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N-myc downstream-regulated gene 2 (NDRG2) has been studied for its inhibitory effects against growth and metastasis of many tumor cell types. In this study, we showed NDRG2 expression was correlated with favorable recurrence-free survival of patients with breast cancer and inhibited metastasis of breast cancer cells (4T1). NDRG2 expression was examined in 189 breast carcinoma tissues and paired normal breast tissues using immunohistochemistry. Histological and clinicopathological data were correlated using Pearson's chi-square test of independence. NDRG2 expression in human breast cancer tissues was inversely associated with lymph node metastasis and pTNM stage. Furthermore, patients with breast cancer with a high level of NDRG2 expression showed favorable recurrence-free survival (P = 0.038). To study the effect of NDRG2 on metastasis in vivo, we established an NDRG2-overexpressing mouse breast cancer cell line (4T1-NDRG2) and measured the metastasis and survival of 4T1-NDRG2 tumor-bearing mice. To test whether transforming growth factor β (TGF-β)- mediated metastasis of 4T1 was inhibited by NDRG2 expression, TGF-Smad-binding element (SBE)-luciferase activity and/or measurement of active TGF-β were performed in cell or tumor tissue level. 4T1-NDRG2 cells grew gradually and showed less metastatic activity in vivo and low invasiveness in vitro. 4T1-NDRG2 cells showed lower SBE-luciferase activity and lower level of active autocrine TGF-β than 4T1-Mock did. Correctly, our data show that NDRG2 significantly suppress tumor metastasis by attenuating active autocrine TGF-β production, and the attenuation might be typically associated with the favorable recurrence-free survival of patients clinically.

Abstract. Epigallocatechin gallate (EGCG), a major constituent of green tea, has potential as a treatment for a variety of diseases, including cancer. EGCG induces apoptosis and inhibits tumorigenesis through multiple signaling pathways in breast cancer cells. β-catenin signaling modulators could be useful in the prevention and therapy of breast cancer. However, the precise anticancer effect of EGCG through the β-catenin signaling pathway in breast cancer is unclear. The present study investigated the association between β-catenin expression and clinicopathological factors of breast cancer patients, and the effect of EGCG on β-catenin expression in breast cancer cells. β-catenin expression was analyzed according to the clinicopathological factors of 74 patients with breast cancer. All patients were females diagnosed with invasive ductal carcinoma. Western blot analysis revealed that β-catenin was expressed at higher levels in breast cancer tissue than in normal tissue. β-catenin expression was associated with lymph node metastasis (P=0.04), tumor-node-metastasis stage (P=0.03) and estrogen receptor status (P<0.01). EGCG decreased MDA-MB-231 cell viability and significantly downregulated the expression of β-catenin, phosphorylated Akt and cyclin D1. Remarkably, additive effects of LY294002 and wortmannin, two phosphatidylinositol-3 kinase inhibitors, were observed. The present results suggest that EGCG inhibits the growth of MDA-MB-231 cells through the inactivation of the β-catenin signaling pathway. Based on these promising results, EGCG may be a potential treatment for triple negative breast cancer patients.

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PurposeChemotherapies for breast cancer generally have strong cellular cytotoxicity and severe side effects. Thus, significant emphasis has been placed on combinations of naturally occurring chemopreventive agents. Silibinin is a major bioactive flavonolignan extracted from milk thistle with chemopreventive activity in various organs including the skin, prostate, and breast. However, the mechanism underlying the inhibitory action of silibinin in breast cancer has not been completely elucidated. Therefore, we investigated the effect of silibinin in MCF-7 human breast cancer cells and determined whether silibinin enhances ultraviolet (UV) B-induced apoptosis.MethodsThe effects of silibinin on MCF-7 cell viability were determined using the MTT assay. The effect of silibinin on PARP cleavage, as the hallmark of apoptotic cell death, and p53 protein expression in MCF-7 cells was analyzed using Western blot. The effect of silibinin on UVB-induced apoptosis in MCF-7 cells was analyzed by flow cytometry.ResultsA dose- and time-dependent reduction in viability was observed in MCF-7 cells treated with silibinin. Silibinin strongly induced apoptotic cell death in MCF-7 cells, and induction of apoptosis was associated with increased p53 expression. Moreover, silibinin enhanced UVB-induced apoptosis in MCF-7 cells.ConclusionSilibinin induced a loss of cell viability and apoptotic cell death in MCF-7 cells. Furthermore, the combination of silibinin and UVB resulted in an additive effect on apoptosis in MCF-7 cells. These results suggest that silibinin might be an important supplemental agent for treating patients with breast cancer.

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Purpose: Breast reconstruction in patients who have undergone a mastectomy is performed less frequently in Korea than in Western countries. The aim of this study was to investigate the psychosocial problems related to a mastectomy and awareness of reconstruction after a mastectomy in breast cancer survivors. Methods: From March to April 2010, 252 patients who underwent a mastectomy were recruited for this survey. The questionnaire included sociodemographic characteristics of patients, psychosocial problems related to mastectomy, and reasons not to receive breast reconstruction. Results: Patients had difficulty going to a public bath (70.3%) or going to a swimming pool or the beach (74.6%). More than half of patients answered that their physical activity had decreased due to persistent shoulder or arm pain after the mastectomy. The most common psychological problem that patients experienced was distress over the loss of charm as a woman (66.8%), followed by considering themselves disabled (62.0%), and worries about recurrence (59.4 %). The most common reason not to receive a breast reconstruction was the high cost of the operation (59.4%), followed by anxiety about complications (46.7%). Only 16.2% of patients reported that they did not receive enough information about reconstruction from their doctor. Of 229 patients, 43.7% would consider undergoing breast reconstruction in the future. Conclusion: Breast cancer survivors who underwent a mastectomy suffered from various psychosocial problems, and high cost was a major reason for not undergoing breast reconstruction. Broader health insurance coverage should be provided for breast reconstruction in breast cancer survivors.

Natural landscape views have positive sides, such as providing restorative effects to urban residents, and negative sides, such as deepening wealth inequality. Previous studies have mainly focused on the positives and rarely on the negatives. From this perspective, this study aimed to analyze the unequal impact of natural landscape views on housing prices for apartments in Seoul. We proposed a visual perception model to analyze natural landscape views and, based on a hedonic price model, we used ordinary least squares and quantile regression to estimate the marginal impacts on housing prices. The results show that: (1) natural landscape views had positive impacts on housing prices, but their impacts did not reach the level of structural and locational characteristics such as apartment area and the distance to subway stations; (2) natural landscape views had different marginal impacts by housing price range and, in particular, had much higher value-added effects on higher-priced apartments, meaning that if old apartment complexes are redeveloped into high-rise ones, the improvement in natural landscape views generates great profit for apartment owners and intensifies wealth inequality; (3) the geographic information system-based visual perception model effectively quantified the natural landscape views of wide areas and is thus applicable for the rigorous analysis of various landscape views.