血管内皮生长因子在人脑胶质瘤的定位及表达

目的 通过检测人脑胶质瘤及瘤周组织中血管内皮生长因子(VEGF)的基因表达及定位,探讨VEGF促进肿瘤血管生成及瘤周组织水肿的作用机制。方法采用原位杂交方法检测23例人脑胶质瘤及瘤周组织中VEGF基因表达情况,并与7例正常脑组织进行对照研究。不着色者为阴性,细胞胞浆着色呈棕黄(褐)色者为阳性。结果VEGF在胶质瘤组织主要表达于毛细血管、血管内皮细胞及肿瘤细胞,瘤周组织表达于变异的星形胶质细胞,而正常脑组织几乎无表达。胶质瘤组织标本中血管内皮细胞及瘤细胞内VEGF的表达率分别为22.60±2.31和20.18±4.25,而瘤周组织标本中血管内皮细胞及变异的星形胶质细胞内VEGF的表达率分别为8.44±3.17和45.20±6.11,正常脑组织标本中血管内皮细胞及细胞内VEGF的表达率分别为1.76±1.20和1.84±1.51,胶质瘤组织与瘤周组织阳性细胞表达率显著高于正常脑组织(P<0.01);胶质瘤组织中血管内皮细胞VEGF的阳性表达率高于瘤周组织(P<0.01);而瘤周组织星形胶质细胞的阳性表达率高于肿瘤组织(P<0.01)。结论提示VEGF在脑胶质瘤及瘤周组织中的高表达与肿瘤血管生成及瘤周组织水肿的发生密切相关。     

人脑膜瘤血管内皮细胞生长因子表达的临床意义

目的　探讨脑膜瘤血管内皮生长因子 (VEGF)基因表达与血管生成和脑水肿的关系。方法　应用免疫组织化学方法检测 3 5例脑膜瘤组织中VEGF基因表达 ;Ⅷ因子相关抗原单克隆抗体组织化学染色显示微血管 ,用微血管记数 (MVC)测定血管生成 ;从脑水肿与肿瘤本身的体积之比估计脑水肿程度。结果　 3 5例脑膜瘤VEGF表达率 77% (2 7/3 5 ) ,4例可疑染色 ,其中恶性脑膜瘤和血管母细胞型脑膜瘤呈现高表达 (10 0 % ) ;VEGF表达与脑膜瘤血管生成 ,瘤周脑水肿呈显著正相关 (r =0 .682 3 ,P <0 .0 1;r =0 .765 3 ,P <0 .0 1)。结论　VEGF存在于脑膜瘤组织中 ,在脑膜瘤血管生成和瘤周水肿中发挥重要作用。     

脑膜瘤肿瘤血管形成及瘤周水肿与基质金属蛋白酶-9表达的关系

目的　探讨脑膜瘤中肿瘤血管生成及瘤周水肿与基质金属蛋白酶(MMP) 9表达的关系。方法　采用免疫组织化学法检测5 9例脑膜瘤MMP 9和血小板 内皮细胞黏附因子 1(CD3 1) ,用全自动图像分析系统检测肿瘤组织的CD3 1微血管计数(MVC) ,通过MRI或CT测量瘤周水肿指数,对参数进行综合分析。结果　MMP 9表达强阳性组与弱阳性组、阴性组相比,水肿指数(EI) (分别为2 .86±0 .69、1.2 5±0 .5 3、0 .2 3±0 .18) ,脑水肿发生率(分别为95 .2 %、76.7%、3 7.5 % ) ,微血管计数(MVC分别为2 5 .6±8.5、10 .5±4.6、4.3±1.3 3 )的差异均有统计学意义(P <0 .0 5 )。MMP 9的表达与MVC及瘤周水肿呈正相关(r分别为0 .3 65、0 .5 73 ,P <0 .0 5 )。结论脑膜瘤MMP 9表达、肿瘤血管生成及瘤周水肿形成之间有重要关系;MMP 9能促进脑膜瘤的肿瘤血管生成及瘤周水肿的形成,可能对脑膜瘤瘤周水肿的形成有重要作用     

