• Title/Summary/Keyword: risk expression

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Association between GSTP1 Genotypes and Hormone Receptor Phenotype in Invasive Ductal Carcinomas of Breast

  • Khabaz, Mohamad Nidal;Gari, Mamdooh Abdullah;Al-Maghrabi, Jaudah Ahmed;Nedjadi, Taoufik;Bakarman, Marwan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1707-1713
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    • 2015
  • Eighty six cases of invasive ductal breast carcinomas were utilized to investigate GSTP1 polymorphisms in certain immunohistochemistry (IHC) subtypes of breast cancer with respect to ER, PR and HER2 expression. The frequency of wild allele homozygote, heterozygote and variant allele homozygote genotypes were 46.5%, 52.3% and 1.16% respectively; Whereas 54.3% of the control subjects were GSTP1 wild type allele homozygous, 40.0% were heterozygous and 5.71% mutant allele homozygous. There was dramatic inverted relation between positive IHC ER staining and increasing grade of tumors in general (100%, 88.6%, 40.4%) and especially among tumors with heterozygote genotype of GSTP1 (70%, 35.4%, 22.7). There was increase in positive IHC HER2 staining consistent with higher grades in general (20%, 29.6%, 50.0%), especially among tumors with GSTP1 wild allele homozygote genotype (5.0%, 9.1%, 31.8%). A remarkable reverse relation was also observed between the fraction of IHC hormone receptor phenotype ER+/PR+/ HER2- and increased grade of tumors (60.0%, 45.5%, and 27.3%) especially among tumors with GSTP1 heterozygote genotype, and a similar link was noted regarding ER+/PR-/ HER2- and tumor grade. There was increase in frequency of ER-/PR-/ HER2- (0.0%, 6.8%, and 18.2%) and ER-/PR-/ HER2+ (0.0%, 4.54%, and 40.9%) consistent with the higher grades of tumors in general and especially GSTP1 heterozygote genotype tumors. As a conclusion, there is no correlation between GSTP1 polymorphism and increased risk of breast cancer i.e. the mutant allele is randomly distributed in cancer and control cases. However, there is a link between GSTP1 genotypes and hormone receptor expression status and certain phenotypes of breast cancer, which may have clinical importance.

Ameliorative Effects of Combinative Injection of Ginko biloba Leaves Extract and Vitamin C on Ischemia/Reperfusion Liver Damages Model

  • Xie, Guang-Hua;Choi, Sun Eun;Mun, Myung-Jae;Jeong, Jae-Hun;Park, Kwang-Hyun
    • Korean Journal of Plant Resources
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    • v.31 no.3
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    • pp.268-273
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    • 2018
  • Hepatic ischemia-reperfusion injury (HIRI) is linked with high mortality rate. Several agents have been developed so far to reduce the risk of HIRI. In this study, we investigated the effects of combined treatment of Ginko biloba leaves extract and vitamin C (GLEVC) on hepatic ischemia-reperfusion injury. To explore the protective effects of GLEVC on HIRI rats model were tested. After the development of HIRI by using clamping method rats were then randomly divided into four groups. Different doses of GLEVC were administered in HIRI rat model. The level of ALT, AST, SOD and MDA content in serum were detected in HIRI groups. Moreover, the activity of SOD, content of MDA, and GSH in hepatic tissue were also examined. Bcl-2 and Bax protein expression were detected by immunohistochemical staining method. Compared with sham group, GLEVC has the protective effect on the HIRI-induced model. Level of ALT, AST, and MDA in blood were significantly lower in GLEVC group compared with HIRI-induced group. Moreover, SOD activity and GSH were increased in GLEVC group whereas MDA content was reduced by GLEVC treatment. Furthermore, HIRI-induced Bax protein was reduced upon GLEVC treatment, whereas Bcl-2 protein expression was enhanced. These results demonstrate that GLEVC treatment may provide potential ameliorative therapy by reducing damaged signaling mechanism in hepatic ischemia/reperfusion injury model.

