Quantitative susceptibility mapping to evaluate brain iron deposition and its correlation with physiological parameters in hypertensive patients.

BACKGROUND: Regional excessive iron overload is pernicious to motor functions and cognitive functioning of the brain. The aim of this research was to utilize quantitative susceptibility mapping (QSM) to inspect brain iron accumulation in patients with hypertension (HP), and to evaluate whether it is correlated with physiological parameters. METHODS: Thirty-one HP and 31 age- and sex-matched healthy controls (HC) were included. All participants underwent brain magnetic resonance imaging (MRI), and QSM data were obtained. Differences in brain iron deposition in deep gray matter nuclei of participants were compared between HP and HC. The correlations between iron deposition, body mass index (BMI), maximum systolic blood pressure (SBP), and diastolic blood pressure (DBP) were analyzed. RESULTS: The HP group showed increased susceptibility values in the caudate nucleus (CA), putamen (PU), globus pallidus (GP), and dorsal thalamus (TH), compared with the HC group. There was a significant positive correlation between BMI and the susceptibility values in the dentate nucleus (DN); the maximum SBP and DBP were positively correlated with magnetic susceptibility of the CA, PU, GP, and TH, respectively. CONCLUSIONS: These results are indicative of the role of overload brain iron in deep brain gray matter nuclei in HP and suggest that HP is associated with excess brain iron in certain deep gray matter regions.

Downregulation of chromatin remodeling factor CHD5 is associated with a poor prognosis in human glioma.

Chromodomain helicase DNA-binding protein 5 (CHD5), a member of the CHD family, is involved in key cellular processes including chromatin remodeling, cell cycle regulation, and cellular adhesion. Recent studies have demonstrated that CHD5 is the product of a novel tumor suppressor gene and is implicated in certain tumor types. However, the clinicopathological significance of CHD5 expression in human malignant gliomas remains unclear. To address this problem, CHD5 expression in human gliomas and non-neoplastic brain tissues was measured using real-time quantitative polymerase chain reaction (RT-PCR) assay, Western blot, and immunohistochemistry. The association of CHD5 immunostaining with clinicopathological factors or prognosis of glioma patients was statistically analyzed. Genetic and protein expression of CHD5 were downregulated in glioma tissues compared to corresponding non-neoplastic brain tissues (both p<0.001). Additionally, decreased expression of CHD5 in glioma was significantly associated with pathological grade (p=0.007); high pathological grade was associated with low CHD5 expression. Loss of CHD5 protein expression was also significantly correlated with a low Karnofsky performance scale score (p=0.01). Moreover, overall survival of patients with low CHD5 protein expression was dramatically shorter than those of patients with high CHD5 protein expression (p=0.003). Multivariate Cox regression analysis indicated that CHD5 expression was an independent prognostic factor for patients with gliomas (p=0.01). In conclusion, these data offer convincing evidence for the first time that CHD5 might act as a tumor suppressor in glioma, may act as a regulator of aggressive development, and is a candidate prognostic marker for this malignancy.

Co-expression of MMP-14 and MMP-19 predicts poor survival in human glioma.

AIM: Matrix metalloproteinase (MMP)-14 and MMP-19 have been demonstrated to play an important role in the development of human gliomas. However, their prognostic values are not clear. The aim of this study was to investigate whether co-expression of MMP-14 and MMP-19 has prognostic relevance in human gliomas. METHODS: Immunohistochemistry and western blot were used to investigate the expression of MMP-14 and MMP-19 proteins in 128 patients with gliomas. RESULTS: The expression levels of MMP-14 and MMP-19 proteins in glioma tissues were both significantly higher (both P < 0.001) than those in non-neoplastic brain tissues according to the immunohistochemistry analysis, which was confirmed by the western blot analysis. Additionally, the overexpression of either MMP-14 or MMP-19 was significantly associated with the advanced WHO grade (both P = 0.02), the low Karnofsky performance score (KPS) (P = 0.008 and 0.01, respectively) and the poor overall survival (both P = 0.01). Moreover, the Multivariate Cox proportional-hazards regression analysis revealed that the increased expressions of MMP-14 and MMP-19 were both independent prognostic factors for poor overall survival (both P = 0.02). Furthermore, the co-expression of MMP-14 and MMP-19 was additively and more significantly (P = 0.006) associated with adverse prognosis in patients with gliomas than respective expression of MMP-14 and MMP-19. CONCLUSIONS: These findings indicated for the first time that the co-expression of MMP-14 and MMP-19 is significantly correlated with prognosis in glioma patients, suggesting that the co-expression of these proteins may be used as both an early diagnostic and independent prognostic marker.

