释系统,并简单介绍血脑屏障的特点,并对脑胶质瘤的研究进展做出展望。     

CD105与CD248在星形细胞胶质瘤组织中的表达及其意义

目的分析脑星形细胞胶质瘤组织中CD105与CD248的表达情况,并探讨其意义。方法采用免疫组织化学染色法检测128份不同分级的脑星形细胞胶质瘤组织及16份正常脑组织中CD105与CD248的表达。结果正常脑组织中未检测到CD105与CD248的表达。胶质瘤组织中CD105与CD248的阳性表达率分别为69.71%和58.59%,且胶质瘤病理级别与二者的表达呈正相关(P0.01)。结论 CD105与CD248在星形细胞胶质瘤组织中的表达与肿瘤恶性程度有关,其可能参与了脑星形细胞胶质瘤的发展,以二者为靶点的抗血管生成疗法将为星形细胞胶质瘤的生物治疗提供新的方向。     

疏水性聚丙烯中空纤维膜中n-甲酰吗啉膜吸收含苯废气过程模拟

以疏水性聚丙烯中空纤维膜为气液膜接触器,n-甲酰吗啉水溶液为吸收剂,研究了膜气体吸收工艺分离C6H6/N2的传质过程. 在非润湿条件下,建立了膜气体吸收C6H6传质微分模型,模拟了C6H6在疏水性聚丙烯中空纤维膜管程及膜孔内的传质过程,并对C6H6的吸收速率进行预测. 结果表明,在实验条件下,膜气体吸收C6H6的速率为(0.89~6.13)′10-2 mg/(m2×s),微分模型对吸收速率预测的平均误差为1.9%,能准确描述中空纤维膜吸收C6H6的过程.     

富勒烯的色谱分离模型

在分子热力学理论的基础上 ,建立了高效液相色谱中富勒烯的分离因子与柱温、碳数、流动相组成之间的定量相关模型 ,用不同来源的 C70 和 C6 0 ～ C96 实验数据对该模型进行了检验 ,结果表明本模型具有广泛的适用性和相当令人满意的可靠性     

骨髓间充质干细胞对大鼠脑胶质瘤C6细胞系分化的影响

目的探讨骨髓间充质干细胞(Bone mesenchymal stem cells,BMSCs)对大鼠脑胶质瘤C6细胞系分化的影响及其相关机制。方法用Transwell小室共培养BMSCs与C6细胞,采用细胞计数法检测C6细胞增殖水平;流式细胞术检测C6细胞的细胞周期;免疫荧光与免疫组化法分别检测波形蛋白(vimentin)和胶质纤维酸性蛋白(Glia lfibrillary acidic protein,GFAP)的表达;生化法检测谷氨酰胺合成酶(Glutamine synthetase,GS)的活性。结果 BMSCs对C6细胞的增殖具有抑制作用;与BMSCs进行双层培养72h的C6细胞出现G0/G1期细胞周期阻滞,双层培养组的C6细胞GFAP表达明显增强,同时vimentin表达减弱,并且这两种分化标志物在细胞内的分布及排列发生了改变;双层培养组C6细胞内GS活性升高。结论 BMSCs能诱导C6细胞向成熟星形胶质细胞分化,可能与BMSCs分泌的某些细胞因子有关。     

水蒸气在中空纤维复合膜中渗透的微分阻力模型

建立了水蒸气在中空纤维复合膜中渗透的微分阻力模型,用实验验证了模型的可靠性。采用该模型估算出中空纤维膜的结构参数,研究了水蒸气在各层膜中的阻力,并以H2O/C2H2系统为例,考察了膜的结构参数对H2O/C2H2选择性的影响。     

C/C预制体孔隙率与气相硅浸渗制备C/SiC复合材料性能关系的模型研究

建立了C/C预制体孔隙率与C/SiC复合材料组成的关系模型,并通过表征不同孔隙率的C/C预制体气相硅浸渗制备的C/SiC复合材料的组成和力学性能对模型进行了验证。研究发现,实验结果与模型预测结果基本一致。随着C/C预制体孔隙率的增大,C/SiC复合材料的密度出现先上升后下降的规律,力学性能也遵从同样的规律。XRD分析和相含量测试结果均表明复合材料的相含量与模型预测结果基本一致。实验结果与模型预测结果产生偏差的主要原因是裂解碳反应不完全。     

