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Background/Aims: Transforming growth factor-beta proteins (TGF-βs) are multifunctional growth factors and powerful modulators of the epithelial-mesenchymal transition (EMT) in a variety of cancer types including breast and lung cancer cells. Here, we demonstrated the inhibitory effect of berberine (BBR) on tumor growth and metastasis of triple negative breast cancer (TNBC) cells via suppression of TGF-β1 expression. Methods: The levels of mRNA expression were analyzed by real-time PCR. The levels of MMP-2, MMP-9 and TGF-β1 protein expression were analyzed by zymography and confocal microscopy, respectively. Cell migration was analyzed by wound healing assay. Tumorigenicity of TNBC cells such as tumor growth and metastasis was analyzed using xenograft models. Results: In a clinical data set, aberrant TGF-β1 expression was associated with poor prognosis of breast cancer patients. Our in vitro results using TNBC cells showed that the expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 and the capacity for cell migration were increased by TGF-β1 treatment. In contrast, basal levels of MMP-2 and MMP-9 were suppressed by a specific TGF-β receptor I inhibitor, SB431542. In addition, TGF-β1–induced MMP-2 and MMP-9 expression and cell migration were decreased by SB431542. Interestingly, we showed for the first time that BBR decreased the level of TGF-β1, but not TGF-β2, in TNBC cells. Furthermore, BBR significantly decreased the level of MMP-2 expression as well as the capacity for cell migration in TNBC cells. Finally, we examined the effect of BBR on in vivo tumor growth and lung metastasis in MDA-MB231 and 4T1 breast cancer xenograft models and showed that both were significantly decreased following BBR treatment. Conclusion: BBR suppresses tumorigenicity of TNBC cells through inhibition of TGF-β1 expression. Therefore, we demonstrate that BBR could be a promising drug for treatment of TNBC. [ABSTRACT FROM AUTHOR]

Background/Aims: Berberine (BBR) is an isoquinoline alkaloid and is beneficial for the anticancer effect on a variety of human tumor cells. However, BBR's anti-angiogenesis property and its clinical potential as an inhibitor of tumor angiogenesis in breast cancer cells have not been fully elucidated. Here, we investigated the effect of BBR on TPA-induced VEGF and fibronectin (FN) as well as VEGF-induced FN in breast cancer cells. Methods: The secretion of VEGF protein was detected by ELISA. Fibronectin mRNA and protein expression was analyzed by Real-Time PCR and western blotting, respectively. The overexpressions of CA-MEK, and CA-Akt were examined by adenovirus system. Results: Our results showed that TPA, a tumor promoter, significantly increased the level of VEGF and FN expression in both MCF7 and T47D breast cancer cells. On the other hand, TPA-induced VEGF and FN expression was suppressed by LY294002, a PI-3K inhibitor. In contrast, the level of FN expression also significantly increased by constitutively active (CA)-AKT overexpression. We also found that TPA-induced VEGF and FN expression was decreased by BBR treatment. Finally, our results showed that VEGF augmented the expression of FN whereas VEGF-induced FN expression was decreased by BBR treatment. Conclusion: Taken together, we suggest that BBR may suppress TPA-induced VEGF and FN as well as VEGF-induced FN through the inhibition of the PI-3K/AKT pathway in breast cancer cells. Therefore, we suggest that BBR may be used as a candidate drug for the inhibition of angiogenesis of human breast cancer. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The clinical meaning of intramammary lymph nodes (iMLNs) is uncertain. We wanted to describe the clinical characteristics and understand the implications of iMLNs detected by sentinel LN biopsy (SLNB). Methods: We reviewed the clinical, radiological and pathological records of women diagnosed with invasive carcinoma of the breast at the Samsung Medical Center between January 2001 and January 2011. A total of 69 patients were identified, and SLNB was performed in 31 patients. Results: Of the 69 patients included in the study, 22 (31.9%) had metastases in iMLNs. The presence of lymphovascular invasion and the number of axillary LN metastases were associated with iMLN metastasis. Of the 31 patients who underwent SLNB, there were no cases with axillary LN metastasis when axillary SLNB was negative, even in cases of iMLN-positive patients. Of the 10 patients in whom intramammary SLNs (iMSLNs) were detected during SLNB, 8 patients without iMLN metastases were also negative for axillary LNs. Conclusion: Patients with metastatic iMLNs had more aggressive cancers with lymphovascular invasion and increased axillary LN metastases. When iMSLN was detected by SLNB, performing of axillary dissection could be determined by the status of the iMSLN itself. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cyclooxygenase-2 (COX-2) has been reported to be elevated in many cancers, including breast and colorectal cancers, resulting in accumulation of prostaglandin E2 in the cancer cell environment. In this study, we investigated the effect of pifithrin (PFT)-α, an inhibitor of p53 transactivation, on COX-2 expression in breast and fibrosarcoma cells. Our results showed that COX-2 expression was dose-dependently increased by PFT-α in MDA-MB231 breast cancer cells with mutant p53. In addition, the expression level of COX-2 was also increased by PFT-α in normal fibroblasts as well as in HT1080 fibrosarcoma cells with p53 wild-type cells. To verify the regulatory mechanism of COX-2 in response to PFT-α, we pretreated cells with a mitogen-activated protein kinase (MAPK) kinase (MEK)1/2 inhibitor (UO126) and a phosphoinositide-3 (PI-3K) inhibitor (LY294002). PFT-α-induced COX-2 expression was significantly decreased by UO126 and LY294002 in MDA-MB231 cells. However, the phosphorylation of extracellular signal-regulated kinase (ERK) was increased by PFT-α, but not Akt phosphorylation. Finally, we confirmed the correlation of the MEK and PI-3K pathway and COX-2 expression using the constitutively active (CA)-MEK and myr-Akt adenovirus systems. COX-2 expression was increased by CA-MEK transfection, but not by myr-Akt. Taken together, we have demonstrated that PFT-α-induced COX-2 expression is regulated through a MEK/ERK pathway in MDA-MB231 human breast cancer cells. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: This study was designed to assess the necessity of delayed complete axillary lymph node dissection (cALND) for patients whose sentinel lymph nodes (SLNs) were negative for tumors on intraoperative frozen section analysis, but later proven positive on hematoxylin and eosin staining or immunohistochemistry. Methods: We identified 341 patients who underwent sentinel lymph node biopsy (SLNB) with cALND at the Samsung Medical Center between 1998 and 2008, and reviewed the clinicopathological records of women diagnosed with invasive carcinoma of the breast. Results: Of the 341 patients, 59 underwent delayed cALND due to negative results on frozen section. Only 1 patient had a non-SLNs metastasis in the group of delayed cALND. Delayed cALND was associated with higher rates of breast-conserving surgery, smaller primary tumor and metastasis size in SLNs, fewer metastatic lymph nodes and SLNs and a lower TNM stage. The detection of metastases of SLNs on frozen section and the number of metastatic SLNs were related to the detection of additional metastases of nonsentinel lymph nodes (NSLNs) in cALND. Conclusion: Our findings suggest that the lack of detection of metastases on frozen sections may be a predictive factor for nonmetastasis in NSLNs. cALND could therefore be omitted in such cases. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]