胶质瘤中miR-134的表达及意义

目的 探讨miR-134在人脑胶质瘤组织和胶质瘤细胞系U87、U251中的表达及意义.方法 采用实时荧光定量PCR检测11例正常脑组织、42例不同级别脑胶质瘤组织、人脑胶质瘤细胞系U87和U251中miR-134的表达情况.结果 与正常脑组织相比,miR-134在不同级别胶质瘤中的表达均明显下降(均P＜0.05).WHOⅢ～Ⅳ级胶质瘤组织中miR-134表达明显低于WHO Ⅰ～Ⅱ级(P＜0.05).与正常脑组织相比,miR-134在胶质瘤细胞系U87、U251中的表达亦显著降低(均P＜0.05).结论 miR-134在胶质瘤中呈低表达,提示其可能参与胶质瘤的发生、发展.     

miR-137调控人脑胶质瘤细胞增殖侵袭能力的体内外研究

目的探讨miR-137调控人脑胶质瘤细胞的增殖侵袭性生长能力及其机制。方法采用实时PCR分析miR-137在不同品系胶质瘤细胞及不同级别胶质瘤样本中的表达;脂质体介导miR-137模拟物转染胶质瘤细胞,实时PCR检测转染后miR-137的表达;应用MTT法、流式细胞术评价细胞生长和增殖的生物学特征变化;划痕实验、transwell细胞体外迁移实验检测肿瘤细胞迁移、侵袭能力;动物实验评价体内条件下肿瘤生长能力变化;Western blot、免疫组织化学染色检测肿瘤细胞Ki-67、MMP9表达水平。结果实时PCR分析显示：miR-137在胶质瘤中低表达。miR-137模拟物转染LN229和U87细胞后,实时PCR显示：miR-137表达上调;MTT法及流式细胞术显示细胞生长受抑,出现G0/G1期阻滞;划痕实验及transwell实验证实：细胞迁移侵袭能力下降;进一步Western blot、免疫组织化学染色显示：增殖侵袭相关蛋白Ki-67、MMP9表达降低;动物实验反映：肿瘤细胞生长受抑制。结论 miR-137高表达可抑制胶质瘤细胞生长和侵袭能力,提示miR-137可作为基因治疗脑胶质瘤的候选靶点。     

基因表达谱芯片在脑胶质瘤中的研究进展

基因表达谱芯片在基因芯片中应用最广泛,具有高效、灵敏、高通量、平行化等优点,可检测脑胶质瘤发生发展中成千上万个基因的表达情况,绘制基因表达图谱,筛选特异性表达基因,从而揭示脑胶质瘤在基因水平上的本质。近年,利用表达谱芯片技术检测脑胶质瘤中miRNA的表达情况取得一定进展,这对全面研究脑胶质瘤的发生、发展具有重要意义,本文对此进行综述。     

DNA甲基化和miRNA在胶质瘤中的研究进展

DNA甲基化、微RNA（miRNA）在胶质瘤的发生、发展中起重要作用。多条癌症通路相关基因启动子区域的CpG岛甲基化发生频率与胶质瘤的发生与发展、组织类型和病理分级密切相关。miRNA的异常表达通过调控靶向基因、作用于癌症相关通路及脑肿瘤干细胞等机制扮演着抑癌或致癌角色。而miRNA的表达也受到甲基化的调控,这对综合评价肿瘤的发生、发展具有重要的意义。本文即对这两者在胶质瘤中的作用机制进行综述。     

血浆IGFBP-2在脑胶质母细胞瘤治疗前后变化

目的 探讨脑胶质瘤病人血浆类胰岛素样生长因子结合蛋白2(insulin-like growthfactor binding protein 2,IGFBP-2)浓度动态监测在病人病情判定、预测复发中的临床意义.方法 用酶联免疫法(ELISA)对健康体检者、不同级别胶质瘤及胶质母细胞瘤病人综合治疗后复发前后血浆IGFBP-2浓度进行统计学比较,随访其中55例胶质母细胞瘤病人2.5年,分析术前血浆IGFBP-2的浓度与其无瘤生存期的关系.结果 血浆IGFBP-2浓度随着胶质瘤级别的升高而增加(F=17.745,P=0.000);胶质母细胞瘤病人经过手术、放疗、化疗综合治疗后,未复发病人血浆IGFBP-2明显下降(t=2.164,P=0.041),而复发后明显升高(t=8.295,P=0.000);血浆中IGFBP-2浓度<600ng/ml的脑胶质母细胞瘤病人的无瘤生存期明显长于浓度>600ng/ml的胶质母细胞瘤病人(Z=2.272,P=0.023).结论 血浆IGFBP-2浓度的动态监测对判定胶质瘤病人病变恶性程度、预测胶质母细胞瘤的复发有一定的临床意义.     

