S100蛋白在儿童髓母细胞瘤组织中的表达及与预后的关系

目的 探讨S100蛋白在儿童髓母细胞瘤组织中的表达,分析与肿瘤临床特点之间的关系和对儿童髓母细胞瘤预后的影响.方法 应用免疫组化SP法检测S100蛋白在44例儿童髓母细胞瘤中的表达,并结合长期随访资料进行生存曲线分析.结果 S100阳性表达率为68.18%.S100表达与儿童髓母细胞瘤患者性别、年龄、有无侵犯四脑室、有...     

儿童髓母细胞瘤患者临床因素与预后的相关性分析

目的 探讨影响儿童髓母细胞瘤(MB)患者预后的临床因素.方法 选择中山大学附属第一医院神经外科自2001年11月至2010年7月收治的儿童MB患者47例,采用Kaplan-Meier生存分析法和Cox回归模型分析患者年龄、性别、病程、肿瘤部位、术前转移、肿瘤切除程度、病理亚型、脑干侵袭程度、放疗与手术的时间间隔、化疗对生存时间即预后的影响.结果 本组患者2年生存率为91.4%,5年生存率为50%.Kaplan-Meier生存分析显示肿瘤全切或次全切者生存率高于大部分切除者,术前无转移患者生存率高于有转移者,放疗与手术的时间间隔≤42 d者生存率高于时间间隔>42 d者,差异均有统计学意义(P<0.05).Cox 回归模型分析显示术前转移、放疗与手术的时间间隔为儿童MB患者预后的影响因素,术前无转移、放疗与手术的时间间隔≤42 d患者预后较好.结论 术前有无转移和放疗与手术的时间间隔是影响儿童MB患者预后的独立因素.

Abstract：

Objective To analyze the correlation between the prognosis of pediatric medulloblastoma (MB) and its relevant clinical factors. Methods Forty-seven children with MB,admitted to our hospital from November 2001 to July 2010, were chosen;a retrospective analysis, using Kaplan-Meier survival tested by log-rank and Cox proportional hazards regression model, was performed to identify the correlation between the prognosis of pediatric MB and relevant clinical factors which included age, gender, course of disease, tumor location, pathological subtype, preoperative metastasis,extent of tumor resection, interval between surgery and radiation, brainstem invasion and chemotherapy.Results The 2-year survival rate of these patients was 91.4%, and 5-year survival rate 50%.Kaplan-Meier curves indicated that patients with total or subtotal tumor resection had a significantly higher survival rate than those with partial resection (P<0.05);patients without preoperative metastasis had a significantly higher survival rate than those with preoperative metastasis (P<0.05);and patients with interval between surgery and radiation≤42 d had a significantly higher survival rate than those with interval between surgery and radiation >42 d (P<0.05). Cox proportional hazards regression analysis indicated that preoperative metastasis (RR, 6.808;95%CI, 1.844 to 25.113;P<0.05) and interval between surgery and radiation (RR, 5.642;95% CI, 2.042 to 15.587;P<0.05) were the influencing factors for prognosis of MB. Patients without preoperative metastasis and with interval between surgery and radiation ≤42 d enjoyed good prognosis results. Conclusion Both preoperative metastasis and interval between surgery and radiation are independent factors for prognosis of pediatric MB.     

儿童髓母细胞瘤的治疗

报道２～１５岁儿童髓母细胞瘤５４例，６例因肿瘤转移他处死亡，２例因肿瘤出血死亡，４６例采用手术治疗，手术死亡２例，死亡率为４．４％。全切除肿瘤３９例，部分切除３例，亚全切除４例，随访４０例，１例因肿瘤属Ｔ－４级死亡，临床治愈２７例，症状改善１２例，５年生存率为５０％，推荐放射治疗为首选，就诊断及治疗进行了讨论。     

儿童髓母细胞瘤基础研究进展

髓母细胞瘤(medulloblastoma,MB)是儿童中枢神经系统最常见的恶性肿瘤。根据2007年WHO中枢神经系统肿瘤分类分为四种亚型:促纤维增生/结节型髓母细胞瘤、髓母细胞瘤伴广泛结节、间变性髓母细胞瘤、大细胞型髓母细胞瘤。它     

