Internal Carotid Artery Constriction with or without Superficial Temporal Artery-Middle Cerebral Artery Bypass for Patients with Giant Internal Carotid Aneurysms.

BACKGROUND: The optimal management of giant internal carotid aneurysms (GICAs) is disputed owing to their low incidence. The aim of this study was to describe the use of internal carotid artery (ICA) constriction as therapeutic management of GICAs. METHODS: This retrospective cohort study analyzed data from medical histories and follow-up of 14 patients with GICAs. Before surgery, the patients underwent balloon test occlusion and magnetic resonance perfusion evaluation. ICA constriction was considered only for patients with negative balloon test occlusion. A transverse incision of about 50% of the initial part of the ICA was done, and the free margins on both sides were sutured, causing 70%-90% stenosis. ICA constriction alone was selected (11 cases) if both anterior communicating artery and posterior communicating artery compensatory blood flow existed and magnetic resonance perfusion was ≤II1 on the affected side. If there was only 1 compensatory vessel from the anterior communicating artery and posterior communicating artery, and/or magnetic resonance perfusion was >II1, ICA constriction was combined with low-flow bypass (3 cases). RESULTS: The mean follow-up time of the 14 patients was 43.5 months (interquartile range: 38.8-51.3 months). Of these 14 patients, 5 achieved O'Kelly-Marotta grades C and D. Clinical improvement occurred in 12 of 14 patients. No patients experienced new-onset stroke. CONCLUSIONS: ICA constriction exhibits a perforator protective effect. This procedure could be a promising alternative to ICA ligation in patients with GICAs and negative balloon test occlusion.

Ischemic stroke following STA-MCA double bypass.

OBJECTIVES: The surgical technique of STA-MCA double bypass is used to improve blood flow supplied by the distal middle cerebral artery (MCA) to the cerebral territory. This retrospective study from a single center aimed to compare the outcomes following STA-MCA double bypass in 12 patients with recurrent ischemic stroke. MATERIALS AND METHODS: We retrospectively analyzed the data from patients with internal carotid artery occlusion (ICAO) who had undergone STA-MCA double bypass in our center from January 2016 to December 2020. The surgical indications, evaluation of circle of Willis (CoW), changes in cerebral hemodynamic, surgical results, and follow-up results were analyzed. RESULTS: Post-operative perfusion-weighted imaging showed hemodynamic improvement in all 12 patients. Ten patients (83.33%) showed clinical improvement, and 2 patients (16.67%) had stable disease. No intracranial infections or acute ischemic events occurred. The post-operative National Institutes of Health Stroke Scale score and modified Barther scores were significantly improved after 180 days of follow-up. Twenty three (96%) anastomoses maintain patency of their bypass vessels, and none had recurrent cerebral infarction during a minimum of 36 months follow-up. CONCLUSION: In this small study, in patients with recurrent ischemic stroke without other types of treatment, STA-MCA double bypass surgery was more effective in the subgroup of patients with ICAO and poor blood supply to the CoW and an area of cerebral hypoperfusion that exceeded the area supplied by the MCA.

The effects of 7-nitroindazole on serum neuron-specific enolase and astroglia-derived protein (S100ß) levels after traumatic brain injury.

We investigated the possible role of 7-nitroindazole (7-NI) in regulating serum neuron-specific enolase (NSE) and S100ß levels in a rat model of traumatic brain injury (TBI). We also explored the possible mechanism by which 7-NI may affect the level of NSE and S100ß. A total of 160 healthy adult male Sprague-Dawley rats were randomly divided into 2 groups: i) The saline-treated group and ii) the 7-NI-treated group. Using the random number table, the groups were further divided into four subgroups: i) The sham-injured group; ii) the TBI 6 h group; iii) the TBI 12 h group; and iv) the TBI 24 h group (n=20). Controlled cortical impact in rats was established. Serum NSE and S100ß levels, nitric oxide (NO) level, water content, Evans blue (EB) content, malondialdehyde (MDA) level and total superoxide dismutase (T-SOD) level in the brain tissue were measured. NO synthase (NOS) activity was measured at 6, 12 and 24 h after TBI. Pathological changes in brain tissue were studied by hematoxylin and eosin (H&E) staining at each time-point. NSE and S100ß levels, NO content, water content, EB content and MDA level in the brain tissue increased significantly after TBI. NOS activity was also increased significantly after TBI while T-SOD content in brain tissue was significantly reduced after TBI. H&E staining showed that brain damage was aggravated gradually after TBI. We concluded that the early application of 7-NI significantly reduced serum NSE and S100ß levels after TBI. The neuroprotective effects of 7-NI may be associated with reduced NOS activity, reduced NO content, alleviated brain edema, lower blood-brain barrier permeability and oxidative stress. Serum NSE and S100ß levels can reflect the therapeutic effect of 7-NI, which suggest a good diagnostic value.

