Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. Claudins are aberrantly expressed in aggressive breast cancer. However, the relationship between claudins and VM formation is not clear. We examined VM in two human breast cancer cell lines with different aggressive capabilities (MDA-MB-231 and MCF-7 cells) and one human umbilical vein endothelial cell line (HUVEC). Both HUVEC and MDA-MB-231 cells formed vascular channels in Matrigel cultures, while MCF-7 cells did not. Western blot analysis revealed a possible correlation between claudin-4 and -6 expression in breast cancer cell lines and tumor aggressiveness, with protein levels correlating with the ability to form vascular channels. Treatment of MDA-MB-231 and HUVEC cells with claudin-4 monoclonal antibodies completely inhibited the ability of cells to form vascular channels. Moreover, knockdown of claudin-4 by short hairpin RNA completely inhibited tubule formation in MDA-MB-231 cells. Overexpression of claudin-4 in MCF-7 cells induced formation of vascular channels. Immunocytochemistry revealed that membranous claudin-4 protein was significantly associated with vascular channel formation. Collectively, these results indicate that claudin-4 may play a critical role in VM in human breast cancer cells, opening new opportunities to improve aggressive breast cancer therapy.
In this study, we present a method for identifying sources of water pollution and their relative contributions in pollution disasters. The method uses a combination of principal component analysis and factor analysis. We carried out a case study in three rural villages close to Beijing after torrential rain on July 21, 2012. Nine water samples were analyzed for eight parameters, namely turbidity, total hardness, total dissolved solids, sulfates, chlorides, nitrates, total bacterial count, and total coliform groups. All of the samples showed different degrees of pollution, and most were unsuitable for drinking water as concentrations of various parameters exceeded recommended thresholds. Principal component analysis and factor analysis showed that two factors, the degree of mineralization and agricultural runoff, and flood entrainment, explained 82.50% of the total variance. The case study demonstrates that this method is useful for evaluating and interpreting large, complex water-quality data sets.
The potential contaminations of 16 trace elements (Cr, Mn, Ni, Cu, Zn, As, Cd, Sb, Ba, Pb, Co, Be, V, Ti, Tl, Al) in drinking water collected in two remote areas in China were analyzed. The average levels of the trace elements were lower than the allowable concentrations set by national agencies, except for several elements (As, Sb, Mn, and Be) in individual samples. A health risk assessment model was conducted and carcinogenic and non-carcinogenic risks were evaluated separately. The results indicated that the total carcinogenic risks were higher than the maximum allowed risk level set by most organizations (1 × 10(-6)). Residents in both study areas were at risk of carcinogenic effects from exposure to Cr, which accounted for 80-90 % of the total carcinogenic risks. The non-carcinogenic risks (Cu, Zn, Ni) were lower than the maximum allowance levels. Among the four population groups, infants incurred the highest health risks and required special attention. Correlation analysis revealed significant positive associations among most trace elements, indicating the likelihood of a common source. The results of probabilistic health risk assessment of Cr based on Monte-Carlo simulation revealed that the uncertainty of system parameters does not affect the decision making of pollution prevention and control. Sensitivity analysis revealed that ingestion rate of water and concentration of Cr showed relatively high sensitivity to the health risks.
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