显微外科治疗儿童髓母细胞瘤

目的 用显微技术切除儿童髓母细胞瘤,砬少手术并发症,提高术后生存质量。方法 对３４例儿童髓平细胞瘤的临床资料进行分析。结果 ３４例均采用显微手术治疗,全切２７例,次全切除４例,部分切除３例,手术死亡２例,死亡率为５．９％,获随该列,临床治愈２４例,着状改善６例,５年生存率为５０％。结论 微创的显微外科技术是保证减少术后并发症,获得良好预后的关键。对于大多数患儿,建议术后辅以放疗。     

儿童髓母细胞瘤的综合治疗

儿童中枢神经系统原发肿瘤占所有儿童期肿瘤的 2 0 % ,发生率仅次于白血病居于第二位。髓母细胞瘤(ｍｅｄｕｌｌｏｂｌａｓｔｏｍａＭＢ)占儿童原发脑肿瘤的 2 0 % ,其发生率仅次于星形细胞瘤[1] 。发病高峰年龄在 7岁左右。髓母细胞瘤具有高度的软脑膜转移倾向 ,尤其在低龄儿童中常见。髓母细胞瘤 (ＭＢ)起源于小脑蚓部向四脑室生长 ,是最常见的儿童原发恶性脑肿瘤 ,是中枢神经系统恶性程度最高的神经上皮性肿瘤之一 ,属于原始神经外胚层肿瘤 (ｐｒｉｍｉｔｖｅｎｅｕｒｃｅｐｉｔｈｅｌｉａｌｔｕｍｏｒｓＰＮＥＴＳ)的一种 ,在ＷＨＯ的神…     

髓母细胞瘤的治疗与预后分析

目的探讨儿童及成人髓母细胞瘤患者的治疗及预后情况。方法回顾性研究80例经病理证实的髓母细胞瘤，对其成人与儿童患者的生存情况与肿瘤切除程度、脑脊液分流情况、放疗方式对其预后的影响作多因素分析比较。结果61例（76％）获得6个月至14年随访。5年生存率与10年生存率分别为50．8％和27．9％。成人患者5年生存率较儿童高（P＜0．05），而10年生存率两组相近。肿瘤全切或次全切除生存率高于大部分切除（P＜0．05）。全脑加脊髓放疗可改善患者近期生存率（P＜0．05）。3例患儿生存超过Collins危险期。结论手术与术后常规放疗是治疗髓母细胞瘤的关键。全切除或次全切除肿瘤、全脑加脊髓放疗可明显提高生存率。少数患者有可能获得长期生存。     

脑多肽(CP)对局灶性脑卒中C-Jun基因表达的影响

为了研究脑多肽(cerebral polypeptides,CP)对光化学局灶性脑缺血性卒中的C-Jun基因表达的影响,我们采用光化学方法选择性造成SD大鼠大脑皮层局灶性缺血模型42只,将其再分为两组-脑缺血模型组及CP治疗组(各n=21),另一组为盐水对照组(n=21)。应用免疫组化ABC法观察了脑卒中后[其中21只CP治疗组在脑缺血卒中后15分钟时,由尾静脉注入1％CP(1mL/kg),余两组给予等量生理盐水]各时间点C-Jun基因表达及含量变化。结果发现:脑缺血模型组在大脑皮层、齿状回、海马及下丘脑室旁核均有Jun样免疫阳性反应,并具有时间依赖性,30min开始表达,3～6h达高峰,24h后消退。CP治疗组Jun样免疫阳性反应明显增强,持续表达时间持久,达48h。盐水对照组Jun样免疫反应甚微。CP治疗组卒中侧Jun免疫阳性标记无论在数量还是染色深度上均显著高于模型组(P<0.01),而卒中对侧两组无显著差异(P>0.05)。通过本实验证明光化学局灶性脑卒中后C-Jun基因表达增强,而脑多肽对其有明显强化作用,从基因调控水平提示了中枢神经系统的再生反应,展现了CP对C-Jun基因表达增强作用的机理。     

C-Fos mapping and EEG characteristics of multiple mice brain regions in pentylenetetrazol-induced seizure mice model

ABSTRACT

Purpose: To confirm different local brain activities characterized in pentylenetetrazol (PTZ)-induced seizure model.

Methods: we induced seizure response by a single dose of PTZ injection (45 mg/kg, i.p.). Local activity was recorded in different brain regions by EEG in time and c-Fos staining at different time points (0.5 h, 1 h, 2 h, 4 h) after PTZ treatment.

