• Journal of Cancer Prevention
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• v.21 no.2
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• pp.88-94
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• 2016

Background: Breast cancer is the most common malignant disease in women. The patients with advanced breast cancer develop metastasis to bone. Bone metastasis and skeletal-related events by breast cancer are frequently associated with the invasiveness of breast cancer cells and osteoclasts-mediated bone resorption. Forsythia koreana is used in oriental traditional medicine to treat asthma, atopy, and allergic diseases. The aim of this study was to evaluate the inhibitory effects of F. koreana extracts on the invasion of breast cancer cells and bone resorption by osteoclasts. Methods: Cell viability was measured by an MTT assay and the migration and invasion of MDA-MB-231 cells were detected by a Boyden chamber assay. The formation of osteoclasts and pit was detected using tartrate-resistant acid phosphatase staining and calcium phosphate-coated plates, respectively. The activities of matrix metalloproteinases (MMPs) and cathepsin K were evaluated by gelatin zymography and a cathepsin K detection kit. Results: The fruit and leaf extracts of F. koreana significantly inhibited the invasion of MDA-MB-231 cells at noncytotoxic concentrations. The fruit extract of F. koreana reduced the transforming growth factor ${\beta}1-induced$ migration, invasion and MMPs activities of MDA-MB-231 cells. In addition, the fruit, branch, and leaf extracts of F. koreana also inhibited the receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation and osteoclast-mediated bone-resorbing activity by reducing the activities of MMPs and cathepsin K. Conclusions: The extracts of F. koreana may possess the potential to inhibit the breast cancer-induced bone destruction through blocking invasion of breast cancer cells, osteoclastogenesis, and the activity of mature osteoclasts.

• Journal of Food Hygiene and Safety
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• v.25 no.3
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• pp.209-214
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• 2010

Metastasis is the primary cause of from breast cancer mortality. Cell migration and invasion play important roles in neoplastic metastasis. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix (ECM), plays an important role in cancer cell invasion. NF-${\kappa}B$ is transcription factor important in the regulation of MMP-9, as the promoter of MMP-9 gene contains binding sites for NF-${\kappa}B$. Brazilin, an active component of sappan wood (Caesalpinia sappan), decreases TPA-induced MMP-9 expression and invasion in MCF-7 cells. Also, brazilin suppressed NF-${\kappa}B$ activation in TPA-treated MCF-7 cells. Taken together, we demonstrated that the inhibition of TPA-induced MMP-9 expression and cell invasion by brazilin is mediated by the suppression of the NF-${\kappa}B$ pathway in MCF-7 cells. This result suggest brazilin provide a potential therapeutic app roach for the treatment of breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1047-1049
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• 2015

Background: This systematic analysis was conducted to investigate pathological diagnosis of vertebral tumor metastasis with unknown primaries. Methods: Clinical studies conducted to pathologically investigate vertebral tumor metastasis were identified using a predefined search strategy. Pooled diagnosis (PD) of each pathological confirmation was calculated. Results: For vertebral tumor metastasis, 5 clinical studies which included 762 patients were considered eligible for inclusion. Systematic analysis suggested that, for all patients with vertebral tumor metastasis, dominant PD was pathologically confirmed with lung cancer in 21.7% (165/762), with breast cancer in 26.6% (203/762) and with prostate cancer in 19.2% (146/762). Other diagnosis that could be confirmed included lymphoma, multiple myeloma, renal cancer, for example, in this cohort of patients. Conclusions: This systemic analysis suggested that breast, lung and prostate lesions could be the most common pathological types of cancer for vertebral tumor metastasis formunknown primaries, and other common diagnoses could include lymphoma, multiple myeloma, renal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1783-1789
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• 2014

