Depleting ANTXR1 suppresses glioma growth via deactivating PI3K/AKT pathway.

Gliomas are commonly known as primary brain tumors and associated with frequent recurrence and an unsatisfactory prognosis despite extensive research in the underlying molecular mechanisms. We aimed to examine the role of ANTXR1 in glioma tumorigenesis and explore its downstream regulatory mechanism. ANTXR1 expression in clinical specimens and its relationship with some pathological characteristics were detected using immunohistochemical staining. After silencing/upregulating ANTXR1 through lentiviral transfection in glioma cell lines, qRT-PCR and western blotting were used to examine mRNA and protein levels, and cell phenotype was also detected. ANTXR1-knockdown and -overexpression cells were then processed by AKT activator and PI3K inhibitor, respectively, to verify downstream PI3K/AKT pathway regulated by ANTXR1. Xenograft nude mice models were constructed to verify the role of ANTXR1 in vivo. We found overexpression of ANTXR1 in both cell lines in comparison with those in normal brain tissues. Glioma cell growth and migratory ability were dramatically impaired as a result of silencing ANTXR1 by shANTXR1 lentiviruses. ANTXR1 blockade also accelerated cell apoptosis and held back cell cycle via targeting G2 phrase during cell mitosis. In vivo xenograft models verified in vitro findings above. Further exploration disclosed that AKT activator promoted anti-tumor effects mediated by ANTXR1 knockdown, while PI3K inhibitor limited pro-tumor effects mediated by ANTXR1 overexpression, indicating that ANTXR1 functioned in glioma cells through regulating PI3K/AKT pathway. ANTXR1 could play an indispensable role in glioma tumorigenesis via activating PI3K/AKT-mediated cell growth. Our study provides a theoretical basis for targeting ANTXR1 as a molecular target in glioma clinical therapeutics.

Effects of machine perfusion strategies on different donor types in liver transplantation: a systematic review and meta-analysis.

BACKGROUND: The increasing use of extended criteria donors (ECD) sets higher requirements for graft preservation. Machine perfusion (MP) improves orthotopic liver transplantation (OLT) outcomes, but its effects on different donor types remains unclear. The authors' aim was to assess the effects of hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), or normothermic regional perfusion (NRP) versus static cold storage (SCS) on different donor types. MATERIALS AND METHODS: A literature search comparing the efficacy of MP versus SCS in PubMed, Cochrane, and EMBASE database was conducted. A meta-analysis was performed to obtain pooled effects of MP on ECD, donation after circulatory death (DCD), and donor after brainstem death. RESULTS: Thirty nine studies were included (nine randomized controlled trials and 30 cohort studies). Compared with SCS, HMP significantly reduced the risk of non-anastomotic biliary stricture (NAS) [odds ratio (OR) 0.43, 95% confidence interval (CI) 0.26-0.72], major complications (OR 0.55, 95% CI 0.39-0.78), and early allograft dysfunction (EAD) (OR 0.46, 95% CI 0.32-0.65) and improved 1-year graft survival (OR 2.36, 95% CI 1.55-3.62) in ECD-OLT. HMP also reduced primary non-function (PNF) (OR 0.40, 95% CI 0.18-0.92) and acute rejection (OR 0.62, 95% CI 0.40-0.97). NMP only reduced major complications in ECD-OLT (OR 0.56, 95% CI 0.34-0.94), without favorable effects on other complications and survival. NRP lowered the overall risk of NAS (OR 0.27, 95% CI 0.11-0.68), PNF (OR 0.43, 95% CI 0.22-0.85), and EAD (OR 0.58, 95% CI 0.42-0.80) and meanwhile improved 1-year graft survival (OR 2.40, 95% CI 1.65-3.49) in control DCD-OLT. CONCLUSIONS: HMP might currently be considered for marginal livers as it comprehensively improves ECD-OLT outcomes. NMP assists some outcomes in ECD-OLT, but more evidence regarding NMP-ECD is warranted. NRP significantly improves DCD-OLT outcomes and is recommended where longer non-touch periods exist.