人脑膜瘤水通道蛋白4表达及其生物学意义

目的 研究水通道蛋白4(aquaporin 4 AQP4)在人脑膜瘤中的表达与脑膜瘤的病理学分型的相关性,并探讨其与瘤周脑组织水肿的关系及其可能机制.方法 取伴水肿(MRI证实)的良性脑膜瘤组织15例,无水肿良性脑膜瘤组织21例,恶性脑膜瘤15例和正常脑组织6例,应用免疫组织化学方法检测AQP4在脑组织的表达,并结合临床病理参数进行综合分析.结果 在不伴脑水肿的良性脑膜瘤组、伴水肿的良性脑膜瘤组以及恶性脑膜瘤组中阳性表达率均升高,正常脑组织中几乎未见阳性表达.伴水肿的良性脑膜瘤组织中AQP4阳性表达率高于无水肿良性脑膜瘤组(P＜0.05),恶性脑膜瘤组织中AQP4阳性表达率明显高于不伴脑水肿良性组(P＜0.01),AQP4的表达和脑膜瘤病理分级无相关性(P＞0.05).AQP4的表达与瘤周水肿显著相关(P＜0.05).结论 AQP4在脑膜瘤中的高表达与脑组织水肿的发生密切相关.检测脑膜瘤AQP4的表达对了解脑膜瘤生物学行为和判断预后有重要价值.     

复发脑膜瘤血管内皮生长因子及增殖细胞核抗原的表达

目的探讨脑膜瘤细胞增殖能力、肿瘤复发与血管内皮生长因子（VEGF）蛋白表达之间的关系。方法应用免疫组织化学方法检测36例复发脑膜瘤及30例原发脑膜瘤标本的VEGF和增殖细胞核抗原（PCNA）表达。结果复发脑膜瘤VEGF蛋白阳性表达率89％（32／36）明显高于原发脑膜瘤43％（13／30）（X2=25．59，P〈0．01）。复发脑膜瘤PCNA指数（65．72±9．22）高于原发脑膜瘤（20．81±7．43，P〈0．05）。VEGF蛋白表达强阳性、弱阳性及阴性者的PCNA指数分别为78．64±10．02、49．45±8．31、6．23±1．45，差异有统计学意义（P〈0．01）。结论VEGF蛋白的表达水平与脑膜瘤的复发和增殖能力有关，VEGF蛋白表达水平可能是脑膜瘤复发的预测指标之一。     

X刀治疗脑膜瘤的临床应用

目的 探讨X刀治疗颅内脑膜瘤的临床效果。方法 回顾分析X刀治疗52例颅内脑膜瘤的临床资料。治疗周边剂量10Gy—20Gy，平均13Gy。随访方法为临床检查和头颅CT增强扫描检查。结果 治疗后出现一侧肢体轻偏瘫1例(1．9％)，局灶性癫痫发作2例(3．8％)；影像学显示无症状性瘤周水肿较术前明显12例(23．1％)。影像学随访40例(76．9％)，时间3月—92月，平均23月，肿瘤体积缩小18例(45．0％)，无变化22例(55．0％)。结论 X刀治疗颅内脑膜瘤安全、有效。     

脑膜瘤复发与微血管密度、血管内皮生长因子表达的关系

目的 探讨脑膜瘤复发与微血管密度(MVD)、血管内皮生长因子(VEGF)的表达与其复发的相关性.方法 采用免疫组织化学MaxVisionTM法,分别检测复发组脑膜瘤33例和非复发组脑膜瘤26例的MVD和VEGF的表达,分析肿瘤复发与两者的关系.结果 非复发组与复发组脑膜瘤的MVD平均值分别为34.2923±17.2422、71.410±39.475,复发组明显高于非复发组(P<0.05);其中复发组脑膜瘤I级与Ⅱ、Ⅲ级的MVD平均值分别为54.7304±25.3080、109.780±39.642,Ⅱ、Ⅲ级的MVD平均值明显高于I级者(P<0.05).VEGF蛋白表达在复发组脑膜瘤I级的阳性率39.13%(9/23)高于非复发组的阳性率11.54%(3/26)(P<0.05).38例VEGF蛋白表达阴性的脑膜瘤中MVD平均值为37.9263±15.2300,21例VEGF蛋白表达阳性的脑膜瘤中MVD平均值为86.0286±28.7464,VEGF蛋白的表达与MVD平均值呈正相关(r=0.7888,P<0.05). 结论 VEGF和MVD联合检测可作为反映脑膜瘤临床病理特征的指标之一,两者高水平的表达提示复发的可能性较大.     

