脑多形性胶质母细胞瘤1例

脑多形性胶质母细胞瘤(Glioblastoma multiforme,GBM)临床常见,而本例为不典型的病例. 1 病例资料 患者,女,74岁,右利手,退休医生.因“突发左侧肢体乏力4h余”于2011年5月15日上午9时入院.患者既往有高血压病病史,曾有上消化道出血、十二指肠球部溃疡等病史,近期无急性发作,但一直未服用抗血小板聚集药物,否认其他特殊病史.     

基因芯片技术在多形性胶质母细胞瘤中的应用

多形性胶质母细胞瘤(gliobaltoma multiforme.BM．WHOIV)，是恶性程度最高的原发性脑肿瘤，尽管联合应用多种治疗，其中位生存期仍不足1年。随着人类基因组计划的实施，目前对胶质瘤的发病机制和诊断治疗的研究已跃人基因水平。人们注意到肿瘤是多个基因突变积累，造成癌基因激活和抑癌基因失活的结果。在多形性胶质母细胞瘤中，已有文献报道     

多形性胶质母细胞瘤手术后长期生存一例

1.病历介绍患者,男,39岁,因"反复头痛半月,加重并伴右侧偏瘫、呕吐及意识障碍1天"于2004年11月16日急入院.经头颅CT诊断为:左颞叶巨大脑肿瘤并出血(肿瘤大小约6.45 cm×4.72 cm×4.0 cm).入院第二天进行手术,术前认真讨论并制订严密的手术方案,手术过程中脑瘤不但被完全切除,而且邻近脑组织和周围神经血管作了最大限度的保护.     

多形性胶质母细胞瘤的影像学诊断

多形性胶质母细胞瘤(glioblastoma multiforme,GBM)是成人常见的中枢神经系统恶性神经上皮性肿瘤,在神经上皮性肿瘤中占22.3%,有报道占颅内肿瘤的10.2%。GBM是由星形细胞瘤恶性转变而来,是星形细胞瘤中最恶性的类型[1]。笔者对我院2001年1月以来经手术病理证实的21例GBM的CT和M     

老年多形性胶质母细胞瘤术后替莫唑胺同步放疗临床效果观察

目的观察老年多形性胶质母细胞瘤术后替莫唑胺同步放疗的临床效果。方法选择2013年1月至2015年1月来开封市肿瘤医院收治的多形性胶质母细胞瘤术后老年患者60例,术后随机分为对照组和治疗组,各30例。对照组行调强放疗,治疗组行调强放疗+替莫唑胺,对比疗效。结果治疗组平均生存周期为(21.4±3.6)个月,明显高于对照组平均生存周期(12.6±2.7)个月(P<0.05);治疗组生存率明显高于对照组(P<0.05)。结论在老年多形性胶质母细胞瘤术后采用调强放疗+替莫唑胺共同治疗效果更明显,能有效提高生存率,可推广应用。     

IGKV基因在人多形性胶质母细胞瘤治疗前后的变化分析

目的研究多形性胶质母细胞瘤(GBM)组织放射治疗前后基因表达谱中相关基因表达差异的变化及意义。方法采用BioStarH-141s含13 929条人类全长基因cDNA表达谱芯片,对5例多形性胶质母细胞瘤组织进行放疗前及放疗60 Gy后检测,并分析它们之间免疫相关基因表达差异。结果多形性胶质母细胞瘤放疗60Gy后与放疗前比较,表达差异基因中改变最明显的功能群是免疫系统相关的基因,IGKV基因上调。细胞增殖、细胞凋亡、细胞周期、DNA修复系统也有部分基因发生明显变化。结论提示对多形性胶质母细胞瘤组织照射60Gy后基因表达谱改变的研究可以更好地阐明放射敏感性差异机理,为放疗前或放疗早期寻找到预测放射敏感性分子标志提供理论依据。     

