联合应用mTI-ASL和IVIM技术在鉴别高级别胶质瘤术后复发与假性进展中的应用价值

目的: 探讨应用多反转时间动脉自旋标记(multiple inversion time-pulsed arterial spin labeling,mTI-ASL)和体素内不相干运动(intravoxel incoherent motion,IVIM)技术在脑胶质瘤术后复发与假性进展中的鉴别价值。方法: 选择2018年01月至2020年01月就诊于我院高级别胶质瘤术后放化疗后首次复查常规MR增强扫描出现异常强化的患者,行mTI-ASL及IVIM序列扫描,将获取图像数据资料进行相关后处理分析,分别手动勾画感兴趣区,测量术后异常强化区各项定量参数,即真性扩散系数(true diffusion coefficient,D)、假性扩散系数(pseudo-diffusion coefficient,D*)及灌注分数(perfusion fraction,f)、脑血流量(cerebral blood flow,CBF)和动脉通过时间(arterial transit time,ATT)。分别采用独立样本t检验比较两组感兴趣区相关参数值,从而评估mTI-ASL和IVIM技术在两者鉴别诊断中的价值。结果: (1)脑胶质瘤术后复发组CBF值(6.413±0.438)、ATT值(0.198±0.033),比假性进展组CBF值(4.654±0.372)、ATT值(0.165±0.208)高,两者比较具有统计学意义(P＜0.01)。(2)脑胶质瘤术后复发组D值(1.118±0.178),比假性进展组D值(1.380±0.236)低,两者比较具有统计学意义(P＜0.01)。(3)脑胶质瘤术后复发组D*值(17.126±4.274)、f值(0.269±0.095),比假性进展组D*值(12.755±3.974)、f值(0.169±0.052)高,两者比较具有统计学意义(P＜0.01)。结论:应用 mTI-ASL和IVIM技术有助于脑胶质瘤术后复发与假性进展的鉴别诊断。     

多模态技术联合术中唤醒麻醉在Broca区胶质瘤患者语言功能区定位中的作用

目的探讨多模态技术联合术中唤醒麻醉在Broca区胶质瘤患者语言功能区定位中的作用和手术疗效。方法回顾性分析2011年1月至2017年12月复旦大学附属华山医院神经外科行手术切除的Broca区胶质瘤患者的临床资料,共42例。术前采用功能磁共振成像和弥散张量成像技术重建语言皮质激活区域和皮质下传导通路,术中在唤醒麻醉下通过直接电刺激技术定位语言皮质和皮质下传导通路,并在术中磁共振、实时神经影像导航系统引导下行肿瘤切除。根据肿瘤是否侵犯中央前回腹侧部(vPMC)将患者分为未侵犯vPMC(仅侵犯额下回后部)组24例,侵犯vPMC组18例,评估并比较两组患者语言功能区定位情况和疗效。结果42例患者均完成术中语言功能区定位,34例(81.0%)至少有1个阳性定位点;3例(7.1%)在定位过程中出现癫痫局灶性发作。25例患者肿瘤为全切除,17例为非全切除。术后病理学证实世界卫生组织(WHO)肿瘤分级Ⅱ级者23例,Ⅲ级者14例,Ⅳ级者5例。术后1个月内(近期)16例(38.1%)患者有语言功能障碍,其中12例3个月内恢复,4例(9.5%)未恢复。术后所有患者随访6~84个月(中位数为24个月),14例出现肿瘤进展,其中11例死亡。与未侵犯vPMC组比较,侵犯vPMC组肿瘤的WHO级别高(P=0.011),术后近期语言功能障碍的发生比率高[分别为10/18、25.0%(6/24),P=0.044],无进展生存期[分别为(28.4±5.2)个月、(80.7±3.2)个月]和总生存期[分别为(38.8±5.8)个月、(80.8±3.2)个月]均短。差异均有统计学意义(均P<0.001)。结论多模态技术联合术中唤醒麻醉治疗Broca区胶质瘤有助于在最大化切除肿瘤的同时,保护患者的语言功能。其中肿瘤侵犯vPMC比仅侵犯额下回后部者引起近期语言功能障碍率更高,预后更差。     

Orbitofrontal extensions of the insular glioma based on subdivision of the uncinate fasciculus

The insular gliomas were classified based on their locations and extensions to the adjacent areas.The insular and orbitofrontal cortices with underlying fiber tracts were studied on ten (20 sides) human cadaveric brains and two heads. Twenty patients with insular gliomas with the orbitofrontal or septal region extensions were studied on preoperative magnetic resonance imaging (MRI).Insular gliomas can extend to the orbitofrontal area dorsolaterally and/or ventromedially through the subdivision of the uncinate fasciculus. The dorsolateral part of the uncinate fasciculus interconnects the temporopolar area to the lateral orbitofrontal cortex through insula, and the ventromedial part of the uncinate fasciculus interconnects the temporopolar area to the medial orbital cortex, gyrus rectus, and septal region. The gyrus rectus infiltration on MRI indicates a ventromedial involvement by passing through the ventromedial part of the uncinate fasciculus. Diffusion tensor imaging (DTI) MRI demonstration of the UF is difficult due to the interruption of the fiber tracts by tumor. Tumor infiltration extending to the gyrus rectus requires a 15° lateral tilting with vertex toward contralateral side, as well as 70° head rotation to the contralateral side of lesion, for exposure of frontal base, septal region, and lateral border of the anterior perforating substance at the same time with the exposure of whole sylvian fissure via transsylvian approach of the insular tumors.An understanding of the orbitofrontal extension of the insular tumor based on the subdivisions of UF is useful in preoperative surgical planning and can assist for gross total resection.     

