Search

Human cytomegalovirus (HCMV) infection is associated with human glioblastoma, the most common and aggressive primary brain tumor, but the underlying infection mechanism has not been fully demonstrated. Here, we show that EphA2 was upregulated in glioblastoma and correlated with the poor prognosis of the patients. EphA2 silencing inhibits, whereas overexpression promotes HCMV infection, establishing EphA2 as a crucial cell factor for HCMV infection of glioblastoma cells. Mechanistically, EphA2 binds to HCMV gH/gL complex to mediate membrane fusion. Importantly, the HCMV infection was inhibited by the treatment of inhibitor or antibody targeting EphA2 in glioblastoma cells. Furthermore, HCMV infection was also impaired in optimal glioblastoma organoids by EphA2 inhibitor. Taken together, we propose EphA2 as a crucial cell factor for HCMV infection in glioblastoma cells and a potential target for intervention.

Abstract. Background. Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma. Methods. CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared. Results. Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF compared with the corresponding tumor tissue samples (3.56 ± 0.75 vs. 2.22 ± 0.32, P = 0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.1% ± 6.0% vs. 73.8% ± 6.0%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3 histone, family 3A (H3F3A) which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF. Conclusion. Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.

Enhancer RNAs, a type of long non-coding RNAs (lncRNAs), play a critical role in the occurrence and development of glioma. RNA-seq data from 161 glioblastoma multiforme (GBM) samples were acquired from The Cancer Genome Atlas database. Then, 70 eRNAs were identified as prognosis-related genes, which had significant relations with overall survival (log-rank test, p < 0.05). AC003092.1 was demonstrated as an immune-related eRNA by functional enrichment analysis. We divided samples into two groups based on AC003092.1 expression: AC003092.1 High (AC003092.1_H) and AC003092.1 Low (AC003092.1_L) and systematically analyzed the influence of AC003092.1 on the immune microenvironment by single-sample gene-set enrichment analysis and CIBERSORTx. We quantified AC003092.1 and TFPI2 levels in 11 high-grade gliomas, 5 low-grade gliomas, and 7 GBM cell lines. Our study indicates that AC003092.1 is related to glioma-immunosuppressive microenvironment, and these results offer innovative sights into GBM immune therapy.

Background: Pilocytic astrocytomas (PAs) are slow growing neoplasms and usually located at the cerebellum. There has been certainty regarding the truthful benefit of surgical resection for patients with PA. Gross total resection (GTR) of PAs, especially those being situated in deep regions, remains a surgical challenge. Generally, they are considered as benign and usually develop in young patients. PAs, belonging to WHO I can be cured by radical resection. The patients with PA have excellent prognosis if complete resection can be conducted. The use of fluorescein in vermis PA surgery has not been yet reported. Our data presents fluorescein facilitates surgical resection of vermis PA. Methods: Five milligrams per kilogram of fluorescein sodium was intravenously injected directly before general anesthesia for the three patients with PA. The yellow 560 filter was employed for microsurgical tumor resection. Surgical outcomes were assessed concerning the extent of resection. Results: Most portion of PA in the three cases was found to be highly fluorescent after intravenous fluorescein sodium injection, which markedly enhanced tumor visibility. Gross total resection in all of the patients was achieved without further neurological deficits. No adverse effects and complications resulting from fluorescein sodium were observed over the postoperative course. Conclusions: Intraoperative guidance by fluorescein sodium as a new, simple, safe, and practical procedure can enhance the fidelity of tumor tissue and increase the possibility of completely resecting PAs. [ABSTRACT FROM AUTHOR]

Currently, immunotherapy by blocking the immune checkpoint inhibitors, such as anti-PD-1, has been carried out in many clinical studies on recurrent glioma, and the preliminary results are satisfactory, which provides a rationale for the exploration of immune checkpoint inhibitors in glioma. B7-H6 is a newly discovered member of the B7 family, which triggers antitumor of natural killer cell cytotoxicity and cytokine secretion by binding the NKp30 receptor. B7-H6 mRNA and protein expressions, which are not detected in normal tissues, are expressed mainly on the cell surface of various primary tumors and cell lines. However, up until now, there is no data about the clinical significance of B7-H6 expression in astrocytoma patients. The present study provides an investigation on the relationship between prognostic and clinical value of B7-H6 protein in astrocytoma tissues. All the astrocytic glioma tissues were stained for B7-H6. Immunohistochemistry stain of 122 astrocytoma samples showed that immunoreactivity of B7-H6 was seen predominantly in the cytoplasm. The B7-H6 expression did not show significant relevance with patient age, sex distribution, Karnofsky performance status score, extent of resection, and tumor location in astrocytoma patients, but B7-H6 positive expression is significantly associated with World Health Organization grade (P=0.046). However, the survival rate after operation presented no significant difference of B7-H6 expression in astrocytoma patients. Kaplan-Meier analysis and the log-rank test revealed that B7-H6 expression cannot predict the overall survival. In all, it seems that the B7-H6 expression might be a marker to differentiate the World Health Organization grade level of astrocytoma, but the prognosis value of B7-H6 in astrocytoma should be studied in detail. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is a frequent head and neck cancer in southern China and Southeast Asia. The majority of NPC patients are managed by radiation oncologists, medical oncologists and head and neck surgeons. Actually, neurosurgical interventions are warranted under specific circumstances. In this article, we described our experience as neurosurgeons in the management of NPC patients. Methods: Medical records of NPC patients who received neurosurgical procedure at Sun Yat-sen University Cancer Center were reviewed. Results: Twenty-seven patients were identified. Among 27 cases, neurosurgical procedures were performed in 18 (66.7%) with radiation-induced temporal necrosis, 2 (7.4%) with radiation-induced sarcoma, 4 (14.8%) with synchronous NPC with primary brain tumors, 2 (7.4%) with recurrent NPC involving skull base, and 1 (3.7%) with metachronous skull eosinophilic granuloma, respectively. The diagnosis is challenging in specific cases and initial misdiagnoses were found in 6 (22.2%) patients. Conclusions: For NPC patients with intracranial or skull lesions, the initial diagnosis can be occasionally difficult because of the presence or a history of NPC and related treatment. Unawareness of these entities can result in misdiagnosis and subsequent improper treatment. Neurosurgical interventions are necessary for the diagnosis and treatment for these patients. [ABSTRACT FROM AUTHOR]

