原发性中枢神经系统淋巴瘤(PCNSL)是一种罕见的结外非霍奇金淋巴瘤,可累及脑,眼、软脑膜以及脊髓,具有高度侵袭性.PCNSL对放化疗及免疫治疗敏感,但单方案常短期内复发.目前公认的治疗包括诱导治疗和巩固治疗.本文就原发性中枢神经系统淋巴瘤的发病、进展以及治疗的研究进展做一综述.

Background: MicroRNAs are found to be aberrantly expressed in multiple cancers, including glioblastoma (GBM), and microRNA-221 (miR-221) has been verified as an oncogene in various human cancers. Nevertheless, the role of miR-221 in GBM is unclear. This study aimed to investigate the miR-221 expression level in GBM and to evaluate its function and underlying mechanisms. Methods: Western blotting and qPCR were used to determine the expression of human hedgehog-interacting protein (HHIP) and miR-221 levels. MiR-221-inhibited cell models were constructed, and siRNA was used for HHIP silencing. Cell proliferation was analyzed by MTT and colony formation assays and a subcutaneous xenograft model. Cell migration and invasion was analyzed by wound healing and Transwell invasion assays. A dual luciferase reporter assay system was used to clarify the relationship between miR-221 and HHIP. Results: The results of this study revealed that miR-221 expression was upregulated in GBM tissues and A172, U251, as well as T98G cells, as detected by real-time PCR analysis. MTT, Transwell, and colony formation assays revealed that miR-221 knockdown could suppress GBM cells from proliferating, migrating, and invading in vitro. Moreover, animal experiments showed that tumor growth in vivo was inhibited when miR-221 expression decreased. Furthermore, HHIP was predicted and verified to be a target of miR-221 by bioinformatics analysis, and luciferase and western blot assays. In addition, HHIP silencing rescued the suppressive effect of a miR-221 inhibitor on the proliferation, migration, and invasion of GBM cells. Conclusions: Our results indicated that miR-221 is upregulated in GBM and enhances tumor progression by targeting HHIP, which suggests this may be a potential therapeutic target for GBM.

目的:探讨后路显微镜辅助硬膜内病变切除联合脊柱内固定术治疗硬膜内转移癌的手术效果.方法:回顾性分析我院骨科2011年1月～2016年1月收治的随访资料完整的硬膜内转移癌患者10例.所有患者均采用后路显微镜辅助硬膜内病变切除联合脊柱内固定术.其中男性6例,女性4例,年龄44～63岁,中位年龄为55岁,原发肿瘤包括肺癌3例,乳腺癌3例,肾癌2例,舌癌和食管癌各1例,肿瘤位于颈椎管内1例,胸椎管内4例,胸腰段2例,腰椎管内3例.硬膜内髓外转移8例,硬膜内髓内转移2例.记录患者的手术时间、术中出血量、术后并发症发生率、生存时间.以视觉模拟评分(visual analogue scale,VAS)、椎管内肿瘤McCormick分级及功能状态(karnofsky performance score,KPS)评分分别对患者的术前、术后1个月的转移灶引起的疼痛、术后3个月神经及整体情况进行评估.结果:10例椎管内硬膜下转移癌患者的手术时间为130～260min(180.0±25.4min),术中出血量400～2100ml(1050.0±350.4)ml,术后的生存时间10～19个月(中位生存时间为11个月).所有患者术后疼痛均有明显的缓解,术后1个月VAS疼痛评分从术前的6.70±0.67分降至1.70±0.67分(P＜0.05).术后3个月KPS评分从术前的42.00±4.21分提升至术后的69.00±7.37分(P＜0.05).术后3个月Mc-Cormick分级9例较术前明显的提升,1例3级患者术后无明显改善,无术后神经症状恶化的病例.术后并发症2例(脑脊液漏1例,术后血肿1例),均为髓内转移患者,分别经保守及二次手术后好转.结论:后路显微镜辅助硬膜内病变切除联合脊柱内固定术治疗硬膜内转移癌,可以提高患者的生活质量,但对于脊髓内转移患者手术应谨慎施行.