Oncogenic role of SOX9 expression in human malignant glioma.

SOX9 belongs to the SOX (Sry-related high-mobility group box) family and acts as a transcription factor that plays a central role in the development and differentiation of multiple cell lineages. Recent studies have demonstrated that SOX9 is required for the carcinogenesis in several cancer types. The aim of this study was to investigate the clinicopathological significance of SOX9 expression in human malignant glioma. SOX9 mRNA expression was detected by real-time quantitative RT-PCR assay in glioma and nonneoplastic brain tissues. Then, the association of SOX9 mRNA expression with clinicopathological factors or prognosis of glioma patients was statistically analyzed. In addition, the small interfering RNA was used to knockdown SOX9 expression in a glioma cell line and to analyze the effects of SOX9 inhibition on cell growth, cell cycle and apoptosis of glioma cell line. The expression level of SOX9 mRNA in glioma tissues was significantly higher than that in corresponding nonneoplastic brain tissues (P < 0.001). In addition, a high level of SOX9 mRNA expression was significantly more common in glioma tissues with advanced WHO grade than those with low grade (P = 0.02). The increased expression of SOX9 mRNA was also significantly correlated with low Karnofsky performance score (P = 0.008). Meanwhile, the disease-free and overall survival rates of patients with high SOX9 mRNA expression were obviously lower than those of patients with low SOX9 mRNA expression (both P = 0.01). Multivariate analysis showed that high SOX9 mRNA expression was an independent prognostic factor for glioma patients (P = 0.02). Moreover, the down-regulation of SOX9 could inhibit the cell growth, induce the cell arrest in G2/M phase of cell cycle and enhance the apoptosis in glioma cells. Our data suggest for the first time that the over-expression of SOX9 mRNA is closely associated with poor clinical outcome of patients with malignant gliomas, and targeting SOX9 may be a novel therapeutic strategy for this tumor.

Elevated expression of chloride intracellular channel 1 is correlated with poor prognosis in human gliomas.

BACKGROUND: Chloride intracellular channel 1 (CLIC1) is expressed ubiquitously in human tissues and is involved in the regulation of cell cycle, cell proliferation and differentiation. Recent studies have shown that CLIC1 is highly expressed in several human malignant tumors. However, its roles in human gliomas are still unclear. The aim of this study was to investigate the clinicopathological significance and prognostic value of CLIC1 expression in human gliomas. METHODS: CLIC1 expression in human gliomas and nonneoplastic brain tissues was measured by real-time quantitative RT-PCR assay and immunohistochemistry. Its association with clinicopathological factors or prognosis in patients with gliomas was statistically analyzed. RESULTS: The expression of CLIC1 at both mRNA and protein levels was significantly increased in high-grade (Grade III~IV) glioma tissues compared with that in low-grade (Grade I~II) and nonneoplastic brain tissues, and was up-regulated with ascending tumor World Health Organization (WHO) grades. The elevated expression of CLIC1 protein was also significantly correlated with low Karnofsky performance score (KPS) (P=0.008). Moreover, both univariate and multivariate analysis shown that high CLIC1 expression was significantly associated with poor prognosis in patients with gliomas (P<0.001 and P=0.01, respectively). In particular, the elevated CLIC1 expression also correlated with shorter overall survival in different glioma subgroups stratified according to the WHO grading. CONCLUSIONS: Our data provide the first evidence that CLIC1 expression might play an important role in the regulation of aggressiveness in human gliomas. The elevated expression of CLIC1 might represent a valuable prognostic marker for this disease.

Aberrant expression of N-methylpurine-DNA glycosylase influences patient survival in malignant gliomas.