Inhibition of Cell Invasion by Ethyl Alcohol Extracts of Hizikia fusiforme in AGS Human Gastric Adenocarcinoma Cells (AGS 인체 위암세포에서 톳 에탄올 추출물에 의한 침윤성 저해)

  • Choi, Yung-Hyun
    • Journal of Life Science
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    • v.20 no.12
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    • pp.1784-1791
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    • 2010
  • In this study, we investigated the effects of ethyl alcohol extracts of Hizikia fusiforme (EHF) on the correlation between tightening of tight junctions (TJs) and anti-invasive activity in human gastric adenocarcinoma AGS cells. Inhibitory effects of EHF on cell proliferation, motility, and invasiveness were found to be associated with increased tightness of the TJs, which was demonstrated by an increase in transepithelial electrical resistance. Activities of matrix metalloprotease (MMP)-2 and -9 in AGS cells were dose-dependently inhibited by treatment with EHF, and this was also correlated with a decrease in expression of their mRNA and proteins; however, tissue inhibitor of metalloproteinase (TIMP)-1 and -2 mRNA levels were increased. Additionally, immunoblotting results indicated that EHF repressed the levels of claudin proteins (claudin-1, -3, and -4), major components of TJs that play key roles in control and selectivity of paracellular transport. Furthermore, EHF decreased expression of insulin such as growth factor-1 receptor proteins, while concurrently increasing that of thrombospondin-1 and E-cadherin. In conclusion, these results suggest that EHF treatment may inhibit tumor cell motility and invasion, and therefore act as a dietary source to decrease the risk of cancer metastasis.

A study on the actual conditions of trade secrets in the MSDS and the improvement of the relevant system (사업장 MSDS 영업비밀 적용실태 및 제도 개선방안에 관한 연구)

  • Lee, Jong Han;Lee, Kown Seob;Park, Jin Woo;Han, Kyu Nam
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.21 no.3
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    • pp.128-138
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    • 2011
  • Objectives: It has been pointed out that there are problems in handling and managing chemicals due to trade secrets of Material Safety Data Sheet(MSDS). To date, some company intentionally leave out of several parts and use an inaccurate expression in MSDS. In particular, with the result of the inspection of the government and labour community, it is required that the 2nd section in MSDS included the composition and information on ingredients has to be provided with comprehensive expression to secure more reliability. Methods: Therefore, this study is aimed: 1) to recognize the current status of trade secrets of MSDS in workplaces with both domestic manufacturers of chemical products and multinational corporations; 2) to make contributions to prevention of the industrial accidents by providing the accurate information of MSDS; 3) to improve the risk communication system related with chemicals; 4) to impress workers on the importance of right of known for MSDS. With the result we analyzed the status of trade secrets in MSDS in 73 companies, such as petrochemistry production, paint production, metal processing oil production, detergent production, and international company related with chemicals, we have found that 38,150 (45.5%) have the trade secrets parts in the total number of 83,832 in MSDS. Also, based on the 288 MSDS gathered by the Occupational Safety and Health Research Institute (OSHRI) from 2005 to 2009, 41.7% of the MSDS are classified into the trade secrets. Conclusions: Therefore, to procure an assurance system of MSDS, we suggest that a MSDS picking up and checking system be legislated in the Occupational Safety and Health Act to protect workers from the unidentified chemical hazards due to the secret trade of MSDS.

What is Epigenetics? -Focusing on Basic Concepts and Mechanisms- (최근 보건의료분야에서 활발하게 연구되고 있는 "Epigenetics"란 무엇인가? -기본개념 및 기전을 중심으로-)

  • Lee, Sun-Dong;Park, Sung-Kyun;Ko, Seong-Gyu;Shin, Heon-Tae;Kim, Myung-Dong
    • Journal of Society of Preventive Korean Medicine
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    • v.14 no.2
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    • pp.1-12
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    • 2010
  • The individual differences in disease development and susceptibility have been researched primarily on the subject of genes, environment or the interaction between genes and the environment respectively. However, there have been limitations in explaining complex diseases, and the differences in health and diseases in monozygotic and dizygotic twins. Fortunately, thanks to active research on the relationship between genes and the environment, and epigenetics, there has been much progress in the understanding of body's reactions and changes. Epigenetics is referred to as a study of gene expression through the interactions of DNA methylation, chromatin's histone and the change of structure in tail, RNA editing without any change in DNA sequence. In this paper, we introduce the basic concepts and mechanisms of epigenetics. The result of the epigenetics is heritable ; can regulate gene expressions ; is reversible ; and has many variable forms depending on cell types. The influences of epigenetics occur throughout life, but it is mainly determined in utero during early pregnancies. Diseases occur or the risk rises if these influences continue after birth until adult life when problems occur in excess/lack of nutrition, environmental plasticity, or already inputted data. Therefore, there is a need for change and innovation, especially in interest and investment in health education for young women near pregnancies and correct treatment of epigenetic-related diseases.

