Associations between VDR polymorphisms (ApaI, BsmI, Cdx-2, FokI, TaqI) and the risk of ovarian cancer under different genetic models.

<p>Associations between VDR polymorphisms (ApaI, BsmI, Cdx-2, FokI, TaqI) and the risk of ovarian cancer under different genetic models.</p

Forest plot for the association between variant FokI in the VDR and risk of ovarian cancer (TT vs. CC).

<p>NECC, new England case-control study; NHS, nurses’ health study; WHS, women’s health study; MALOVA, malignant ovarian cancer study; SEARCH, studies of epidemiology and risk factors in cancer heredity: ovarian cancer study; GEOCS, genetic epidemiology of ovarian cancer study; UKOPS, united kingdom ovarian cancer population study.</p

Characteristics of publications identified for the meta-analysis.

<p><b>Abbreviations:</b> PB, population-based case-control study; NCC, nested case-control study; PCR-RFLP, polymerase chain reaction-restriction fragment length polymorphism; NECC, new England case-control study; NHS, nurses’ health study; WHS, women’s health study; MALOVA, malignant ovarian cancer study; SEARCH, studies of epidemiology and risk factors in cancer heredity: ovarian cancer study; GEOCS, genetic epidemiology of ovarian cancer study; HAW, Hawaii ovarian cancer study; UKOPS, united kingdom ovarian cancer population study.</p

Dihydroartemisinin Exerts Its Anticancer Activity through Depleting Cellular Iron via Transferrin Receptor-1

<div><p>Artemisinin and its main active metabolite dihydroartemisinin, clinically used antimalarial agents with low host toxicity, have recently shown potent anticancer activities in a variety of human cancer models. Although iron mediated oxidative damage is involved, the mechanisms underlying these activities remain unclear. In the current study, we found that dihydroartemisinin caused cellular iron depletion in time- and concentration-dependent manners. It decreased iron uptake and disturbed iron homeostasis in cancer cells, which were independent of oxidative damage. Moreover, dihydroartemisinin reduced the level of transferrin receptor-1 associated with cell membrane. The regulation of dihydroartemisinin to transferrin receptor-1 could be reversed by nystatin, a cholesterol-sequestering agent but not the inhibitor of clathrin-dependent endocytosis. Dihydroartemisinin also induced transferrin receptor-1 palmitoylation and colocalization with caveolin-1, suggesting a lipid rafts mediated internalization pathway was involved in the process. Also, nystatin reversed the influences of dihydroartemisinin on cell cycle and apoptosis related genes and the siRNA induced downregulation of transferrin receptor-1 decreased the sensitivity to dihydroartemisinin efficiently in the cells. These results indicate that dihydroartemisinin can counteract cancer through regulating cell-surface transferrin receptor-1 in a non-classical endocytic pathway, which may be a new action mechanism of DHA independently of oxidative damage.</p> </div

Flow chart for the literature search in the meta-analysis.

<p>Flow chart for the literature search in the meta-analysis.</p

Higher blood 25(OH)D level may reduce the breast cancer risk: evidence from a Chinese population based case-control study and meta-analysis of the observational studies.

Experimental data suggest a protective effect of vitamin D on breast cancer; however, epidemiologic results remain inclusive. With a Chinese population-based case-control study and meta-analysis of the observational studies, we here systematically evaluated the association of blood 25(OH)D level and breast cancer risk. With 593 breast cancer cases and 580 cancer-free controls from Shanghai, China, we found that 80% of the normal women had severe vitamin D deficiency (less than 20 ng/mL) and 15.2% had mild deficiency (20 to 30 ng/mL) and only 4.8% of women had sufficient vitamin D level (>30 ng/mL) while the proportion was 96.1%, 3.2% and 0.7% respectively for the breast cancer patients. Compared to those with the lowest quartile of plasma 25(OH)D level, women with highest quartile 25(OH)D level showed a significant decreased breast cancer risk (Q4 vs.Q1: OR = 0.10, 95% CI = 0.06-0.15) and every 1 ng/ml increment of plasma 25(OH)D level led to a 16% lower odds of breast cancer (OR = 0.84, 95% CI = 0.81-0.87; P<0.001). From the meta-analysis of the observational studies, we found that women with highest quantile of blood 25(OH)D level was associated with a significantly reduced breast cancer risk compared to those with lowest quantile of blood 25(OH)D level for the 11 nested case-control and retrospective studies (pooled OR = 0.86, 95% CI = 0.75-1.00) and 10 case-control studies (7 population based, OR = 0.35, 95% CI = 0.24-0.52; 3 hospital based, OR = 0.08, 95% CI = 0.02-0.33). These results suggest that vitamin D may have a chemo-preventive effect against breast cancer

Forest plot for the association between variant FokI in the VDR and risk of ovarian cancer (CT vs. CC).

<p>NECC, new England case-control study; NHS, nurses’ health study; WHS, women’s health study; MALOVA, malignant ovarian cancer study; SEARCH, studies of epidemiology and risk factors in cancer heredity: ovarian cancer study; GEOCS, genetic epidemiology of ovarian cancer study; UKOPS, united kingdom ovarian cancer population study.</p

The proposed mechanisms by which DHA disrupts iron homeostasis.

<p>The proposed mechanisms by which DHA disrupts iron homeostasis.</p