• Title/Summary/Keyword: breast carcinoma

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Effects of Flos Sophorae Ethanol Extract on NF-${\kappa}B$ Dependent MMP-9 Expression in Human Breast Cancer Cell (유방암세포에서 괴화 에탄올 추출물의 NF-${\kappa}B$ 의존적인 MMP-9 발현의 조절 규명을 위한 연구)

  • Kim, Jeong Mi;Lee, Young Rae;Hwang, Jin Ki;Kim, Mi Seong;Kim, Ha Rim;Park, Yeon Ju;You, Yong Ouk;Kim, Seong Cheol;Ryu, Do Gon;Kwon, Kang Beom
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.28 no.1
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    • pp.22-28
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    • 2014
  • Flos Sophorae, the dried flower bud of Sophora japonica L, possesses anti-inflammatory properties, prevents and treats blood capillary and hypertension diseases and can also be used as a hemostat. However, the effect of Flos Sophorae on breast cancer invasion is unknown. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is a major component in cancer cell invasion. In this study, we investigated the inhibitory effect of Flos Sophorae extract (FSE) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Matrix metalloproteinase-9 (MMP-9) expression and cell invasion, as well as the molecular mechanisms involved in Michigan Cancer Foundation-7 (MCF-7) cells. FSE inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-${\kappa}B$). These results indicate that FSE-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-${\kappa}B$ pathway in MCF-7 cells. Thus, FSE may have therapeutic potential for controlling breast cancer invasiveness.

Inhibition of human breast carcinoma by BLC (Sargassum fulvellum) and BLC/HEN Egg in vitro and in vivo

  • Jo, Eun-Hye;Cho, Sung-Dae;Ahn, Nam-Shik;Jung, Ji-Won;Yang, Se-Ran;Park, Joon-Suk;Hwang, Jae-Woong;Lee, Sung-Hoon;Park, Jung-Ran;Kim, Sun-Jung;Park, Hyun-Kyung;Lee, Yong-Soon;Kang, Kyung-Sun
    • Korean Journal of Veterinary Research
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    • v.45 no.1
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    • pp.85-91
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    • 2005
  • Much of the interest on the chemopreventive properties of herbs and plants has been raised, whereas little is regarding to anti-tumor effect of farming and aquatic products. In the present study, the anti-tumor effect of hot-water extract of a seaweed, BLC (Sargassum fulvellum) and BLC/HEN egg was investigated using MCF-7 cells in vitro and in vivo systems. We found that the BLC extract and BLC/HEN egg inhibited cell proliferation in a dose-dependent manner, which might be mediated through up-regulation of p53. Furthermore, this test compound can directly induce apoptosis in MCF-7 cells, which might be mediated through up-regulation of a pro-apoptotic Bax protein and down-regulation of a anti-apoptotic Bcl-2 protein, not by immune system. Nude mice bearing established breast tumors (with exogenous estradiol) were treated with BLC extract and BLC/HEN egg. Treatment BLC extract and BLC/HEN egg caused a 42% and 71% inhibition of tumor growth, respectively. Both agents caused a significant inhibition of volume and weight growth of estrogen independent human breast tumors established from MCF-7 cells. Our results suggested that BLC extract and BLC/HEN egg have the efficacious effect of human breast cancer not only in vitro but also in vivo.

GENE EXPRESSION PATTERNS INDUCED BY $TAXOL^{(R)}$ AND CYCLOSPORIN A IN ORAL SQUAMOUS CELL CARCINOMA CELL LINE USING CDNA MICROARRAY (cDNA Microarray를 이용한 구강편평세포암종 세포주에서 $Taxol^{(R)}$과 Cyclosporin A로 유도된 유전자 발현양상)