lncRNA MLK7-AS1通过抑制miR-375的表达促进胶质瘤U251细胞的增殖和侵袭

目的 探讨长链非编码RNA（lncRNA）MLK7-AS1在人脑胶质瘤组织中表达及其对胶质瘤U251细胞增殖、侵袭的影响。方法 选择2016~2017年手术切除的脑胶质瘤组织标本45例，2007版WHO分级Ⅰ级8例，Ⅱ级15例，Ⅲ级10例，Ⅳ级12例。另选择其中10例瘤旁正常脑组织作对照。体外培养U251细胞和人正常星形胶质细胞（NHA）。U251细胞根据转染质粒分成四组:转染miR-375 mimic组、转染si-MLK7-AS1组、同时转染miR-375 inhibitor和si-MLK7-AS1组以及只转染miR-375 inhibitor组。RT-qPCR检测MLK7-AS1和miR-375的表达水平；荧光素酶报告基因实验验证MLK7-AS1与miR-375之间的关系；CCK-8法检测U251细胞增殖活性，Transwell实验检测U251细胞侵袭能力。结果 高级别胶质瘤组织MLK7-AS1表达水平明显高于低级别胶质瘤组织（P<0.05），而后者明显高于瘤旁正常脑组织（P<0.05）；高级别胶质瘤组织miR-375表达水平明显低于低级别胶质瘤组织（P<0.05），而后者明显低于瘤旁正常脑组织（P<0.05）。U251细胞MLK7-AS1表达水平明显高于NHA（P<0.05），miR-375表达水平明显低于NHA（P<0.05）。序列分析显示MLK7-AS1和miR-375 存在特异性结合序列，荧光素酶报告基因实验表明U251细胞MLK7-AS1负调控miR-375表达。沉默MLK7-AS1表达通过上调miR-375表达明显抑制U251细胞增殖和侵袭（P<0.05）。结论 lncRN AMLK7-AS1可能通过调节miR-375的表达水平在人脑胶质瘤中发挥着促癌的作用     

lncRNA RGMB-AS1在脑胶质瘤预后评估中的价值

目的 探讨长链非编码RNA（lncRNA）RGMB-AS1在脑胶质瘤病人预后评估中的作用。方法 选取2014年9月~2017年6月经术后病理检查证实的脑胶质瘤140例（低级别64例，高级别76例），另选取颅脑损伤内减压术中切取正常脑组织25例为对照。实时荧光定量PCR法检测lncRNA RGMB-AS1的表达水平，以RGMB-AS1表达量的中位数为截断值，分为高表达组和低表达组。用Kaplan-Meier法比较总体生存期（OS）和无进展生存期（PFS），用Cox比例回归风险模型分析影响胶质瘤病人预后的因素。结果 140例胶质瘤中，lncRNA RGMB-AS1高表达70例，低表达70例。胶质瘤组织lncRNA RGMB-AS1的相对表达量明显高于对照组（P<0.05）。多因素Cox比例回归风险模型分析结果显示年龄≥50岁、术前KPS评分<80分、WHO分级Ⅲ~Ⅳ级、lncRNA RGMB-AS1高表达是胶质瘤病人PFS和OS的独立影响因素（P<0.05）。lncRNA RGMB-AS1高表达胶质瘤病人PFS和OS较低表达病人均明显缩短（P<0.05）。无论是高级别胶质瘤，还是低级别胶质瘤，lncRNA RGMB-AS1高表达病人PFS和OS较低表达病人均明显缩短（P<0.05）。结论 lncRNA RGMB-AS1表达水平与脑胶质瘤病例级别呈正相关，lncRNA RGMB-AS1高表达脑胶质瘤病人生存期较低表达病人明显缩短。这提示lncRNA RGMB-AS1表达水平可作为脑胶质瘤病人预后评估指标。     

The flavonoid rutin and its aglycone quercetin modulate the microglia inflammatory profile improving antiglioma activity