Elevated E2F7 expression predicts poor prognosis in human patients with gliomas.

E2F transcription factors have been studied extensively in a broad range of organisms as major regulators of cell cycle, apoptosis, and differentiation. The E2F family includes the atypical member E2F7, which has been rarely studied in gliomas. The aim of this study is to determine the expression status of E2F7 in gliomas, its relationship to clinicopathological features, and patients' outcome. The mRNA levels of E2F7 in the human brain and different grades of gliomas were analysed using datasets from the publically available Oncomine database. One of the most significant co-expression factors, CDK1, together with E2F7, was further validated by immunohistochemistry in 90 different grades of gliomas. Furthermore, univariate and multivariate analyses were performed to identify prognostic variables relative to patient and tumour characteristics and treatment modalities. E2F7 mRNA expression was found to be elevated in gliomas by Oncomine-database analysis. Immunohistochemistry showed an increase in E2F7 labelling index in high- versus low-grade gliomas (62.1±11.8% vs. 18.9±10.2%, p<0.0001). There was a positive correlation between E2F7 and CDK1 immunoreactivity (Spearman r=0.446, p=0.037). Clinicopathological evaluation suggested that E2F7 expression was associated with tumour grade (p<0.0001) and recurrence (p=0.025). In Cox multivariate analysis, pathological classification and recurrence were independent prognostic factors of gliomas, and E2F7 was significantly related to progression-free survival (p=0.011), but not overall survival (p=0.062). Our findings suggested that E2F7 might act as an independent prognostic factor of gliomas and might constitute a potential therapeutic target for this disease.

Anti-tumor activity of phenoxybenzamine hydrochloride on malignant glioma cells.

Phenoxybenzamine hydrochloride (PHEN) is a selective antagonist of both α-adrenoceptor and calmodulin that exhibits anticancer properties. The aim of this study was to explore the anti-tumor function of PHEN in glioma. Cell proliferation assay was used to assess glioma cell growth. Migration and invasion capacity of glioma cells was monitored by wound-healing and transwell assay, respectively. Neurosphere formation test was adopted for the tumorigenesis of glioma cells, which was also confirmed by soft agar cloning formation test in vitro and a nude mouse model in vivo. Finally, we explored the potential pathway utilized by PHEN using Western blot and immunofluoresce staining. PHEN exhibited a significant inhibitory effect on the proliferation of both U251 and U87MG glioma cell lines in a positive dose-dependent manner. PHEN apparently attenuated the malignancy of glioma in terms of migration and invasion and also suppressed the tumorigenic capacity both in vitro and in vivo. Mechanism study showed that PHEN promoted tumor suppression by inhibiting the TrkB-Akt pathway. The results of the present study demonstrated that PHEN suppressed the proliferation, migration, invasion, and tumorigenesis of glioma cells, induced LINGO-1 expression, and inhibited the TrkB-Akt pathway, which may prove to be the mechanisms underlying the anti-tumor effect of PHEN on glioma cells.

Differential lncRNA expression profiles in recurrent gliomas compared with primary gliomas identified by microarray analysis.

Glioma, especially high-grade glioma, is highly malignant with high rate of recurrence and poor prognosis. The mechanisms of glioma progression and recurrence have not been elucidated. Previous studies showed that long non-coding RNAs (lncRNAs) involved in the development and progression of glioma. However, the roles of lncRNAs in the recurrence of glioma remain unknown. We use high throughput microarray to screen the differentially expressed lncRNAs and mRNAs in recurrence gliomas compared with primary gliomas. We found a total of 1,111 lncRNAs were differentially expressed in recurrent group. Among these, 639 lncRNAs were up-regulated, while 472 lncRNAs were down-regulated (fold Change ≥2.0). GO (Gene ontology) and pathway analysis revealed that the potential functions of differentially expressed lncRNAs were closely connected with the processes of cancer progression and pathogenesis. LncRNA classification and subgroup analysis further identified three important clusters of differentially expressed lncRNA-mRNA pairs which have potential gene regulatory functions. This study for the first time showed abundant differentially expressed lncRNAs in recurrent gliomas. Some lncRNAs may play important roles in glioma recurrence, such as previously reported H19, CRNDE, HOTAIRM1 or unreported AC016745.3, XLOC_001711, RP11-128A17.1. Moreover, this study set a basis for future researches on specific lncRNA which may contribute to the recurrence of glioma. Further studies on these lncRNAs will help to elucidate the mechanism of glioma recurrence at genetic level and find therapeutic targets for glioma patients.

