Cancer stem cell metabolism: target for cancer therapy

Increasing evidence suggests that cancer stem cell (CSC) theory represents an important mechanism underlying the observed failure of existing therapeutic modalities to fully eradicate cancers. In addition to their more established role in maintaining minimal residual disease after treatment and forming the new bulk of the tumor, CSCs might also critically contribute to tumor recurrence and metastasis. For this reason, specific elimination of CSCs may thus represent one of the most important treatment strategies. Emerging evidence has shown that CSCs have a different metabolic phenotype to that of differentiated bulk tumor cells, and these specific metabolic activities directly participate in the process of CSC transformation or support the biological processes that enable tumor progression. Exploring the role of CSC metabolism and the mechanism of the metabolic plasticity of CSCs has become a major focus in current cancer research. The targeting of CSC metabolism may provide new effective therapies to reduce the risk of recurrence and metastasis. In this review, we summarize the most significant discoveries regarding the metabolism of CSCs and highlight recent approaches in targeting CSC metabolism

An Investigation of Narration Rates for the Reading While Listening Strategy

This study investigated the effects of Reading While Listening narration rates on elementary students\u27 comprehension. Slow, normal and sentence interval narration rates were used. Results showed higher comprehension scores with the slow narration rate for students with low reading levels, and normal rate for high and medium level reader

Impact of the Metabolic Syndrome on the Clinical Outcome of Patients with Acute ST-Elevation Myocardial Infarction

We sought to determine the prevalence of metabolic syndrome (MS) in patients with acute myocardial infarction and its effect on clinical outcomes. Employing data from the Korea Acute Myocardial Infarction Registry, a total of 1,990 patients suffered from acute ST-elevation myocardial infarction (STEMI) between November 2005 and December 2006 were categorized according to the National Cholesterol Education Program-Adult Treatment Panel III criteria of MS. Primary study outcomes included major adverse cardiac events (MACE) during one-year follow-up. Patients were grouped based on existence of MS: group I: MS (n=1,182, 777 men, 62.8±12.3 yr); group II: Non-MS (n=808, 675 men, 64.2±13.1 yr). Group I showed lower left ventricular ejection fraction (LVEF) (P=0.005). There were no differences between two groups in the coronary angiographic findings except for multivessel involvement (P=0.01). The incidence of in-hospital death was higher in group I than in group II (P=0.047), but the rates of composite MACE during one-year clinical follow-up showed no significant differences. Multivariate analysis showed that low LVEF, old age, MS, low high density lipoprotein cholesterol and multivessel involvement were associated with high in-hospital death rate. In conclusion, MS is an important predictor for in-hospital death in patients with STEMI

PIAS1 regulates CP2c localization and active promoter complex formation in erythroid cell-specific α-globin expression

Data presented here extends our previous observations on α-globin transcriptional regulation by the CP2 and PIAS1 proteins. Using RNAi knockdown, we have now shown that CP2b, CP2c and PIAS1 are each necessary for synergistic activation of endogenous α-globin gene expression in differentiating MEL cells. In this system, truncated PIAS1 mutants lacking the ring finger domain recruited CP2c to the nucleus, as did wild-type PIAS1, demonstrating that this is a sumoylation-independent process. In vitro, recombinant CP2c, CP2b and PIAS1 bound DNA as a stable CBP (CP2c/CP2b/PIAS1) complex. Following PIAS1 knockdown in MEL cells, however, the association of endogenous CP2c and CP2b with the α-globin promoter simultaneously decreased. By mapping the CP2b- and CP2c-binding domains on PIAS1, and the PIAS1-binding domains on CP2b and CP2c, we found that two regions of PIAS1 that interact with CP2c/CP2b are required for its co-activator function. We propose that CP2c, CP2b, and PIAS1 form a hexametric complex with two units each of CP2c, CP2b, and PIAS1, in which PIAS1 serves as a clamp between two CP2 proteins, while CP2c binds directly to the target DNA and CP2b mediates strong transactivation