CDK1在多形性胶质母细胞瘤中的表达及其相关性研究

目的 现代学者通过多种方法进行研究发现，细胞周期蛋白依赖性激酶1(cyclin-dependent protein kinase 1,CDK1)在当今已知的多种肿瘤组织中呈现出高表达现象，而且还可能与肿瘤发展密切相关。但如今对于CDK1基因在多形性胶质母细胞瘤（glioblastoma multiforme,GBM）中的作用尚不明晰。所以，研究主要是对CDK1基因在多形性胶质母细胞瘤的增殖调节中起到的影响进行初步探讨。方法 从GEPIA在线数据库与proteinatlas在线数据库中提取了CDK1在各种肿瘤中的表达。选取2019年8月至2021年9月期间赤峰学院附属医院收治的54例多形性胶质母细胞瘤患者，记录年龄、性别、部位、复发和IDH1变异等情况后进行相关性分析，并通过免疫组化染色比较CDK1在多形性胶质母细胞瘤和癌旁正常组织中的表达水平，并观察其差异，进而得出结论。结果 通过上述2个数据库中的资料发现，与正常组织相比，多形性胶质母细胞瘤中CDK1基因的表达水平上调。多形性胶质母细胞瘤临床病理特征中和复发有关（P=0.016），和年龄、性别、部位和IDH1变异情况无关。通过进一步的...     

立体定向建立裸鼠人脑多形性胶质细胞瘤模型及生长特性研究

目的:体外原代培养人脑多形性胶质母细胞瘤细胞,应用不同细胞数量接种裸鼠脑内建立颅内胶质瘤实验动物模型,观察其生长特性。方法:采用酶消化法原代培养4例人脑多形性胶质细胞瘤,分别取生长状态良好的胶质瘤细胞悬液20μL,按1.0×105个/10μL,1.0×106个/10μL,1.0×107个/10μL立体定向接种于裸鼠脑右侧尾状核区。在整体、组织和细胞水平观察并记录肿瘤生长情况,于成瘤后第5wk处死荷瘤鼠检测是否存在肿瘤远处转移,同时对肿瘤组织行HE和免疫组织化学染色检测胶质瘤的病理学特征。结果:细胞悬液接种可成功获得多形性胶质细胞瘤模型,成功率较高,但潜伏期延长,各种接种量的实验组成瘤率均为100%,未见颅外转移病灶,在组织病理学上接近人脑胶质瘤。结论:多形性胶质细胞瘤细胞接种裸鼠建立脑胶质瘤动物模型,成瘤率高,颅内生长稳定,肿瘤组织病理学及形态学特性与人脑胶质瘤相似,可作为临床胶质瘤基础研究的理想模型。     

多形性胶质母细胞瘤112例临床分析

目的 探讨多形性胶质母细胞瘤(GBM)手术后联合不同辅助治疗手段对患者预后的影响.方法 对112例首诊GBM患者的临床资料进行随访及回顾性分析.采用Kaplan-Meier法计算生存率并绘制生存曲线,用log-rank检验方法进行单因素分析,对影响生存时间的多因素进行COX回归分析.结果 112例患者纳入分析,随访结束存活18例,随访期间死亡94例,平均生存时间(14.7±1.69)个月.手术全切、IDH1突变阳性、术后2~4周内开始放疗、Stupp方案后长周期维持替莫唑胺影响患者的总生存时间.COX回顾分析显示患者手术全切(P=0.003)、术后2~4周开始放疗(P=0.000)是影响生存时间的独立因素.挽救性治疗手段对生存时间的影响,差异无统计学意义(P>0.05).结论 手术全切及术后早期开始放疗能延长GBM患者生存期,以IDH1/2基因为代表的分子检测能很好地判断高级别胶质瘤的生存预后.     

VM-26对人多形性胶质母细胞瘤BT-325细胞增殖的影响

目的　研究替尼泊甙 (VM -2 6)对人多形性胶质母细胞瘤BT -3 2 5细胞增殖的影响。方法　应用免疫细胞化学方法 ,观察BT -3 2 5细胞经不同剂量 (1μg/ml和 5μg/ml)VM -2 6作用后的不同时间 (48小时、72小时 )克隆形成率的变化以及PCNA、CyclinD1表达的改变。结果　克隆形成率实验显示VM -2 6作用后克隆形成率降低 ,与对照组比较差别显著 (P <0 .0 1) ;对照组PCNA和CyclinD1均为强阳性 ;经VM -2 6作用后 ,PCNA和CyclinD1表达均受到显著的抑制 ,尤以 5μg/ml、72小时组效果最佳 ,与对照组比较差别显著 (P <0 .0 1)。结论　VM -2 6可显著抑制BT -3 2 5细胞恶性增殖     

