Preirradiation ifosfamide,carboplatin, and etoposide (ICE) for the treatment of high-grade astrocytomas in children

Background Astrocytomas are the most common form of primary intracranial tumor; however, survival of patients with high-grade tumors has not changed much compared with that reported in the early 1970s.Objective Our objective was to assess the efficacy, security, and survival rate of postoperative chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) in pediatric patients with anaplastic astrocytomas (AA) and glioblastoma multiforme (GM).Methods In a phase II study, we evaluated 25 children with AA or GM. The proposed treatment was four courses of chemotherapy with ICE followed by hyperfractionated radiotherapy, and then four more courses of ICE. Patients were evaluated using MRI after surgery, after the second course of chemotherapy, and again after the last. Toxicity was determined before each course.Results The overall and disease-free survival at 60 months was 67% and 56% respectively. For supratentorial localization it was 92% at 60 months and 20% at 18 months for brain stem tumors. Fourteen patients had a complete response and 9 died as a result of tumor progression.Conclusions Postoperative chemotherapy with ICE reduces the tumor size and increases the survival rate of pediatric patients with malignant astrocytomas with minimal toxicity.A commentary on this paper is available at     

Regulation of monocyte chemoattractant protein-1 expression in adult human non-neoplastic astrocytes is sensitive to tumor necrosis factor (TNF) or antibody to the 55-kDa TNF receptor

Infiltration of the central nervous system (CNS) by monocytes is a characteristics of many non-malignant disease processes, although the signals regulating such traffic are unclear. Tumor necrosis factor (TNF) and other inflammatory cytokines have been shown to elicit production of monocyte chemoattractant activity in glioma cells, but the regulation of such activity in non-neoplastic adult astrocytes has not been examined. We previously observed that TNF constituted a proliferative signal for non-neoplastic adult human astrocytes in vitro involving the 55-kDa TNF receptor. In the present study, we demonstrate that TNF exposure enhances the expression of monocyte chemoattractant protein-1 (MCP-1) mRNA and functional monocyte chemoattractant activity in non-neoplastic astrocytes. Results indicated that MCP-1 mRNA expression was maximal within 3 h, and was further augmented by the protein synthesis inhibitor cycloheximide (CY). Antibody (htr-9) directed against the 55-kDa TNF receptor also elicited MCP-1 mRNA expression while antibody to the 75-kDa TNF receptor (utr-1) was ineffective. Secretion of monocyte chemoattractant activity was significantly greater in TNF- or htr-9-treated astrocytes than in utr-1-treated or untreated controls; activity was abolished by treatment with antibody to MCP-1. These findings suggest that non-neoplastic adult human astrocytes may contribute to CNS inflammatory responses by mediating recruitment of peripheral blood monocytes.     

合并结节性硬化复征的室管膜下巨细胞型星形细胞瘤(附9例报告)

目的探讨合并结节性硬化复征的室管膜下巨细胞型星形细胞瘤患者的l临床、影像学以及病理学表现特征。方法对1998—2005年收治的9例合并结节性硬化复征的室管膜下巨细胞型星形细胞瘤患者的临床和影像学表现、病理学特点、治疗原则及随访结果进行回顾分析。结果9例室管膜下巨细胞型星形细胞瘤均位于室间孔周围，符合结节性硬化复征的临床诊断标准；男女之比为8：1。CT检查肿瘤实体部分呈等或稍高密度，肿瘤边界清楚，瘤内有钙化灶。MRI扫描T1WI肿瘤实体部分多呈等信号，少数可呈稍低信号；T2WI呈等或稍高信号；增强扫描肿瘤实体部分呈均匀强化。其中8例同时伴室管膜下结节，5例伴有皮质结节。其中6例经额叶皮质入路，3例经胼胝体一穹窿间入路切除肿瘤；肿瘤完全切除者7例，次全切除（〉90％）者2例，无一例手术死亡。随访2—8年，肿瘤完全切除者无复发。结论室管膜下巨细胞型星形细胞瘤为结节性硬化复征的特征性病变，手术完全切除者预后良好。结节性硬化复征所伴室管膜下病变如位于室间孔周围，引起脑积水或呈现逐渐生长趋势者。应考虑室管膜下巨细胞型星形细胞瘤的诊断，尽早施行手术治疗。     

Post-laminectomy rotokyphoscoliosis causing paraplegia in long term: case report

CONTEXT: Childhood laminectomy can lead to spinal deformity. This is a report of a case of paraplegia caused by rotokyphoscoliosis, a late complication of laminectomy. FINDINGS: A 55-year-old woman developed paraplegia due to post-laminectomy kyphoscoliosis. She had surgery for a spinal tumor at age 13 years. She developed kyphosis 2 years after the laminectomy, which has been gradually progressing over the years. She experienced weakness of lower limbs that progressed to paraplegia. There was no evidence for tumor recurrence. To our knowledge, this is the first reported case of post-laminectomy kyphoscoliosis causing late-onset paraplegia. Conclusions/clinical relevance: This case highlights a possible long-term complication of laminectomy without stabilization or untreated kyphoscoliosis. Children should be followed closely after laminectomy because development of spinal deformity is very common. Without intervention, the kyphosis might progress and in the long term, serious neurological complications may result, including paraplegia.     

