神经导航联合黄荧光染色技术在小脑幕上胶质瘤切除中的作用

目的探讨神经导航联合黄荧光染色技术在小脑幕上胶质瘤手术中的作用。方法回顾性分析2016年1月至2018年3月于武汉大学中南医院神经外科行手术治疗的172例小脑幕上胶质瘤患者的临床资料。其中55例采用神经导航联合黄荧光染色技术(简称导航+荧光组),117例采用常规手术技术(常规手术组)。81例患者的肿瘤位于功能区,术中均使用神经电生理监测和(或)术中唤醒麻醉技术。对比两组患者的肿瘤全切除率,进一步采用单因素和多因素logistic回归分析影响肿瘤全切除率的相关因素。结果172例患者中,肿瘤全切除者58例(33.7%),其中导航+荧光组的肿瘤全切除率为45.5%(25/55),常规手术组为28.2%(33/117),两组比较差异有统计学意义(P=0.026)。多因素logistic回归分析结果显示,功能区肿瘤(OR=0.502,95%CI:0.253~0.998,P=0.049)、术中应用导航+荧光(OR=2.173,95%CI:1.080~4.371,P=0.030)是影响肿瘤全切除的独立因素。81例功能区肿瘤患者中,肿瘤全切除者21例(25.9%),其中13例(61.9%)术中应用导航+荧光;60例非全切除者中,16例(26.7%)术中应用导航+荧光;两组比较差异有统计学意义(P=0.004)。多因素logistic回归分析显示,术中应用导航+荧光是影响功能区肿瘤全切除的独立因素(OR=3.896,95%CI:1.331~11.405,P=0.013)。结论神经导航联合术中黄荧光染色技术有利于提高脑胶质瘤的切除程度。     

FANCD2 re-expression is associated with glioma grade and chemical inhibition of the Fanconi Anaemia pathway sensitises gliomas to chemotherapeutic agents

Brain tumours kill more children and adults under 40 than any other cancer. Around half of primary brain tumours are glioblastoma multiforme (GBMs) where treatment remains a significant challenge. GBM survival rates have improved little over the last 40 years, thus highlighting an unmet need for the identification/development of novel therapeutic targets and agents to improve GBM treatment. Using archived and fresh glioma tissue, we show that in contrast to normal brain or benign schwannomas GBMs exhibit re-expression of FANCD2, a key protein of the Fanconi Anaemia (FA) DNA repair pathway, and possess an active FA pathway. Importantly, FANCD2 expression levels are strongly associated with tumour grade, revealing a potential exploitable therapeutic window to allow inhibition of the FA pathway in tumour cells, whilst sparing normal brain tissue. Using several small molecule inhibitors of the FA pathway in combination with isogenic FA-proficient/deficient glioma cell lines as well as primary GBM cultures, we demonstrate that inhibition of the FA pathway sensitises gliomas to the chemotherapeutic agents Temozolomide and Carmustine. Our findings therefore provide a strong rationale for the development of novel and potent inhibitors of the FA pathway to improve the treatment of GBMs, which may ultimately impact on patient outcome.     

PTEN基因诱导人脑胶质瘤SHG-44细胞凋亡及bcl-2蛋白表达下调

目的　探讨PTEN基因对人脑胶质瘤SHG 44细胞凋亡及凋亡相关基因bcl 2表达的影响 ,阐明PTEN基因抑制肿瘤细胞增殖的机理。方法　PTEN基因体外转染SHG 44细胞 ,筛选阳性细胞克隆 ,以原位杂交、免疫组化方法检测PTEN基因的表达情况采用透射电镜、流式细胞仪和核DNA琼脂糖凝胶电泳检测细胞的凋亡情况以免疫荧光法检测bcl 2基因的表达。结果　PTEN基因转染的SHG 44细胞有PTEN基因和蛋白的表达。透射电镜下可见转染PTEN基因后细胞核染色质浓缩边集、胞浆浓缩、核碎裂及凋亡小体形成等典型的凋亡表现 ;流式细胞仪示细胞周期从G1 期到S期发生抑制 ,并且在G1 期峰前出现一明显的凋亡峰 (1 2 .9% ) ;细胞核DNA琼脂糖凝胶电泳呈现凋亡细胞特有的梯状条带 ;bcl 2的表达也显著下调。转染空载体和未转染的SHG 44细胞无明显的凋亡表现。结论　PTEN基因可诱导SHG 44细胞凋亡 ,并下调bcl 2蛋白的表达 ,这可能是PTEN基因抑制肿瘤细胞增殖的分子机制之一     