miR-137对U87胶质瘤细胞中EZH2表达和细胞增殖的影响

目的研究miR-137对U87胶质瘤细胞EZH2表达及细胞增殖的影响。方法先用双荧光素酶报告基因检测系统筛选靶向EZH2 3'-非翻译区(3'-UTR)的miRNA,然后采用逆转录聚合酶链反应(RT-PCR)和Western blot检测在胶质瘤细胞中作用最强的miRNA对EZH2 mRNA和蛋白表达的影响,再用MTT法检测该miRNA对U87胶质瘤细胞增殖的影响。结果胶质瘤细胞中低表达的9个miRNA被预测靶向EZH2的3'-UTR。双荧光素酶报告基因检测表明:miR-126、miR-137和miR-138能使荧光素酶活性显著降低,其中miR-137的作用最强(P<0.01)。RT-PCR和Western blot结果也显示miR-137能抑制EZH2 mRNA和蛋白的表达。MTT结果显示:miR-137能抑制U87胶质瘤细胞增殖,过表达EZH2基因可拮抗miR-137对胶质瘤细胞增殖的抑制作用。结论 miR-137可抑制U87胶质瘤细胞增殖,可能与抑制EZH2基因表达有关。     

胶质母细胞瘤非手术治疗研究进展

胶质母细胞瘤(glioblastoma,GBM)是中枢神经系统中最常见的原发性恶性肿瘤,其生物学特性为浸润性生长,难治疗,易复发,预后差等。目前,虽然手术是脑胶质瘤治疗最基本、最直接的治疗手段,但是因为GBM具有高度侵袭性,呈现弥漫浸润性生长,与周围健康脑组织缺乏组织学边界,且常常位于脑功能区域,肿瘤的完全切除往往难以完成。因此探索针对GBM安全有效的非手术治疗策略仍然是研究的热点。近年来,针对GBM的非手术治疗有了很大的进展,本文就脑胶质瘤非手术治疗展开综述。     

circRNA在胶质母细胞瘤中的研究进展

<正>胶质母细胞瘤（glioblastoma multiforme,GBM）是一种高度恶性的颅内原发性肿瘤,WHO分级Ⅳ级。目前,GBM的标准治疗是手术切除联合放化疗,但中位生存期仅为15个月,5年生存率不足5%。如何更好地治疗GBM,改善病人生存时间和生活质量仍然是一个巨大的挑战[1]。因此,研究GBM恶性进展的调控机制、探索GBM早期肿瘤标志物,对GBM的早期诊断、治疗和预后评估具有重要意义。环状RNA(circRNA)是一类单链共价闭合的非编码RNA,没有5’帽结构和3’末端多聚（A）尾巴。     

miR-29c对脑胶质瘤U251细胞生物学活性的影响

目的 探讨miR-29c对脑胶质瘤U251细胞生物学活性的影响及可能机制.方法 体外培养胶质瘤U251细胞,实验组将miR-29c mimics转染至细胞,miR mimcs转染作为对照组.应用实时荧光定量PCR检测转染后miR-29c表达量的改变,MTT实验测定细胞增殖,流式细胞术检测细胞凋亡情况,体外侵袭实验分析miR-29c转染后细胞的体外侵袭能力,Western blot检测转染后转录因子YY1蛋白的表达.结果 荧光定量PCR结果显示:实验组miR-29c表达量为(106.65±15.51),较对照组显著上调(P＜0.01).与对照组比较,实验组U251细胞的增殖能力明显降低(P＜0.01),凋亡率增加(P＜0.05),体外侵袭能力明显减弱(P＜0.01),YY1蛋白表达下调(P＜0.01).结论 miR-29c可能通过调控YY1蛋白的表达抑制胶质瘤细胞的生物活性.     

miR -21抑制替莫唑胺诱导U87细胞凋亡的体外实验研究

目的 探讨miR -21过表达在替莫唑胺诱导胶质瘤U87细胞凋亡中的作用及其机制.方法 miR - 21过表达载体转染U87细胞,Hoechst 33258染色和流式细胞分析凋亡,Westem blot验证Bax和Bcl -2表达及检测Caspase -3活性.结果 替莫唑胺可显著诱导U87细胞凋亡,上调Bax 表达、下调Bcl-2表达及增加Caspase -3活性.U87细胞预转染miR -21过表达载体后,替莫唑胺的这种效应可部分被抑制.结论 miR -21过表达可通过下调Bax/Bcl -2比率及Caspase -3活性部分抑制替莫唑胺诱导的U87细胞凋亡,提示胶质瘤中miR -21过表达可能是胶质瘤对替莫唑胺耐药的一大新的因素.     

