• Title/Summary/Keyword: BreastScreen

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The PcG protein hPc2 interacts with the N-terminus of histone demethylase JARID1B and acts as a transcriptional co-repressor

  • Zhou, Wu;Chen, Haixiang;Zhang, Lihuang
    • BMB Reports
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    • v.42 no.3
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    • pp.154-159
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    • 2009
  • JARID1B (jumonji AT rich interactive domain 1B) is a large nuclear protein that is highly expressed in breast cancers and is proposed to function as a repressor of gene expression. In this paper, a phage display screen using the N-terminus of JARID1B as bait identified one of the JARID1B interacting proteins, namely PcG protein (Polycomb group) hPc2. We demonstrated that the C-terminal region, including the COOH box, was required for the interaction with the N-terminus of JARID1B. In a reporter assay system, co-expression of JARID1B with hPc2 significantly enhanced the transcriptional repression. These results support a role for hPc2 acting as a transcriptional co-repressor.

Analysis of the cause-specific proportional hazards model with missing covariates (누락된 공변량을 가진 원인별 비례위험모형의 분석)

  • Minjung Lee
    • The Korean Journal of Applied Statistics
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    • v.37 no.2
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    • pp.225-237
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    • 2024
  • In the analysis of competing risks data, some of covariates may not be fully observed for some subjects. In such cases, excluding subjects with missing covariate values from the analysis may result in biased estimates and loss of efficiency. In this paper, we studied multiple imputation and the augmented inverse probability weighting method for regression parameter estimation in the cause-specific proportional hazards model with missing covariates. The performance of estimators obtained from multiple imputation and the augmented inverse probability weighting method is evaluated by simulation studies, which show that those methods perform well. Multiple imputation and the augmented inverse probability weighting method were applied to investigate significant risk factors for the risk of death from breast cancer and from other causes for breast cancer data with missing values for tumor size obtained from the Prostate, Lung, Colorectal, and Ovarian Cancer Screen Trial Study. Under the cause-specific proportional hazards model, the methods show that race, marital status, stage, grade, and tumor size are significant risk factors for breast cancer mortality, and stage has the greatest effect on increasing the risk of breast cancer death. Age at diagnosis and tumor size have significant effects on increasing the risk of other-cause death.

Identification of Anti-Cancer Targets of Eco-Friendly Waste Punica granatum Peel by Dual Reverse Virtual Screening and Binding Analysis

  • Usha, Talambedu;Goyal, Arvind Kumar;Lubna, Syed;Prashanth, H.P.;Mohan, T. Madhan;Pande, Veena;Middha, Sushil Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10345-10350
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    • 2015
  • Background: Punica granatum (family: Lythraceae) is mainly found in Iran, which is considered to be its primary centre of origin. Studies on pomegranate peel have revealed antioxidant, anti-inflammatory, anti-angiogenesis activities, with prevention of premature aging and reducing inflammation. In addition to this it is also useful in treating various diseases like diabetes, maintaining blood pressure and treatment of neoplasms such as prostate and breast cancer. Objectives: In this study we identified anti-cancer targets of active compounds like corilagin (tannins), quercetin (flavonoids) and pseudopelletierine (alkaloids) present in pomegranate peel by employing dual reverse screening and binding analysis. Materials and Methods: The potent targets of the pomegranate peel were annotated by the PharmMapper and ReverseScreen 3D, then compared with targets identified from different Bioassay databases (NPACT and HIT's). Docking was then further employed using AutoDock pyrx and validated through discovery studio for studying molecular interactions. Results: A number of potent anti-cancerous targets were attained from the PharmMapper server according to their fit score and from ReverseScreen 3D server according to decreasing 3D scores. Conclusion: The identified targets now need to be further validated through in vitro and in vivo studies.