  • Kim, Yong-Kwan;Lee, Jae-Hoon;Kim, Chul-Hwan
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.28 no.3
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    • pp.202-212
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    • 2006
  • It is well-known that paclitaxel($Taxol^{(R)}$), which is extracted from the pacific and English yew, has been used as a chemotherapeutic agent for ovarian carcinoma and advanced breast carcinoma and Cyclosporin A, which is highly lipophilic cyclic peptide and isolated from a fungus, has been also used as an useful immunosuppressive drug after transplantation and is associated with cellular apoptosis. Since 1953, in which James Watson, Rosalind Franklin and Francis Crick discovered the double helical structure of DNA, a few kinds of techniques for identifying gene expression have been developed. In postgenomic period, many of researchers have used the DNA microarray which is high throughput screening technique to screen large numbers of gene expression simultaneously. In this study, we searched and screened the gene expression in the oral squamous cell carcinoma cell lines treated with $Taxol^{(R)}$, cyclosporin or cyclosporin combined with $Taxol^{(R)}$ using cDNA microarray. The results were as following; 1. It was useful that the appropriate concentration of Cyclosporin A and $Taxol^{(R)}$ used in oral squamous cell carcinoma cell line was under 1${\mu}g/ml$ and 3${\mu}g/ml$. 2. In the experimental group in which $Taxol^{(R)}$ and $Taxol^{(R)}$ + Cyclosporin A were used, the cell growth was extremely decreased. 3. In the group in which Cyclosporin A was used, the MTT assay was rarely decreased which means the activity of succinyl dehydrogenase is remained in mitochondria but in the group in which the mixture of Cyclosporin A and $Taxol^{(R)}$ were used, the MTT assay was extremely decreased. 4. In the each group in which Cyclosporin A(3 ${\mu}g/ml$) and $Taxol^{(R)}$(1 ${\mu}g/ml$) were used, the cell arrest was appeared in $G_2/M$ phase and in the group in which $Taxol^{(R)}$(3 ${\mu}g/ml$) was used, the cell arrest was appeared in both S phase and $G_2/M$ phase. 5. In the oral squamous cell carcinoma cell line treated with $Taxol^{(R)}$, several genes including ANGPTL4, RALBP1 and TXNRD1, associated with apoptosis, SUI1, MAC30, RRAGA and CTGF, related with cell growth, HUS1 and DUSP5, related with cell cycle and proliferation, ATF4 and CEBPG, associated with transcription factor, BTG1 and VEGF, associated with angiogenesis, FDPS, FCER1G, GPA33 and EPHA4 associated with signal transduction and receptor activity and AKR1C2 and UGTA10 related with carcinogenesis were detected in increased levels. The genes that showed increaced expression in the oral squamous cell carcinoma cell line treated with Cyclosporin A were CYR61, SERPINB2, SSR3 and UPA3A which are known as genes associated with cell growth, carcinogenesis, receptor activity and transcription factor. The genes expressed in the HN22 cell line treated with cyclosporin combined with $taxol^{(R)}$ were ALCAM and GTSE1 associated with cancer invasiveness and cell cycle regulation.

Surgical Treatment of Metastatic Lung Cancer (전이성 폐암의 외과적 치료)

