扩散张量成像在不典型脑膜瘤与星形细胞肿瘤鉴别诊断中的价值

目的探讨扩散张量成像(DTI)鉴别不典型脑膜瘤与星形细胞肿瘤的价值。材料与方法搜集45例经病理证实的脑肿瘤患者(不典型脑膜瘤17例;不同级别星形细胞肿瘤28例),均做了MR DTI,获得FA图和ADC图,分别测量肿瘤实质区、瘤周区与健侧正常脑白质区的平均FA值和ADC值。用统计学软件SPSS19.0分别对不典型脑膜瘤与星形细胞肿瘤两组肿瘤实质区、瘤周区和健侧正常脑白质区FA值和ADC值进行统计学分析,统计结果均以x±s表示,P<0.05为差异有统计学意义。结果不典型脑膜瘤肿瘤实质区、瘤周区、健侧正常脑白质区FA值分别为0.23±0.05、0.20±0.04、0.28±0.04;星形细胞肿瘤上述3个区FA值分别为0.05±0.01、0.14±0.03、0.26±0.04,上述两组肿瘤实质区、瘤周区FA值比较均有显著统计学差异(P值均<0.01),不典型脑膜瘤肿瘤实质区和瘤周区FA值高于星形细胞肿瘤(P<0.05)。不典型脑膜瘤肿瘤实质区、瘤周区、健侧正常脑白质区ADC值分别为(0.82±0.13)、(1.22±0.32)、(0.73±0.10)×10-9mm2/s;星形细胞肿瘤上述3个区ADC值分别为(1.82±0.17)、(1.71±0.10)、(0.70±0.06)×10-9mm2/s。上述两组肿瘤实质区、周区ADC值比较均有显著统计学差异(P值均<0.01)。结论测量肿瘤实质区和瘤周区FA值和ADC值可鉴别不典型脑膜瘤和星形细胞肿瘤。     

Modulation of Energy Metabolism in C6 Glioma Cells as Possible Mechanism Contributing to Zinc Neurotoxicity

Elevated tissue levels of zinc (Zn) have been associated with neurodegenerative diseases such as global ischemia, seizure, and Alzheimer's. The mechanism of action of Zn in causing neuronal injury is not clear. One of the possible mechanisms is the ability of Zn to alter cellular energy metabolism. Using the C6 glioma cell as a model, the present study aimed to determined the effects of increasing concentrations of Zn on cellular energy states, as defined by the levels of adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), and adenosine 5'-monophosphate (AMP), the total adenosine nucleotides (TAN) (TAN = ATP + ADP + AMP), and the energy charge potential (ECP = [ATP + 0.5 ADP]/TAN). Uptake of Zn was visualized by the appearance of N-(6-methoxy-8-quinolyl)-p-toluene sulfonamide (TSQ)-stained fluorescent granules after a 3-h exposure to Zn in the medium. At [Zn] = 1 mM, cells appeared apoptotic. Levels of ATP and TAN decreased as the level of Zn increased. The change mirrors the increase in cell death as determined by the trypan blue exclusion test. However, when the ratio of ATP:ADP:AMP within the TAN was calculated, the percentage of ATP in the TAN increased significantly, while that of AMP decreased. The change in the relative AMP level mirrored the change in cell viability as measured by the MTT assay, which indicated a decreased in mitochondrial activity. Cellular ECP increased significantly from 0.85 ± 0.007 to 0.92 ± 0.04. The elevated ECP and relative ATP level, together with a significant decrease in the relative AMP level, are all indicators of inhibition of cellular metabolism. These results support the notion that acute exposure of C6 glioma cells to a high concentration of Zn might initially result in a decrease in relative AMP and an inhibition of mitochondrial activity. However, the ultimate toxic action of Zn on the C6 glioma cells appears to be due to a gradual inhibition of energy utilization, leading to cell shrinkage and apoptosis.     

OPN和MMP-9在脑胶质瘤中的表达及其临床意义

目的探讨骨桥蛋白（OPN）和基质金属蛋白酶-9（MMP-9）在胶质瘤中的表达及其临床意义。方法采用免疫组织化学二步法检测60例不同级别胶质瘤、30例非肿瘤脑组织中QPN和MMP-9的表达情况。结果OPN与MMP-9在脑胶质瘤中的表达阳性率分别为75．0％、7117％,与非肿瘤脑组织比较均明显升高（均P〈001）;在胶质瘤组织中OPN与MMP-9表达呈显著正相关（P〈0．05）。结论胶质瘤中OPN与MMP-9的表达阳性率显著高于非肿瘤脑组织,并与胶质瘤的病理级别及预后密切相关,可作为临床评价胶质瘤恶性程度和侵袭性的良好指标。胶质瘤中OPN与MMP-9表达呈正相关,两者在胶质瘤的发生、发展中可能起协同作用。     

SEPT7对胶质瘤细胞系TJ905生物学特性的影响

目的研究SEPT7对胶质瘤细胞系TJ905的生物学特性的影响。方法SEPT7表达缺失的人脑胶质瘤细胞系TJ905转染SEPT7构建体,pcDNA3载体转染组为空载对照,应用蛋白印迹鉴定转染是否成功。采用MTT法检测转染SEPT7构建体的细胞增殖活性,流式细胞术分析细胞周期分布变化,Annexin V法评价细胞的凋亡,Martrigel三维立体培养法分析侵袭能力。结果转染SEPT7后,胶质瘤细胞增殖活性降低,细胞周期分析结果为S期细胞比例（SPF）降低、G0／G1期阻滞;蛋白印迹检测细胞周期因子显示正向调节因子cyclinD1、cyclinE、CDk2、CDk4表达下降,负向调节因子p21、p16表达升高,肿瘤细胞侵袭能力明显受到抑制,并可诱发细胞凋亡。结论SEPT7转染人胶质瘤细胞系TJ905,可使细胞SPF降低、G0／G1期出现阻滞、抑制细胞侵袭和增殖、促进凋亡。     