Cancer Detection Rates in a Population-Based, Opportunistic Screening Model, New Delhi, India

  • Shridhar, Krithiga;Dey, Subhojit;Bhan, Chandra Mohan;Bumb, Dipika;Govil, Jyostna;Dhillon, Preet K
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1953-1958
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    • 2015
  • Background: In India, cancer accounts for 7.3% of DALY's, 14.3% of mortality with an age-standardized incident rate of 92.4/100,000 in men and 97.4/100,000 in women and yet there are no nationwide screening programs. Materials and Methods: We calculated age-standardized and age-truncated (30-69 years) detection rates for men and women who attended the Indian Cancer Society detection centre, New Delhi from 2011-12. All participants were registered with socio-demographic, medical, family and risk factors history questionnaires, administered clinical examinations to screen for breast, oral, gynecological and other cancers through a comprehensive physical examination and complete blood count. Patients with an abnormal clinical exam or blood result were referred to collaborating institutes for further investigations and follow-up. Results: A total of n=3503 were screened during 2011-12 (47.8% men, 51.6% women and 0.6% children <15 years) with a mean age of 47.8 yrs (${\pm}15.1yrs$); 80.5% were aged 30-69 years and 77.1% had at least a secondary education. Tobacco use was reported by 15.8%, alcohol consumption by 11.9% and family history of cancer by 9.9% of participants. Follow-up of suspicious cases yielded 45 incident cancers (51.1% in men, 48.9% in women), consisting of 55.5% head and neck (72.0% oral), 28.9% breast, 6.7% gynecological and 8.9% other cancer sites. The age-standardized detection rate for all cancer sites was 340.8/100,000 men and 329.8/100,000 women. Conclusions: Cancer screening centres are an effective means of attracting high-risk persons in low-resource settings. Opportunistic screening is one feasible pathway to address the rising cancer burden in urban India through early detection.

Toxicogenomic Analysis and Identification of Estrogen Responsive Genes of Di (n-ethylhexyl) Phthalate in MCF-7 Cells

  • Kim, Youn-Jung;Yun, Hye-Jung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.1 no.3
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    • pp.149-156
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    • 2005
  • Di (n-ethylhexyl) phthalate (DEHP) is thought to mimic estrogens in their action, and are called endocrine disrupting chemicals. DEHP is used in numerous consumer products, especially those made of flexible polyvinyl chloride and have been reported to be weakly estrogenic. In this study, DEHP were tested for estrogenic properties in vitro models and with microarray analysis. First, the E-screen assay was used to measure the proliferation of DEHP in MCF-7 cells, a human breast cancer cell line. DEHP induced an increase in MCF-7 cell proliferation at concentration of $10^{-4}M$. Second, we carried out a microarray analysis of MCF-7 cells treated with DEHP using human c-DNA microarray including 401 endocrine system related genes. Of the genes analyzed, 60 genes were identified showing significant changes in gene expression resulting from DEHP. Especially, 4 genes were repressed and 4 genes were induced by DEHP compared to $17{\beta}-estradiol$. Among these genes, trefoil factor 3 (intestinal), breast cancer 1, early onset and CYP1B1 are involved in estrogen metabolism and regulation. Therefore it suggests that these genes may be associated with estrogenic effect of the DEHP on transcriptional level. The rationale is that, as gene expression is a sensitive endpoint, alterations of these genes may act as useful biomarkers to define more precisely the nature and level of exposure to kinds of phthalates.

Women's Cancer Screening According to Body Mass Index in a Cohort of Rural Korean Women (강원지역 농촌코호트 여성의 체질량 지수에 따른 여성암 검진행위)

