CDC6 overexpression contributes to the malignant phenotype of glioma via IL6/JAK2/STAT3 signaling.

Glioma, a prevalent primary tumor of the central nervous system, is targeted by molecular therapies aiming to intervene in specific genes and signaling pathways to inhibit tumor growth and spread. Our previous bioinformatics study revealed that significant CDC6 overexpression in gliomas was closely correlated with poor patient prognosis. Through qPCR, western blotting, and immunohistochemistry, we will further validate CDC6 expression in clinical glioma specimens, while the effects of silencing and overexpressing CDC6 in the U87 and LN229 glioma cell lines on malignancy will be assessed through MTS, EdU, transwell, and migration assays. Luciferase reporter assays, ChIP, qPCR, and western blotting were used to explore the upstream and downstream molecular mechanisms of CDC6. Our study confirmed the abnormal overexpression of CDC6 in gliomas, particularly in glioblastomas. CDC6 promotes glioma cell activity, proliferation, invasion, and migration by activating the IL6-mediated JAK2/STAT3 signaling pathway. The transcription Factor E2F8 directly regulates CDC6 transcription, playing a crucial role in its abnormal overexpression in gliomas. This research provides vital evidence supporting CDC6 as a molecular target for glioma therapy.

Case report: Low-dose radiation-induced meningioma with a short latency period.

Patients with radiation-induced meningioma (RIM), most of whom had received head radiation therapy or had been exposed to ionizing radiation during childhood or adolescence, are at risk of developing cranial meningiomas throughout their lifetimes because of the long latency period. Although intermediate-to-high-dose ionizing radiation exposure is an established risk factor for RIM, risk factors for low-dose RIM remain incompletely defined. This study presents the case of a 56-year-old woman diagnosed with radiation-induced giant meningioma 2.5 years after undergoing an interventional embolization procedure for a brain aneurysm. This is the first report of RIM attributable to a brain intervention with an extremely short latency period. The total radiation dose received by the patient during the operation was 1367.3 mGy, representing a low dose. Our case report strengthens the evidence that even low radiation doses can increase the risk of RIM. These findings provide a realistic basis for the theoretical study of RIM and suggest some new ideas for RIM treatment. The need for caution in the use of radioactive treatments and optimization of interventional procedures is highlighted.

New natural compound inhibitors of PDGFRA (platelet-derived growth factor receptor α) based on computational study for high-grade glioma therapy.

Background: High-grade glioma (HGG) is a malignant brain tumor that is common and aggressive in children and adults. In the current medical paradigm, surgery and radiotherapy are the standard treatments for HGG patients. Despite this, the overall prognosis is still very bleak. Studies have shown that platelet-derived growth factor receptor α (PDGFRA) is an essential target to treat tumors and inhibiting the activity of PDGFRA can improve the prognosis of HGG. Thus, PDGFRA inhibitors are critical to developing drugs and cancer treatment. Objective: The purpose of this study was to screen lead compounds and candidate drugs with potential inhibitors against platelet-derived growth factor receptor α (PDGFRA) from the drug library (ZINC database) in order to improve the prognosis of patients with high-grade glioma (HGG). Materials and methods: In our study, we selected Imatinib as the reference drug. A series of computer-aided technologies, such as Discovery Studio 2019 and Schrodinger, were used to screen and assess potential inhibitors of PDGFRA. The first step was to calculate the LibDock scores and then analyze the pharmacological and toxicological properties. Following this, we docked the small molecules selected in the previous steps with PDGFRA to study their docking mechanism and affinity. In addition, molecular dynamics simulation was used to determine whether the ligand-PDGFRA complex was stable in nature. Results: Two novel natural compounds 1 and 2 (ZINC000008829785 and ZINC000013377891) from the ZINC database were found binding to PDGFRA with more favorable interaction energy. Also, they were predicted with less Ames mutagenicity, rodent carcinogenicity, non-developmental toxic potential, and tolerant with cytochrome P450 2D6 (CYP2D6). The dynamic simulation analysis demonstrated that ZINC000008829785-PDGFRA and ZINC000013377891-PDGFRA dimer complex had more favorable potential energy compared with Imatinib, and they can exist in natural environments stably. Conclusion: ZINC000008829785 and ZINC000013377891 might provide a solid foundation for drugs that inhibit PDGFRA in HGG. In addition to being safe drug candidates, these compounds had important implications for improving drugs targeting PDGFRA.

Epigenome-wide association study reveals CpG sites related to COG of neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor in infants and children. Its variable location and complex pathogenesis make NB hard for early diagnosis and risk classification. METHODOLOGY: We analyzed the methylation data of 236 samples from patients with NB in Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Kaplan-Meier survival analysis was used for comparing overall survival of NB patients in different groups. Epigenome-wide association study (EWAS) was conducted to screen CpGs significantly associated with NB patients' Children's Oncology Group (COG). Logistic regression method was used for constructing a model to predict NB patients' COG. RESULTS: NB patients in low COG showed significantly superior prognosis than those in high COG. A total of seven CpG sites were found closely related to COG. Logistic regression model based on those CpGs showed superior performance in separating NB patients in different COGs. CONCLUSIONS: The present study highlights the important role of DNA methylation in NB development, which might provide evidence for treatment decisions for children NB.

