Fibulin-5 is a Prognostic Marker that Contributes to Proliferation and Invasion of Human Glioma Cells

Fibulin-5 has recently been considered as a potential tumor suppressor in human cancers. Several studieshave shown that it is down-regulated in a variety of tumor types and inhibits tumor growth and metastasis. Thisstudy was aimed to investigate the clinical significance of fibulin-5 in glioma and its role in cell proliferationand invasion. We found that the expression of fibulin-5 in glioma tissues was significantly lower than those innormal brain (NB) tissues. Negative expression was significantly correlated with advanced clinical stage (gradeIII+IV) . Furthermore, Fibulin-5 negative expression was correlated with a shorter overall survival of gliomapatients. Multivariate Cox repression analysis indicated that fibulin-5 was an independent factor for predictingoverall survival of glioma patients. Overexpression obviously inhibited cell proliferation in U251 and U87cells. Furthermore, it significantly reduced the number of migrating and invading glioma cells. In conclusion,impaired expression of fibulin-5 is correlated with the advanced tumor stage in glioma. Otherwise, Fibulin-5 isan independent prognostic marker for predicting overall survival of glioma patients. Mechanistically, it mayfunction as a tumor suppressor via inhibiting cell proliferation and invasion in gliomas.     

Expression of microRNA-218 and its Clinicopathological and Prognostic Significance in Human Glioma Cases

Background: MicroRNAs are a class of noncoding RNAs which regulate multiple cellular processes duringtumor development. The purpose of this report is to investigate the clinicopathological and prognostic significanceof miR-218 in human gliomas. Materials and Methods: Quantitative RT-PCR (qRT-PCR) was conducted todetect the expression of miR-218 in primary normal human astrocytes, three glioma cell lines and 98 pairedglioma and adjacent normal brain tissues.Associations of miR-218 with clinicopathological variables of gliomapatients were statistically analyzed. Finally, a survival analysis was performed using the Kaplan-Meier methodand Cox’s proportional hazards model. Results: The expression level of miR-218 in primary normal humanastrocytes was significantly higher than that in glioma cell lines (p<0.01). Also, the expression level of miR-218in glioma tissues was significantly downregulated in comparison with that in the adjacent normal brain tissues(p<0.001). Statistical analyses demonstrated that low miR-218 expression was closely associated with advancedWHO grade (p=0.002) and low Karnofsky performance score (p=0.010) of glioma patients. Kaplan-Meier analysiswith the log-rank test showed that patients with low-miR-218 expression had poorer disease-free survival andoverall survival (p=0.0045 and 0.0124, respectively). Multivariate analysis revealed that miR-218 expressionwas independently associated with the disease-free survival (p=0.009) and overall survival (p=0.004) of gliomapatients. Conclusions: Our results indicate that miR-218 is downregulated in gliomas and that its status mightbe a potential valuable biomarker for glioma patients.     

视神经胶质瘤7例的诊断与治疗

目的:总结视神经胶质瘤的临床特点和治疗经验,结合国内外文献探讨本病的临床表现、诊断方法、治疗方案及预后.方法:回顾分析过去 3年间我科收治的 7 例视神经胶质瘤患者的临床资料.结果:本组7例,发病平均年龄为18.7 岁,男女之比为4∶ 3,平均病程24.8个月,显微手术大部切除和近全切除率达 100%,术后尿崩较多见,术后患者临床症状均无加重.结论:视神经胶质瘤为良性肿瘤,预后较好,手术切除、及时处理术后并发症和恰当的放疗是治疗的关键.     

脑胶质瘤颅外转移一例并文献复习

目的 探讨脑胶质瘤颅外转移的可能机制和临床特点.方法 报道一例最近诊治的具有完整临床和病理证据的脑胶质瘤颅外转移患者.结果 脑胶质瘤颅外转移较为罕见,本例患者胸部X线片可见双肺多发转移瘤,胸部CT示多发大小不等的结节软组织肿物影,诊断为脑胶质瘤颅外转移.结论 脑胶质瘤颅外转移的转移路径及机制尚不能明确,多路径机制可能较为合理.开放式的肿瘤切除术可能有助于延长患者的生存时间,但也不排除增加颅外转移的可能.

Abstract：

Objective To explore the mechanisms and clinical characteristics of neuroglioma that was complicated with extracranial metastases. Methods A newly-diagnosed neuroglioma case in our department was reported with completely clinical and pathological data to discuss the extracranial metastases. Meanwhile the domestic and abroad literature were reviewed. Results The extracranial metastasis of glioma was rare. In this cases, X-ray chest displayed multiple metastatic tumors, and CT of chest showed nodules soft tissue mass shadows varied in size. Accordingly the diagnosis was neuroglioma complicated with extracranial metastases. Conclusions The transferring paths and mechanisms are ambiguous. Tumor resections may be helpful in prolonging the survival time and in increasing the potential of the tumor transferring from intracranial to extracranial.     