岛叶低级别胶质瘤的显微外科治疗

目的 探讨显微手术切除岛叶低级别胶质瘤的方法和效果。方法 对30例岛叶低级别胶质瘤病人的临床资料进行回顾性分析。结果 肿瘤全切除12例，近全切除14例，部分切除4例，无手术死亡。术后早期偏瘫6例、失语3例、偏瘫和失语3例，经术后3个月随访，仍有2例轻偏瘫、1例失语。结论 经外侧裂入路应用显微外科技术是治疗岛叶低级别胶质瘤的较理想方法。     

Phase II trial of intravenous lobradimil and carboplatin in childhood brain tumors: a report from the Children’s Oncology Group

Backround: Lobradimil is a synthetic bradykinin analog that rapidly and transiently increases the permeability of the blood-brain barrier (BBB). The combination of lobradimil and carboplatin was studied in pediatric patients with primary brain tumors in a phase II trial, the primary endpoints of which were to estimate the response rate and time to disease progression. Patients and methods: Patients were stratified by histology into five cohorts: brainstem glioma, high-grade glioma, low-grade glioma, medullobastoma/primitive neuroectodermal tumor (PNET), and ependymoma. Patients received carboplatin adaptively dosed to achieve a target AUC of 3.5 mg min/ml per day (7 mg·min/ml/cycle) intravenously over 15 min on 2 consecutive days and lobradimil 600 ng/kg ideal body weight/day on 2 consecutive days each 28 day cycle. Results: Forty-one patients, age 2–19 years, were enrolled; 38 patients, including 1 patient ultimately determined to have atypical neurocytoma, were evaluable for response. No objective responses were observed in the brainstem glioma (n=12) and high-grade glioma (n=9) cohorts, although two patients with high-grade glioma had prolonged disease stabilization (>6 months). The study was closed for commercial reasons prior to achieving the accrual goals for the ependymoma (n=8), medulloblastoma/PNET (n=6) and low-grade glioma (n=2) cohorts, although responses were observed in 1 patient with PNET and 2 patients with ependymoma. Conclusion: The combination of lobradimil and carboplatin was inactive in childhood high-grade gliomas and brainstem gliomas.     

葡萄糖转运体在脑胶质瘤中的表达及其意义

目的 观察葡萄糖转运体(GLUT1、GLUT3)在脑胶质瘤中的表达及其意义。方法 应用Northern blot技术检测不同级别脑胶质瘤葡萄糖转运体mRNA表达情况，用Western blot检测葡萄糖转运体的蛋白水平。结果 Ⅰ／Ⅱ级、Ⅲ级、Ⅳ级胶质瘤GLUT1 mRNA／肌动蛋白(actin)mRNA分别为0．12、0．17、0．21；4．2kb GLUT3 mRNA／actin mRNA分别为0．178、0．568、0．710；2．7kb GLUT3 mRNA／actin mRNA分别为0．075、0．216、0．406。随着脑胶质瘤分级的增高，GLUT1／actin转录物比率有随之增加的趋势，但无显著相关。4．2kb GLUT3是2种转录物中丰度较高的一种，2种转录物的GLUT3／actin比率与胶质瘤的分级呈线性正相关。结论 恶性胶质瘤细胞可能分泌某种因子增强GLUTs mRNA表达，但抑制GLUT1 mRNA翻译而促进GLUT3蛋白表达，使GLUT3成为供应恶性胶质细胞能量代谢底物的主要载体。     

CREPT对胶质瘤U251细胞增殖、侵袭和迁移的影响及机制

目的 探讨肿瘤高表达细胞周期相关蛋白（CREPT）对胶质瘤U251细胞增殖、侵袭和迁移的影响及可能机制。方法 体外培养人胶质瘤细胞株U373、U251、A172、U87-MG、SHG44,并构建过表达或沉默CREPT的U251细胞;免疫印迹法检测蛋白表达水平;CCK-8法检测细胞增殖能力;Transwell实验检测细胞侵袭能力;细胞划痕实验检测细胞迁移能力。结果 U251细胞CREPT蛋白表达水平最高,SHG44细胞最低。沉默CREPT后,U251细胞增殖、侵袭和迁移能力明显下降（P<0.05）,p-Wnt和p-β-catenin蛋白表达水平下降（P<0.05）。过表达CREPT后,U251细胞增殖、侵袭和迁移能力明显增强（P<0.05）,p-Wnt和p-β-catenin蛋白水平明显升高（P<0.05）。Wnt/β-catenin通路抑制剂KYA1797K可逆转过表达CREPT对细胞增殖、侵袭和迁移的影响（P<0.05）。结论 CREPT可能通过激活Wnt/β-catenin通路促进胶质瘤U251细胞的增殖、侵袭和迁移。     