Genome-wide allelotype study of primary glioblastoma multiforme

Objective To investigate the molecular genetic pathogenesis of primary glioblastoma multiforme (GBM) and identify which chromosomes or chromosomal regions of the entire genome may harbor tumor suppressor genes (TSGs) associated with GBM.Methods A high-resolution allelotype study of 21 cases of primary GBM was performed by PCR-based loss of heterozygosity （LOH）analysis. Three hundred and eighty-two fluorescent dye-labeled microsatellite markers covering all 22 autosomes were applied. The mean genetic distance between two flanking markers was about 10 cM.Results LOH was observed on all 39 nonacrocentric autosomal arms examined in this study. The LOH frequencies of 10q, 10p, 9p, 17p and 13q were the highest (&gt;50%). Furthermore, high LOH frequencies were detected in the regions containing known TSGs including PTEN, DMBT1, p16, p15, p53 and RB; the LOH frequencies on 14q, 3q, 22q, 11p, 9q, 19q were also high (&gt;40.5%). Our study observed the following commonly deleted regions: 9p22-23, 10p12.2-14, 10q21.3, 13q12.1-14.1, 13q14.3-31, 17p11.2-12, 17p13, 3q25.2-26.2, 11p12-13, 14q13-31, 14q32.1, 14q11.1-13, 22q13.3, 4q35, 4q31.1-31.2, 6q27 and 6q21-23.3. Conclusions The molecular pathogenesis of GBM is very complicated and associated with a variety of genetic abnormalities on many chromosomal arms. The most closely related chromosomal arms to the pathogenesis of GBM are 10q, 10p, 9p, 17p and 13q. Besides the well-known TSGs including PTEN, DMBT1, p16, p15, p53 and RB, multiple unknown TSGs associated with GBM may be present on the commonly deleted regions detected in the present study.     

人脑胶质母细胞瘤PDX模型的建立

目的：探讨患者来源的异种移植（patient derived xenograft,PDX）胶质母细胞瘤模型的建立方法,为临床和生物学研究提供重要的理论依据和技术支持。方法：收集胶质母细胞瘤组织,建立皮下肿瘤模型,待皮下肿瘤生长取出肿瘤,分散肿瘤细胞并种于小鼠颅内。HE染色比较原发肿瘤组织与PDX肿瘤形态学特点,免疫组织化学染色方法检测Ki?67的表达,比较肿瘤增殖能力。结果：成功建立人脑胶质母细胞PDX模型,原发肿瘤和PDX肿瘤形态学特点相似,PDX肿瘤保留了原发肿瘤的增殖能力。结论：通过建立PDX模型,可以将PDX作为胶质母细胞瘤患者个体化治疗的重要临床前研究工具。     

羊膜对培养的人视网膜色素上皮细胞增殖影响的实验研究

目的　观察羊膜是否对视网膜色素上皮细胞 (Retinalpigmentepithelial ,RPE)的生长有影响 ,探讨羊膜用于治疗增殖性玻璃体视网膜病变 (Proliferativevitreoretinopathy ,PVR)的潜在可能性。方法　运用MTT比色法 ,观察羊膜匀浆在不同浓度 (4 0、80、160 μg ml)及不同作用时相点 (2 4、48、96h)对人RPE增殖的影响。 结果　①在第 2 4小时 ,3个浓度羊膜匀浆均对人RPE增殖起抑制作用 ,而且随浓度增加抑制作用减弱 ,抑制率 (5 0 774%、2 7 3 87%、14 80 2 % )间相差显著 (P <0 0 5 ) ;在第 48、96小时 ,羊膜匀浆在低浓度时 ,对人RPE增殖起抑制作用 ,而在中、高浓度为促增殖作用 ,其中在第 48小时抑制率 (4 494%、-0 944 %、-3 693 % )间相差不显著 (P >0 0 5 ) ,在第 96小时时抑制率 (8 3 88%、-9 42 5 %、-17 65 1% )间相差显著 (P <0 0 5 )。②羊膜匀浆浓度为 40 μg ml ,各时相点对人RPE均为抑制增殖 ,抑制率间相差非常显著 (P <0 0 1) ;在浓度为 80 μg ml、160 μg ml时 ,随着作用时间延长 ,羊膜匀浆对人RPE增殖的作用逐渐由抑制变为促进作用 ,抑制率间相差显著 (P <0 0 5 )。结论　羊膜匀浆在低浓度 ,短时间内对人RPE增殖有抑制作用 ,而在高浓度、长时间则对RPE增殖有促进作用。羊膜匀浆用     