Basal Ganglionic Germinoma With Syncytiotrophoblastic Giant Cells Mimicking a Growing Hematoma.

Basal ganglionic germinoma (BGG) with syncytiotrophoblastic giant cells (STGC) is a rare type of ectopic germ cell tumors with mild elevation of human chorionic gonadotropin level. Intratumoral hemorrhage is not uncommon for BGG, but presenting with repeated hemorrhage is very rare. Herein, we described an extremely rare case of BGG with STGC mimicking a growing hematoma. Furthermore, the characteristics, treatment, and prognosis of BGG with STGC were investigated and reviewed.

Down-regulation of TGF-ß RII expression is correlated with tumor growth and invasion in non-functioning pituitary adenomas.

The two types of TGF-ß receptors play a crucial role in TGF-ß signaling. It has been reported that TGF-ß signaling activity may be associated with the development and invasion of NFPAs. However, the role of TGF-ß receptor signaling in NFPAs has not been fully explored. In this study, the expression of TGF-ß RI and TGF-ß RII in normal anterior pituitaries, invasive NFPAs and non-invasive NFPAs was analyzed by qRT-PCR, western blot, and immunohistochemistry. We found that TGF-ß RII protein and mRNA levels gradually decreased from normal anterior pituitaries, noninvasive NFPAs to invasive NFPAs. There was no significant difference in the expression of TGF-ß RI mRNA and protein level between normal anterior pituitaries and NFPAs. PCNA mRNA level was significantly higher in the invasive NFPAs than noninvasive NFPAs and PCNA mRNA had a negative correlation with TGF-ß RII mRNA. We may draw the conclusion that low expression of TGF-ß RII may contribute to the development and invasion of NFPAs and TGF-ß RII promises to be a useful biomarker for the diagnosis of invasive NFPAs.

[Microsurgical anatomy and DSA research about venous anastomosis of superficial cerebral veins].

OBJECTIVE: To investigate the distribution and clinical significance about venous anastomosis of superficial cerebral vein in normal adult. METHODS: The digital subtraction angiography (DSA) images of the venous phase from 50 normal adults were retrospectively analyzed, and the morphology of venous anastomosis of superficial cerebral veins was observed and measured. While venous anastomosis of superficial cerebral veins of 15 (30 sides) cadaveric heads was observed through blood vessel perfusion. RESULTS: Trolard vein and Labbe vein were the main venous anastomosis of superficial cerebral veins. A total of 55 Trolard veins were found out of 50 sides DSA venous phase images, including left 27, right 28; 34 Trolard veins, left 18, right 16, were found from the 30 sides of the brain hemispheres. 51 Labbe veins, left 25, right 26, were found from the 50 sides DSA venous phase images, and 31 Labbe veins, left 15, right 16, were found from the 30 sides of the brain hemispheres. CONCLUSIONS: Venous anastomosis of superficial cerebral veins is variable. The DSA venous phase image is consistent with the microscopic anatomy, and the preoperative DSA examination is beneficial for the protection of venous anastomosis of superficial cerebral veins.

[Effects of hemoglobin on the expression and distribution of inducible nitric oxide synthase after intracerebral hemorrhage].

OBJECTIVE: To explore the effects of hemoglobin on inducible nitric oxide synthase (iNOS) after intracerebral hemorrhage. METHODS: A total of 60 male Sprague-Dawley rats were randomized into hemoglobin (Hb) and sham-operated groups (n = 30 each). And each group was divided further into 6 subgroups (6 h, 12 h, 24 h, 48 h, 3 d and 7 d). At each timepoint, their neurological behaviors were observed. The expression and distribution of iNOS in perihematomal brain tissue were detected by immunohistochemical staining. The mean optical density of iNOS was assessed and semiquantitatively analyzed. RESULTS: After Hb injection, there was an onset of limb dysfunction. The Bederson score in Hb group increased significantly versus sham group (P < 0.05). At 6 hours post-injection, immunoreactivity of iNOS was obviously observed in astrocytes and inflammatory cells. In some cases, iNOS reactivity was detected in endothelial cells. Maximal expression occurred at 12 hours. The iNOS expression stay at high levels till 48 hours (P < 0.05, versus sham group) and then slowly diminished at 3 and 7 days. The iNOS expression was correlated significantly with the score of neurological behavior (r = 0.641, P < 0.05). CONCLUSION: After intracerebral hemorrhage, hemoglobin induces the expression of iNOS and participates in the course of brain edema.