  • 조성래
    • Journal of Chest Surgery
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    • v.25 no.9
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    • pp.948-954
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    • 1992
  • In spite of recent progress in anticancer chemotherapy, the survival of patients with metastases to the lung treated nonsurgically has been extremely poor. So we adopted more aggressive surgical approaches for the treatment of patients with pulmonary metastases since 1985. We experienced 22 operations of metastatic lung cancer in 19 patients in the department of Thoracic & Cardiovascular Surgery in Kosin Medical College since 1985, so we reviewed the results of treatment retrospectively. The results were as follows: 1. The primary organs of metastatic lung cancer were 4 cases in each of the breast, uterus, and extremities, 3 cases in the rectum, 2 cases in the kidney, 1 case in each of the pelvis and liver, and the pathological findings were 13 cases in carcinoma and 6 cases in sarcoma. 2. The treatments for primary lesions were 15 cases of the operations with anticancer chemotherapy or radiation therapy, 2 cases of choriocarcinoma with anticancer chemotherapy only, 1 cases of uterine cervical carcinoma with chemo-radiation therapy, and 1 case of pelvic synovia sarcoma with intra-arterial anticancer chemotherapy. 3. Disease free intrerval were as follows: 7 cases were in 2 years to 4 years, 4 cases were in 1 year to 2 years, and 5 cases were beyond one year, of them one case was discovered primary lesion and metastatic lung tumor concomittently. 3 cases were above 4 years, of them one case of breast cancer were above 13 years especially. 4. The sites of metastatic lung cancer was 15 lesions in the right lung, and 9 lesions in the left lung, And the lobar sites were 10 lesions in the upper lobe, 2 lesions in the middle lobe, and 12 lesions in the lower lobe. 5. The operative methods of metastatic lung cancer were 7 case of partial resection of lung, 12 cases of pulmonary lobectomy, 1 case of pneumonectomy and 1 case of dissection of mediastinal lymph node. 6. The postoperative complications were 1 case of mild respiratory insufficency, 1 cases of pyothorax, and 1 case of urethral stricture. 7. Postoperative adjuvant therapy were as follows: No adjuvant therapy were 4 cases, anti-cancer chemotherapy were 8 cases, radiation therapy was 1 case, and combined with chemo k radiation therapy were 8 cases. 8. The results of long term follow-up were as follows: The 5 patients were died at 2 months, 22 months, 24 months, 32 months, and 49 months postoperatively, so mean survival period was 32 months postoperatively excluding one patient who was died at 2 months postoperatively. And 14 patients are aliving, of them 3 patients are living in recurred state, and the other 11 patients are living without any evidence of recurrence.

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Hormone Receptor, HER2/NEU and EGFR Expression in Ovarian Carcinoma - is here a Prognostic Phenotype?

  • Demir, Lutfiye;Yigit, Seyran;Sadullahoglu, Canan;Akyol, Murat;Cokmert, Suna;Kucukzeybek, Yuksel;Alacacioglu, Ahmet;Cakalagaoglu, Fulya;Tarhan, Mustafa Oktay
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9739-9745
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    • 2014
  • Purpose: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. Materials and Methods: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. Results: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Conclusions: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.

Anti-invasive Activity of Human Breast Carcinoma Cells by Genistein through Modulation of Tight Junction Function (인체유방암세포의 tight junction 기능 조절을 통한 genistein의 암세포 침윤 억제 효과)

  • Kim, Sung-Ok;Jeang, Yang-Kee;Choi, Yung-Hyun
    • 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.

In vitro Study of Nucleostemin as a Potential Therapeutic Target in Human Breast Carcinoma SKBR-3 Cells

  • Guo, Yu;Liao, Ya-Ping;Zhang, Ding;Xu, Li-Sha;Li, Na;Guan, Wei-Jun;Liu, Chang-Qing
    • 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.

The Antiproliferative Effects of Compounds Isolated from Schisandra chinensis (오미자로부터 분리된 화합물의 암세포 증식 억제 효과)

  • Suh, Won-Se;Park, So Yeon;Min, Byung Sun;Kim, Sea Hyun;Song, Jeong Ho;Shim, Sang Hee
    • 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 ($IC_{50}$ $1.46{\mu}M$).

Regulation of Cyclin D3 by Calpain Protease in Human Breast Carcinoma MDA-MB-231 Cells (인체 유방암세포에서 calpain protease에 의한 cyclin D3의 발현 조절)

  • Choi, Byung-Tae;Kim, Gun-Do;Choi, Yung-Hyun
    • 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.

Reactive oxygen species-dependent apoptosis induction by water extract of Citrus unshiu peel in MDA-MB-231 human breast carcinoma cells

  • Kim, Min Yeong;Choi, Eun Ok;HwangBo, Hyun;Kwon, Da He;Ahn, Kyu Im;Kim, Hong Jae;Ji, Seon Yeong;Hong, Su-Hyun;Jeong, Jin-Woo;Kim, Gi Young;Park, Cheol;Choi, Yung Hyun
    • 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.