胰岛素和IGF-Ⅰ促进成骨样细胞增殖功能的实验研究

目的:应用胰岛素(INS)、胰岛素样生长因子-Ⅰ(IGF-Ⅰ)干预体外培养的人成骨肉瘤细胞MG63(MG63),并以17-β雌二醇(E2)做阳性对照,观察细胞增殖功能的改变;探讨骨质疏松(OP)的发病机制,为治疗OP提供实验依据.方法:将MG63细胞接种到DMEM培养基中培养,并进行药物干预.用四甲基偶氮唑盐(MTT)染色,酶标仪测定细胞OD值.结果:各药物组内OD值比较均有统计学差异(P＜0.05),量效关系呈抛物线形.三药物组间细胞增殖率有统计学差异(P＜0.05).三组药物的最佳药物浓度分别为50nM、10nM、100nM.结论:与E2相同,INS、IGF-Ⅰ两种药物均有促进MG63细胞增殖的作用.     

胶质母细胞瘤中CD133阳性细胞的分布与组织微血管增殖的相关性

目的 观察胶质瘤干细胞标记物CD133和血管内皮细胞标记物CD34在胶质母细胞瘤及瘤周不同部位的表达情况,探讨胶质瘤干细胞在恶性胶质瘤中的侵袭迁移规律.方法 收集52例胶质母细胞瘤病人的组织标本,每例标本分别取肿瘤中心组织、肿瘤和水肿交界区组织及肿瘤周围水肿区组织3部分.采用免疫组织化学染色和Western印迹法检测CD133在各组标本中的表达情况,采用免疫组织化学染色法检测CD34-微血管在组织标本中的分布,并分析两者的相关性.结果 CD133在对照组组织中不表达,而在肿瘤和水肿交界区、肿瘤中心区,瘤周水肿区组织中免疫组化染色表达分值分别为7.3±1.4、5.2±1.1、2.7±1.0,光学显微镜下可见,在交界区CD133+细胞分布密集,往往形成以微血管为中心的假菊型团样结构,在中心区CD133+细胞常在微血管附近簇状分布,在水肿区CD133+细胞以散在分布为主;Western印迹检测吸光度值分别为0.79±0.03、0.38±0.01、0.20±0.04;各区域间的差异有统计学意义(P＜0.05).在高倍视野下,肿瘤和水肿交界区、肿瘤中心区、肿瘤周围水肿区、对照组组织中CD34-微血管密度(个/视野)分别是31.3±4.0、21.8±2.6、15.3±2.4、4.7±1.5;各组之间的差异有统计学意义(P＜0.05).CD133的表达水平和组织微血管的分布呈正相关(r=0.948,P＜0.05).结论 胶质瘤干细胞向微血管生成丰富的交界区富集,认为他和组织微血管之间可能存在密切的"营养"联系;胶质瘤干细胞在胶质母细胞瘤中的分布特征可能与其侵袭迁移有关.