Objective To investigate the expression and prognostic value of AKT1 and AKT2 in patients with glioblastoma (GBM).Methods AKT1 and AKT2 expression was assessed by immunohistochemistry in 93 cases of GBM (tumor group) and 20 normal brain tissues (control group) which were obtained intraoperatively in patients with cerebral vascular malformation.Overall survival (OS) was evaluated graphically with Kaplan-Meier curves.The multivariate analysis for OS was performed using Cox regression analysis.Results The positive expressions of AKT1 and AKT2 in tumor group were 74.19％ (69/93) and 67.74％ (63/93) respectively,which were significantly higher than those in control group (5％,1/20;15％,3/20).Kaplan Meier method showed patients with positive AKT1 or AKT2 expression had significantly shorter OS relative to those with negative expression,indicating significant differences (P ＜ 0.05).The multivariate Cox regression analysis revealed that extent of surgical resection,adjuvant treatment,and AKT1 and AKT2 expression were independent risk factors for OS (P ＜ 0.05) in patients with GBM.Conclusion The expression of AKT1 and AKT2 may be associated with prognosis of GBM,and could be considered as significant prognostic indicators.

Objective To investigate effects of miR-128 on invasion of glioblastoma U87 cells and its molec-ular mechanism. Methods Reverse transcription-quantitative polymerase chain reaction ( RT-PCR ) was used to measure the expression levels of miR-128 in glioblastoma U87 cells and SHG-44 cells. Migration and invasion of U87 cells were analyzed by transwell migration and invasion assays. Luciferase reporter assay was employed to detect cell target genes of miR-128 , while western blot analysis was performed to verify the expression of MMP-7 . Results The results showed that the expressions of miR-128 in SHG-44 cells and U87 cells were 1.00 ± 0.13 and 0.52 ± 0.16 re-spectively, and the difference was statistically significant (P<0.05). Compared with the NC group, the number of invasive cells was 445 ±23 and 313 ±59 respectively, and the difference was statistically significant (P<0.05). Compared with the NC group, when the tumor cells overexpressed miR-128, the expression of MMP-7 protein de-creased significantly, revealing significant difference (P<0.05). Conclusion The miR-128 could inhibit tumor invasion and migration in U87 cells by negatively regulating MMP-7 protein and may be identified as a potential thera-peutic target of glioblastoma.

Radiation therapy is important for the comprehensive treatment of intracranial tumors. However, the molecular mechanisms underlying the pathogenesis of delayed cognitive dysfunction are not well-defined and effective treatments or prevention measures remain insufficient. In the present study, 60 adult male Wistar rats were randomly divided into three groups, which included a control, whole brain radiotherapy (WBRT) (single dose of 30 Gy of WBRT) and nimodipine (single dose of 30 Gy of WBRT followed by nimodipine injection intraperitoneally) groups. The rats were sacrificed 7 days or 3 months following irradiation. At 3 months, the Morris water maze test was used to assess spatial learning and memory function in rats. The results demonstrated that the WBRT group demonstrated a significantly impaired cognitive performance, decreased numbers of hippocampal Cornu Ammonis (CA)1 neurons and upregulated expression of caspase-3 in the dentate gyrus compared with those in the control and nimodipine groups. Reverse transcription-quantitative polymerase chain reaction analysis demonstrated that the WBRT group exhibited increased ratio of B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax)/Bcl-2 compared with that in control and nimodipine groups on day 7 following irradiation. However, the WBRT group exhibited decreased levels of brain-derived neurotrophic factor (BDNF) compared with that in control and nimodipine groups at 3 months following brain irradiation. The levels of growth-associated protein 43 and amyloid precursor protein between the nimodipine group and WBRT group were not statistically significant. The present study demonstrated that neuron apoptosis may lead to delayed cognitive deficits in the hippocampus, in response to radiotherapy. The cognitive impairment may be alleviated in response to a calcium antagonist nimodipine. The molecular mechanisms involved in nimodipine-mediated protection against cognitive decline may involve the regulation of Bax/Bcl-2 and BDNF in the hippocampus.

