• Journal of Life Science
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• v.19 no.9
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• pp.1200-1208
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• 2009

Tight junctions (TJs) that act as paracellular permeability barriers play an essential role in regulating the diffusion of fluid, electrolytes and macromolecules through the paracellular pathway. In this study, we investigated the correlation between the tightening of TJs, permeability and the invasive activity of genistein - a bioactive isoflavone of soybeans - in human breast carcinoma MCF-7 and MDA-MB-231 cells. The inhibitory effects of genistein on cell proliferation, motility and invasiveness were found to be associated with the increased tightness of the TJs, which was demonstrated by an increase in transepithelial electrical resistance and a decrease in paracellular permeability. Additionally, the immunoblotting results indicated that genistein repressed the levels of the proteins that comprise the major components of TJ, claudin-3 and claudin-4, which play a key role in the control and selectivity of paracellular transport. Furthermore, genistein decreased the metastasis-related gene expressions of insulin like growth factor-1 receptor and snail, while concurrently increasing that of thrombospondin-1 and E-cadherin. In addition, we demonstrated that claudins play an important role in the anti-motility and invasiveness of genistein using claudin-3 small interfering RNA. Taken together, our results indicate a possible role for genistein as an inhibitor of cancer cell invasion through the tightening of TJs, which may counteract the up-regulation of claudins. In addition, our results indicate that this may be beneficial for the inhibition of tumor metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2291-2295
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• 2014

Although nucleolar protein nucleostemin (NS) is essential for cell proliferation and early embryogenesis and expression has been observed in some types of human cancer and stem cells, the molecular mechanisms involved in mediation of cell proliferation and cell cycling remains largely elusive. The aim of the present study was to evaluate NS as a potential target for gene therapy of human breast carcinoma by investigating NS gene expression and its effects on SKBR-3 cell proliferation and apoptosis. NS mRNA and protein were both found to be highly expressed in all detected cancer cell lines. The apoptotic rate of the pcDNA3.1-NS-Silencer group ($12.1-15.4{\pm}3.8%$) was significantly higher than those of pcDNA3.1-NS ($7.2-12.0{\pm}1.7%$) and non-transfection groups ($4.1-6.5{\pm}1.8%$, P<0.01). MTT assays showed the knockdown of NS expression reduced the proliferation rate of SKBR-3 cells significantly. Matrigel invasion and wound healing assays indicated that the number of invading cells was significantly decreased in the pcDNA3.1-NS-siRNA group (P<0.01), but there were no significant difference between non-transfected and over-expression groups (P>0.05). Moreover, RNAi-mediated NS down-regulation induced SKBR-3 cell G1 phase arrest, inhibited cell proliferation, and promoted p53 pathway-mediated cell apoptosis in SKBR-3 cells. NS might thus be an important regulator in the G2/M check point of cell cycle, blocking SKBR-3 cell progression through the G1/S phase. On the whole, these results suggest NS might be a tumor suppressor and important therapeutic target in human cancers.

• Korean Journal of Food Science and Technology
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• v.46 no.6
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• pp.665-670
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• 2014

We isolated twelve lignans and three terpenoids were isolated from the n-hexane fraction of Schisandra chinensis extract. Using spectroscopic data and comparison with available literature, the following compounds were identified: (1) wuweizisu C, (2) gomisin N, (3) deoxyschisandrin, (4) gomisin A, (5) schisandrin, (6) chamigrenal, (7) schisanlactone D, (8) methylgomisin O, (9) angeloylgomisin O, (10) (-)-gomisin $L_2$, (11) schisandronic acid, (12) (-)-gomisin $L_1$, (13) (+)-gomisin $K_3$, (14) gomisin J, and (15) tigloylgomisin H. Notably, this was the first finding that compound (8) was isolated from this plant. Each compound was evaluated for its in vitro cytotoxic activities toward HL-60 (human leukemia), HeLa (human cervical carcinoma), and MCF-7 (breast cancer) cell lines. Compounds (7), (8), and (9) exhibited strong cytotoxic effects on HL-60 ($IC_{50}$ 7.37, 6.60, and $8.00{\mu}M$, respectively), whereas compound (6) exhibited weak cytotoxicity towards MCF-7 ($IC_{50}$ $30.50{\mu}M$). In addition, compound (8) showed the strongest activity towards HeLa cells ($IC_{50}$ $1.46{\mu}M$).