Abstract：

Objective To investigate the expression of CD133 and CD34 in different parts of glioblastoma and its margin and explore the invasive path of glioma stem cells within the tumor and surrounding tissue.Methods The surgical specimens were collected from the core of mass,junctional zones between tumor and peritumoral edematous areas and edematous areas in 52 patients with glioblastoma.Immunohistochemical cell staining and Western blot were employed to evaluate the expression of CD133 in different specimens while immunohistochemistry was used to detect the CD34-microvesel postforming.A correlation analysis was performed between them.Results The expression of CD133 was not detected in the control groups while the scores were 7.3 ± 1.4,5.2 ± 1.1,2.7 ± 1.0 in junctional zones,tumor cores and edematous areas with immunohistochemistry and 0.79 ± 0.03,0.38 ± 0.01,0.20 ± 0.04with Western blot respectively.There were significant differences between different groups (P ＜ 0.05).Under light microscope,the CD133-positive cells frequently forming perivascular pseudorosettes were dense in junctional zones and mostly clustered near the microvessels in tumor cores and scattered in edematous areas.At a high magnification (200 ×),the CD34-MVD(/HP) values were 31.3 ±4.0,21.8 ± 2.6,15.3 ±2.4,4.7 ± 1.5 respectively in junctional zones,tumor cores,edematous areas and control tissues.Significant differences were also found in these groups(P ＜ 0.05).The expression level of CD133-positive cell was positively correlated with the distribution of CD34-microvessels (r =0.948,P ＜ 0.05).Conclusion Glioma stem cells tend to assemble in the junctional zones where the microvessels are enriched.There is probably an intimate nourishing relationship with the microvessels.The distribution of glioma stem cells may be related with the invasiveness within glioblastoma.     

Prognostic factors influencing clinical outcomes of glioblastoma multiforme

Background Glioblastoma multiforme （GBM） is the most malignant kind of astrocytic tumors and is associated with a poor prognosis. In this retrospective study, we assessed the clinical, radiological, genetic molecular and treatment factors that influence clinical outcomes of patients with GBM. Methods A total of 116 patients with GBM who received surgery and radiation between January 2006 and December 2007 were included in this study. Kaplan-Meier survival analysis and Cox regression analysis were used to find the factors independently influencing patients＇ progression free survival （PFS） time and overall survival （OS） time. Results Age, preoperative Karnofsky Performance Scale （KPS） score, KPS score change at 2 weeks after operation, neurological deficit symptoms, tumor resection extent, maximal tumor diameter, involvement of eloquent cortex or deep structure, involvement of brain lobe, Ki-67 expression level and adjuvant chemotherapy were statistically significant factors （P 〈0.05） for both PFS and OS in the univariate analysis. Cox proportional hazards modeling revealed that age 〈50 years, preoperative KPS score 〉80, KPS score change after operation 〉0, involvement of single frontal lobe, non-eloquent area or deep structure involvement, low Ki-67 expression and adjuvant chemotherapy were independent favorable factors （P 〈0.05） for patients＇ clinical outcomes. Conclusions Age at diagnosis, preoperative KPS score, KPS score change at 2 weeks postoperation, involvement of brain lobe, involvement of eloquent cortex or deep structure, Ki-67 expression level and adjuvant chemotherapy correlate significantly with the prognosis of patients with GBM.     

A genome-wide allelotype study of primary and corresponding recurrent glioblastoma multiforme in one patient

Glioblastoma multiforme (GBM) is the most common type of primary malignant brain tumor. Although comprehensive therapeutic measures are available, recurrence is very frequent and the prognosis of GBM remains dismal. To date, little is known about the molecular pathogenesis associated with GBM recurrence. According to Knudson ' s two-hit hypothesis of tumor suppressor gene (TSG) inactivation,1 deletion of a chromosomal region, as revealed by loss of heterozygosity (LOH), is often indicative of the presence of a potential TSG. Allelotype studies involving a comprehensive LOH analysis of the whole genome can provide more detailed and thorough information for detecting genetic anomalies than traditional LOH analysis. The present study is designed to conduct a genome-wide allelotype analysis of one patient ' s primary and corresponding recurrent GBM tumors in an effort to reveal molecular genetic alterations associated with the recurrence of this malignancy.     

A genome-wide allelotype study of primary and corresponding recurrent glioblastoma multiforme in one patient

Glioblastoma multiforme (GBM) is the most common type of primary malignant brain tumor. Although comprehensive therapeutic measures are available, recurrence is very frequent and the prognosis of GBM remains dismal. To date, little is known about the molecular pathogenesis associated with GBM recurrence.