Abstract. Breast cancer is a serious disease in the uS. numerous risk factors have been linked to this disease. the safety of using growth promoters, such as zeranol, remains under debate due to the lack of sufficient in vitro and in vivo evidence. using celltiter 96™ aqueous non-radioactive cell proliferation assay, real-time pcr and Western blot analysis, we evaluated the effects of sera harvested from experimental and control heifers before and after one month of zeranol implantation on the growth of human breast cancer cell line mcF-7 as well as the involved mechanisms. We found that sera harvested from the heifers following one month of zeranol implantation were more mitogenically potent in stimulating the proliferation of mcF-7 cells when compared to sera harvested from the same heifers before zeranol implantation and the control heifers. Further investigation found that dextran-coated charcoal suppressed the stimulating effect of the sera on mcF-7 cell growth. the mechanisms involved in the mcF-7 cell proliferation stimulated by zeranol-containing sera may include up-regulation of cyclin d1 and down-regulation of p53 and p21 expression at the mrna and protein levels in the cells. the results suggest that the consumption of beef products containing biologically active residues of zeranol or its metabolites is a risk linked to breast cancer development. Further investigation is required in order to clarify this critical issue.

Epidemiological studies have suggested that there are many risk factors associated with breast cancer. Silencing tumor suppressor genes through epigenetic alterations play critical roles in breast cancer initiation, promotion and progression. As a growth promoter, Zeranol (Z) has been approved by the FDA and is widely used to enhance the growth of beef cattle in the United States. However, the safety of Z use as a growth promoter is still under debate. In order to provide more evidence to clarify this critical health issue, the current study investigated the effect of Z on the proliferation of primary cultured human normal and cancerous breast epithelial cells (PCHNBECs and PCHBCECs, respectively) isolated from the same patient using MTS assay, RT-PCR and Western blot analysis. We also conducted an investigation regarding the mechanisms that might be involved. Our results show that Z is more potent to stimulate PCHBCEC growth than PCHNBEC growth. The stimulatory effects of Z on PCHBCECs and PCHBCECs may be mediated by its down-regulating expression of the tumor suppressor gene p53 at the mRNA and protein levels. Further investigation showed that the expression of DNA methylatransferase 1 mRNA and protein levels is up-regulated by treatment with Z in PCHBCECs as compared to PCHNBECs, which suggests a role of Z in epigenetic modification involved in the regulation of p53 gene expression in PCHBCECs. Our experimental results imply the potentially adverse health effect of Z in breast cancer development. Further study is continuing in our laboratory.

No abstract

In image-based overlay (IBO) measurement, the measurement quality of various measurement spectra can be judged by quality indicators and also the ADI-to-AEI similarity to determine the optimum light spectrum. However we found some IBO measured results showing erroneous indication of wafer expansion from the difference between the ADI and the AEI maps, even after their measurement spectra were optimized. To reduce this inconsistency, an improved image calculation algorithm is proposed in this paper. Different gray levels composed of inner-and outer-box contours are extracted to calculate their ADI overlay errors. The symmetry of intensity distribution at the thresholds dictated by a range of gray levels is used to determine the particular gray level that can minimize the ADI-to-AEI overlay inconsistency. After this improvement, the ADI is more similar to AEI with less expansion difference. The same wafer was also checked by the diffraction-based overlay (DBO) tool to verify that there is no physical wafer expansion. When there is actual wafer expansion induced by large internal stress, both the IBO and the DBO measurements indicate similar expansion results. The scanning white-light interference microscope was used to check the variation of wafer warpage during the ADI and AEI stages. It predicts a similar trend with the overlay difference map, confirming the internal stress.

Abstract. Breast cancer and obesity are serious health problems and their relationship has been studied for many years. Leptin is mainly secreted by adipocytes and plays a key role in breast cancer development. Leptin expression is up-regulated in obese individuals and promotes breast cancer cell growth. On the other hand, exposure to environmental estrogens has been found to be directly related to breast cancer. Zeranol (Z) is a non-steroidal anabolic growth promoter used in the beef industry in the US. This study focused on the evaluation of Z and Z-containing sera (ZS) and its adverse health risk to human consumption of Z-containing meat produced from Z-implanted beef cattle. We hypothesized that Z increases the risk of breast neoplasia in women, particularly in obese women. A cell proliferation assay, ELISA analysis, RT-PCR and Western blot analysis were conducted. Our study demonstrated that Z and ZS collected from Z-implanted heifers stimulated the proliferation of primary cultured human normal breast epithelial cells (HNBECs) by up-regulating cyclin D1 expression. Leptin increased the sensitivity of HNBECs to Z, and Z increased the ability of HNBECs to secrete leptin. These results suggest an interaction between leptin and Z in HNBECs. Furthermore, Z may play a role in leptin-induced breast neoplasia.