Analysis of the IDH1 codon 132 mutation in brain tumors

A recent study reported on mutations in the active site of the isocitrate dehydrogenase (IDH1) gene in 12% of glioblastomas. All mutations detected resulted in an amino acid exchange in position 132. We analyzed the genomic region spanning wild type R132 of IDH1 by direct sequencing in 685 brain tumors including 41 pilocytic astrocytomas, 12 subependymal giant cell astrocytomas, 7 pleomorphic xanthoastrocytomas, 93 diffuse astrocytomas, 120 adult glioblastomas, 14 pediatric glioblastomas, 105 oligodendrogliomas, 83 oligoastrocytomas, 31 ependymomas, 58 medulloblastomas, 9 supratentorial primitive neuroectodermal tumors, 17 schwannomas, 72 meningiomas and 23 pituitary adenomas. A total of 221 somatic IDH1 mutations were detected and the highest frequencies occurred in diffuse astrocytomas (68%), oligodendrogliomas (69%), oligoastrocytomas (78%) and secondary glioblastomas (88%). Primary glioblastomas and other entities were characterized by a low frequency or absence of mutations in amino acid position 132 of IDH1. The very high frequency of IDH1 mutations in WHO grade II astrocytic and oligodendroglial gliomas suggests a role in early tumor development.     

重复光动力疗法治疗鼠C6胶质瘤

目的 观察5-氨基乙酰丙酸(5-ALA)作为光敏剂对大鼠C6胶质瘤移植瘤进行光动力疗法(PDT)的治疗作用.方法 建立大鼠胶质瘤模型,随机分成4组:A组按剂量20 mg/kg在瘤内注射5-ALA,2 h后在肿瘤局部行激光照射(单次PDT);B组操作与A组相同,但于第4、8天注射同等剂量5-ALA,重复PDT;C组给予单纯激光照射,不予任何光敏剂;D组为荷瘤对照组,不给任何治疗.治疗后测量肿瘤体积,绘制肿瘤生长曲线,以观察PDT及重复PDT对肿瘤生长的抑制情况.结果 重复光动力治疗组(B组)肿瘤体积与对照组(C、D组)比较明显缩小,比单次PDT(A组)亦较小,差异有统计学意义(P<0.05).结论 重复PDT比传统的单次PDT对大鼠C6胶质瘤移植瘤肿瘤的抑制效果更加明显.     

替莫唑胺治疗恶性脑胶质瘤97例多中心随机对照研究

目的 评价国产替莫唑胺(TMZ)胶囊治疗恶性脑胶质瘤的临床疗效和安全性.方法 采用多中心、随机、双盲、阳性药平行对照研究,将恶性脑胶质瘤患者随机分为试验组(TMZ组)和环已亚硝脲对照组(CCNU)组.试验组于第1～5天给予TMZ胶囊150 mg/m2口服,第1天需同时口服CCNU安慰剂130 mg/m2;对照组于第1天口服CCNU胶囊130 mg/m2,第1～5天口服TMZ安慰剂150 mg/m2.两组均每28天为1个周期,连续治疗3个周期.结果 共入组97例,可评价疗效者86例:TMZ组42例,CCNU组44例.治疗12周后,TMZ组:完全缓解(CR)1例,部分缓解(PR)14例,稳定(SD)23例,进展(PD)4例;CCNU组:CR 3例,PR 1例,SD 29例,PD 11例.TMZ组和CCNU组的有效率(CR+PR)分别为35.71%和9.09%(P<0.01),临床受益率(CR+PR+SD)分别为90.48%和75.00%(P<0.05).TMZ常见的不良反应为恶心呕吐,多为轻、中度.结论 国产TMZ胶囊治疗恶性脑胶质瘤的疗效优于CCNU,耐受性良好,是一种安全有效的治疗恶性脑胶质瘤的化疗药.     

人脑胶质瘤中miR-221和p27的表达及临床意义

目的 探讨miR-221在胶质瘤中的表达及其与p27 的关系.方法 收集不同病理级别胶质瘤标本,以荧光定量PCR法和免疫印迹法检测其中miR-221及p27的表达,分析其与胶质瘤病理级别的关系.结果 miR-221的表达强度与肿瘤恶性程度呈正相关,与p27的表达呈负相关.结论 miR-221的过农达和p27的表达下降或缺失与胶质瘤,尤其是恶性胶质瘤的发生、发展密切相关.     

AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C

We investigated the effect of compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), on proliferation and viability of human U251 and rat C6 glioma cell lines. Compound C caused G₂/M cell cycle block, accompanied by apoptotic glioma cell death characterized by caspase activation, phosphatidylserine exposure and DNA fragmentation. The mechanisms underlying the pro-apoptotic action of compound C involved induction of oxidative stress and downregulation of antiapoptotic molecule Bcl-2, while no alteration of pro-apoptotic Bax was observed. Compound C diminished AMPK phosphorylation and enzymatic activity, resulting in reduced phosphorylation of its target acetyl CoA carboxylase. AMPK activators metformin and AICAR partly prevented the cell cycle block, oxidative stress and apoptosis induced by compound C. The small interfering RNA (siRNA) targeting of human AMPK mimicked compound C-induced G₂/M cell cycle arrest, but failed to induce oxidative stress and apoptosis in U251 glioma cells. In conclusion, our data indicate that AMPK inhibition is required, but not sufficient for compound C-mediated apoptotic death of glioma cells.