Extracellular S100A4 negatively regulates osteoblast function by activating the NF-κB pathway

  • Kim, Haemin;Lee, Yong Deok;Kim, Min Kyung;Kwon, Jun-Oh;Song, Min-Kyoung;Lee, Zang Hee;Kim, Hong-Hee
    • BMB Reports
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    • v.50 no.2
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    • pp.97-102
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    • 2017
  • Patients with inflammatory bone disease or cancer exhibit an increased risk of fractures and delayed bone healing. The S100A4 protein is a member of the calcium-binding S100 protein family, which is abundantly expressed in inflammatory diseases and cancers. We investigated the effects of extracellular S100A4 on osteoblasts, which are cells responsible for bone formation. Treating primary calvarial osteoblasts with recombinant S100A4 resulted in matrix mineralization reductions. The expression of osteoblast marker genes including osteocalcin and osterix was also suppressed. Interestingly, S100A4 stimulated the nuclear factor-kappaB (NF-${\kappa}B$) signaling pathway in osteoblasts. More importantly, the ex vivo organ culture of mouse calvariae with recombinant S100A4 decreased the expression levels of osteocalcin, supporting the results of our in vitro experiments. This suggests that extracellular S100A4 is important for the regulation of bone formation by activating the NF-${\kappa}B$ signaling pathway in osteoblasts.

Novel Dosimeter for Low-Dose Radiation Using Escherichia coli PQ37

  • Park, Seo-Hyoung;Kim, Tae-Hwan;Cho, Chul-Koo;Lee, Yeon-Hee
    • Journal of Microbiology and Biotechnology
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    • v.11 no.3
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    • pp.524-528
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    • 2001
  • The measurement of radiation response using simple and informative techniques would be of great value in studying the genetic risk following occupational, therapeutic, or accidental exposure to radiation. When patients receive radiation therapy, many suffer from side effects. Since each patient receives a different dose due to different physical conditions, it is important to measure the exact dose of radiation received by each patient to lessen the side effects. Even though several biological dosimetric systems have already been developed, there is no ideal system that can satisfy all the criteria for an idean dosimetric system, especially for low-dose radiation as used in radiation therapy. In this study, an SOS Chromotest of E. coli PQ37 was evaluated as a novel dosimeter for low-dose gamma-rays. E. coli PQ37 was originally developed to screen chemical mutagens using the SOS Chromotest-a colorimtric assay, based on the induction of ${\beta}$-galactosidase ue to DNA damage. The survival fraction of E. coli PQ37 decreased dose-dependently with an increasing dose of cobalt-60 gamma-rays. Also, a good linear correlation was found between the biological damage revealed by the ${\beta}$-galactosidase expression and the doses of gamma-rays. The expression of ${\beta}$-galactosidase activity that responded to low-dose radiation under 1 Gy was $Y=0.404+(0.089{\pm}0.3)D+(-0.018{\pm}0.16)D^2$ (Y, absorbance at 420 nm; D, Dose of irradiation) as calculated using Graph Pad In Plot and Excel. When a rabbit was fed with capsules containing an agar block embdded with E. coli PQ37 showed a linear response to the radiation doses. Accordingly, the results confirm that E. coli PQ37 can be used as a sensitive biological dosimeter fro cobalt-60 gamma-rays. To the best of our knowledge, this is the first time that a bacterium has been used as a biological dosimeter, especially for low-dose radiation.

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Modulatory effects of $\alpha$- and $\gamma$-tocopherols on 4-hydroxyestradiol induced oxidative stresses in MCF-10A breast epithelial cells