Role of MRI in diagnosis and treatment of multiple sclerosis

Magnetic resonance imaging (MRI) has played a unique role in the diagnosis and management of patients with multiple sclerosis (MS). In the recent years, there have been considerable changes in the diagnostic criteria for MS as MR-based studies demonstrated its power in earlier and more accurate diagnosis of the disease. Moreover, MRI metrics have become key supportive outcome measures to evaluate the efficacy of experimental treatments in randomized, controlled trials. MRI can also be used as a prognostic tool in patients with clinically isolated syndrome. Although advanced quantitative MRI measures such as magnetization transfer, spectroscopy, and diffusion imaging have added much more to our knowledge about pathogenesis and natural history of the disease but their cost, availability, complexity and lack of validation have limited their use in routine clinical practice. Conventional MR techniques including proton density, T1/T2-weighted images and fluid-attenuated inversion recovery sequences are now accepted in standard protocols for diagnosis and treatment outcome measures in clinical trials for MS.     

过表达miR-21通过PI3K-AKT 通路抑制替莫唑胺对胶质瘤U87细胞的增殖抑制作用

目的 探讨miR-21 过表达在替莫唑胺(TMZ)诱导胶质瘤U87 细胞增殖中的作用及其机制,明确miR-21 过表达在替莫唑胺临床治疗胶质瘤耐药中的作用.方法 Pre-miR-21 过表达载体转染U87 细胞,通过形态学观察,噻唑蓝(MTT)试验检测细胞增殖情况.Western 印迹验证Akt 和p-Akt 表达及检测PI3K 活性.结果 替莫唑胺可显著抑制U87 细胞生长,下调Akt 和p-Akt 表达及抑制PI3K 活性.U87 细胞预转染pre-miR-21 过表达载体后,替莫唑胺的这种效应可部分被miR-21 过表达所抑制.结论 miR-21 过表达可通过活化PI3K-AKT 通路部分抑制替莫唑胺诱导的U87 细胞凋亡,提示胶质瘤中miR-21 过表达可能是替莫唑胺临床治疗胶质瘤药物抵抗的一大新的因素.     

Prenatal diagnosis of Huntington disease in maternal plasma: direct and indirect study

Background and purpose: The presence of cell‐free fetal DNA in maternal plasma could allow performing a non‐invasive prenatal diagnosis of Huntington disease (HD). The great advantage of this diagnosis is the absence of risk of fetal loss that it entails. Methods: Maternal plasma from four pregnant women in their first trimester of gestation with a fetus at‐risk was studied. In all the four cases, the father was affected. Results: The diagnosis was performed both by a direct study of the mutation and an indirect haplotype study. By the direct analysis, three out of the four fetuses could be correctly diagnosed whilst the indirect analysis was only conclusive in one case. Conclusions: Non‐invasive prenatal diagnosis of HD is possible by the analysis of fetal DNA in maternal plasma. Direct analysis of the mutation has shown higher accuracy than the haplotype analysis except for long expansions. Haplotype analysis would need to be improved for the study of Juvenile‐onset HD. This diagnostic method would be limited to those couples with an affected male however this situation represents 80–90% of the pregnancies at‐risk of HD. Moreover, it could be used as a confirmation test of healthy embryos transferred on pre‐implantation genetic studies of HD.     

Multicentric and multifocal primary cerebral tumours. Methods of diagnosis and treatment

Forty patients with multifocal and multicentric cerebral tumours were retrospectively studied. The patients were divided into two groups: ten patients with multicentric tumours (group A), and 30 patients with multifocal tumours. As far as their preoperative clinical history and the incidence of the various symptoms and signs are concerned, there were no significant differences between the two groups. CT permitted a correct diagnosis in 90% of the cases. All of the patients underwent the removal of the tumour(s) and received radiotherapy; 30 patients also received chemotherapy. In group A, nine patients died and one was lost to follow-up one year after treatment; the average survival was ten months from the appearance of the multicentric tumour. In group B, 29 patients died and one is still alive two years after treatment; the average survival was six months. We consider the problems of diagnosis and the long-term follow-up of patients.