• Journal of Life Science
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• v.16 no.4
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• pp.598-604
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• 2006

The $Ca^{2+}-activated$ neutral protease calpain induced proteolysis has been suggested to play a role in certain cell growth regulatory proteins. Cyclin proteolysis is essential for cell cycle progression. D-type cyclins, which form an assembly with cyclin-dependent kinases (cdk4 and cdk6), are synthesized earlier in G1 of the cell cycle and seem to be induced in response to external signals that promote entry into the cell cycle. Here we show that cyclin D3 protein levels are regulated at the posttranscriptional level by calpain protease. Treatment of human breast carcinoma MDA-MB-231 cells with lovastatin and actinomycin D resulted in a loss of cyclin D3 protein that was completely reversible by the peptide aldehyde calpain inhibitor, LLnL. The specific inhibitor of the 26S proteasome, lactacystin, the lysosome inhibitors, ammonium chloride and chloroquine, and the serine protease inhibitor, phenylmethylsulfonylfluoride (PMSF), did not block the degradation of cyclin D3 by lovastatin and actinomycin D. Results of in vitro degradation of cyclin D3 by purified calpain showed that cyclin D3 protein is degraded in a $Ca^{2+}-dependent$ manner, and the half-life of cyclin D3 protein was dramatically increased in LLnL treated cells. These data suggested that cyclin D3 protein is regulated by the $Ca^{2+}-activated$ protease calpain.

• Nutrition Research and Practice
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• v.12 no.2
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• pp.129-134
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• 2018

BACKGROUND/OBJECTIVES: Although several recent studies have reported the anti-cancer effects of extracts or components of Citrus unshiu peel, which has been used for various purposes in traditional medicine, the molecular mechanisms for their effects remain unclear. In the present study, the anti-cancer activity of a water-soluble extract of C. unshiu peel (WECU) in MDA-MB-231 human breast carcinoma cells at the level of apoptosis induction was investigated. MATERIALS/METHODS: Cytotoxicity was evaluated using the MTT assay. Apoptosis was detected using DAPI staining and flow cytometry analyses. Mitochondrial membrane potential, reactive oxygen species (ROS) assay, caspase activity and Western blotting were used to confirm the basis of apoptosis. RESULTS: The results indicated that WECU-induced apoptosis was related to the activation of caspase-8, and -9, representative initiator caspases of extrinsic and intrinsic apoptosis pathways, respectively, and caspase-3 accompanied by proteolytic degradation of poly(ADP-ribose) polymerase and down-regulation of the inhibitors of apoptosis protein family members. WECU also increased the pro-apoptotic BAX to anti-apoptotic BCL-2 ratio, loss of mitochondrial membrane potential and cytochrome c release from mitochondria to cytoplasm. Furthermore, WECU provoked the generation of ROS, but the reduction of cell viability and induction of apoptosis by WECU were prevented when ROS production was blocked by antioxidant N-acetyl cysteine. CONCLUSIONS: These results suggest that WECU suppressed proliferation of MDA-MB-231 cells by activating extrinsic and intrinsic apoptosis pathways in a ROS-dependent manner.

• The Korean Journal of Nuclear Medicine
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• v.32 no.2
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• pp.151-160
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• 1998

Purpose: Piccolo et al. advocated the usefulness of $^{99m}Tc$-MDP breast scan in differential diagnosis of breast mass with high accuracy. But there are little or no follow-up studies about it as we know. We studied $^{99m}Tc$-MDP uptake pattern and lesion/background ratio in patients complaining palpable breast lesions to evaluate the clinical usefulness of $^{99m}Tc$-MDP scan. Materials and Methods: Total 34 patients were studied with physical examination, mammo-gram and $^{99m}Tc$-MDP scan prospectively. Anteroposterior and both lateral view of breast were obtained 5 minutes after iv injection of 740 MBq $^{99m}Tc$-MDP. Breast uptake pattern of $^{99m}Tc$-MDP was analyzed by a grade system: 0=no uptake, grade 1=bilateral diffuse uptake, grade 2=asymmetric faint uptake, grade 3=focal hot uptake. 20 cases were pathologically confirmed by excision biopsy or aspiration biopsy. 14 cases were normal in physical examination and mammogram. Results: Pathologic results showed 7 carcinomas, 6 benign solid tumors, and 7 fibrocystic changes. Grade 3 pattern of $^{99m}Tc$-MDP uptake was noted in 4/7 carcinomas, 3/6 benign solid tumors, and 1/7 fibrocystic changes. Grade 2 pattern was 217, 0/7, 3/7 respectively. The average L/B ratio was 1.66 in carcinomas, 1.68 in benign solid masses, 1.20 in fibrocystic diseases, 1.05 in normal patients. L/B ratio was higher in carcinoma and benign mass groups than in fibrocystic change and normal control groups(p=0.005). But there was no statistical difference between L/B ratio of malignant mass group and benign mass group. Conclusion: $^{99m}Tc$-MDP scan is not suitable to routine clinical use for breast mass diagnosis. It might be used in limited conditions when whole body bone scan is planned.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.4
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• pp.346-349
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• 2005

Metastatic tumours to oral soft tissue are uncommon and accounts for approximately 1% of malignant oral neoplasms. Because of its rarity and clinical appearance of benign nature, the diagnosis of a metastatic lesion in the oral soft tissue may be challenging, both to clinicians and pathologists. We analyzed the clinical data of 9 patients who had metastatic carcinoma to oral soft tissues. The metastatic site to oral soft tissue was the gingiva in all cases. The most common primary site was lung (6 cases) followed by liver (2 cases) and breast (1 case). The clinical appearance resembled gingiva hyperplasia, pyogenic granuloma or gingival swelling. In one case, the metastatic gingiva lesion was found before detection of primary cancer. The mean survival time after diagnosis of metastatic lesion was 3 months. Although this metastatic lesion is rare, oral and maxillofacial surgeon should recognized that benign inflammatory lesion may be the metastatic malignant lesion or the first sign of undiagnosed underlying malignancy.