目的 探讨术前头部弥散张量成像(DTI)结合术中超声引导下导丝定位技术,在功能区深部脑肿瘤手术的应用价值.方法 自2018年1月至2018年5月,给13例功能区深部脑肿瘤患者术前行头部DTI检查,根据DTI技术重建脑白质纤维三维图像,并与MRI图像整合,明确肿瘤与白质纤维束的三维空间结构关系.采用避开功能区皮层、尽量减少白质纤维束损伤的原则设计手术入路;并在术中超声引导下导丝定位肿瘤.术后72 h内复查头部MRI增强扫描评估肿瘤切除程度,术后4周采用KPS评分评估患者的身体功能状态.结果 本组患者的肿瘤定位均准确,10例患者的肿瘤完全切除,3例患者因术中冰冻病理检查为淋巴瘤,仅取活检.术后病理检查示,胶质瘤6例,转移瘤4例,淋巴瘤3例.术后患者均未出现新的神经功能缺失症状,8例患者的神经功能缺失症状较术前改善,5例患者的症状同术前.结论 对功能区深部脑肿瘤采用术前头部DTI结合术中超声引导下导丝定位技术,能精准定位肿瘤,并能够实时指引手术路径;在最大限度地切除肿瘤的同时,又可有效保护神经功能;是一种简单、安全、有效的辅助手术方法,值得临床推广应用..

Objective To analyze the expression of Egr-1 gene polymorphism in Chinese glioma patients. Method 231 cases of gliomas patients and 121 patients of non-cancer patients were analyzed for Egr-1 gene polymorphism by Taq-man technology, SPSS 15.0 was applied to statistically analyze the successful gene classification results. Result The sta-tistical analysis showed that:in glioma group, the frequency of T/T+C/C and T allele genotype were 29.9%and 47.6%, which were less than those in the control group at 37.2%and 52.1%, respectively, with no statistically significant differ-ence observed (P>0.05). Conclusion There is no significant association between Egr1 gene polymorphism and the risk of glioma.

Objective To investigate the effect of microRNA-133b (miR-133b) on glioblastoma (GBM) cell and to analyze its possible molecular mechanism.Methods Reverse transcription-polymerase chain reaction(RT-PCR) was used to detect the expression of miR-133b in 20 human GBM samples and normal human glial cells HBE.Transwell migration and invasion assays were used to evaluate the effects of miR-133b on cell migration and invasion.Western blotting and a luciferase reporter assay were used to identify the target genes of miR-133b.Results Compared with the HBE, miR-133b was significantly increased in GBM tissues (1.0±0.17 vs.2.42±0.69, P<0.05);In Transwell invasion and migration experiments, compared to group transfected with NC, the cells transfected with miR-133b mimic could inhibit the migration and invasion (P<0.05);In Western blotting, compared to cells that transfected with NC, the cells transfected with miR-133b mimic had a lower expression of MMP-14 protein (P<0.05).Furthermore, MMP-14 was identified as a direct target gene of the miR-133b by luciferase reporter gene analysis.Conclusion miR-133b can inhibit the migration and invasion of GBM by direct targeting MMP-14, and it can be used as a candidate target for diagnosis and treatment of GBM.

AIM:To investigate the role and value in the resec?tion of intracranial different grade gliomas under intraoperative real?time ultrasound. METHODS: A total of 40 patients with gliomas admitted into Tumor Hospital of Harbin Medical University were selected as research objects, and extent of resection was determined by using intraoperative ultrasonic real?time orientate guide. Tumor orientation and extent of resection were observed. RESULTS:A total of 34 cases were total resection tumor;3 cases were subtotal resection;3 cases were partial resection. There were different ultrasound performance between low grade gliomas and high grade gliomas. CONCLUSION: Intraoperative ultrasound guided microneurosurgery operation can identify glioma range and position accurately, which is low cost, real time monitoring, and no radiation. It is worthy of promotion.

