Previous researches have demonstrated the meaning of CTSB for the progress of several tumors, whereas few clues about its immunological characteristic in gliomas. Here we systematically explored its biologic features and clinical significance for gliomas. 699 glioma cases of TCGA and 325 glioma cases of CGGA were respectively included as training and validating cohorts. R software was used for data analysis and mapping. We found that CTSB was remarkably highly-expressed for HGG, IDH wild type, 1p19q non-codeletion type, MGMT promoter unmethylation type and mesenchymal gliomas. CTSB could specifically and sensitively indicate mesenchymal glioma. Upregulated CTSB was an independent hazard correlated with poor survival. CTSB-related biological processes in gliomas chiefly concentrated on immunoreaction and inflammation response. Then we proved that CTSB positively related to most inflammatory metagenes except IgG, including HCK, LCK, MHC II, STAT1 and IFN. More importantly, the levels of glioma-infiltrating immune cells were positively associated with the expression of CTSB, especially for TAMs, MDSCs and Tregs. In conclusion, CTSB is closely related to the malignant pathological subtypes, worse prognosis, immune cells infiltration and immunosuppression of gliomas, which make it a promising biomarker and potential target in the diagnosis, treatment and prognostic assessment of gliomas.

Object: Intraspinal hemangioblastomas are relatively uncommon benign tumors. The surgical strategies remain controversial, and the risk factors with regard to clinical outcome are unclear. The purpose of this study was to analyze the clinical characteristics, imaging findings, surgical strategies, and functional outcomes associated with intraspinal hemangioblastomas. Methods: A series of 92 patients who underwent 102 operations for resection of 116 intraspinal hemangioblastomas at a single institution during 2007–2011 were consecutively enrolled in this study. Of these, 60 patients (65.2%) had sporadic hemangioblastomas and 32 (34.8%) had von Hippel-Lindau disease. Preoperatively, 13 patients underwent digital subtraction angiography (DSA), 15 patients underwent 3D CT angiography (3D CTA), and none underwent preoperative embolization. Clinical characteristics, imaging findings, and operative records were analyzed. The advantages and disadvantages of DSA and 3D CTA were compared. For identification of risk factors that affect prognosis, logistic analysis was performed. Results: The male/female patient ratio was 1.8:1.0 (59 male and 33 female patients). Of the tumors, 41% were intramedullary, 37% were intramedullary-extramedullary, and 22% were primarily extramedullary. Three-dimensional CTA and DSA did not differ significantly in the ability to identify the feeding arteries (p = 1.000) and image qualities (p = 0.367). However, compared with 3D CTA, the effective x-ray dose of spinal DSA was 2.73 times higher and the mean amount of contrast media injected was 1.88 times higher. Spinal DSA was more time consuming (mean 120 minutes) than 3D CTA (scanning time < 1 minute). No complications were observed after 3D CTA; acute paraparesis developed in 1 patient after DSA. Gross-total resection was achieved for 109 tumors (94.0%), and resection was subtotal for 7 tumors. Mean duration of follow-up was 50 months (range 24–78 months). At the most recent follow-up visit, the functional outcome was improved for 38 patients (41.3%), remained stable for 40 (43.5%), and deteriorated for 14 (15.2%). Logistic analysis showed that subtotal resection was a risk factor affecting prognosis (p = 0.003, OR 12.833, 95% CI 2.429–67.806). Conclusions: The authors' study suggests that safe and effective treatment of intraspinal hemangioblastomas can be achieved for most patients, even without preoperative embolization. Gross-total resection, when safe to perform, leads to better outcomes. Compared with spinal DSA, 3D CTA is a promising technique because it is noninvasive, takes less time to perform, requires lower x-ray doses and less contrast media, results in fewer complications, and offers high accuracy for delineating the feeding arteries.

Histopathological, molecular, clinical and radiological characterization of rosette-forming glioneuronal tumor in the central nervous system Histopathological, molecular, clinical and radiological characterization of rosette-forming glioneuronal tumor in the central nervous system

We have prepared novel poly(d,l-lactide-co-glycolide) (PLGA) lipid nanoparticles (PNPs) that covalently conjugate folic acid (FA) and indocyanine green (ICG), in addition to encapsulating resveratrol (RSV) (FA-RSV/ICG-PLGA-lipid NPs, abbreviated as FA-RIPNPs); these nanoparticles have been developed for simultaneous targeted delivery of anticancer drug and fluorescence imaging. The FA-RIPNPs, with an average particle size of 92.8±2.1 nm, were prepared by a facile self-assembly-and-nanoprecipitation method, and they showed excellent stability and biocompatibility characteristics. The FA-RIPNPs exhibited an RSV encapsulation efficiency of approximately 65.6%±4.7% and a maximum release ratio of 78.2%±4.1% at pH 5.0 and 37°C. Confocal fluorescence images showed that FA-RIPNPs may facilitate a high cellular uptake via FA receptor-mediated endocytosis. Furthermore, FA-RIPNPs (containing 50 µg/mL RSV) induced a 81.4%±2.1% U87 cell inhibition rate via apoptosis, a value that proved to be higher than what has been shown for free RSV (53.1%±1.1%, equivalent RSV concentration). With a formulated polyethylene glycol (PEG) shell around the PLGA core, FA-RIPNPs prolonged the blood circulation of both free RSV and ICG, which approximately increased 6.96- and 39.4-fold (t_1/2), respectively. Regarding FA-RIPNP use as a near-infrared probe, in vivo fluorescence images indicated a highly efficient accumulation of FA-RIPNPs in the tumor tissue, which proved to be approximately 2.8- and 12.6-fold higher than the RIPNPs and free ICG, respectively. Intravenous injection of FA-RIPNPs into U87 tumor-bearing mice demonstrated the best tumor inhibition effect for all tested drugs, including free RSV and RIPNPs, with no relapse, showing high biocompatibility and with no significant systemic in vivo toxicity over the course of the treatment (1 month). The results obtained demonstrate the versatility of the NPs, featuring stable fluorescence and tumor-targeting characteristics, with promising future applications in cancer therapy.