人脑胶质瘤血管生成素-2表达及其与管生成和脑水肿的关系

目的 研究血管生成素.2(Ang-2)基因在人脑胶质瘤表达及其与胶质瘤血管生成及瘤周水肿的关系。方法 用半定量逆转录-聚合酶链反应(RT-PCR)、免疫组织化学方法测定42例人脑胶质瘤和8例正常脑组织中Ang-2 mRNA及其蛋白表达情况。用免疫组织化学方法检测肿瘤微血管密度(MVD)。结果 正常脑组织中无或弱表达Ang-2。42例胶质瘤组织中均有Ang-2 mRNA表达,不同级别间Ang-2 mRNA的表达差异有显著性(P<0.05)。随着脑胶质瘤恶性程度的增加,Ang-2 mRNA的表达增高(r=0.894,P<0.01)。免疫组织化学结果显示,胶质瘤细胞及肿瘤血管内皮细胞中均有Ang-2蛋白表达。Ang-2 mRNA表达与MVD、脑水肿指数(EI)显著相关(分别为r=0.853,P<0.01;r=0.784,P<0.01)。结论 Ang-2可能参与胶质瘤血管生成,对胶质瘤瘤周脑水肿及恶性进展有促进作用。     

脑膜瘤的MRI征象与病理分级的关系

目的：研究脑膜瘤的MRI表现及其病理学意义。方法收集57例脑膜瘤标本,分析其MRI征象（包括肿瘤的形态、信号及强化特点、瘤-脑组织界面、瘤周水肿及有无周围组织结构受侵等）,同时观察脑膜瘤的病理分级,对所得的资料进行统计学分析。结果脑膜瘤的形态、信号均匀度、强化均匀度、瘤-脑组织界面、瘤周水肿程度及有无周围组织结构受侵等影像学表现与脑膜瘤的良恶性具有相关性（P＜0.05）。结论脑膜瘤的MRI征象具有一定的特征性,在一定程度上可以反映脑膜瘤的病理特点,达到帮助预测肿瘤良恶性的目的,从而为临床合理选择治疗方案及预后评估提供更大帮助。     

颅内相似部位的血管周细胞瘤与脑膜瘤的MRI影像特点对照初步研究

【摘要】 目的 探讨相似部位颅内血管周细胞瘤与脑膜瘤的MRI特征,以提高鉴别诊断水平,降低误诊率。方法〓收集我院2011年至2015年经手术病理证实的血管周细胞瘤4例与相似部位的脑膜瘤5例,对其MRI表现进行回顾性分析。结果〓左额区血管周细胞瘤1例,脑膜瘤2例;左枕区、左中颅窝底及幕下后颅窝血管周细胞瘤及脑膜瘤均各1例。影像表现分叶征9例(血管周细胞瘤4例;脑膜瘤5例),坏死囊变8例(血管周细胞瘤4例;脑膜瘤4例),血管流空效应4例(血管周细胞瘤4例),瘤周水肿7例(血管周细胞瘤3例;脑膜瘤4例),骨质变化4例(血管周细胞瘤2例,其中1例颅骨转移,1例为邻近骨质破坏;脑膜瘤2例,其中1例骨质硬化,1例骨质破坏),脑膜尾征5例(血管周细胞瘤1例;脑膜瘤4例)。与脑膜瘤相比,血管周细胞瘤的分叶征、瘤周水肿程度及肿瘤内坏死囊变较脑膜瘤更加明显,另外血管周细胞瘤实质部分TIWI信号稍高,可见丰富肿瘤血管,少见脑膜尾征。结论〓在颅内血管周细胞瘤与脑膜瘤的MRI鉴别诊断因素中,肿瘤可见丰富血管影,分叶征程度、瘤内坏死囊变较脑膜瘤明显,颅骨转移等征象,对提高颅内血管周细胞瘤的诊断有一定意义。     

