Glioblastoma multiforme (GBM) tumors are the most common malignant primary brain tumors in adults. Although many GBM tumors are believed to be caused by self-renewing, glioblastoma-derived stem-like cells (GSCs), the mechanisms that regulate self-renewal and other oncogenic properties of GSCs are only now being unraveled. Here we showed that GSCs derived from GBM patient specimens express varying levels of the transcriptional repressor REST, suggesting heterogeneity across different GSC lines. Loss- and gain-of-function experiments indicated that REST maintains self-renewal of GSCs. High REST-expressing GSCs (HR-GSCs) produced tumors histopathologically distinct from those generated by low REST-expressing GSCs (LR-GSCs) in orthotopic mouse brain tumor models. Knockdown of REST in HR-GSCs resulted in increased survival in GSC-transplanted mice and produced tumors with higher apoptotic and lower invasive properties. Conversely, forced expression of exogenous REST in LR-GSCs produced decreased survival in mice and produced tumors with lower apoptotic and higher invasive properties, similar to HR-GSCs. Thus, based on our results, we propose that a novel function of REST is to maintain self-renewal and other oncogenic properties of GSCs and that REST can play a major role in mediating tumorigenicity in GBM.
Serum omentin-1 levels were found to be significantly decreased in patients with Type 2 diabetes (19.7 ± 1 ng/ml) and in patients with Type 2 diabetes with ischaemic heart disease (18.5 ± 1.6 ng/ml) compared with healthy control subjects (27.4 ± 2.6 ng/ml) at P < 0.01. Moreover, serum chemerin levels were found to be significantly increased in patients with Type 2 diabetes (347 ± 14 ng/ml) and in patients with Type 2 diabetes with ischaemic heart disease (341 ± 16.5 ng/ml) compared with healthy control subjects (281 ± 13 ng/ml) at P < 0.01. Interestingly, omentin-1 and chemerin levels were found to be significantly correlated negatively with each other as well as being individually correlated with some selected anthropometric, biochemical and clinical variables. In conclusion, both omentin-1 and chemerin might play as a pivotal role in obesity and its associated disorders as Type 2 diabetes; however, their role in cardiovascular diseases needs to be fully elucidated.
This study compared lipids, the product of lipid peroxidation malondialdehyde (MDA), the acute phase reactant high-sensitive C-reactive protein (hsCRP), endothelin-1 (ET-1), P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) between healthy controls, subjects with ischemic heart disease (IHD) and type 2 diabetes mellitus (DM) subjects who did not perform coronary artery bypass graft (CABG) surgery as well as type 2 DM subjects who performed CABG. HbA1c, lipids, MDA, hsCRP, ET-1, P-selectin, ICAM-1, and VCAM-1 levels were significantly higher in the diabetic groups than in either healthy controls or IHD subjects. In the diabetic groups, there was a negative association among hsCRP and HDL-C. ET-1, ICAM-1 levels, and TAG were positively correlated, as do the association between P-selectin, VCAM-1, and HbA1c%. Also a positive relation was found among hsCRP levels and ICAM-1, as well as MDA and ET-1. P-selectin and ICAM-1 were significantly positively correlated. This study indicates that increased level of oxidative stress marker, proinflammatory markers, and their downstream effectors adhesion molecules occur in type 2 DM.
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