LncRNA FEZF1-AS1 aggravates cell proliferation and migration in glioblastoma.

OBJECTIVES: Glioblastoma (GBM) represents the commonest malignant glioma. Long non-coding RNA (lncRNA) FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) has been validated to play an oncogenic role in multiple human malignancies, while its function in GBM has not been largely reported. We aim to identify the regulatory mechanism of FEZF1-AS1 in GBM. MATERIALS & METHODS: The expression pattern of FEZF1-AS1 was firstly figured out in GBM cells using RT-qPCR. Then, functional assays were conducted to examine the influence FEZF1-AS1 had on the biological properties of GBM cells. The downstream targets of FEZF1-AS1 were predicted and the underlying regulatory mechanism was determined by mechanism assays. RESULTS: FEZF1-AS1 possessed high expression in GBM cells. Down-regulation of FEZF1-AS1 suppressed GBM cell proliferation, migration and invasion while inducing cell apoptosis. With the help of bioinformatics prediction and mechanism assays, FEZF1-AS1 was found to bind to miR-363-3p and NOB1 was determined to be the downstream gene. Finally, results of rescue assays verified that the suppressive function of FEZF1-AS1 inhibition on GBM development were restored by miR-363-3p depletion or overexpression of NOB1. CONCLUSION: FEZF1-AS1 had oncogenic function in the advancement of GBM by targeting miR-363-3p/NOB1, which made FEZF1-AS1 a potential biomarker for GBM treatment.

High expression of PYCARD is an independent predictor of unfavorable prognosis and chemotherapy resistance in glioma.

BACKGROUND: PYD and CARD domain-containing (PYCARD) was upregulated in TMZ-resistant cell lines and glioma tissue and was correlated with poor prognosis, its role in glioma is unclear known. The aim of this study was to elucidate the relationship between PYCARD and glioma based on Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Chinese Glioma Genome Atlas (CGGA) databases. METHODS: Glioma-resistant cells were compared with parental cells based on the GSE53014 and GSE113510 data sets. The relationship between PYCARD, tumor microenvironment, and long noncoding RNAs (lncRNAs) was assessed using logistic regression. Moreover, Kaplan-Meier and Cox regression were used to analyze the relationship between PYCARD expression and survival rate. Gene set enrichment analysis (GSEA) was also used to determine the biological function of PYCARD and lncRNAs. Cell viability and cell migration assays were used to evaluate the ability of cells to migrate and proliferate. Finally, we analyzed the expression patterns of PYCARD genes in a wide range of cancers. RESULTS: Elevated expression of PYCARD promoted glioma cell proliferation and migration. PYCARD expression was significantly positively associated with gamma delta T cells but negatively correlated with M2 macrophages in glioblastoma multiforme (GBM). Likewise, PYCARD expression was significantly positively associated with monocytes but negatively associated with activated mast cells in low grade glioma (LGG). We also found that 3 PYCARD-related lncRNAs in GBM and 4 PYCARD-related lncRNAs in LGG had a predictive value for glioma patients. The pan-cancer analysis showed that PYCARD expression was higher in most cancer groups. CONCLUSIONS: High expression of PYCARD is an independent predictor of unfavorable prognosis and chemotherapy resistance in glioma.

COX10-AS1 Facilitates Cell Proliferation and Inhibits Cell Apoptosis in Glioblastoma Cells at Post-Transcription Level.

