• Nutrition Research and Practice
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• v.9 no.6
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• pp.628-636
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• 2015

BACKGROUND/OBJECTIVES: Obesity is a risk factor of breast cancer in postmenopausal women. Estrogen deprivation has been suggested to cause alteration of lipid metabolism thereby creating a cellular microenvironment favoring tumor growth. The aim of this study is to investigate the effects of estrogen depletion in combination with excess energy supply on breast tumor development. MATERIALS/METHODS: Ovariectomized (OVX) or sham-operated C3H/HeN mice at 4 wks were provided with either a normal diet or a high-fat diet (HD) for 16 weeks. Breast tumors were induced by administration of 7,12-dimethylbenz(a)anthracene once a week for six consecutive weeks. RESULTS: Study results showed higher serum concentrations of free fatty acids and insulin in the OVX+HD group compared to other groups. The average tumor volume was significantly larger in OVX+HD animals than in other groups. Expressions of mammary tumor insulin receptor and mammalian target of rapamycin proteins as well as the ratio of pAKT/AKT were significantly increased, while pAMPK/AMPK was decreased in OVX+HD animals compared to the sham-operated groups. Higher relative expression of liver fatty acid synthase mRNA was observed in OVX+HD mice compared with other groups. CONCLUSIONS: These results suggest that excess energy supply affects the accelerated mammary tumor growth in estrogen deprived mice.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.9-18
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• 2016

Bone matrix is properly maintained by osteoclasts and osteoblasts. In the tumor microenvironment, osteoclasts are increasingly differentiated by the various ligands and cytokines secreted from the metastasized cancer cells at the bone metastasis niche. The activated osteoclasts generate osteolytic lesions. For this reason, studies focusing on the differentiation of osteoclasts are important to reduce bone destruction by tumor metastasis. The N-myc downstream-regulated gene 2 (NDRG2) has been known to contribute to the suppression of tumor growth and metastasis, but the precise role of NDRG2 in osteoclast differentiation induced by cancer cells has not been elucidated. In this study, we demonstrate that NDRG2 expression in breast cancer cells has an inhibitory effect on osteoclast differentiation. RAW 264.7 cells, which are monocytic preosteoclast cells, treated with the conditioned media (CM) of murine breast cancer cells (4T1) expressing NDRG2 are less differentiated into the multinucleated osteoclast-like cells than those treated with the CM of 4T1-WT or 4T1-mock cells. Interestingly, 4T1 cells stably expressing NDRG2 showed a decreased mRNA and protein level of intercellular adhesion molecule 1 (ICAM1), which is known to enhance osteoclast maturation. Osteoclast differentiation was also reduced by ICAM1 knockdown in 4T1 cells. In addition, blocking the interaction between soluble ICAM1 and ICAM1 receptors significantly decreased osteoclastogenesis of RAW 264.7 cells in the tumor environment. Collectively, these results suggest that the reduction of ICAM1 expression by NDRG2 in breast cancer cells decreases osteoclast differentiation, and demonstrate that excessive bone resorption could be inhibited via ICAM1 down-regulation by NDRG2 expression.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.429-433
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• 2013

Objectives: To explore the correlation between multi-slice spiral CT (MSCT) perfusion parameters and the expression of vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase-2 (MMP-2) in breast cancer. Methods: Forty five breast cancer patients and 16 patients with benign breast tumor, both confirmed by pathology examination, were enrolled. All underwent MSCT perfusion imaging to obtain perfusion maps and data for parameters including blood flow (BF), blood volume (BV) and permeability surface (PS). Cancer patients did not receive treatment prior to surgery. The expression of VEGF and MMP-2 were examined with both immunohistochemistry and Western blotting. Results: The levels of VEGF and MMP-2 by immunohistochemistry were significantly higher in the breast cancer group (P < 0.01) than the benign tumor group. Relative OD values from Western blotting were also higher in cancer cases (P < 0.05). Similarly, the mean MSCT perfusion parameters (BF, BV, PS) were significantly higher in the breast cancer group (P < 0.01), BF and BV positively correlating with VEGF expression (r = 0.878 and 0.809 respectively, P < 0.01); PS and VEGF and MMP-2 expression were also positively correlated (r= 0.860, 0.786 respectively, P < 0.01). Conclusion: There is a correlation between breast cancer MSCT perfusion parameters and VEGF andMMP-2 expression, which might be useful for detection of breast lesions, qualitative diagnosis of breast cancer, and evaluation of breast cancer treatment.