目的 观察MAGE-A4 mRNA在脑胶质瘤中的表达情况,探讨其表达与病理级别、KPS评分等临床参数及总生存期的关系.方法 采用逆转录聚合酶链反应(RT-PCR)方法检测MAGE-A4 mRNA在78例脑胶质瘤组织、12例正常脑组织和7例正常睾丸组织中的表达,分析其表达与性别、年龄、KPS评分及病理级别等临床参数及总生存期关系.结果 MAGE-A4 mRNA在正常睾丸组织、正常脑组织及胶质瘤中的表达率分别为100％、0％、47.44％,差异有统计学意义(P＜0.05);MAGE-A4 mRNA表达与病理分级相关(P＜0.05);胶质瘤患者总生存期与病理分级、KPS评分相关(P＜0.05).结论 MAGE-A4在脑胶质瘤组织中有特异性表达,并且与病理级别显著相关,而在正常脑组织中没有表达,故MAGE-A4可以作为脑胶质瘤免疫治疗的理想靶点;胶质瘤患者KPS评分和病理分级,可作为判断患者预后依据.

The roles of secreted frizzled-related protein-1 (SFRP1) and β-catenin in human cancer have been widely studied, and it has recently been demonstrated that these proteins are associated with numerous human carcinomas. However, their clinical significance in glioblastoma multiforme (GBM) has not been examined. The current study aimed to analyze the correlation between the expression of SFRP1 and β-catenin, and clinicopathological characteristics in GBM patients. The expression of SFRP1 and β-catenin was assessed by immunohistochemistry in 113 samples of GBM and 40 normal brain tissues. Compared with normal brain tissues, GBM tissues exhibited significantly lower expression of SFRP1, and higher expression of β-catenin (both P<0.05). A Kaplan-Meier analysis revealed that patients with positive SFRP1 expression had a significantly longer overall survival (OS) time relative to those with negative SFRP1 expression (P<0.000), and that patients with positive β-catenin expression had a shorter OS time than those with negative β-catenin expression (P<0.000). A multivariate Cox regression analysis indicated that adjuvant treatment, SFRP1 expression and β-catenin expression were independent prognostic factors for OS (P<0.000, P=0.008 and P=0.001, respectively) in patients with GBM. The current data suggest that expression of SFRP1 and β-catenin may be considered significant prognostic indicators for patients with GBM.

Objective To study the expression and correlation of DNA methyltransferase 1( DNMT1) and p27 protein in pri?mary and secondary glioblastoma multiforme. Methods From Jan 1 2000 to Jan 31 2012, 32 cases of primary glioblastoma multiforme specimens, 32 cases of secondary glioblastoma multiforme specimens and 13 cases of normal brain tissues were enrolled. The expression of DNMT1 and p27 protein was detected in those tissues. Results The positive expression rates of DNMT1 protein in primary and sec?ondary glioblastoma multiforme tissues, as well as in normal tissues were 59. 4%, 81. 3% and 0. The positive expression rates of p27 protein were 50. 0%, 25. 0% and 100. 0% in primary and secondary glioblastoma multiforme tissues, and normal brain tissues ( P<0. 05) . The positive expression of DNMT1 and p27 protein in primary and secondary glioblastoma multiforme tissues had significant difference (P<0. 05). There was no correlation between the expressions of both proteins(r=0. 41, P>0. 05). Conclusion The ex?pression of DNMT1 and p27 protein is different in primary and secondary glioblastoma multiforme tissues. The combined detection of DNMT1 and p27 protein may serve as an index to estimate different types of glioblastoma multiforme.

Increasing evidence has suggested that microRNA-133b (miR-133b) is important in regulating the genesis of different types of cancer. However, the effects and the underlying mechanisms of miR-133b in the development of glioblastoma (GBM) remain largely unknown. The aim of the present study was to investigate the role of miR-133b in GBM and to determine the molecular mechanisms underlying its action. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression levels of miR-133b in 21 human GBM samples and 9 normal brain tissue samples. A wound healing assay, and Transwell migration and invasion assays were used to evaluate the effects of miR-133b on cell migration and invasion. Western blotting and a luciferase reporter assay were used to identify the target genes of miR-133b. It was found that miR-133b suppressed GBM cell migration and invasion, and matrix metalloproteinase 14 (MMP14) was identified as a direct target gene. In conclusion, miR-133b may suppress GBM migration and invasion through directly targeting MMP14, highlighting its potential as a novel agent for the treatment of GBM invasion.