Altered Elemental Distribution in Male Rat Brain Tissue as a Predictor of Glioblastoma Multiforme Growth—Studies Using SR-XRF Microscopy

Glioblastoma multiforme (GBM) is a particularly malignant primary brain tumor. Despite enormous advances in the surgical treatment of cancer, radio- and chemotherapy, the average survival of patients suffering from this cancer does not usually exceed several months. For obvious ethical reasons, the search and testing of the new drugs and therapies of GBM cannot be carried out on humans, and for this purpose, animal models of the disease are most often used. However, to assess the efficacy and safety of the therapy basing on these models, a deep knowledge of the pathological changes associated with tumor development in the animal brain is necessary. Therefore, as part of our study, the synchrotron radiation-based X-ray fluorescence microscopy was applied for multi-elemental micro-imaging of the rat brain in which glioblastoma develops. Elemental changes occurring in animals after the implantation of two human glioma cell lines as well as the cells taken directly from a patient suffering from GBM were compared. Both the extent and intensity of elemental changes strongly correlated with the regions of glioma growth. The obtained results showed that the observation of elemental anomalies accompanying tumor development within an animal’s brain might facilitate our understanding of the pathogenesis and progress of GBM and also determine potential biomarkers of its extension. The tumors appearing in a rat’s brain were characterized by an increased accumulation of Fe and Se, whilst the tissue directly surrounding the tumor presented a higher accumulation of Cu. Furthermore, the results of the study allow us to consider Se as a potential elemental marker of GBM progression.     

Pathogenesis of Brain Edema and Investigation into Anti-Edema Drugs

Brain edema is a potentially fatal pathological state that occurs after brain injuries such as stroke and head trauma. In the edematous brain, excess accumulation of extracellular fluid results in elevation of intracranial pressure, leading to impaired nerve function. Despite the seriousness of brain edema, only symptomatic treatments to remove edema fluid are currently available. Thus, the development of novel anti-edema drugs is required. The pathogenesis of brain edema is classified as vasogenic or cytotoxic edema. Vasogenic edema is defined as extracellular accumulation of fluid resulting from disruption of the blood-brain barrier (BBB) and extravasations of serum proteins, while cytotoxic edema is characterized by cell swelling caused by intracellular accumulation of fluid. Various experimental animal models are often used to investigate mechanisms underlying brain edema. Many soluble factors and functional molecules have been confirmed to induce BBB disruption or cell swelling and drugs targeted to these factors are expected to have anti-edema effects. In this review, we discuss the mechanisms and involvement of factors that induce brain edema formation, and the possibility of anti-edema drugs targeting them.     

Pro- and Antiangiogenic Factors in Gliomas: Implications for Novel Therapeutic Possibilities

Angiogenesis, a complex, multistep process of forming new blood vessels, plays crucial role in normal development, embryogenesis, and wound healing. Malignant tumors characterized by increased proliferation also require new vasculature to provide an adequate supply of oxygen and nutrients for developing tumor. Gliomas are among the most frequent primary tumors of the central nervous system (CNS), characterized by increased new vessel formation. The processes of neoangiogenesis, necessary for glioma development, are mediated by numerous growth factors, cytokines, chemokines and other proteins. In contrast to other solid tumors, some biological conditions, such as the blood–brain barrier and the unique interplay between immune microenvironment and tumor, represent significant challenges in glioma therapy. Therefore, the objective of the study was to present the role of various proangiogenic factors in glioma angiogenesis as well as the differences between normal and tumoral angiogenesis. Another goal was to present novel therapeutic options in oncology approaches. We performed a thorough search via the PubMed database. In this paper we describe various proangiogenic factors in glioma vasculature development. The presented paper also reviews various antiangiogenic factors necessary in maintaining equilibrium between pro- and antiangiogenic processes. Furthermore, we present some novel possibilities of antiangiogenic therapy in this type of tumors.     