Background: The EMSY gene encodes a BRCA2-binding partner protein that represses the DNA repair function of BRCA2 in non-hereditary breast cancer. Although amplification of EMSY gene has been proposed to have prognostic value in breast cancer, no data have been available concerning EMSY tissue expression patterns and its associations with clinicopathological features. Materials and Methods: In the current study, we examined the expression and localization pattern of EMSY protein by immunohistochemistry and assessed its prognostic value in a well-characterized series of 116 unselected breast carcinomas with a mean follow up of 47 months using tissue microarray technique. Results: Immunohistochemical expression of EMSY protein was detected in 76% of primary breast tumors, localized in nuclear (18%), cytoplasmic (35%) or both cytoplasmic and nuclear sites (23%). Univariate analysis revealed a significant positive association between EMSY expression and lymph node metastasis (p value=0.045) and larger tumor size (p value=0.027), as well as a non-significant relation with increased risk of recurrence (p value=0.088), whereas no association with patients' survival (log rank test, p value=0.482), tumor grade or type was observed. Conclusions: Herein, we demonstrated for the first time the immunostaining pattern of EMSY protein in breast tumors. Our data imply that EMSY protein may have impact on clinicipathological parameters and could be considered as a potential target for breast cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2953-2957
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• 2016

Background: Breast Cancer (BCa) is the most common malignant tumour in Mexican women. In BCa, several studies have linked ${\beta}2-adrenergic$ receptor activation with increased tumour growth and progression as related with Epinephrine-NorEpinephrine (E-NE) stimulation. The aim of this study was to describe Beta-Blocker (BB) treatment related with reduction of the risk of metastasis in Mexican patients with BCa. Materials and Methods: We collected data of 120 patients seen at the High-Specialty Naval General Hospital in Mexico City (HOSGENAES), all of these with a histopathological diagnosis of BCa. Four groups of patients were divided as follows: without Systemic Arterial Hypertension (SAH); with SAH treatment with non-selective BB; with SAH treatment with selective BB, and with SAH treatment with other antihypertensive drugs. Chi-square, Mantel-Haenszel, Student t, and ANOVA tests were performed for data analysis. Results: On average, patients were $54.8{\pm}11.8$ years of age. Risk factors such as smoking and consuming alcohol exhibited a frequency of 33 and 36.5% respectively. Clinical stages III- IV were found in 50% of patients, while, 30% of patients had arterial hypertension (n=29 and N=96, respectively) and 17.5% used BB. One hundred percent of patients with arterial hypertension treated with BB for ${\beta}1$ - and ${\beta}2$ -adrenergic-receptors did not present metastasis globally, but patients treated with ${\beta}1$ BB presented 30% of metastasis while patients treated with no BB or without SAH had around 70% of metastasis. Conclusions: In Mexican patients with BCa and SAH treated with non-selective (${\beta}1$- and ${\beta}2-adrenergic$ receptors) BB, a decrease in the risk for metastasis was observed at the time of diagnosis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.591-598
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• 2012

Aim and background: MicroRNAs (miRNAs) are a class of naturally occurring small noncoding RNAs that regulate gene expression, cell growth, differentiation and apoptosis by targeting mRNAs for translational repression or cleavage. The present study was conducted to study miRNAs in Egyptian breast cancer (BC) and their relation to metastasis, tumor invasion and apoptosis in addition to their association with the ER and PR statuses. Methods: Real Time RT-PCR was performed to identify the miRNA expression level of eight miRNAs and eight metastatic-related genes in 40 breast cancer samples and their adjacent non-neoplastic tissues. The expression levels of each miRNA relative to U6 RNA were determined using the $^{2-{\Delta}}CT$ method. Also, miRNA expression profiles of the BC and their corresponding ANT were evaluated. Results: The BC patients showed an up-regulation in miRNAs (mir-155, mir-10, mir-21 and mir-373) with an upregulation in MMP2, MMp9 and VEGF genes. We found down regulation in mir-17p, mir-126, mir-335, mir-30b and also TIMP3, TMP1 and PDCD4 genes in the cancer tissue compared to the adjacent non-neoplastic tissues. Mir -10b, mir -21, mir-155 and mir373 and the metastatic genes MMP2, MMP9 and VEGF were significantly associated with an increase in tumor size (P < 0.05). No significant difference was observed between any of the studied miRNAs regarding lymph node metastasis. Mir-21 was significantly over-expressed in ER-/PR-cases. Conclusion: Specific miRNAs (mir-10, mir-21, mir-155, mir-373, mir-30b, mir-126, mir-17p, mir-335) are associated with tumor metastasis and other clinical characteristics for BC, facilitating identification of individuals who are at risk.