Noscapine inhibits tumor growth in TMZ-resistant gliomas

Noscapine, a common oral antitussive agent, has been shown to have potent antitumor activity in a variety of cancers. Treatment of glioblastoma multiforme (GBM) with temozolomide (TMZ), its current standard of care, is problematic because the tumor generally recurs and is then resistant to this drug. We therefore investigated the effects of noscapine on human TMZ-resistant GBM tumors. We found that noscapine significantly decreased TMZ-resistant glioma cell growth and invasion. Using the intracranial xenograft model, we showed that noscapine increased survival of animals with TMZ-resistant gliomas. Thus noscapine can provide an alternative therapeutic approach for the treatment of TMZ-resistant gliomas.     

立体定向植入缓释型5-Fu治疗恶性复发脑胶质瘤

目的探讨立体定向植入5-氟尿嘧啶多聚缓释体(缓释型5-FU)在治疗恶性脑胶质瘤中的作用。方法 2004年2月至2006年12月,将45例经手术切除后组织细胞学确诊、且术后复发的恶性胶质瘤患者分成两组:A组25例复发胶质瘤(采取患者自愿原则),行立体定向术植入缓释型5-Fu粒子肿瘤间质内化疗,同时配合直线粒子加速器外放疗。B组20例复发胶质瘤,采用直线粒子加速器外放疗为对照组。观察客观疗效,临床受益反应,毒性反应,并发症及生存情况。结果随访时间6~36个月。A组随访17例,B组随访13例。6和12个月累积生存率两组为53.0%比35.6%和20.5%比12.5%(P<0.05)。中位生存时间两组为8.2比4.1个月。平均生存时间两组为8.7比5.0个月(P<0.05)。结论立体定向植入缓释型5-Fu治疗脑恶性胶质瘤有疗效肯定,可延长患者生存,提高生存质量,无明显毒副作用,是一种安全有效的治疗方法。     

Physical exercise increases adult neurogenesis and telomerase activity, and improves behavioral deficits in a mouse model of schizophrenia

Epidemiological studies indicate that among other early life challenges, maternal infection with influenza during pregnancy increased the risk of developing schizophrenia in the child. One morphological manifestation of schizophrenia is hippocampal atrophy. In the hippocampus, playing a key role in learning and memory formation, new granule cell neurons are produced throughout life from resident precursor cells. We hypothesize that individuals exposed to a maternal anti-viral immune response would presumably enter life with a challenged neural precursor cell pool and might later be susceptible to psychiatric pathologies due to reduced adult neurogenesis.We used the injection of double-stranded RNA (polyriboinosinicpolyribocytidylic acid - PolyI:C) in pregnant C57Bl/6 and nestin-GFP reporter mice to induce a maternal viral-like infection and schizophrenia-like behavior in the offspring.In the progeny we found impairments in the open field test and in sensorimotor gating as measured by pre-pulse inhibition of the startle response. The behaviorial deficits were accompanied by reduced baseline adult hippocampal neurogenesis. Telomerase activity in neural precursor cells was reduced from birth on and telomere shortening was found in the same cell type in adult life. When we subjected the progeny of viral-like infected dams to voluntary exercise, a known stimulus of adult hippocampal neurogenesis, we could rescue the phenotype in behavior, adult neurogenesis, and cellular senescence.In summary, maternal viral-like immune response reduced telomerase activity and resulted in telomere shortening in neural precursor cells. Further we demonstrate that beneficial behavioral and cellular effects induced by exercise can be studied in a rodent model of schizophrenia.     

The impact of molecular and clinical factors on patient outcome in oligodendroglioma from 20 years’ experience at a single centre

The increased chemosensitivity of oligodendroglial tumours has been associated with loss of heterozygosity (LOH) of the p arm of chromosome 1 and the q arm of chromosome 19 (LOH 1p/19q). Other clinical and molecular factors have also been identified as being prognostic and predictive of treatment outcome. We reviewed 105 patients with oligodendroglioma treated at a single centre over 20 years. Median survival in oligodendroglioma patients with LOH 1p/19q was significantly longer (10.9 vs. 2.0 years). In the anaplastic oligodendroglioma group, univariate analysis demonstrated decreased patient age, presentation with seizures, use of adjuvant chemotherapy and LOH 1p/19q as predictors of improved survival. Multivariate analysis confirmed LOH 1p/19q as a significant predictor of improved survival (hazard ratio, 3.4; p = 0.015). Median survival in patients with anaplastic oligodendroglioma with LOH 1p/19q was 15.4 years vs. 1.2 years for those without LOH 1p/19q. This study confirms the utility of LOH 1p/19q as a prognostic marker in oligodendroglioma.