The transducible TAT-RIZ1-PR protein exerts histone methyltransferase activity and tumor-suppressive functions in human malignant meningiomas.

Malignant meningiomas are a rare meningioma subtype and tend to have post-surgical recurrence. Significant endeavors have been taken to identify functional therapeutic targets to halt the growth of this aggressive cancer. We have recently discovered that RIZ1 is downregulated in high-grade meningiomas, and RIZ1 overexpression inhibits proliferation while promoting cell apoptosis of the IOMM-Lee malignant meningioma cell line. In this report, we show that the N-terminal PR domain of RIZ1 alone possessed growth-inhibitory activity and anticancer activity in primary human meningioma cells. Interestingly, the effects seem to be dependent on differential RIZ1 protein levels. Transducible TAT-RIZ1-PR protein could also inhibit meningioma tumor growth in nude mice models. We further demonstrate that PR protein exerts histone methyltransferase activity. A microarray analysis of TAT-RIZ1-PR-treated human malignant meningioma cells reveals 969 differentially expressed genes and 848 alternative splicing exons. Moreover, c-Myc and TXNIP, two putative downstream targets of H3K9 methylation, may be involved in regulating RIZ1 tumor-suppressive effects. The reciprocal relationship between RIZ1 and c-Myc was then validated in primary meningioma cells and human tumor samples. These findings provide insights into RIZ1 tumor suppression mechanisms and suggest that TAT-RIZ1-PR protein is a potential new epigenetic therapeutic agent for advanced meningiomas.

Association between the XRCC1 polymorphisms and glioma risk: a meta-analysis of case-control studies.

BACKGROUND: X-ray repair cross-complementing group 1 (XRCC1) is one of the DNA repair genes encoding a scaffolding protein that participate in base excision repair (BER) pathway. However, studies on the association between polymorphisms in this gene and glioma have yielded conflicting results. This meta-analysis was performed to derive a more precise estimation between XRCC1 polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) and glioma risk. METHODS: Data were collected from several electronic databases, with the last search up to November 28, 2012. Meta-analysis was performed by critically reviewing 9 studies for Arg399Gln polymorphism (3146 cases and 4296 controls), 4 studies for Arg194Trp polymorphism (2557 cases and 4347 controls), and 4 studies for Arg280His polymorphism (1936 cases and 2895 controls). All of the statistical analyses were performed using the software programs STATA (version 11.0). RESULTS: The combined results showed that Arg399Gln polymorphism was significantly associated with glioma risk (Gln/Gln versus Arg/Arg: OR = 1.52, 95% CI = 1.03-2.23; recessive model: OR = 1.32, 95% CI = 1.01-1.73; additive model: OR = 1.21, 95% CI = 1.00-1.47), whereas Arg194Trp/Arg280His polymorphisms were all not significantly associated with glioma risk. As for ethnicity, Arg399Gln polymorphism was associated with increased risk of glioma among Asians (Gln/Gln versus Arg/Arg: OR = 1.78, 95% CI = 1.29-2.47; Arg/Gln versus Arg/Arg: OR = 1.28, 95% CI = 1.05-1.56; recessive model: OR = 1.59, 95% CI = 1.16-2.17; dominant model: OR = 1.36, 95% CI = 1.13-1.65; additive model: OR = 1.32, 95% CI = 1.15-1.52), but not among Caucasians. Stratified analyses by histological subtype indicated that the Gln allele of Arg399Gln polymorphism showed borderline association with the risk of glioblastoma among Caucasians. However, no evidence was observed in subgroup analyses for Arg194Trp/Arg280His polymorphisms. CONCLUSIONS: Our meta-analysis suggested that Arg399Gln polymorphism was associated with increased risk of glioma among Asians and borderline increased risk for glioblastoma among Caucasians, whereas Arg194Trp/Arg280His polymorphisms might have no influence on the susceptibility of glioma in different ethnicities.