• The Korean Journal of Cytopathology
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• v.6 no.1
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• pp.18-26
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• 1995

In order to compare cytologic findings ol breast carcinoma in fine needle aspiration cytology (FANC) with histologic findings and prognostic factors including histologic grading, lymph node metastasis and stage, 79 cases of infiltrating ductal carcinoma diagnosed by FANC and confirmed by histology were analysed. We especially attempted to col relate nuclear grade, cellularity and smear pattern with histologic grade, type, status of lymph node metastasis and stage. The results are as fellows. 1. High nuclear grade was correlated with high histologic grade, lymph node metastasis and advanced stage. 2. Individual cell pattern was more frequently identified in high histologic grade and scirrhous or solid-tubular type than in low histolgic grade and papillotubular type. 3. Cellularity increased with higher histologic grade and lymph node metastsis. However cellularity was low in scirrhous type. 4. There is no relationship between nuclear grade and histologic type, between smear pattern and lymph node metastasis or stage, and between cellularity and stage. These results suggest that cytologic findings of breast carcinoma such as nuclear grade, cellularity and smear pattern are indicative of histologic findings in relation to histolgic grade and type. Especially, nuclear grade of FANC may yield valuable prognostic information.

• BMB Reports
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• v.52 no.2
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• pp.139-144
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• 2019

Breast cancer (BRC) is the most invasive cancer in women. Although the survival rate of BRC is gradually increasing due to improved screening systems, development of novel therapeutic targets for inhibition of BRC proliferation, metastasis and recurrence have been constantly needed. Thus, in this study, we identified overexpression of SETDB1 (SET Domain Bifurcated 1), a histone methyltransferase, in RNA-seq data of BRC derived from TCGA portal. In Gene Ontology (GO) analysis, cell migration-related GO terms were enriched, and we confirmed down-regulation of cell migration/invasion and alteration of EMT /MET markers after knockdown of SETDB1. Moreover, gene network analysis showed that SMAD7 expression is regulated by SETDB1 levels, indicating that up-regulation of SMAD7 by SETDB1 knockdown inhibited BRC metastasis. Therefore, development of SETDB1 inhibitors and functional studies may help develop more effective clinical guidelines for BRC treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2989-2993
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• 2016

The commonest cancer in Egyptian females occurs in the breast cfDNA is a non-invasive marker for tumor detetion and prognostic assessment in many types of cancer including breast cancer. This study aimed to assess the role of cfDNA and its fragmentation pattern in breast cancer prognosis and treatment response. Forty female patients with malignant breast tumors and a comparable group of healthy blood donors were enrolled prospectively. cfDNA levels and fragmentation patterns were investigated after cfDNA extraction, gel electrophoresis and gel analysis. The percentage of breast cancer patients positive for cfDNA (92.5%) was significantly higher than that of controls (55%). Also, mean concentration of cfDNA was significantly higher than in the control group (P<0.05). Most Her-2 positive patients had long cfDNA fragments, this being significant as compared to Her-2 negative patients (P<0.05). Metastasis was also positively linked to significantly higher cfDNA (P<0.05) and the mean cfDNA integrity index was significantly higher in non-responders compared to treatment responders (P<0.05). In conclusion, both qualitative and quantitative aspects of cfDNA and its different fragments in breast cancer patients could be related to prognosis, metastasis and treatment response. Long cfDNA fragments could be particularly useful for prediction purposes.

• Korean Journal of Pharmacognosy
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• v.38 no.1
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• pp.62-66
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• 2007

Ethanol extract from Salvia miltiorrhiza (SME) was tested for breast cancer chemoprevention and metastasis by measuring the activites of cytochrome P45O 1A1, aromatase, ornithine decarboxylase (ODC), and matrix metalloproteinase (MMP)-9. SME significantly inhibited cytochrome P45O 1A1-mediated ethoxyresorufin O-deethylase (EROD) activity in a dose-dependent manner in a concentration range of 100${\sim}$l,200 ${\mu}g/ml$ (p<0.01). Microsomal aromatase (estrogen synthase) activity was suppressed 54.9%${\sim}$77.5% by the SME at concentration of 600${\sim}$l,200 ${\mu}g/ml$. ODC activity induced by 12-O-tet-radecanoylphorbol-13-acetate (TPA) was significantly reduced by the SME 900 and 1,200 ${\mu}g/ml$ (p<0.05) in MCF-7 breast cancer cells. In addition, SME (900 and 1,200 ${\mu}g/ml$) markedly inhibited MMP-9 activity, a key role in cancer metastasis. Therefore, SME is worth further investigation with respect to breast cancer chemoprevention or therapy.