AIM: To examine the expression of N-methylpurine-DNA glycosylase (MPG) gene and protein in glioma samples with different WHO grades and its association with patients' survival. METHODS: Immunohistochemistry assay, quantitative real-time PCR and Western blot analysis were carried out to investigate the expression of MPG gene and protein in 128 glioma and 10 non-neoplastic brain tissues. RESULTS: MPG gene expression level in glioma tissues was significantly higher than that in non-neoplastic brain tissues (P < 0.001). Immunohistochemistry also showed that MPG protein was over-expressed in glioma tissues, which was consistent with the resutls of Western blot analysis. Additionally, the expression levels of MPG gene and protein both increase from grade I to grade IV glioma according to the results of real-time PCR, immunohistochemistry and western blot analysis. Moreover, the survival rate of MPG-positive patients was significantly lower than that of MPG-negative patients (P < 0.001). We further confirmed that the over-expression of MPG was a significant and independent prognostic indicator in glioma by multivariate analysis (P < 0.001). CONCLUSIONS: Our data showed the over-expression of MPG gene and protein in human gliomas, and also suggested for the first time that MPG be an unfavorable independent prognostic indicator for glioma patients.

Increased expression of FAT10 is correlated with progression and prognosis of human glioma.

FAT10, as a small ubiquitin-like modifier, plays an important role in various cellular processes, including mitosis, immune response, and apoptosis, the dys-regulation of which may arise tumorigenesis. Therefore, the aim of this study was to examine the expression of FAT10 at gene and protein levels in glioma samples with different WHO grades and its association with survival. One hundred and twenty-eight glioma specimens and 10 non-neoplastic brain tissues were collected. Immunohistochemistry assay, quantitative real-time PCR and Western blot analysis were carried out to investigate the expression of FAT10. Kaplan-Meier method and Cox's proportional hazards model were used in survival analysis. Immunohistochemistry showed that FAT10 protein was over-expressed in glioma tissues. FAT10 mRNA and protein levels were both higher in glioma compared to control on real-time PCR and Western blot analysis (both P < 0.001). Additionally, its expression levels increase from grade I to grade IV glioma according to the results of real-time PCR, immunohistochemistry analysis and Western blot. Moreover, the survival rate of FAT10-positive patients was significantly lower than that of FAT10-negative patients (P < 0.001). We further confirmed that the increased expression of FAT10 was a significant and independent prognostic indicator in glioma by multivariate analysis (P < 0.001). Our data provides convincing evidence for the first time that the increased expression of FAT10 at gene and protein levels is correlated with poor outcome in patients with glioma. FAT10 may promote the aggressiveness of glioma and may be a potential prognosis predictor of glioma.

Repeat gamma knife radiosurgery for recurrent or refractory trigeminal neuralgia.

BACKGROUND: Repeat gamma knife radiosurgery (GKRS) is considered to be an effective treatment for refractory or recurrent trigeminal neuralgia (TN). AIMS: The purpose of this report was to demonstrate the relationship between the outcome of repeat GKRS and prior operative procedures on patients with recurrent or refractory TN. MATERIALS AND METHODS: A retrospective analysis was performed on 34 patients with refractory or recurrent TN who had undergone repeat GKRS; 21 patients had undergone other types of procedures, 11 of whom had undergone more than three such procedures prior to radiosurgery. The maximum dose of the repeat procedure was between 60 and 75 Gy. The mean follow-up time was 21.6 months. STATISTICAL ANALYSIS USED: The log-rank test and Fisher's exact test were used to analyze the data. RESULTS: Excellent pain relief was achieved in 14 patients (41.2%) after repeat GKRS, while a successful outcome occurred in 29 of 34 patients (85.3%). Better pain relief occurred in the patients who did not have a prior procedure or who had undergone fewer than three prior procedures (P=0.042). Twenty-four of 25 patients (96.0%) who had recurrent pain had a successful operation and five of nine patients (55.6%) who did not have significant relief of pain after the first procedure had a successful operation. The difference was statistically significant (P<0.01). Only four patients had mild complications. CONCLUSION: It is more likely to relieve pain in patients with recurrent or refractory TN who did not have a prior procedure or who had fewer than three procedures before undergoing their first GKRS. Moreover, it seems that patients who had a good response following the initial GKRS had better results after a repeat procedure.