• Investigative Magnetic Resonance Imaging
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• v.23 no.2
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• pp.125-135
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• 2019

Purpose: The purpose of this study was to evaluate dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI), and diffusion-weighted imaging (DWI) variables, for axillary lymph node (ALN) metastasis in the early stage of breast cancer. Materials and Methods: January 2011-April 2015, 787 patients with early stage of breast cancer were retrospectively reviewed. Only cases of invasive ductal carcinoma, were included in the patient population. Among them, 240 patients who underwent 3.0-T DCE-MRI, including DWI with b value 0 and $800s/mm^2$ were enrolled. MRI variables (adjacent vessel sign, whole-breast vascularity, initial enhancement pattern, quantitative kinetic parameters, signal enhancement ratio (SER), tumor apparent diffusion coefficient (ADC), peritumoral ADC, and peritumor-tumor ADC ratio) clinico-pathologic variables (age, T stage, multifocality, extensive intraductal carcinoma component (EIC), estrogen receptor, progesterone receptor, HER-2 status, Ki-67, molecular subtype, histologic grade, and nuclear grade) were compared between patients with axillary lymph node metastasis and those with no lymph node metastasis. Multivariate regression analysis was performed, to determine independent variables associated with ALN metastasis, and the area under the receiver operating characteristic curve (AUC), for predicting ALN metastasis was analyzed, for those variables. Results: On breast MRI, moderate or prominent ipsilateral whole-breast vascularity (moderate, odds ratio [OR] 3.45, 95% confidence interval [CI] 1.28-9.51 vs. prominent, OR = 15.59, 95% CI 2.52-96.46), SER (OR = 1.68, 95% CI 1.09-2.59), and peritumor-tumor ADC ratio (OR = 6.77, 95% CI 2.41-18.99), were independently associated with ALN metastasis. Among clinico-pathologic variables, HER-2 positivity was independently associated, with ALN metastasis (OR = 23.71, 95% CI 10.50-53.54). The AUC for combining selected MRI variables and clinico-pathologic variables, was higher than that of clinico-pathologic variables (P < 0.05). Conclusion: SER, moderate or prominent increased whole breast vascularity, and peritumor-tumor ADC ratio on breast MRI, are valuable in predicting ALN metastasis, in patients with early stage of breast cancer.

• Nutritional Sciences
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• v.6 no.3
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• pp.160-166
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• 2003

To examine the evidence that wheat bran is protective against breast cancer development and that its main mechanism of action is by modulating estrogen metabolism. This review explores the role of different experimental factors on the anticancer effects of wheat bran and the relationship of changes to estrogen metabolism by wheat bran on breast cancer risk The timing of the experimental diets in relation to carcinogen administration, the length of feeding of the experimental diets, and the level of dietary fat had an impact on the effectiveness of different doses of wheat bran in reducing breast carcinogenesis. Wheat bran supplementation resulted in significant reductions in human plasma estrogen levels but not in that of animals tested. The change in excretory metabolism of estrogen by wheat bran feeding in animals was not related to any of the tumor indices measured. The protective effect of wheat bran in breast carcinogenesis is greatest at the promotional phase and when supplemented in a high fat diet. Doses of wheat bran in the 9-12% range in diet have been consistently protective. The inconsistency observed with higher doses of wheat bran may be dependent on the animal model used. Although wheat bran's inhibitory effects on tumor growth may involve changes to estrogen metabolism, the fiber and phytochemical components of wheat bran may also act through estrogen-independent mechanisms. For a better understanding of the effect of wheat bran on breast carcinogenesis, studies comparing the effects of different wheat bran components both alone and in combination need to be performed.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3505-3508
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• 2015

Background: Ras genes are thought to play an important role in human cancer since they have been found to be activated frequently in several types of tumors including breast cancer, where the overall incidence of K-RAS oncogene activation is 0-10%. Evaluation of K-RAS gene not only for mutational frequency but also for mutation types in this downstream signaling gene pathway is necessary to determine the mechanisms of action. The present study was conducted to test the hypothesis that K-RAS activation is involved in breast cancer risk of south Indian population. Materials and Methods: A total of 70 paired pathologically confirmed tumor and non-tumor tissues from the same breast cancer patients were analysed for most common K-RAS mutations of codon 12,13 and 61 by polymerase chain reaction followed by restriction digestion and direct nucleotide sequencing method. Results: We found that a high rate of homozygous and heterozygous mutations of codon 12, but not codon 13 and 61, may influence the invasive ductal carcinoma of breast risk in this study. Conclusions: Our study indicated that only codon 12 may be involved in initiating breast carcinogenesis in India.