  • Kim, Bo-Hwan;Koh, Sang-Baek;Hur, Hea-Kung;Park, Jong-Ku;Park, So-Mi
    • Journal of Korean Academy of Nursing
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    • v.39 no.5
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    • pp.641-650
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    • 2009
  • Purpose: This study was done to examine the difference in cancer screening with mammography and Papanicolaou smear according to Body Mass Index (BMI). Methods: The participants in this study were 5,912 women ages 40 to 69 yr, selected from the Korean Genomic Regional Cohort in Kangwon province. Mammography and Papanicolaou smear were assessed by questionnaire and body weight (kg) and height (m) measured to calculate BMI. Results: The distribution of BMI was as follows: low weight (1.5%), normal weight (31.1%), over weight (24.6%), mildly obese (36.4%) and severely obese (6.3%). After adjusting for age, education and monthly income, compared with normal weight women, overweight women (odds ratio [OR]=1.283, 95% confidence interval [CI]=1.089-1.513) and mildly obese women (OR=1.214, 95% CI=1.048-1.406) were less likely to have had mammography. In contrast to mammography, cancer screening with Papanicolaou smear was not significantly different by BMI. Conclusion: Obese women in rural areas are less likely to screen for breast cancer by using mammography than non obese women. To ensure regular screening for breast cancer, health care providers need to give scrupulous care to obese women and remove barriers originated from obesity. Also, educational and clinical implications are considered to increase the Papanicolaou smear rate.

Screening of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors In Vitro and Its Application to Pullets (HMG-CoA Reductase의 저해제 탐색과 가금의 콜레스테를 저하 효과)

  • Moon, Young-Ja;Yeom, Keum-Hee;Sung, Chang-Keun
    • The Korean Journal of Food And Nutrition
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    • v.15 no.4
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    • pp.307-313
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    • 2002
  • The primary objective of these studies was to screen the materials showing inhibitions of HMG-CoA reductase in vitro. The secondary objective was to determine the effect of garlic, lovastatin and copper on cholesterol concentrations in plasma, liver and breast tissues in pullets. The degree of inhibition of the selective samples on HMG-CoA reductase activity was determined in vitro. The inhibition ratios of water soluble garlic extracts, lovastatin (methanol extracts) and copper to HMG-CoA reductase activity were 51.3%, 87.5%, and 82.0%, respectively. Control diet (basal diet) and experimental diets, garlic powder (3% in diet), lovastatin (300mg/Kg of diet) and copper (200mg/Kg of diet) were fed to pullets in order to investigate the changes of cholesterol concentration in plasma and tissues. Total cholesterol, HDL- and LDL-cholesterol in blood plasma were significantly reduced in pullets fed diet containing 3% garlic powder. However, copper significantly increased total cholesterol compared to control and lovastatin did not affect plasma cholesterol concentration. Total cholesterol and triglyceride of liver and breast tissues in pullets were not affected by adding the cholesterol-lowering materials to diets. The data suggests that it is not easy for HMG-CoA reductase inhibitors to reduce cholesterol levels in body due to complication of cholesterol metabolism. However, garlic administration can lower the levels of plasma cholesterol in pullets.

Estrogenic and Antiestrogenic Insecticides in MCF7-BUS Cell Line (피레스로이드계 살충제의 MCF7-BUS세포에 대한 에스트로겐 및 항에스트로겐 효과)

  • 오승민;정규혁
    • YAKHAK HOEJI
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    • v.45 no.6
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    • pp.694-700
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    • 2001
  • Synthetic pyrethroids are analysis of a natural chemical moiety, pyrethrin derived from the pyrethrum plant Chrysanthemum. The natural pyrethrin structure has been modified to be highly lipophilic and photostable, creating an effective pesticide and resulting in an increased presence in the environment. Worldwide, they are commonly used insecticides against ticks, mites, mosquitoes, and as treatment for human head lice and scabies. Therefore, human exposure to their compounds in extensive. Several studies on the effects of pyrethroids on thyroid hormone regulation, estrogen and androgen function have been reported and yet little has been done try assess their potential hormonal activities. Among humans, a pyrethroid compound was suggested to be the causal agent for gynecomastia in a group of Haitian men. The reports suggest that some pyrethroid compounds are capable of disrupting endocrine function. Therefore, we examined estrogenic/antiestrogenic potential of three pyrethroid insecticides, that is permethrin, allethrin and fenvalerate in human breast cancer cell and action mechanism mediated by the estrogen receptor. Fenvalerate showed weak estrogenic activity but aallethrin and permethrin showed no effect. In combination with high levels (10$^{-10}$ M, 10$^{-11}$ M) of 17$\beta$-estradiol and three synthetic pyrethroids inhibited cert proliferations in MCF7-BUS cell by 17$\beta$-estradiol. Whereas, fenvalerate increased cell proliferative activity at lower level of estradiol (10$^{-12}$ M, 10$^{-13}$ M). The relative affinities to the estrogen receptor were observed by allethrin and permethrin treatment, but not by fenvalerate. These results indicated that some of pyrethroid insecticides may modulate estrogen functions in human breast cancer cell. The action mechanisms of estrogen receptor mediated antiestrogenicity by allethrin and permethrin were postulated.