Both intraparenchymal papillary meningioma and papillary meningioma with cyst formation of brainstem have never been reported. The authors present an extremely rare case of patient with intraparenchymal papillary meningioma of brainstem. A 23-year-old Chinese male presented with a 4-month history of progressive left upper limb and facial nerve palsy. Magnetic resonance imaging revealed a cystic-solid, heterogeneously enhancing mass in pons and right cerebral peduncle with no dural attachment. The tumor was totally removed via subtemporal approach. During surgery, the lesion was found to be completely intraparenchymal. Histological and immunohistochemical examinations were compatible with the diagnosis of papillary meningioma. The lesion recurred nine months after primary surgery, a second surgery followed by radiotherapy was performed. Till to now (nearly 2 years after the treatment), the patient is tumor free survival. Intraparenchymal meningioma of brainstem with cystic formation is very rare, however, it should be considered as a differential diagnosis of a brainstem neoplasm. The present case strongly recommended that postoperative radiotherapy was essential for the patients with papillary meningiomas. [ABSTRACT FROM AUTHOR]

Background Radiation-induced temporal lobe necrosis is a rare and serious late complication in irradiated patients with nasopharyngeal carcinoma (NPC). Treatment of radiation-induced temporal lobe necrosis with surgery has been seldom thoroughly investigated. Methods We retrospectively analyzed the clinical data of 14 patients with radiation-induced temporal lobe necrosis treated with surgical intervention. Results Radiation-induced temporal lobe necrosis presented as obvious cystic formation or as heterogeneous enhanced nodule on MRI. Among 3 patients with 18F-fluorodeoxyglucose (18F-FDG) PET-CT scan, increased uptake of 18F-FDG was observed in 2 cases. Four patients were anesthestized nasotracheally and 1 was through tracheostomy during surgery because of other radiation complications, including trismus and skull base osteoradionecrosis. The temporal approach was applied in all cases, with the removal of bone flap in 11 patients. During follow-up, 1 patient died of exhaustion. Conclusions Surgery benefits selected patients with NPC with radiation-induced temporal lobe necrosis. The goals of surgery are to relieve the increased intracranial pressure and to establish the accurate diagnosis. © 2010 Wiley Periodicals, Inc. Head Neck, 2010 [ABSTRACT FROM AUTHOR]

The article presents a case study of a 51‑year old man, who was presented with a 5‑month history of acute pain bilaterally on the posterolateral aspect of his hip. It mentions that neurological examination revealed that the Lasegue sign was bilaterally positive, along with mild motor weakness. It mentions diagnosis of lumber nerve root cavernous angioma.

Objectives Malignant gliomas are common primary brain tumors with dismal prognosis. The blood-brain barrier and unacceptable systemic toxicity limit the employment of chemotherapeutic agents. BCNU-impregnated biodegradable polymers (Gliadel®) have been demonstrated to prolong the survival of patients with malignant gliomas. Until now, no biodegradable drug delivery system has been commercially available in China. In the present study, we evaluated the safety of implants with high-dose BCNU in Chinese patients with recurrent malignant gliomas. Patients and methods Adults with supratentorial recurrent malignant glioma were eligible. High-dose BCNU-loaded PLGA implants (20 mg of BCNU in each implant) were placed in the debulking cavity. The implants were investigated by a classical 3+3 design. Four levels of BCNU, up to 12 implants, were evaluated. Pharmacokinetic sampling was performed. The toxicity of the implants and the survival of patients were recorded. Results Fifteen recurrent patients were enrolled with 12 glioblastomas and 3 anaplastic gliomas. Among 15 patients, 3 were treated with 3 implants (60 mg of BCNU), 3 with 6 implants (120 mg), 3 with 9 implants (180 mg) and 6 with 12 implants (240 mg). No dose-limiting toxicity was observed in the cohort of patients. Subgaleal effusion was the most common adverse event, presenting in 7 patients (46.7%). The median overall survival (OS) was 322 days (95% CI, 173-471 days). The 6-month, 1-year and 2-year survival rates were 66.7%, 40% and 13.3%, respectively. Conclusions The high-dose BCNU-loaded PLGA implants were safe for Chinese patients with recurrent malignant gliomas and further investigation for efficacy is warranted. [ABSTRACT FROM AUTHOR]