• Journal of Haehwa Medicine
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• v.16 no.2
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• pp.241-249
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• 2007

Objectives : The purpose of this study is to suggest better directions in researches about findging new drug derived from herbs in South Korea. Methods : We investiated some literatures on anti-breast cancer herbal extracts which is used in South Korea, and made diagrams. Results : The results are summarized as follows. Many herbs are used in treatment of breast cancer based on oriental medical records. After finding anti tumor effects of genistein in soy extracts in 1987, searching new substances that have anti-tumor effects in breast cancer is accelerated. In Korea, these trends of the research have been activated since 2000. But substance researches about breast cancer are much less than subatance researches about advanced gastric cancer, although the two cancers have similar incidence rate. And all of the researches that we found are in vitro experiments. Conclusions : From the results, it is expected that there are many anti-breast cancer herbal substances which are proved in vitro experiments. We need more studies in animals and human bodies.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9199-9202
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• 2014

Background: Kurdish women with breast cancer have more unfavorable prognostic factors than their Turkish and Arab counterparts. However, the effects of these factors on breast cancer survival among these ethnic groups remain unclear. We therefore investigated the impact of ethnicity on survival in breast cancer patients in Turkey. Materials and Methods: Ethnicity, age, stage at diagnosis, tumor characteristics, treatments given (surgery, chemotherapy, radiotherapy and hormone therapy), and survival times were recorded. Kaplan-Meier analysis was used to estimate the overall survival times and survival plots. Log-rank test was used to compare the survival curves.Results: Of the 723 breast cancer patients included in the study, 496 (68.7%) were Turkish, 189 (26.2%) were Kurdish, 37 (5.1%) were Arabic and 1 was Armenian. Kurdish women with breast cancer had larger tumor sizes and higher rates of hormone receptor negative tumors than Turkish and Arab patients. Mean follow-up time was 118.4 [95% Confidence Interval (CI): 95.4-141.3] months, and it was 129.9 (95% CI: 93.7-166.2), 124.2 (95% CI: 108.4-140.1) and 103.1 (95% CI: 85.9-120.4) months for Turkish, Arabic and Kurdish patients, respectively. Conclusions: Kurdish ethnicity is associated with higher rates of hormone receptor negative and triple-negative tumors and with worse survival. Clinical and epidemiological research is warranted to elucidate reasons underlying overall survival, variations in tumor biology, differences in treatment responsiveness, and effects of social factors among ethnic groups in Turkey.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7843-7847
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• 2014

Background: Although breast cancer (BC) is one of the most common malignant diseases in women, the majority of the studies describing the characteristics of BC in elderly patients have been limited to survival assessments or tumor features, without using younger BC patients as a reference group. The aim of our study was to describe and compare tumor characteristics and management patterns in elderly versus younger breast cancer patients in Turkey. Materials and Methods: We retrospectively analyzed 152 patients with invasive breast cancer who underwent surgery in our institution between 2002 and 2012. Patients were divided into 2 groups according to age at the time of diagnosis. Results: There were 62 patients in the elderly group (${\geq}65$ years) and 90 patients in the younger group (<65 years). Compared to the younger group, tumors in the elderly group were more likely to be larger (p=0.018), of lower grade (p=0.005), and hormone receptor-positive (p>0.001). There were no significant differences regarding histology, localization, lymph node involvement, or types of surgical procedures between the 2 groups. Comorbidities were more common in elderly patients (p<0.001). In addition, elderly patients were more likely to receive hormonal therapy (p<0.001) and less likely to receive radiotherapy (p=0.08) and chemotherapy (p=0.003). There was no difference in survival and locoregional recurrence rates between the groups. Conclusions: The results of this study demonstrate that breast cancer in elderly patients has more favorable tumor features, warranting less aggressive treatment regimens after surgery.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6219-6225
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• 2014

Background: Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. Materials and Methods: The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Results: Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Conclusions: Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.