光动力联合顺铂治疗大鼠脑胶质瘤的生存期观察

目的 探讨光动力（PDT）联合顺铂治疗大鼠脑恶性胶质瘤的杀伤效应、机制及对大鼠生存期影响.方法 健康Wistar雄性大鼠30只,体重280～300g,建立C6胶质瘤模型,2周后随机分为3组,对照组、顺铂治疗组、PDT联合顺铂治疗组,分别进行生存观察和生存分析.结果 大鼠平均生存时间：对照组（38.2±3.5）d,顺铂组（39.6±4.0）d,PDT联合顺铂组（41.9±4.0）d.联合顺铂组与对照组及顺铂组比较,生存分析曲线差异有显著性（P〈0.05）.结论 光动力（PDT）联合顺铂治疗对大鼠脑胶质瘤有明显的杀伤和抑制作用,光动力开放血脑屏障、血瘤屏障后为化疗药物有效作用于肿瘤组织提供新途径,延长大鼠生存期.     

人脑胶质瘤表皮生长因子受体表达及预后的相关性研究

目的　检测表皮生长因子受体 (EGFR)蛋白在人脑瘤中的表达 ,探讨EGFR表达与胶质瘤病理分级、患者年龄、肿瘤大小和预后的关系。方法　应用免疫组化方法检测 46例人脑胶质瘤标本中EGFR表达 ,分析其与胶质瘤恶性程度、年龄、肿瘤大小和预后的关系。结果　低分化胶质瘤 (WHOⅢ +Ⅳ级 )EGFR表达 69.57% (1 6/ 2 3) ,高分化胶质瘤 (WHOⅠ +Ⅱ级 )EGFR表达 30 .43 % (7/ 2 3) ,两者之间差异显著 (P <0 .0 1 ) ;EGFR表达与胶质瘤病理分级呈正相关 (r =0 .6882 ,P <0 .0 0 1 )EGFR表达阳性与阴性患者生存时间差异显著 (P <0 .0 5)。结论　EGFR在胶质瘤的发生、发展中起重要作用 ,与肿瘤分化程度、患者预后密切相关 ,与患者年龄及肿瘤大小无关     

Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features – “Ependymosarcoma”

By analogy to gliosarcoma, the term “ependymosarcoma” has recently been coined to thematize the rare phenomenon of a malignant mesenchymal component arising within an ependymoma. We report on an example of this paradigm, involving tanycytic ependymoma as the host tumor in a 40-year-old female who underwent two tumor extirpation procedures at one-year interval. She first presented with severe headaches, and was seen by imaging to harbor a moderately enhancing mass 2.5 cm in diameter at the rostral septum pellucidum accompanied by occlusive hydrocephalus. Microscopically, the tumor consisted of solid, wavy fascicles of elongated cells that were occasionally interrupted by vague perivascular pseudorosettes. Mitotic activity was absent, and less than 1% of nuclei immunoreacted for MIB-1. A histological diagnosis of tanycytic ependymoma (WHO grade II) was rendered, and no adjuvant therapy given. At recurrence, the lesion was 3.5 cm in diameter, intensely enhancing, and had already seeded into the subarachnoid space. Histology showed a biphasic glial–sarcomatous architecture with remnants of the original ependymoma now displaying hypercellularity and atypical – yet not frankly anaplastic – features. The sarcomatous moiety consisted of spindle and epithelioid cells densely interwoven with reticulin fibers. While the ependymal component was GFAP and S100 protein positive, and featured punctate staining for EMA, none of these markers was expressed in the adjacent sarcoma. Instead, the latter reacted for vimentin and smooth muscle actin. To the best of our knowledge, this is the first documentation of tanycytic ependymoma undergoing malignant transformation, one driven by a highly anaplastic mesenchymal component, corresponding to “ependymosarcoma”.