非典型脑膜瘤术后复发影响因素分析

目的分析影响非典型脑膜瘤复发的影响因素。方法回顾性分析2013-01—2016-12间在郑州大学第一附属医院行手术治疗且经病理学证实的94例非典型脑膜瘤患者。通过多因素Cox回归分析方法评价影响术后复发的临床因素。结果94例患者发病年龄12~78岁,男∶女=1∶1.29。82例肿瘤全切除,12例肿瘤次全切除。所有患者术后随访11~66个月,中位时间36个月。其中行手术及辅助放疗43例,仅行手术治疗51例。其间31例肿瘤复发。1 a、3 a无进展生存率分别为87.2%、57.1%,1 a、3 a、5 a总生存率为98.2%、78.1%、73.4%。单因素分析表明年龄≥50岁、非原发性、位于颅底、脑侵犯、Ki67指数>10%及次全切除,与非典型脑膜瘤术后高复发率有关。多因素分析结果表明,年龄、脑侵犯、Ki67指数及切除程度是影响肿瘤复发的独立危险因素。结论非典型脑膜瘤具有高复发率和高病死率,年龄≥50岁、非原发性、位于颅底、脑侵犯、Ki67指数>10%及次全切除与非典型脑膜瘤术后高复发率有关,其中年龄、脑侵犯、Ki67指数及切除程度是影响肿瘤复发的独立危险因素。最大安全范围切除肿瘤是最主要的治疗措施,对于不完全切除的肿瘤和位于矢状窦旁或颅底的肿瘤推荐接受辅助放疗。     

Correlation between the efferent venous drainage of the tumor and peritumoral edema in intracranial meningiomas: superselective angiographic analysis of 25 cases

OBJECT: The extent of peritumoral brain edema (PTBE) associated with meningiomas can be highly variable. The authors studied the correlation between the development of efferent venous drainage from the tumor and the degree of PTBE that occurs in intracranial meningiomas. METHODS: Twenty-five patients with 27 intracranial supratentorial meningiomas were investigated to identify the correlation between the efferent venous drainage system of the tumor and peritumoral edema. The overall mean age of the patients was 54 years. Seventeen patients (68%) were female and eight (32%) were male. All patients underwent magnetic resonance imaging and digital subtraction angiography. In each meningioma, superselective angiography of the dominant feeding artery was performed, including the late venous phase to evaluate the development of the tumor's draining vein. An edema index (EI) was introduced to serve as an objective means by which to judge the extent of PTBE. Eleven meningiomas (41%), in which the mean EI was 0.14 +/- 0.10, clearly showed dominant draining veins originating from the tumor itself. In the other 16 meningiomas (59%), superselective angiography demonstrated no efferent venous drainage from the tumor, which could account for this group's mean EI value of 1.49 +/- 1.05 (p < 0.001). CONCLUSIONS: The current results suggest that hypoplasia of the efferent draining vein from the meningioma itself contributes to PTBE formation. The development of an efferent venous system mitigates against the formation of PTBE. Intratumoral venous congestion can be considered the main cause of PTBE in meningiomas.     

Peritumoral brain edema in meningiomas--influence of vascular supply on its development.

In a series of 35 patients with intracranial meningiomas, factors influencing the development of peritumoral brain edema (PTBE) were analyzed. We used numbers of the Edema Index as the extent of PTBE, which was obtained from the size of the meningioma and associated PTBE on a T2-weighted image of magnetic resonance imaging. We evaluated a relationship between the Edema Index and some factors that may play a role in the development of PTBE. Tumors in the frontal region and at the sphenoid ridge tended to be associated with larger PTBE than those in other locations (P less than 0.05). Histologically, meningotheliomatous and transitional meningiomas tended to be associated with larger PTBE than fibroblastic meningiomas (P less than 0.05). The meningiomas that had a vascular supply from the intrinsic cerebral arteries on angiography significantly correlated with severe PTBE compared with those supplied only from the meningeal side (P less than 0.01). We concluded that location, histology, and vascular supply from intrinsic cerebral arteries were the factors influencing PTBE. It is stressed that the vascular supply from the intrinsic cerebral arteries may have an influence on the extensive PTBE of meningioma.     