The Importance of Small Extracellular Vesicles in the Cerebral Metastatic Process

Brain metastases represent more than 50% of all cerebral tumors encountered in clinical practice. Recently, there has been increased interest in the study of extracellular vesicles, and the knowledge about exosomes is constantly expanding. Exosomes are drivers for organotropic metastatic spread, playing important roles in the brain metastatic process by increasing the permeability of the blood–brain barrier and preparing the premetastatic niche. The promising results of the latest experimental studies raise the possibility of one day using exosomes for liquid biopsies or as drug carriers, contributing to early diagnosis and improving the efficacy of chemotherapy in patients with brain metastases. In this review, we attempted to summarize the latest knowledge about the role of exosomes in the brain metastatic process and future research directions for the use of exosomes in patients suffering from brain metastatic disease.     

Brain Mitochondrial Lipid Abnormalities in Mice Susceptible to Spontaneous Gliomas

Alterations in mitochondrial function have long been considered a hallmark of cancer. We compared the lipidome and electron transport chain activities of non-synaptic brain mitochondria in two inbred mouse strains, the C57BL/6J (B6) and the VM/Dk (VM). The VM strain is unique in expressing a high incidence of spontaneous brain tumors (1.5%) that are mostly gliomas. The incidence of gliomas is about 210-fold greater in VM mice than in B6 mice. Using shotgun lipidomics, we found that the mitochondrial content of ethanolamine glycerophospholipid, phosphatidylserine, and ceramide was higher, whereas the content of total choline glycerophospholipid was lower in the VM mice than in B6 mice. Total cardiolipin content was similar in the VM and the B6 mice, but the distribution of cardiolipin molecular species differed markedly between the strains. B6 non-synaptic mitochondria contained 95 molecular species of cardiolipin that were symmetrically distributed over 7 major groups based on mass charge. In contrast, VM non-synaptic mitochondria contained only 42 molecular species that were distributed asymmetrically. The activities of Complex I, I/III, and II/III enzymes were lower, whereas the activity of complex IV was higher in the mitochondria of VM mice than in B6 mice. The high glioma incidence and alterations in electron transport chain activities in VM mice compared to B6 mice could be related to the unusual composition of mitochondrial lipids in the VM mouse brain. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

The neuroprotective functions of transforming growth factor Beta proteins

Transforming growth factor beta (TGF-β) proteins are multifunctional cytokines whose neural functions are increasingly recognized. The machinery of TGF-β signaling, including the serine kinase type transmembrane receptors, is present in the central nervous system. However, the 3 mammalian TGF-β subtypes have distinct distributions in the brain suggesting different neural functions. Evidence of their involvement in the development and plasticity of the nervous system as well as their functions in peripheral organs suggested that they also exhibit neuroprotective functions. Indeed, TGF-β expression is induced following a variety of types of brain tissue injury. The neuroprotective function of TGF-βs is most established following brain ischemia. Damage in experimental animal models of global and focal ischemia was shown to be attenuated by TGF-βs. In addition, support for their neuroprotective actions following trauma, sclerosis multiplex, neurodegenerative diseases, infections, and brain tumors is also accumulating. The review will also describe the potential mechanisms of neuroprotection exerted by TGF-βs including anti-inflammatory, -apoptotic, -excitotoxic actions as well as the promotion of scar formation, angiogenesis, and neuroregeneration. The participation of these mechanisms in the neuroprotective effects of TGF-βs during different brain lesions will also be discussed.     