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Estrogenic Activity of Sanguiin H-6 through Activation of Estrogen Receptor α Coactivator-binding Site

  • Trinh, Tuy An;Park, Eun-Ji;Lee, Dahae;Song, Ji Hoon;Lee, Hye Lim;Kim, Ki Hyun;Kim, Younghoon;Jung, Kiwon;Kang, Ki Sung;Yoo, Jeong-Eun
    • Natural Product Sciences
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    • v.25 no.1
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    • pp.28-33
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    • 2019
  • A popular approach for the study of estrogen receptor ${\alpha}$ inhibition is to investigate the protein-protein interaction between the estrogen receptor (ER) and the coactivator surface. In our study, we investigated phytochemicals from Rubus coreanus that were able to disrupt $ER{\alpha}$ and coactivator interaction with an $ER{\alpha}$ antagonist. The E-screen assay and molecular docking analysis were performed to evaluate the effects of the estrogenic activity of R. coreanus extract and its constituents on the MCF-7 human breast cancer cell line. At $100{\mu}g/mL$, R. coreanus extract significantly stimulated cell proliferation ($574.57{\pm}8.56%$). Sanguiin H6, which was isolated from R. coreanus, demonstrated the strongest affinity for the $ER{\alpha}$ coactivator-binding site in molecular docking analysis, with a binding energy of -250.149. The initial results of the study indicated that sanguiin H6 contributed to the estrogenic activity of R. coreanus through the activation of the $ER{\alpha}$ coactivator-binding site.

Screening and functional validation of lipid metabolism-related lncRNA-46546 based on the transcriptome analysis of early embryonic muscle tissue in chicken

  • Ruonan, Chen;Kai, Liao;Herong, Liao;Li, Zhang;Haixuan, Zhao;Jie, Sun
    • Animal Bioscience
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    • v.36 no.2
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    • pp.175-190
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    • 2023
  • Objective: The study was conducted to screen differentially expressed long noncoding RNA (lncRNA) in chickens by high-throughput sequencing and explore its mechanism of action on intramuscular fat deposition. Methods: Herein, Rose crown and Cbb broiler chicken embryo breast and leg muscle lncRNA and mRNA expression profiles were constructed by RNA sequencing. A total of 96 and 42 differentially expressed lncRNAs were obtained in Rose crown vs Cobb broiler chicken breast and leg muscle, respectively. lncRNA-ENSGALT00000046546, with high interspecific variability and a potential regulatory role in lipid metabolism, and its predicted downstream target gene 1-acylglycerol-3-phosphate-O-acyltransferase 2 (AGPAT2), were selected for further study on the preadipocytes. Results: lncRNA-46546 overexpression in chicken preadipocyte 2 cells significantly increased (p<0.01) the expression levels of AGPAT2 and its downstream genes diacylglycerol acyltransferase 1 and diacylglycerol acyltransferase 2 and those of the fat metabolism-related genes peroxisome proliferator-activated receptor γ, CCAAT/enhancer binding protein α, fatty acid synthase, sterol regulatory element-binding transcription factor 1, and fatty acid binding protein 4. The lipid droplet concentration was higher in the overexpression group than in the control cells, and the triglyceride content in cells and medium was also significantly increased (p<0.01). Conclusion: This study preliminarily concludes that lncRNA-46546 may promote intramuscular fat deposition in chickens, laying a foundation for the study of lncRNAs in chicken early embryonic development and fat deposition.