Glioblastoma (GBM) is an invasive cancer with poor prognosis in patients. Researching on molecular functions in GBM has attracted more and more attention. Actin gamma 1 (ACTG1) was reported as a pathogenic gene in skin cancer and colorectal cancer. Present study was designed to explore the biological role and underlying mechanism of ACTG1 in GBM cells. It was uncovered that ACTG1 presented high expression trends in GBM cells. Moreover, ACTG1 suppression hindered cell proliferation and boosted cell apoptosis in GBM. Then, according to the results of bioinformatics analysis and mechanism assays including RIP, RNA pull down and luciferase reporter assay, ACTG1 was verified to be targeted by miR-361-5p in GBM. Next, COX10-AS1 (COX10 antisense RNA 1) was identified as an endogenous sponge for miR-361-5p in GBM. Moreover, COX10-AS1 acted as a competing endogenous RNA (ceRNA) to positively regulate ACTG1 expression via sponging miR-361-5p. The following rescue assays demonstrated that COX10-AS1 promoted GBM cell proliferation and inhibited GBM cell apoptosis through ACTG1 up-regulation at a miR-361-5p dependent way. On the whole, present study uncovered a novel ceRNA pattern in which COX10-AS1 sponged miR-361-5p to elevate ACTG1 expression, therefore accelerating tumorigenesis in GBM. The findings suggested new promising targets for GBM treatment.

Malignant Peripheral Nerve Sheath Tumor of the Trigeminal Nerve Involving the Middle and Posterior Cranial Fossa.

BACKGROUND: Although benign trigeminal schwannomas are uncommon, malignant peripheral nerve sheath tumors (MPNSTs) of the trigeminal nerve are extraordinarily rare. CASE DESCRIPTION: A 56-year-old female presented with a 2-month-long history of numbness of the right face and progressive weakness of the left limbs. Preoperative neuroimages indicated a giant tumor involving the middle and posterior cranial fossa with similar radiologic characteristics to benign trigeminal schwannomas. However, histopathologic and immunochemical examinations confirmed the tumor to be an MPNST. A nearly gross total resection was obtained with a combined frontotemporal extradural and subtemporal anterior petrosal approach. The postoperative course was uneventful, and the patient received adjuvant radiotherapy subsequently. There was no recurrence of the tumor with a 6-month-long follow-up. CONCLUSION: MPNSTs of the trigeminal nerve are exceedingly rare. This study described the 21st case of MPNSTs of the trigeminal nerve. MPNSTs of the trigeminal nerve showed similar radiologic characteristics to benign trigeminal schwannomas, and accurate diagnosis depended on pathologic and immunochemical examinations. Gross total resection followed by radiotherapy is the usual treatment.

Integrated genomic characterization of cancer genes in glioma.

BACKGROUND: Cancers are caused by the acquisition of somatic mutations. Numerous efforts have been made to characterize the key driver genes and pathways in glioma, however, the etiology of glioma is still not completely known. This study was implemented to characterize driver genes in glioma independently of somatic mutation frequencies. METHODS: Driver genes and pathways were predicted by OncodriveCLUST, OncodriveFM, Icages, Drgap and Dendrix in glioma using 31,958 somatic mutations from TCGA, followed by an integrative characterization of driver genes. RESULTS: Overall, 685 driver genes and 215 driver pathways were determined by the five tools. FSTL5, HCN1, TMEM132D, TRHDE and KRT222 showed the strongest expression correlation with other genes in the co-expression network of glioma tissues. ST6GAL2, PIK3CA, PIK3R1, TP53 and EGFR are at the core of the protein-protein interaction network. 133 driver genes were up-regulated and associated to poor prognosis, 43 driver genes were down-regulated and related to favorable clinical outcome in glioma patients. The driver genes such as MSH6 and RUNX1T1 might serve as candidate prognostic biomarkers and therapeutic targets in glioma. CONCLUSIONS: The set of new cancer genes and pathways sheds insights into the tumorigenesis of glioma and paves the way for developing driver gene-targeted therapy and prognostic biomarkers in glioma.

Surgically Clipping a Posterolaterally Projecting Posterior Communicating Artery Aneurysm With Anterior Petroclinoid Fold Fenestration.

The anterior petroclinoid fold (APF) is a ligamentous structure consisting of collagen fiber and extends from the petrous apex to the anterior clinoid process. During the surgical clipping of some posterolaterally projecting posterior communicating artery aneurysms, it may pose a technical challenge due to obscuration of the aneurismal neck by the APF. Herein, the authors describe a simple and effective technique utilizing fenestration of the APF to facilitate visualization and surgical clipping of these aneurysms. To the best knowledge of us, this technique of the APF fenestration has been reported in only a few patients.