胶质瘤是颅内最常见的恶性肿瘤,发病率逐年增高.越来越多的证据表明IDH1基因突变与胶质瘤密切相关.本文就近年来有关胶质瘤与IDH1基因突变的研究作一综述.IDH1基因编码胞浆内NADP依赖的异柠檬酸脱氢酶,后者能够对异柠檬酸进行催化生成α-酮戊二酸.在40％的胶质瘤中存在IDH1突变,在继发性胶质母细胞瘤中变异率最高.作为一种代谢的关键酶,IDH1突变后可以将α-KG转变成2-HG,后者具有促进细胞增殖和促进肿瘤发生的作用.而且,IDH1突变可以导致胶质瘤代谢和表现遗传学方面的改变.同时,IDH1突变可以通过增加HIF-lα水平及活性增加血管生成.目前在不同级别的胶质瘤当中,IDH1突变已经成为一个与预后密切相关的独立预测因素.对IDH1突变的研究有助于深入了解胶质瘤病因及干预措施的具体机制,有助于胶质瘤的分子水平分类和治疗.

Translationally controlled tumor protein (TCTP) is a highly conserved, growth-associated and small molecule protein, which is highly expressed in various types of tumor cell. TCTP can promote the growth and suppress apoptosis of tumor cels. However, few studies have reported the effects of TCTP in gliomas. In the present study, a glioma cell line was established, which was stably transfected with TCTP short hairpin ribonucleic acid (shRNA), to investigate the impact of downregulated expression of TCTP on the proliferation, apoptosis and invasion of glioma cells. Western blot and reverse transcription-quantitative polymerase chain reaction analyses demonstrated that TCTP shRNA effectively reduced the expression of TCTP in the U251 glioma cell line. MTT and colony formation assays revealed that downregulated expression of TCTP significantly inhibited glioma cell proliferation. Cell cycle analysis using flow cytometry revealed that the cells in the pRNA-H1.1-TCTP group were arrested in the G0/G1 phase of the cell cycle. Western blot analysis detected downregulated expression levels of cyclins, including Cyclin D1, Cyclin E and Cyclin B. Annexin V-fluorescein isothiocyanate/propidium iodide and Hoechst staining demonstrated that the apoptotic rate of the cells in the pRNA-H1.1-TCTP group was significantly higher than that of the cells in the pRNA-H1.1-control group, with upregulated expression levels of B-cell-associated X protein and cleaved-caspase-3 and downregulated expression of B-cell lmyphoma-2 in the apoptotic process. Wound healing and Transwell assays revealed that downregulated expression of TCTP significantly inhibited the migration and invasiveness of the glioma cells; and the expression levels and activities of matrix metalloproteinase (MMP)-2 and MMP-9 were also significantly affected. In conclusion, the present study demonstrated that downregulated expression of TCTP significantly inhibited proliferation and invasion, and induced apoptosis in the glioma cells. These results suggested that TCTP may be important in glioma development and metastasis. Therefore, TCTP is expected to become an effective target for glioma gene therapy.

Objective: To analyze the clinical manifestations, imaging features, and pathological characteristics of primary central nervous system lymphoma (pcnsl) and to explore the methods of diagnosis and treatment. Methods: The clinical, laboratory, imaging and pathological data from 31 cases with pcnsl seen in our hospital between july 1995 and june 2006 were retrospectively analyzed. Of the 31 cases, 18 received chemotherapy and radiotherapy after surgery, and 5 cases were treated with surgery alone. Results: Pcnsl often appeared with nonspecific symptoms, such as elevated intracranial pressure and nerve dysfunction, leading to a relatively high misdiagnosis rate. All patients' csf cellular examination was negative. All of the 31 cases were b-cell lymphoma. Twenty-four of the 31 cases were followed up for 6-98 months. The mean survival was 20 months in the group that received surgery combined with chemotherapy and radiotherapy and 10 months in the group that underwent surgery alone. Conclusion: Pcnsl has no specific clinical manifestations, thus it is difficult to diagnose. The pathological examination might be the only reliable method to confirm pcnsl. The main objective of surgical therapy is to lower the intracranial pressure. Recurrence may occur after surgery alone, so a combined therapy with additional radiotherapy and chemotherapy is needed to prolong patients' survival period.