  • Lee, Eun-Ju;Oh, Seung-Yeon;Kim, Mi-Kyung;Ahn, Sei-Hyun;Son, Byung-Ho;Sung, Mi-Kyung
    • Nutrition Research and Practice
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    • v.3 no.3
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    • pp.185-191
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    • 2009
  • The elevated level of circulating estradiol increases the risk of breast tumor development. To gain further insight into mechanisms involved in their actions, we investigated the molecular mechanisms of 4-hydroxyestradiol (4-$OHE_2$) to initiate and/or promote abnormal cell growth, and of $\alpha$- or $\gamma$-tocopherol to inhibit this process. MCF-10A, human breast epithelial cells were incubated with $0.1{\mu}M$ 4-$OHE_2$, either with or without $30{\mu}M$ tocopherols for 96 h. 4-$OHE_2$ caused the accumulation of intracellular ROS, while cellular GSH/GSSG ratio and MnSOD protein levels were decreased, indicating that there was an oxidative burden. 4-$OHE_2$ treatment also changed the levels of DNA repair proteins, BRCA1 and PARP-1. $\gamma$-Tocopherol suppressed the 4-$OHE_2$-induced increases in ROS, GSH/GSSG ratio, and MnSOD protein expression, while $\alpha$-tocopherol up-regulated BRCA1 and PARP-1 protein expression. In conclusion, 4-$OHE_2$ increases oxidative stress reducing the level of proteins related to DNA repair. Tocopherols suppressed oxidative stress by scavenging ROS or up-regulating DNA repair elements.

Possible Prognostic Role of HER2/Neu in Ductal Carcinoma In Situ and Atypical Ductal Proliferative Lesions of the Breast

  • Daoud, Sahar Aly;Ismail, Wesam Maghawri;Abdelhamid, Mohamed Salah;Nabil, Tamer Mohamed;Daoud, Sahar Aly
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.8
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    • pp.3733-3736
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    • 2016
  • HER2/neu is a well-established prognostic and predictive factor for invasive breast cancer. However, the role of HER2/neu in ductal breast carcinoma in situ (DCIS) is debated and recent data have suggested that it is mainly linked to in situ local recurrence. Although molecular data suggest that atypical ductal hyperplasia (ADH) and duct carcinoma in situ (DCIS) are related lesions, albeit with vastly different clinical implications, the role of HER2/neu expression in atypical ductal hyperplasia is not well defined either. The aim of this study was to evaluate over expression of HER2/neu in DCIS and cases of ADH in comparison with invasive breast carcinoma. Archival primary breast carcinoma paraffin blocks (n=15), DCIS only (n=10) and ductal epithelial hyperplasia and other breast benign lesions (n=25) were analyzed for HER2/neu immunoexpression. Follow up was available for 40% of the patients. HER2/neu was positive in 80%of both DCIS and invasive carcinoma, and 67% of atypical ductal hyperplasia (ADH) cases. Thus at least a subset of patients with preinvasive breast lesions were positive, which strongly suggests a role for Her2/neu in identifying high-risk patients for malignant transformation. Although these are preliminary data, which need further studies of gene amplification within these patients as well as a larger patient cohort with longer periods of follow up, they support the implementation of routine Her2/neu testing in patients diagnosed as pure DCIS and in florid ADH.

The various mechanisms of Korean traditional medicines for anti-cancer (한약의 다양한 항암기전)

  • Park, Yeong-Chul;Park, Yong-Ki;Lee, Sun-Dong
    • The Korea Journal of Herbology
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    • v.27 no.3
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    • pp.39-55
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    • 2012
  • Objectives : Recently there have been encouraging results, from a western perspective, in the cancer research field regarding the anticancer effects of herbal medicine. This paper was aimed to review herbal medicine playing its anticancer role in terms of apoptosis, inflammation control, differentiation and telomerase. Methods : New studies for tang, medicinal herb itself or effective ingradients of medicinal herb showing anti-cancer effectiveness were reviewed and summarized in terms of pharmacological action. Results : Ethanol extracts of $Spatholobus$ $suberectus$ greatly inhibited cancer cell growth inducing cell apoptosis and cytotoxic effects. $Scutellaria$ $baicalensis$ may be responsible for its anticancer activity showing inhibition of $PGE_2$ synthesis via suppression of COX-2 expression. Saikosaponins isolated from $Bupleurum$ induced the differentiation of C6 glioma cells, cancer cells, into astrocytes, normal cells. Acetone extract of $Bupleurum$ $scorzonerifolium$ inhibited proliferation of human lung cancer cells via inducing apoptosis and suppressing telomerase activity. Conclusions : Herbal medicine inhibited cancer cell growth inducing cell apoptosis and cytotoxic effects. Inflammation persisting for a decade eventually elevates the risk of cancer sufficiently that it is discernible in case control epidemiological studies. Differentiation therapy is defined as a therapy to treat cancers by inducing differentiation of the stem cells. Telomerase expression is a hallmark of cancer. Nearly the complete spectrum of human tumors has been shown to be telomerase positive.