Results: EEG recordings showed distinctive features of activation in different brain areas. With the aggravation of behavioral manifestations of seizures, the frequency and amplitude of the discharges on EEG were increasing gradually. The epileptic response on EEG immediately ended after reaching the maximum stage of seizures, followed by a short period of suppression. The labeling of c-Fos was enhanced in the medial prefrontal cortex, the piriform cortex, the amygdala, hippocampal CA1, CA3 and dentate gyrus, but inapparent in the striatum. The most potent changes in c-Fos were observed in cortex, amygdala nuclei, and dentate gyrus. EEG and c-Fos immunolabeling in neuronal activation showed discrepancies in the striatum. For each brain region, the maximum c-Fos labeling was observed at 2 h after injection and diminished at 4 h. The level of c-Fos immunoreactivity was even lower than the control group, which was accompanied by increased labeling of parvalbumin neurons (PVNs).

Conclusions: These findings validated PTZ-induced seizure as a seizure model with a specific spatial-temporal profile. Neuronal activity was enhanced and then subsequently inhibited during seizure evolution.

Abbreviations: AEDs: anti-epileptic drugs; AF: Alexa Fluor; CA1: Cornu Ammonis area 1; CA3: Cornu Ammonis area 3; DAB, 3: 3P-diaminobenzidine; DAPI: 4‘,6-diamidino-2-phenylindole; DG: dentate gyrus; EEG: electroencephalogram; GABA: gamma-aminobutyric acid; IEG: immediate early gene; mPFC: medial prefrontal cortex; NAc: nucleus accumbens; PB: phosphate buffer; PBS: phosphate buffered saline; PBST: phosphate buffered saline with Tween; PFA, paraformaldehyde; PTZ: pentylenetetrazol; PVN: parvalbumin neuron; ROI: regions of interest; SE: status epilepticus.     

Relationship between CacyBP/SIP expression and prognosis in astrocytoma

The aim of this study was to investigate the expression of calcyclin-binding protein (also known as Siah-1-interacting protein [CacyBP/SIP]) in astrocytoma and to determine its prognostic value in overall survival of patients with glioblastoma multiforme (GBM). Tissue specimens were obtained from 77 Chinese patients who had undergone surgery for astrocytoma. The expression of CacyBP/SIP was examined by immunohistochemistry. The relationship between CacyBP/SIP and proliferating cell nuclear antigen index (PCNA) expression was investigated, and the prognostic value of CacyBP/SIP expression in patients with astrocytomas was analyzed. Of 77 tumors, 49 (63.6%) were negative for CacyBP/SIP expression. Loss of CacyBP/SIP expression was significantly associated with a high histological grade and with poor survival in univariate and multivariate analyses. Cox multivariable analysis showed that loss of CacyBP/SIP expression correlated with poor prognosis in patients with astrocytomas and was an independent prognostic factor (p < 0.05). The mean survival time of patients with tumors that had lost expression of CacyBP/SIP was 25.58 months (95% confidence interval [CI], 15.36-25.81 months), compared to a mean survival time of 36.37 months (95% CI, 27.90-44.84 months) for patients with CacyBP/SIP-expressing tumors. CacyBP/SIP expression was also negatively correlated with PCNA expression in astrocytoma tissue (p < 0.05). Our findings suggest that CacyBP/SIP may have an important role as a negative regulator of astrocytoma development and progression, and that CacyBP/SIP might be a useful molecular marker for predicting the prognosis of astrocytoma.     

DNA拓扑异构酶Ⅱα的表达与颅咽管瘤预后的关系

目的检测颅咽管瘤组织中DNA拓扑异构酶Ⅱα(DNATopoⅡα)的表达情况,分析其表达与肿瘤复发的关系,探讨其是否可作为判定颅咽管瘤预后的一个有效指标。方法设计前瞻性队列研究方案,采用免疫组化方法和图像分析技术测定63例颅咽管瘤组织切片中DNA拓扑异构酶Ⅱα的表达水平,评价颅咽管瘤釉质上皮瘤与鳞状乳头瘤病理亚型、复发组与非复发组、原发组与复发组之间肿瘤细胞的增殖能力。结果32例釉质上皮瘤14例复发,31例鳞状乳头瘤6例复发;釉质上皮瘤与鳞状乳头瘤病理亚型之间以及复发组与非复发组肿瘤之间DNA拓扑异构酶Ⅱα的表达水平有显著性差异(P<0.05),而原发组与复发组肿瘤之间DNA拓扑异构酶Ⅱα的表达水平无统计学差异(P>0.05)。结论颅咽管瘤的病理亚型以及DNA拓扑异构酶Ⅱα的表达水平与肿瘤的预后和复发有关,可作为预测肿瘤复发危险性的一个参考指标;DNA拓扑异构酶Ⅱα的表达水平在原发组和复发组肿瘤之间无显著性差异,提示肿瘤在复发过程中瘤细胞的增殖活性无明显变化。     