In a previous study, we reported that resveratrol exerts antitumor effects through the estrogen receptor in prolactinoma. The autophagy/lysosomal degradation pathway plays an important role in damage control and energy efficiency. In this study, we investigated the involvement of autophagy and the related signaling pathways in resveratrol-induced apoptosis of GH3 cells. We demonstrate that resveratrol inhibits cell proliferation and induces apoptosis in a dose-dependent manner in GH3 cells. The cleavage of PARP was also observed, and the activation of caspase-3 and caspase-8 was detected. Consistent with this finding, the inhibition of caspase activation effectively attenuated resveratrol-induced cell apoptosis. In addition, the decreased level of Bcl-2 was also observed. The induction of autophagy was confirmed by the detection of the formation of autophagic vacuoles, and the increase in microtubule-associated protein 1 light chain 3 (LC3)-II and beclin-1 levels, two hallmarks of autophagy. Pre-treatment with bafilomycin A1 or 3-methyladenine, inhibitors of autophagy, enhanced the resveratrol-mediated caspase activation and cell death. Moreover, resveratrol induced the activation of ERK1/2, as well as the downregulation of Akt and mTOR phosphorylation. Taken together, these findings indicate that resveratrol induces caspase-dependent apoptosis and decreases Bcl-2 levels. In addition, resveratrol-induced autophagy is regulated by the PI3K/Akt/mTOR and ERK1/2 pathways. Furthermore, the inhibition of autophagy increases the cytotoxicity of resveratrol to GH3 cells.

目的 探讨神经导航辅助下微骨窗入路显微手术切除脑内深部肿瘤的方法和疗效.方法 收集140例脑深部肿瘤患者,分为对照组(54例)和试验组(86例).对照组患者采用传统手术治疗,试验组患者采用神经导航辅助的显微手术切除肿瘤.结果 试验组患者中,全切除78例(90.7％),近全切除5例(5.8％),大部分切除2例(2.3％),活检1例(1.2％).对照组患者中,全切除40例(74.1％),近全切除9例(16.7％),大部分切除5例(9.3％).两组患者的骨窗大小、手术时间和全切率比较,差异有统计学意义(P＜0.05).结论 神经导航辅助微骨窗入路可显著提高脑深部肿瘤患者的治疗效果,提高全切率,缩短手术时间,并减少手术创伤.

目的 观察鼠脑胶质瘤组织中调节性T细胞(Treg)的表达变化,并探讨其对脑胶质瘤的作用.方法 ①建立9L/Fisher344大鼠脑胶质瘤模型,分别于造模后7、14、21 d和临终状态时处死大鼠,获取胶质瘤组织及对侧正常脑组织标本,行流式细胞学检测,观察Treg细胞比例变化.②将Fisher344大鼠随机分为实验组和对照组各15只,实验组在造模前3d腹腔内注射抗CD2s单克隆抗体(PC61),对照组注射相同剂量的IgG-1.两组在造模后14 d分别处死5只大鼠,比较两组胶质瘤中Treg细胞的浸润情况,剩余大鼠观察生存时间.结果 鼠脑胶质瘤组织中浸润的Treg细胞比例明显高于正常脑组织(P＜0.01),并随时间延长而增高,到临终时达到高峰.应用PC61后,实验组脑胶质瘤中Treg细胞比例明显低于对照组(P＜0.05),且大鼠的生存时间明显长于对照组(P＜0.05).结论 Treg细胞在鼠脑胶质瘤组织中的表达明显升高,清除Treg细胞能明显抑制鼠脑胶质瘤的生长;Treg细胞在胶质瘤生长过程中发挥重要作用.