Protein Tyrosine Phosphatase Receptor Type Z in Central Nervous System Disease

Gliomas are among the most common tumors of the central nervous system and include highly malignant subtypes, such as glioblastoma, which are associated with poor prognosis. Effective treatments are therefore urgently needed. Despite the recent advances in neuroimaging technologies, differentiating gliomas from other brain diseases such as multiple sclerosis remains challenging in some patients, and often requires invasive brain biopsy. Protein tyrosine phosphatase receptor type Z (PTPRZ) is a heavily glycosylated membrane protein that is highly expressed in the central nervous system. Several reports analyzing mouse tumor models suggest that PTPRZ may have potential as a therapeutic target for gliomas. A soluble cleaved form of PTPRZ (sPTPRZ) in the cerebrospinal fluid is markedly upregulated in glioma patients, making it another promising diagnostic biomarker. Intriguingly, PTPRZ is also involved in the process of remyelination in multiple sclerosis. Indeed, lowered PTPRZ glycosylation by deletion of the glycosyltransferase gene leads to reduced astrogliosis and enhanced remyelination in mouse models of demyelination. Here, we review the expression, molecular structure, and biological roles of PTPRZ. We also discuss glioma and demyelinating diseases, as well as the pathological role of PTPRZ and its application as a diagnostic marker and therapeutic target.     

Molecular and Circulating Biomarkers of Brain Tumors

Brain tumors are the most common malignant primary intracranial tumors of the central nervous system. They are often recognized too late for successful therapy. Minimally invasive methods are needed to establish a diagnosis or monitor the response to treatment of CNS tumors. Brain tumors release molecular information into the circulation. Liquid biopsies collect and analyze tumor components in body fluids, and there is an increasing interest in the investigation of liquid biopsies as a substitute for tumor tissue. Tumor-derived biomarkers include nucleic acids, proteins, and tumor-derived extracellular vesicles that accumulate in blood or cerebrospinal fluid. In recent years, circulating tumor cells have also been identified in the blood of glioblastoma patients. In this review of the literature, the authors highlight the significance, regulation, and prevalence of molecular biomarkers such as O₆-methylguanine-DNA methyltransferase, epidermal growth factor receptor, and isocitrate dehydrogenase. Herein, we critically review the available literature on plasma circulating tumor cells (CTCs), cell-free tumors (ctDNAs), circulating cell-free microRNAs (cfmiRNAs), and circulating extracellular vesicles (EVs) for the diagnosis and monitoring of brain tumor. Currently available markers have significant limitations. While much research has been conductedon these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature.     

The fatty acid composition of human gliomas differs from that found in nonmalignant brain tissue

To compare the fatty acid composition of tumor tissue from glioma patients with that of normal brain tissue, tissue samples were obtained from 13 glioma patients and from 3 nonmalignant patients. Following lipid extraction, total fatty acid composition was measured using gas-liquid chromatography. Samples were further separated into phospholipids and neutral lipids. Representative samples were then separated into phospholipid classes by thin-layer chromatography and the fatty acid composition assayed. Levels of the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA), were significantly reduced (P=0.029) in the glioma samples compared with normal brain samples; mean values were 4.8±2.9% and 9.2±1.0%, respectively. This reduction in glioma DHA content was also observed in terms of phospholipids (4.6±2.1% vs. 9.6±0.8%,P=0.002). The phosphatidylserine and phosphatidylethanolamine phospholipid classes were reduced in the glioma samples. Differences were also noted in the n-6 PUFA content between glioma and normal brain samples. The glioma content of the n-6 PUFA linoleic acid was significantly greater (P<0.05) than that observed in the control samples in terms of total lipids. Thus, the fatty acid composition of human gliomas differs from that found in nonmalignant brain tissue.     

A possible block in the intermediary metabolism of glucose into proteins and lipids in the brains of undernourished rats

[U-¹⁴C] Glucose or [1-¹⁴C] L-leucine was injected intraperitoneally into 28-day-old undernourished rats and control sibs who were killed 6 hr later. Brain proteins and lipids were extracted and the lipids fractionated by silicic acid column chromatography into cholesterol, glycolipids and phospholipids. The specific activity of labeled carbon derived from [U-¹⁴C] glucose in brain proteins was reduced by 25% in undernourished animals when compared to controls. A similar reduction was seen in the specific activity of brain lipids of undernourished animals: 14% for cholesterol, 21% for phospholipids and 35% for glycolipids. When [1-¹⁴C] l-leucine was used as a direct precursor of brain protein synthesis, the specific activity in the undernourished group was only 5% less than that found for the controls. This was not statistically significant. The results suggest that there may be a block in the intermediary metabolism of glucose in the brains of undernourished rats that reduces the availability of glucose carbon to the precursor pool used for protein and lipid synthesis.