Cyclin D1、Rb和P16基因在脑星形细胞瘤中表达的研究

 目的通过检测脑星形细胞瘤组织中Cyclin D1、Rb和P16基因蛋白表达,分析其表达变化与不同病理类型肿瘤的相关性.方法选用54例Ⅰ～Ⅳ级星形细胞瘤手术后存档蜡块标本为实验标本,应用流式细胞术(FCM)分别定量检测Ⅰ～Ⅳ级星形细胞瘤组织中Cyclin D1、Rb和P16基因蛋白表达量.结果Cyclin D1蛋白的表达量随肿瘤恶性度的升高而显著增加,与病理组织学分级呈明显相关性(P＜0.01);Rb蛋白和P16蛋白表达量(F1值)在低恶性组升高,高恶性组降低,两组相比差异有显著性意义(P＜0.05或P＜0.01).结论Cyclin D1基因蛋白表达随星形细胞瘤恶性度升高而增强;Rb和P16在高恶性度星形细胞瘤均有不同程度的表达缺失,说明细胞周期调节因子的改变在肿瘤的演化中起重要作用.     

人脑星形细胞肿瘤中FHIT、PCNA蛋白表达关系的研究

目的研究人脑星形细胞肿瘤中FHIT、PCNA蛋白的差异表达，探讨它们与病理分级之间的关系。方法应用免疫组化SP法检测了50例星形细胞肿瘤中不同级别的FHIT、PCNA蛋白的表达水平，以10例非肿瘤脑组织作对照。结果非肿瘤脑组织FHIT、PCNA蛋白阳性表达率分别为100％，0％，星形细胞肿瘤中FHIT、PCNA蛋白阳性表达率分别为40％，86％；尽管在星形细胞肿瘤中FHIT、PCNA蛋白表达总体差异有统计学意义（P〈0．05），但Ⅲ级与Ⅳ级比较差异无统计学意义（P〉0．05）；经统计学分析FHIT、PCNA蛋白呈显著负相关（P〈0．01）。结论FHIT、PCNA蛋白的表达可能与星形细胞肿瘤的恶性程度有关，星形细胞肿瘤中FHIT、PCNA蛋白表达之间的显著负相关，提示FHIT蛋白可能对细胞增殖具有负性调控作用。     

星形细胞瘤的术后放射治疗疗效及预后

目的　探讨星形细胞瘤的术后放射治疗疗效及预后影响因素。方法　对可评价的 2 0 1例星形细胞瘤术后患者进行回顾性分析 ,其中Ⅰ～Ⅱ级 6 2例 (30 .8% ) ,Ⅲ～Ⅳ级 139例 (6 9.2 % ) ,年龄 <4 0岁 117例(5 8.2 % ) ,>4 0岁 84例 (41.8% ) ;手术全切 85例 ,次全切 116例 ;卡氏评分≥ 70分者 16 3例 ;≤ 6 0分者 38例。所有病例均为术后 3周～ 1月内进行放疗 ,射线选60 Coγ射线。结果　Ⅰ～Ⅱ级和Ⅲ～Ⅳ级 1、3、5年存活率分别为95 .2 %、85 .5 %、5 4 .8%和 81.3%、2 1.6 %、10 .8% ,其中 3、5年存活率低分级组与高分级组相比均有非常显著性差异。年龄 <4 0岁组的 3、5年存活率显著高于年龄 >4 0岁组 ,卡氏评分 70以上者预后明显好于 70分以下者 ,5年存活率分别为 30 .1%和 0。结论　星形细胞瘤患者术后辅以放疗是提高疗效的重要手段 ,年龄、病理分级、健康指数、手术方法等是影响星形细胞瘤术后放射治疗预后的重要因素。     

环氧化酶-2和表皮生长因子受体在星形细胞瘤中表达的意义

目的探讨环氧化酶-2（COX-2）、表皮生长因子受体（EGFR）在星形细胞瘤中的表达及其相关性。方法用免疫组织化学s—p法检测68例不同病理级别星形细胞瘤组织与5例正常脑组织中COX-2、EGFR及PCNA蛋白的表达,并计算增殖指数（PI）,分析COX-2表达与EGFR及PI之间的相关性。结果正常脑组织中COX-2、EGFR表达均为阴性,高度恶性组的COX-2阳性表达率明显高于低度恶性组（73．53％vs 44．18％,P〈0．01）,高度恶性组PI（％）明显高于低度恶性组和对照组（46．11±10．68VS23．0g4-6．25,4．52±0．95,P〈0．01）。在低度恶性组与高度恶性组中,COX-2表达阳性的肿瘤其PI明显高于阴性者（P〈0．01）。高度恶性组的EGFR阳性表达率明显高于低度恶性组（67．65％vs38．24％,P〈0．01）。COX-2蛋白在EGFR阳性组的表达明显高于阴性组。结论COX-2、EGFR的表达与星形细胞瘤的病理分级有关,COX-2可促进肿瘤细胞增殖,并与EGFR的表达密切相关,EGFR信号通路可能参与COX-2表达的调控。     

人脑星形细胞瘤中组蛋白修饰方式及意义

目的探讨组蛋白修饰与人脑星形细胞瘤发生及病理分级的关系。方法选取西京医院神经外科2006年至2008年经病理证实的星形细胞瘤患者肿瘤组织标本67例和正常脑组织标本10例,通过免疫组化方法,检测组蛋白3个位点（H3K4diMe、H4K12Ac、H3K18Ac）的修饰水平。结果在正常脑组织中组蛋白3个位点均无修饰;在星形细胞瘤中均有修饰,有2个位点（H3K4diMe、H4K12Ac）的修饰水平随星形细胞瘤病理级别的增高而升高,且呈现明显差异（P〈0．05）,但H3K18Ac的修饰水平并末随肿瘤病理级别的增高发生显著变化。结论组蛋白修饰与人脑星形细胞瘤的发生有关,且修饰水平的变化与病理级别相关。