Glioma stem cells (GSC) are a subpopulation of tumor cells with special abilities to proliferate and differentiate in gliomas. They are one of the main causes of tumor recurrence, especially under hypoxic conditions. Although long noncoding RNAs (lncRNA) are known to be involved in numerous biological processes and are implied in the occurrence of certain diseases, their role in tumor development and progression remains poorly understood. Here we explored the mechanisms by which lncRNA derived from hypoxic GSCs (H-GSC) cause glioma progression. Isolation and identification of the Linc01060 gene, the exosomes containing them, and the proteins from tumor cells regulating the gene allowed for studying the effects of Linc01060 on proliferation and glycometabolism. H-GSC exerted their effects by transferring exosomes to glioma cells, resulting in a significant increase in Linc01060 levels. Mechanistically, Linc01060 directly interacted with the transcription factor myeloid zinc finger 1 (MZF1) and enhanced its stability. Linc01060 facilitated nuclear translocation of MZF1 and promoted MZF1-mediated c-Myc transcriptional activities. In addition, c-Myc enhanced the accumulation of the hypoxia-inducible factor-1 alpha (HIF1a) at the posttranscriptional level. HIF1a bound the hormone response elements of the Linc01060 promoter, upregulating the transcription of Linc01060 gene. Clinically, Linc01060 was upregulated in glioma and was significantly correlated with tumor grade and poor clinical prognosis. Overall, these data show that secretion of Linc01060-containing exosomes from H-GSCs activates prooncogenic signaling pathways in glioma cells to promote disease progression.Significance: These findings suggest that inhibition of Linc01060containing exosomes or targeting the Linc01060/MZF1/c-Myc/ HIF1a axis may be an effective therapeutic strategy in glioma.

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Growth factors in the brain are important to depression. We investigated the relationship between serum insulin-like growth factor (IGF-1) and IGF-binding protein-3 (IGFBP-3) concentration and risk of depression and the effect of psychological intervention on outcomes of high-grade glioma patients with preoperative depression. A total of 249 high-grade glioma patients participated in blood sample collection for IGF-1 and IGFBP-3 detection by ELISA and the Hospital Anxiety and Depression Scale testing. The association between IGF-I or IGFBP-3 and depression risk was assessed using conditional logistic regression, and Student's t tests were used to evaluate differences in change of the Karnofsky Performance Status Scale (KPS) in subgroups after performance of psychosocial intervention. The survivals of patients in subgroups were tested by Kaplan-Meier (log-rank test). We found the risk of depression was elevated with increased IGF-I (HR = 6.320, 95% CI 2.456-16.265, top vs. bottom quartile) and IGFBP-3 concentrations (HR = 3.411, 95% CI 1.345-8.648) after adjustment of confounders. KPS was increased significantly in the intervention groups, but not significantly in the usual care groups after performance of psychosocial intervention. The survival of depressed patients in the usual group was significantly worse than those of other subgroups after performance of psychosocial intervention. Depression is prevalent among patients with high-grade gliomas, and factors of the IGF axis are positively associated with risk of depression and might be involved in the etiology of depression in high-grade glioma patients. Depression correlates with quality of life and outcomes of patients. Therefore, some psychological interventions are needed and may help patients to relieve depression and improve the life quality of glioma patients.

Label-retaining cells, which are characterized by dormancy or slow cycling, may be identified in a number of human normal and cancer tissues, and these cells demonstrate stem cell potential. In glioblastoma, label-retaining assays to enrich glioma stem cells remain to be fully investigated. In the present study, glioblastoma sphere cells cultured in serum-free medium were initially stained with the cell membrane fluorescent marker DiI. The fluorescence intensity during cell proliferation and sphere reformation was observed. At 2 weeks, the DiI-retaining cells were screened by fluorescence-activated cell sorting and compared phenotypically with the DiI-negative cells in terms of in vitro proliferation, clonogenicity and multipotency and for in vivo tumorigenicity, as well as sensitivity to irradiation and temozolomide treatment. It was observed that DiI-retaining cells accounted for a small proportion, <10%, within the glioblastoma spheres and that DiI-retaining cells proliferated significantly more slowly compared with DiI-negative cells (P=0.011, P=0.035 and P=0.023 in the of NCH421k, NCH441 and NCH644 glioblastoma sphere cell lines). Significantly increased clonogenicity (P=0.002, P=0.034 and P=0.016 in the NCH441, NCH644 and NCH421k glioblastoma sphere cell lines) and three-lineage multipotency were observed in DiI-retaining cells in vitro compared with DiI-negative cells. As few as 100 DiI-retaining cells were able to effectively generate tumors in the immunocompromised mouse brain, whereas the same number of DiI-negative cells possessed no such ability, indicating the increased tumorigenicity of DiI-retaining cells compared with DiI-negative cells. Furthermore, DiI-retaining cells demonstrated significant resistance following irradiation (P=0.012, P=0.024 and P=0.036) and temozolomide (P=0.003, P=0.005 and P=0.029) compared with DiI-negative cells in the NCH421k, NCH441 and NCH644 glioblastoma sphere cell lines, respectively. It was concluded that label-retaining cells in glioblastoma spheres manifest clear stem cell features and that the label-retaining assay may be utilized to further enrich glioma stem cells cultured under serum-free conditions for additional study.

To analyze the clinical characters, prognostic factors, patterns of relapse and treatment outcomes for medulloblastoma in adults. The clinical materials of 73 consecutive adult patients (age, ≥16 years) with medulloblastoma were analyzed retrospectively. Follow-up data were available in 62 patients, ranging from 10 to 142 months (median, 78.4 months). Outcome in survival was assessed by the progression-free survival (PFS) and overall survival (OS). Univariate and multivariate analysis were performed to determine the prognostic factors. Total or near-total tumor resection was achieved in 37 cases (59.7 %), subtotal in 19 cases (30.6 %), and partial resection in 6 cases (9.7 %).Twenty-two patients experienced recurrences, and 45 % percent of all recurrences occurred more than 4 years after initial surgery. The PFS rates at 5 and 8 years were 60.1 and 37.0 %, respectively. The OS rates at 5 and 8 years were 82.6 and 57.3 %, respectively. In univariate analysis, less tumor resection, non-desmoplastic pathology, and brainstem involvement were risk factors for worse PFS and OS (P < 0.05). High-risk category was associated with just lower PFS, but not OS. In multivariate analysis, complete resection and desmoplastic pathology were independently predictive factors of improved PFS and OS. In adult medulloblastoma, late relapse is common and therefore long-term follow-up is important for evaluating the real impact of treatments. Risk category had prognostic value just for PFS, but not for OS. Complete resection and desmoplastic histology are independently predictive factors for favorable outcomes.

Surgical resection has been the standard treatment for SEGAs, and it is generally curative with complete resection. However, not all SEGAs are amenable to safe and complete resection. Gamma Knife stereotactic radiosurgery provides another treatment option as a primary or adjuvant treatment for SEGAs, but it has highly variable response effects with sporadic cases demonstrating its efficacy. Recently, biologically targeted pharmacotherapy with mammalian target of rapamycin (mTOR) inhibitors such as sirolimus and everolimus has provided a safe and efficacious treatment option for patients with SEGAs. However, SEGAs can recur few months after drug discontinuation, indicating that mTOR inhibitors may need to be continued to avoid recurrence. Further studies are needed to evaluate the advantages and adverse effects of long-term treatment with mTOR inhibitors. This review presents an overview of the current knowledge and particularly highlights the surgical and medical options of SEGAs in patients with TSC.

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