Malignant Glioma with Neuronal Marker Expression : A Clinicopathological Study of 18 Cases

OBJECTIVE: Malignant gliomas with neuronal marker expression (MGwNM) are rare and poorly characterized. Increasingly diverse types of MGwNM have been described and these reported cases underscore the dilemmas in the classification and diagnosis of those tumors. The aim of this study is to provide additional insights into MGwNM and present the clinicopathological features of 18 patients. METHODS: We reviewed the medical records of 18 patients diagnosed as MGwNM at our institute between January 2006 and December 2012. Macroscopic total resection was performed in 11 patients (61%). We evaluated the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) and expression of isocitrate dehydrogenase 1 (IDH-1) in all cases, and deletions of 1p and 19q in available cases. RESULTS: The estimated median overall survival was 21.2 months. The median progression-free survival was 6.3 months. Six patients (33%) had MGMT methylation but IDH1 mutation was found in only one patient (6%). Gene analysis for 1p19q performed in nine patients revealed no deletion in six, 19q deletion only in two, and 1p deletion only in one. The extent of resection was significantly correlated with progression free survival on both univariate analysis and multivariate analysis (p=0.002 and p=0.013, respectively). CONCLUSION: In this study, the overall survival of MGwNM was not superior to glioblastoma. The extent of resection has a significant prognostic impact on progression-free survival. Further studies of the prognostic factors related to chemo-radio therapy, similar to studies with glioblastoma, are mandatory to improve survival.

Mode of Oral Ethanol Feeding Affects Liver Oxidative Stress Levels and Methylation Status: Study on NS5A-Transgenic Mice.

Alcohol consumption accelerates the progression and worsens the outcomes of hepatitis C viral (HCV) infection in heavy and moderate drinkers. Our aim was to investigate the effects of two modes of oral ethanol feeding on induction of oxidative stress, impaired methylation status and downstream changes in proteasome activity in livers of NS5A-transgenic (Tg) mice. Methods: Ethanol was administered either in water (chow fed mice given 20% ethanol in water; designated chow-EtOH) or fed in Lieber De Carli liquid diet (LCD-EtOH). Appropriate controls were used. The mechanisms of alcohol and NS5A-induced changes in oxidative stress, liver methylation status and 20S proteasome activity were determined after 5 weeks of the feeding regimen. Results: Ethanol administration using both feeding regimens induced oxidative stress and suppressed cytosolic proteasome activity. However, only LCD-EtOH diet induced fatty changes in the liver which correlated with higher levels of oxidative stress, impaired methylation potential and reduced cytosolic and nuclear proteasome activity. However, LCD diet by itself triggered lipid peroxidation. Conclusion: We conclude that both modes of oral ethanol feeding (chow and LCDbased) induce oxidative stress in NS5A-Tg mice that suppresses proteasome activity. Nonetheless, impaired methylation potential, higher level of oxidative stress and suppression of nuclear proteasome was observed only in LCD-EtOH mice. However, the effects of LCD-control liquid diet in inducing lipid peroxidation in NS5A-Tg mice, in certain cases, tended to mask the effects of ethanol.

Promoter methylation status of PTEN, SYK and survivin genes in breast cancer tissues derived from Chinese women

Background: Epigenetic mechanisms of gene transcription, including inactivation of tumor suppressor genes by hypermethylation and activation of oncogenes by hypomethylation, have been shown to contribute to breast tumorigenesis. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) and Spleen tyrosine kinase (SYK) are both tumor suppressor genes and survivin is a novel member of the inhibitor of apoptosis (IAP) family which may promote tumorigenesis.Objective: To investigate the methylation status of PTEN, SYK, and survivin genes in breast cancer derived from Chinese women.Materials and methods: We examined the methylation status of these three genes in 52 paraffin-embedded breast cancer tissues using methylation-specific PCR (MSP) assay in conjunction with sequencing analysis.Results: PTEN and SYK were both methylated in 15.4% (8/52) of breast tumor tissues, while the survivin gene was all demethylated in the examined samples. Random selection of MSP products sequence analyses to three genes all revealed a homogenous methylation status in the CpG sites.Conclusion: The present study showed a moderate methylation status of PTEN and SYK, and an unmethylation status of survivin in breast tumor tissues derived from Chinese women, which suggested methylation mechanisms might be involved in the aberrant expression of these three genes in breast cancer development.