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Sommario Gli autori riportano uno studio retrospettivo su 40 pazienti affetti da tumori cerebrali multifocali e multicentrici del sistema nervoso centrale. I pazienti sono stati suddivisi in due gruppi: 1) gruppo A formato da 10 pazienti con tumore multicentrico; 2) gruppo B formato da 30 pazienti con tumore multifocale. Non si sono osservate significative differenze fra i due gruppi per quanto riguarda la durata della storia e l'incidenza dei sintomi e dei segni neurologici. La TC ha permesso una corretta diagnosi nel 90% dei casi. Tutti i pazienti sono stati sottoposti ad intervento chirurgico ed a radioterapia e 30 anche a chemioterapia. Nel gruppo A, 9 pazienti sono deceduti ed uno è stato perso al follow-up un anno dopo il trattamento. La sopravvivenza media è stata di 10 mesi dalla comparsa del tumore. Nel gruppo B, 29 pazienti sono deceduti ed uno è vivente due anni dopo il trattamento. La sopravvivenza media à stata di 6 mesi. Abbiamo trattato i problemi diagnostici e prognostici di questa patologia.

     

DNA-PKcs抑制剂在胶质母细胞瘤治疗中的作用与前景

胶质母细胞瘤是人类中枢神经系统肿瘤中恶性程度最高、预后最差的一类肿瘤,尽管目前对于胶质母细胞瘤可采取手术、辅助放射、化学药物等治疗方式,其预后仍然较差。新的起源学说认为胶质母细胞瘤中的胶质瘤干细胞可能起源于脑室下区,并且与该区的神经干细胞相关。而这种具有干细胞特性的肿瘤细胞与其他干细胞一样,拥有极强的DNA损伤修复能力,并且可以通过这种DNA损伤修复作用来增强肿瘤对于放射治疗的顽固抗性。该文探讨通过抑制DNA损伤修复的关键酶来拮抗胶质母细胞瘤的放疗抗性,提高患者预后的可能性。     

微小RNA与抑郁症自杀机制及电休克疗法的研究进展

微小RNA的表达水平与抑郁症自杀方面具有重要的关联,与此同时电休克疗法也可能影响抑郁症相关的某些基因,并可能影响疗效。因此探究微小RNA与抑郁症自杀以及电休克疗法的相互作用机制成为非常有价值的研究领域。目前相关研究已取得一定的成果,也有亟待解决的问题,为此现对近年来研究发现的与抑郁症及其自杀相关的微小RNA表达特征,以及抑郁症对电休克疗法应答方面涉及的微小RNA进行回顾和综述。通过对相关文献的梳理与分析为未来的研究方向及临床应用提供借鉴。     

脊髓室管膜下瘤诊断和显微外科治疗

目的总结脊髓室管膜下瘤的临床特点和治疗方法。方法回顾性分析9例脊髓室管膜下瘤的临床资料,均采用显微外科手术治疗,结合术中所见对诊断和治疗进行分析。结果肿瘤全切除3例,近全切除4例,大部分切除2例。病理检查显示:室管膜下瘤8例,室管膜下瘤含室管膜瘤成分1例。术后肢体肌力不同程度好转7例,减退2例;括约肌障碍恢复正常1例;短期浅、深感觉障碍均较术前略加重;无手术死亡病例。随访12~36个月,非全切病人中肿瘤复发3例。结论脊髓室管膜下瘤少见,手术可缓解病人临床症状,显微镜下全切除是最佳治疗选择。     

128-Channel somatosensory evoked potentials in the differential diagnosis of parkinsonian disorders

PurposeThe differential diagnosis of parkinsonian disorders can be very difficult, especially at an early stage. In this study, we investigated whether SEP amplitude recorded by 128-channel EEG is useful for diagnosis of parkinsonian disorders, and in particular whether SEP asymmetry can differentiate corticobasal degeneration (CBGD) from other parkinsonian disorders.MethodsWe recorded median nerve SEPs in 47 patients suspected of CBGD, supranuclear palsy or definite Parkinson's disease at an early stage. We compared SEP asymmetry and parietal peak amplitudes of the patients after grouping them based on their clinical diagnosis after 1–5 years of follow-up. In nine subjects the diagnosis remained unclear.ResultsThree of 13 patients with a clinical diagnosis of CBGD had an abnormal SEP asymmetry. Furthermore, we found extremely high N20 amplitudes in three other patients with CBGD. However, similar asymmetry abnormalities were found in patients with other Parkinsonian disorders.ConclusionDespite the use of 128-channel SEP recordings and analysis techniques, which are more accurate than conventional techniques, sensitivity and specificity of cortical median nerve SEP asymmetry and parietal amplitude for differentiating CBGD from other parkinsonian disorders were low at an early stage of the disease. A possible reason for this may be that the hand area of the primary somatosensory cortex was not yet affected in most CBGD patients.