• Journal of the East Asian Society of Dietary Life
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• v.17 no.4
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• pp.563-570
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• 2007

This study was performed to observe the antioxidative effects, antimutagenic capacity, and cytotoxic activity of the 70% ethanol extract, and fractions, of Agaricus blazei Murill mycelium, using DPPH free radical scavenging ability, the Ames test, and SRB assay, respectively. Among the fractions, ethyl acetate showed the most effective antioxidative capacity according to the $RC_{50}$(73.6 $\mu$g/mL) of the scavenging effect on the DPPH radical. The inhibition rate of both the aqueous fraction and 70% ethanol extract(200 $\mu$g/plate) toward the Salmonella typhimurium TA100 strain was 94.6%, and it was 89.4% against the mutagenesis induced by MNNG(0.4 $\mu$g/plate). In addition, an identical concentration of the 70% ethanol extract in the TA98 strain, and the ethyl acetate fraction in the TA100 strain, showed inhibition rates of 80.3% and 76.9%, respectively, the highest activities against the mutagenesis induced by 4NQO(0.15 $\mu$g/plate). The cytotoxic effects of the 70% ethanol extract and its fractions increased with increasing sample concentration against human cervical adenocarcinoma(HeLa), human hepatocellular carcinoma(Hep3B), human breast adenocarcinoma(MCF-7), human stomach adenocarcinoma(AGS), and human lung carcinoma (A549). A 1 mg/mL concentration of the ethyl acetate fraction showed cytotoxicities of 77%, 83.8%, 82.1%, 83.1%, and 92.6% against HeLa, Hep3B, MCF-7, AGS and A549, respectively.

• The Korean Journal of Cytopathology
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• v.8 no.1
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• pp.35-46
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• 1997

The authors reviewed 167 malignant effusions from 110 patients, of which the primary site was established on the basis of either biopsy or surgical resection of the primary neoplasm. Main factors analysed were the distribution of primary organs and the cytohistoiogic correlation of body cavity effusions. The 167 fluid specimens from 110 patients consisted of 90 cases(53.9%) of pleural, 68(40.7%) of peritoneal, and 9(5.4%) of pericardial origins. Histologically they consisted of 82 cases(74.5%) of adenocarcinoma, 8(7.3%) of malignant lymphoma, 6(5.5%) of squamous ceil carcinoma, and 3(2.7%) of small cell carcinoma. The most common site among the primary lesions was the stomach in 25 cases(22.7%) followed by the lung in 21(19.1%), ovary on 17(15.5%), and breast in 7(6.4%). As for the distribution of primary tumors in adenocarcinoma, the most common site was lung un 16 cases (48.5%) in pleural fluid and stomach in 22(48.9%) in peritoneal fluid. In pericardial effusions, all 5 cases were from the lung. As a whole, the cytologic findings of malignant effusion were fairly representative of histologic characteristics of primary lesions. Thus, when the primary lesion Is unknown, careful evaluation of effusion cytology is presumed to be a helpful tooi for tracing the primary tumor.

• Journal of Korean Neurosurgical Society
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• v.46 no.6
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• pp.538-544
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• 2009

Objective : Primary treatment of spinal metastasis has been external beam radiotherapy. Recent advance of technology enables radiosurgery to be extended to extracranial lesions. The purpose of this study was to determine the clinical effectiveness and safety of stereotactic radiosurgery using Cyberknife in spinal metastasis. Methods : From June, 2002 to December, 2007, 129 patients with 167 spinal metastases were treated with Cyberknife. Most of the patients (94%) presented with pain and nine patients suffered from motor deficits. Twelve patients were asymptomatic. Fifty-three patients (32%) had previous radiation therapy. Using Cyberknife, 16-39 Gy in 1-5 fractions were delivered to spinal metastatic lesions. Radiation dose was not different regarding the tumor pathology or tumor volume. Results : After six months follow-up, patient evaluation was possible in 108 lesions. Among them, significant pain relief was seen in 98 lesions (91%). Radiological data were obtained in 83 lesions. The mass size was decreased or stable in 75 lesions and increased in eight lesions. Radiological control failure cases were hepatocellular carcinoma (5 cases), lung cancer (1 case), breast cancer (1 case) and renal cell carcinoma (1 case). Treatment-related radiation injury was not detected. Conclusion : Cyberknife radiosurgery is clinically effective and safe for spinal metastases. It is true even in previously irradiated patients. Compared to conventional radiation therapy, Cyberknife shows higher pain control rate and its treatment process is more convenient for patients. Thus, it can be regarded as a primary treatment modality for spinal metastases.