Spatial and temporal relationships between C-Fos expression and kindling of audiogenic seizures in Wistar rats

In a strain of Wistar rats selected in our laboratory, audiogenic seizures (AS), characterized by a wild running phase followed by a tonic seizure, can be elicited by exposure to sound. In these animals repeated daily stimulations induce permanent changes which reflect the extension of seizure activity from the brainstem to the forebrain. C-Fos immunoreactivity was used to further characterize the sound-susceptibility of the strain and to specify the spatiotemporal relationships between c-Fos expression and development of AS kindling. AS susceptible rats appeared to be more sensitive to a subthreshold sound as compared to controls. Sound-evoked wild running induced a similar pattern of c-Fos as a full AS in naive rats, confirming the epileptic nature of this early component. AS-induced c-Fos labeling in the auditory pathways of the brainstem extended to the forebrain with repetition of AS and marked increases in c-Fos expression sequentially occurred in the amygdala and perirhinal cortex, followed by the frontoparietal cortex, the piriform cortex, and finally the hippocampus and entorhinal cortex. These results show that the kindled AS preferentially propagate from the brainstem, through the amygdala and the perirhinal cortex, to the motor cortex, with the piriform cortex and hippocampus as secondary targets. No more c-Fos expression was detected 24 h after an AS. A down-regulation of cortical c-Fos induction was observed 1 and 2 days after daily exposure to kindled AS, with full recovery of c-Fos expression after a 5-day seizure-free period. This suggests a regulatory function of c-Fos expression in development of kindling.     

c-Jun、bFGF、HSP70在丹参改善颞叶缺血大鼠空间记忆障碍中的表达变化

目的：探讨在丹参改善单侧颞叶缺血大鼠空间记忆障碍中c-Jun,bFGF和HSP70的表达变化。方法：采用立体定向光化学方法选择性地导致大鼠左侧颞叶皮层缺血,术前30分钟及术后第3天分别给丹参组大鼠腹腔注射丹参10g／kg,用Morris水迷宫及图像自动监视系统监测大鼠行为。然后取脑进行病理学及c-Jun、bFGF和HSP70免疫组化分析。结果：经丹参治疗,颞叶缺血性损害大鼠的空间记忆障碍得到显著改善,颞叶缺血损害程度显著减轻,缺血灶内c-Jun、bFGF和HSP70表达明显减少。结论：丹参可以明显改善单侧颞叶缺血性损害大鼠的空间记忆障碍,其机制可能与丹参减轻颞叶缺血损害,下调c－Jun、bFGF和HSP70表达有关。     

垂体腺苷酸环化酶激活肽对大鼠脑缺血再灌注损伤后缺血皮层 p-ERK及c-Fos表达的影响

目的观察大鼠局灶性脑缺血再灌注损伤后活化的胞外信号调节激酶和c-Fos的表达变化及垂体腺苷酸环化酶激活肽(PACAP)对其表达的影响。方法采用大鼠局灶性脑缺血再灌注损伤模型,72只大鼠随机分成假手术组、缺血再灌注对照组、缺血再灌注PACAP治疗组,大脑中动脉阻塞2h分别再灌注2、12、24、48h。再灌注后各时间点进行神经功能学评分后处死大鼠,免疫组织化学法分别检测3组大鼠p-ERK及c-Fos表达水平。结果缺血再灌注不同时间点PACAP组大鼠神经功能学评分较缺血再灌注对照组减低。脑缺血诱导JNK活化,缺血再灌注对照组缺血侧皮层p-ERK 2h达高峰后渐下降;c-Fos分别在2、24h表达高峰。与之相比,PACAP组各时间点p-ERK表达升高,24、48h c-Fos表达下降。结论PACAP对局灶性脑缺血再灌注损伤有保护作用,部分依赖于其上调了磷酸化EPK的表达,并下调了延迟表达的c-Fos基因。