VEGF和MVD在术前接受过肝动脉栓塞化疗的肝癌组织中的表达及临床意义

目的探讨血管内皮细胞生长因子(VEGF)和平均微血管密度(MVD)在接受术前经导管肝动脉栓塞化疗(TACE)肝癌细胞中的表达和在二期切除肝癌复发预后中的意义。方法选取91例术前TACE和50例未行TACE肝癌手术切除标本,采用免疫组化方法检测两组标本VEGF、CD34的表达情况和MVD值。分析两组VEGF的表达情况和MVD值的差异,以及62例术前TACE后根治性切除的肝癌中VEGF的表达水平与复发的关系。结果 VEGF表达于肝细胞质中,CD34选择性表达于血管内皮细胞,术前TACE组和未行TACE组VEGF的表达(6.9±4.7vs5.1±4.4)和MVD值(62.0±35.4vs45.6±29.0)差异有统计学意义(P0.05)。术前TACE后根治性二期切除患者,复发组(45例)与未复发组(17例)肿瘤组织中VEGF阳性率分别为82.2%和41.2%,差异有统计学意义(P0.05)。VEGF阳性组1、3、5年无瘤生存率分别为50.9%、%、22.5%,VEGF阴性组分别为88.5%、68.2%、28.153.0%,差异有统计学意义(P0.05)。多因素分析表明治疗前存在播散结节及VEGF的表达水平是影响TACE后二期切除患者复发的独立危险因素。结论 TACE后残癌组织血管生成增多,术前TACE后二期根治性切除肝癌VEGF的表达与患者术后复发转移密切相关。     

Effect of systemic celecoxib on human meningioma after intracranial transplantation into nude mice

Background

Meningiomas are mostly benign, but they may have a notorious tendency to recur when total resection is not possible. Systemic chemotherapeutical treatment has been largely disappointing. The treatment of meningiomas with the cyclooxygenase-2 (COX-2) inhibitor celecoxib showed inhibitory-growth effects in vitro and in vivo after subcutaneous transplantation into mouse. So far, celecoxib has never been tested in an orthotopic model of meningioma. In this work, we tested the effects of celecoxib on the growth of human benign meningiomas after transplantation into the prefrontal cortex of nude mice after confirming the inhibitory in vitro effect on these cells.

Methods

Primary cell cultures were stereotactically implanted into mice and were treated with 0, 750, or 1,500 ppm celecoxib for 3 months. The mice were then killed and blood was analyzed for celecoxib concentration. The mice brains were histologically processed for measurement of tumor volume, COX-2 expression, proliferation index (PI), intratumoral microvessel density (iMVD), and vascular endothelial growth factor (VEGF) expression.

Results

Treatment with celecoxib had no effect on tumor volume, despite the fact that we found a dose-dependent inhibitory effect on cell cultures and there was a sufficiently high celecoxib concentration in blood plasma and brain tissue. Additionally, celecoxib had neither an effect on COX-2 and VEGF expression nor on the PI and iMVD.

Conclusions

Our findings suggest that celecoxib may not be effective on meningioma growth in clinical settings. In general, these results may indicate that the effect of treatment on brain tumors should not only be tested in a heterotopic environment but also in the orthotopic location of these tumors.     

乳腺癌发生与演进过程中血管生成作用的评价

目的 探讨人乳腺癌前病变、原位癌及浸润性癌中CD34、血管内皮生长因子(VEGF)及其受体Flk-1/KDR的表达变化及血管生成异常与乳腺癌发生发展的关系.方法 应用免疫组织化学技术检测30例正常乳腺、30例普通性增生、30例非典型增生(AH)、20例导管内癌、50例浸润性导管癌组织中微血管密度(MVD)、VEGF及Flk-1/KDR的表达.结果 各组CD34、VEGF及Flk-1/KDR的表达程度不同,浸润性导管癌组最高.随病程演进MVD逐渐增加(P<0.05),VEGF及其受体Flk.1/KDR在血管内皮细胞表达渐进性增高(P<0.05),但在病程初期各主要指标改变不明显,显著变化始于AH阶段.MVD在AH与导管内癌组间差异无统计学意义(P>0.05),VEGF及Flk-1/KDR的表达在AH与导管内癌组间差异有统计学意义(P<0.05).结论 血管生成异常可能是乳腺癌发生过程中的早期事件.VEGF及Flk-1/KDR的表达异常可能是乳腺普通性增生-AH-乳腺癌这一癌性转化过程中血管生成异常的主要始动因素,其可能成为乳腺癌早期诊治的靶标.     

