Fc gamma receptor IIb in tumor-associated macrophages and dendritic cells drives poor prognosis of recurrent glioblastoma through immune-associated signaling pathways.

Background: Among central nervous system tumors, glioblastoma (GBM) is considered to be the most destructive malignancy. Recurrence is one of the most fatal aspects of GBM. However, the driver molecules that trigger GBM recurrence are currently unclear. Methods: The mRNA expression data and clinical information of GBM and normal tissues were collected from the Chinese Glioma Genome Atlas The Cancer Genome Atlas (TCGA), and REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) cohorts. The DESeq2 R package was used to identify the differentially expressed genes between primary and recurrent GBM. ClueGO, Kyoto Encyclopedia of Genes and Genomes (KEGG), Biological Process in Gene ontology (GO-BP), and the Protein ANalysis THrough Evolutionary Relationships (PANTHER) pathway analyses were performed to explore the enriched signaling pathways in upregulated DEGs in recurrent GBM. A gene list that contained potential oncogenes that showed a significant negative correlation with patient survival from The Cancer Genome Atlas was used to further screen driver candidates for recurrent GBM. Univariate Cox proportional hazards regression analyses were used to investigate the risk score for the mRNA expression of the candidates. Single-cell RNA sequencing (scRNA-Seq) analyses were used to determine the cell type-specific distribution of Fc gamma receptor II b (FcγRIIb) in GBM. Immunohistochemistry (IHC) was used to confirm the FcγRIIb-positive cell populations in primary and paired recurrent GBM. Results: Through DEG analysis and overlap analysis, a total of 10 genes that are upregulated in recurrent GBM were screened. Using validation databases, FcγRIIb was identified from the 10 candidates that may serve as a driver for recurrent GBM. FCGR2B expression, not mutation, further showed a highly negative correlation with the poor prognosis of patients with recurrent GBM. Furthermore, scRNA-Seq analyses revealed that tumor-associated macrophage- and dendritic cell-specific FCGR2B was expressed. Moreover, FcγRIIb also showed a strong positive correlation coefficient with major immune-associated signaling pathways. In clinical specimens, FcγRIIb-positive cell populations were higher in recurrent GBM than in primary GBM. Conclusion: This study provides novel insights into the role of FcγRIIb in recurrent GBM and a promising strategy for treatment as an immune therapeutic target.

[Application of intraoperative contrast-enhanced ultrasound in different pathological grades of glioma].

OBJECTIVE: To explore the feasibility and value of intra-operative contrast-enhanced ultrasound in different pathological grades of glioma. METHODS: A total of 46 patients with glioma were selected to undergo the contrast-enhanced ultrasound. They were divided into 3 groups according to their pathological grades. RESULTS: All 46 tumors were hyperechoic after examinations and the borders became much more distinct. Different level of tumors had their representative ultrasonic findings. CONCLUSIONS: Intraoperative contrast-enhanced ultrasound is quite useful for determining the position and border of tumors. And it is also excellent in detecting the residual tumor tissues post-operatively. And it can improve the resection accuracy and operative precision, especially for Grade IV glioma with internal necrosis, cyst and surrounding brain edema.

Effects of a fatty acid synthase inhibitor on adipocyte differentiation of mouse 3T3-L1 cells.

AIM: To investigate the influence of C75, a fatty acid synthase inhibitor, on adipocyte differentiation. METHODS: Mouse 3T3-L1 preadipocytes were induced to differentiation by insulin, isobutylmethylxanthine, and dexamethasone. Oil red O staining was performed and activity of glycerol-3-phosphate dehydrogenase (GPDH) was measured. The level of peroxisome proliferators-activated receptor gamma (PPARgamma) mRNA was assayed by semi-quantitative reverse transcription PCR. RESULTS: C75 blocked the adipogenic conversion in a dose-dependent manner and the inhibitory effects occurred both in the early phases (48 h) and in the latter phases (8 d) of the process. Treatment with C75 for 8 d induced more decrease in lipid content than 48 h (P<0.01). Treatment with C75 50 mg/L for 48 h or 8 d decreased GPDH activity by 52.8 % and 31.2 % of Vehicle, respectively. Treatment with C75 10-50 mg/L for 48 h or 8 d down-regulated PPARgamma mRNA expression compared with control (P<0.01). CONCLUSION: C75 blocked the adipocyte differentiation, which was related with down-regulation of PPARgamma mRNA.