Microglia cells are the immune effector in the Central Nervous System (CNS). However, studies have showed that they contribute more to glioma progression than to its elimination. Rutin and its aglycone quercetin are flavonoids present in many fruits as well as plants and have been demonstrated to bear anti-inflammatory, antioxidant and antitumor properties also to human glioblastoma cell lines. Previous studies also demonstrated that rutin, isolated from the Brazilian plant Dimorphandra mollis Bent., presents immunomodulatory effect on astrocytes and microglia. In this study, we investigate the antitumor and immunomodulatory properties of rutin and its aglycone quercetin on the viability of glioma cells alone and under direct and indirect interaction with microglia. Flavonoid treatment of rat C6 glioma cells induced inhibition of proliferation and migration, and also induced microglia chemotaxis that was associated to the up regulation of tumor necrosis factor (TNF) and the down regulation of Interleukin 10 (IL-10) at protein and mRNA expression levels, regulation of mRNA expression for chemokines CCL2, CCL5 and CX3CL1, and Heparin Binding Growth Factor (HDGF), Insulin-like growth factor (IGF) and Glial cell-derived neurotrophic factor (GDNF) growth factors. Treatment of human U251 and TG1 glioblastoma cells with both flavonoids also modulated negatively the expression of mRNA for IL-6 and IL-10 and positively the expression of mRNA for TNF characterizing changes to the immune regulatory profile. Treatment of microglia and C6 cells either in co-cultures or during indirect interaction, via conditioned media from glioma cells treated with flavonoids or via conditioned media from microglia treated with flavonoids reduced proliferation and migration of glioma cells. It also directed microglia towards an inflammatory profile with increased expression of mRNA for IL-1β, IL-6, IL-18 and decreased expression of mRNA for nitric oxide synthase 2 (NOS2) and prostaglandin-endoperoxide synthase 2 (PTGS2), arginase and transforming growth factor beta (TGF-β), as well as Insulin-like growth factor (IGF). Treatment of U251 cells with flavonoids also reduced tumorigenesis when the cells were xenotransplanted in rat brains, and directed microglia and also astrocytes in the microenvironment of tumor cell implantation as well as in the brain parenchyma to a not favorable molecular inflammatory profile to the glioma growth, as observed in cultures. Together these results demonstrate that the flavonoid rutin and its aglycone quercetin present antiglioma effects related to the property of modulating the microglial inflammatory profile and may be considered for molecular and preclinical studies as adjuvant molecules for treatment of gliomas.     

A pediatric case of anaplastic astrocytoma with a gliomatosis cerebri; the growth pattern and changes in serum VEGF-121 levels after bevacizumab treatment

Gliomatosis cerebri (GC) is a rare diffusely infiltrating glial neoplasm that carries a poor prognosis. Because tumors are undetectable in most patients at early-stage of the onset, a useful diagnostic method is expected. We compared serum vascular endothelial growth factor (VEGF)-121 levels in patients with GC or glioblastoma and controls. VEGF-121 levels were significantly higher in one patient with GC and patients with glioblastoma than in controls. VEGF-121 levels decreased in a patient with GC after bevacizumab-based therapy. Thus, VEGF-121 may be useful for diagnosing GC, its disease-monitoring and understanding its etiology.     

Inhibition of BCNU-Resistance in Glioma Cell Lines by Small Interfering Rna Targeting to Interleukin-8 Gene

It had been found that interleukin-8 （IL-8） was associated with drug resistance. We previously demonstrated that the resistance to 1, 3-bis （2-chloroethyl）-1-nitrosourea （BCNU） of glioma cell line SWOZI was much higher than that of cell line SOWZ2, which were both cloned from the same parental glioma cell line SWO38. In this study, IL-8 was found to be upregulated both in SWOZ1 and SWOZ2-BCNU, a BCNU-resistant glioma cell line. To further investigate the function of IL-8, the BCNU-resistant cell lines SWOZ1 and SWOZ2-BCNU were treated with siRNAs targeting IL-8. The results of quantitative RT-PCR showed that a decreased level of IL-8 mRNA expression in SWOZI and SWOZ2-BCNU for more than 90% compared to negative control and was confirmed by western blot assay （P 〈 0.05） after treated by siRNAs targeting IL-8. Subsequently, the cytotoxicity of BCNU to these cell lines was detected using the cell counting kit-8 assay. As a result, the BCNU resistance was reversed for about 50% both in these two cell lines （P 〈 0.05）. Our data demonstrated that inhibition of IL-8 with specific siRNAs can reverse the BCNU resistant phenotype in glioma cell lines, indicating that IL-8 may play an important role in BCNU-resistance in glioma.     

Alterations in the Cellular Immune Response of Patients with Cerebral Glioma,Benign Intracranial Tumour,and Spontaneous Subarachnoid Haemorrhage Measured In Vitro by the Leucocyte Migration Inhibition Test

Leucocyte migration inhibition in response to ubiquitous antigens was studied in 104 patients as an in vitro indicator of cell-mediated immunity. Patients with cerebral glioma, benign intracranial tumours, and subarachnoid haemorrhage demonstrated impaired inhibition of leucocyte migration compared with control subjects. The greatest impairment occurred in patients with subarachnoid haemorrhage, while the least impairment was seen in patients with glioma. Significant rises in inhibition of leucocyte migration in response to antigen preparations from glioma and normal brain were seen in the early post-operative period in patients with glioma and subarachnoid haemorrhage. Impaired cellular immunity, together with sensitivity of lymphocytes to brain-derived antigens, are features of cerebral disease in general and not specific for glioma.