白细胞介素6、信号传导和转录活化因子3和血管内皮生长因子在人脑胶质瘤中的表达及相关性研究

目的研究人脑不同级别胶质瘤中白细胞介素（IL）-6，信号传导和转录活化因子3（STAT3）和血管内皮生长因子（VEGF）的表达，探讨IL-6、STAT3和VEGF与肿瘤病理级别和侵袭性的关系。方法采用免疫组织化学法，检测70例人脑胶质瘤，10例脑膜瘤和5例正常脑组织中IL-6、STAT3和VEGF的表达。结果胶质瘤中IL-6、STAT3和VEGF的表达水平在高级别组（Ⅲ、Ⅳ级）明显高于低级别组（Ⅰ、Ⅱ级），两组间差异有统计学意义（P〈0．01），STAT3的表达与IL-6和VEGF的表达均呈正相关（P〈0．01）。结论IL-6、STAT3和VEGF的表达与胶质瘤的恶性程度有密切关系；且三者协同在胶质瘤发生、发展过程中起重要作用。三者的相关性证实VEGF基因由STAT3蛋白调节，而STAT3又由IL-6刺激活化。     

Outcomes of Preserving the Hypertrophic Arachnoid Membrane in the Brain–meningioma Interface: Long-term Follow-up

Abnormal hypertrophic arachnoid membranes are often observed in the brain–meningioma interface during microsurgery. They contain fibrosis and tumor cell clusters; however, preservation of the membranes does not always cause recurrence from the brain surface, and the optimal treatments in the interface remain unclear. We investigated the incidence of recurrence on the brain surface following extra-arachnoid dissection with an approach emphasizing preservation of the arachnoid membranes in meningiomas of World Health Organization (WHO) Grade I. The features of dissection cleavages in the interface were prospectively recorded at surgery. The patients were followed up with MR imaging regularly. In total, 111 patients were included. The median follow-up time was 97.0 (interquartile range [IQR] 70.0–124.0) months. The cleavages in the interface were classified into three subgroups: the Extra-H group (n = 56) with extra-arachnoid resection and preservation of hypertrophic arachnoid membranes, the Extra-N group (n = 39) with extra-arachnoid resection having normal membranes, and the Subpial resection group (n = 16). Tumors recurred in 13 (11.7%) patients at both the brain and dura mater (n = 1) or at the dura mater alone (n = 12). The median recurrence-free survival (RFS) of all recurrences was significantly related to the Simpson grades (P <0.01). For brain surface recurrence, the median RFS was not related to the subgroups. The Karnofsky Performance Scores (KPSs) significantly improved in the patients except for the Subpial group at 3 months after surgery. This study revealed that hypertrophic arachnoid membranes preserved on the brain surface rarely caused recurrence from the brain in WHO Grade I meningiomas after a long-term follow-up.     

Expression of VEGF and collagen XVIII in meningiomas: correlations with histopathological and MRI characteristics

Background

The objective of this study was to assess the possibility of predicting histological characteristics of meningiomas on the basis of preoperative MRI and the correlation of the expression of vascular endothelial growth factor (VEGF) and collagen XVIII with histological parameters already established as predictive of the course of these tumors.

Methods

Expression of VEGF and collagen XVIII as well as other histological characteristics was examined in meningioma tissues from 20 patients. Preoperative MRI, including dynamic imaging of contrast enhancement, was analyzed. Times to maximum enhancement and maximum intensity increase were noted from dynamic imaging. The relative intensity of the tumor in fluid-attenuated inversion recovery (FLAIR), T2-weighted and contrast enhanced T1-weighted images, as well as volumes of tumor and edema, was calculated. The edema-tumor volume ratio was defined as the edema index (EI).

Results

Both VEGF and collagen XVIII were expressed in all meningioma samples. Edema was present in 60 % of cases. The strongest correlation of VEGF expression was to EI. Among histological parameters, microvessel density (MVD) and cellularity correlated moderately with VEGF. Collagen XVIII expression correlated strongly with the maximal intensity increase after contrast agent administration (ρ?=?0.71, P?=?0.001) as well as with MVD and intensity of the meningioma on FLAIR images.

Conclusion

Meningiomas with faster and more intense enhancement in dynamic studies, indicative of good tumor blood supply and permeability of vasculature, are associated with high levels of collagen XVIII and VEGF expression. Occurrence of peritumoral edema in meningiomas is strongly correlated with expression of VEGF.