• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.67-74
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• 2009

Exposures to environmental chemicals that mimic endogenous hormones are proposed for a number of adverse health effects, including infertility, abnormal prenatal and childhood development and above all cancers. In addition, recently miRNA (micro RNA) has been recognized to play an important role in various diseases and in cellular and molecular responses to toxicants. In this study, endocrine disrupting environmental toxicant, nonylphenol (NP) was treated to MCF-7 (Human breast cancer cell) and HepG2 (Human hepatocellular liver carcinoma) cell line at 3 hrs and 48 hrs time point and miRNA analysis using $mirVana^{TM}$ miRNA bioarray was performed and compared with total mRNA microarray data for the same cell line and treatment. Robust data quality was achieved through the use of dye-swap. Analysis of microarray data identifies a total of 20 and 11 miRNA expressions at 3 hrs and 48 hrs exposure to NP in MCF-7 cell line and a total of 14 and 47 miRNA expression at 3 hrs and 48 hrs exposure respectively to NP in HepG2 cell line. Expression profiling of the selected miRNA (let-7c, miR-16, miR-195, miR-200b, miR200c, miR-205, and miR-589) reveals changes in the expression of target genes related to metabolism, immune response, apoptosis, and cell differentiation. The present study can be informative and helpful to understand the role of miRNA in molecular mechanism of chemical toxicity and their influence on hormone dependent disease. Also this study may prove to be a valuable tool for screening potential estrogen mimicking pollutants in the environment.

• Journal of Korean Medicine for Obesity Research
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• v.8 no.1
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• pp.81-88
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• 2008

Objectives To investigate the relationship between Heart Rate Variability and menopause among obese middle-aged women in Korea. Subjects and Methods Forty middle-aged women (age 49.05 $\pm$ 2.64 years) with BMI > $23kg/m^2$ were recruited by local advertisement. Blood profiles of estrogen, FSH, LH, glucose, total cholesterol, HDL-cholesterol, and triglyceride were measured. Autonomic Nervous System (ANS) was estimated by short-term spectral analysis of heart rate variability (HRV). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were accessed using Computerized Tomography (CT), Bioimpedance Analysis (BIA), and anthropometry. To scrutinize the influence of ANS on obesity-related factors, we divided the subjects into pre- and post-menopausal women. Results The total cholesterol, FSH and LH were significantly higher in post-menopausal obese women group. The estradiol and standard deviation of all normal R-R intervals (SDNN), high-frequency components (HF) of the HRV were significantly lower in postmenopausal obese women group (P<0.05). Adipose tissue distribution and blood profiles were not significantly different between two groups. Conclusion Menopause induced a decrease in SDNN and HF values and increase in total cholesterol level in obese women although the VAT itself was not related with ANS in obese women.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.251-254
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• 2012

Purpose: To explore the relationship between auxiliary lymph node metastasis and clinical features, and to identify the factors that affect metastasis occurrence. Methods: A total of 164 cases of primary breast cancer were selected to investigate features such as age, concomitant chronic disease and pathologic diagnosis. Immunohistochemistry was used to detect the expression of the estrogen receptor (ER) and CerbB-2. Logistic regression was employed to analyze the factors that affect the incidence of lymph node metastases. Results: The incidence of lymph node metastases was 46.3% among elderly patients with breast cancer. Based on logistic regression, chronic disease, scale of tumor, age, and ER expression affected the occurrence of lymph node metastases; the ORs were 3.05, 2.18, 0.34, and 3.83, respectively. Between different pathologic diagnoses and the risk factors, the OR scores were 12.7 and 8.02, respectively, for aggressive ductal carcinoma and aggressive lobular carcinoma auxiliary lymph node metastases. Conclusion: The incidence of lymph node metastases is affected by chronic disease, scale of tumor, age, ER expression and pathologic diagnosis.

• BMB Reports
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• v.53 no.5
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• pp.284-289
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• 2020

Tamoxifen, a nonsteroidal estrogen receptor (ER) antagonist, is used routinely as a chemotherapeutic agent for ER-positive breast cancer. However, it is also causes side effects, including retinotoxicity. The retinal pigment epithelium (RPE) has been recognized as the primary target of tamoxifen-induced retinotoxicity. The RPE plays an essential physiological role in the normal functioning of the retina. Nonetheless, potential therapeutic agents to prevent tamoxifen-induced retinotoxicity in breast cancer patients have not been investigated. Here, we evaluated the action mechanisms of sulfasalazine against tamoxifen-induced RPE cell death. Tamoxifen induced reactive oxygen species (ROS)-mediated autophagic cell death and caspase-1-mediated pyroptosis in RPE cells. However, sulfasalazine reduced tamoxifen-induced total ROS and ROS-mediated autophagic RPE cell death. Also, mRNA levels of tamoxifen-induced pyroptosis-related genes, IL-1β, NLRP3, and procaspase-1, also decreased in the presence of sulfasalazine in RPE cells. Additionally, the mRNA levels of tamoxifen-induced AMD-related genes, such as complement factor I (CFI), complement factor H (CFH), apolipoprotein E (APOE), apolipoprotein J (APOJ), toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4), were downregulated in RPE cells. Together, these data provide novel insight into the therapeutic effects of sulfasalazine against tamoxifen-induced RPE cell death.

• Health Policy and Management
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• v.11 no.3
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• pp.71-88
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• 2001

The purpose of this study is to analyze the cost-effectiveness of four medications for treating and preventing osteoporosis -HRT therapy(conjugated equine estrogen 0.625mg for 25 days and medroxyprogesterone acetate 5mg for 01112 days), Alendronate(10mg and 5mg), Active Vitamin D(Calcitriol), and Calcium. Total costs include the direct medical cost -examination fee, consultation fee, prescription fee, fee for preparing medications, and the price of pharmaceuticals- and the indirect cost of patients such as traffic expenses and time cost. In addition, the costs of monitoring in adverse reactions are added. The effects of four medications are expressed as BMD(Bone Mineral Density) percent change measured by DEXA(Dual Energy X-ray Absorptiometry) in lumbar spine(L2-L4) and femoral neck site. A mixed model based on meta analysis provides the estimates of effectiveness, which are then appled to the hypothetical cohort consisting of postmenopausal women at the age of 50-59. HRT therapy is the most cost-effective medication at 172,433.64 won (lumbar spine site) and 546,328.28 won (femoral neck site) per BMD percent change for osteoporosis. Alendronate 10mg is more cost-effective than Alendronate 5mg as 345,971.23 won and 378,441.63 won per lumbar BMD percent change at 0.991ｇ/$cm^2$, respectively. Alendronate 10mg is more cost-effective than Alendronate 5mg as 1,329,257.89 won and 1,467,291.23 won per femoral neck BMD percent change at 0.834ｇ/$cm^2$, respectively.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10067-10070
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• 2015

Background: Unopposed estrogen has a central role in development of endometrial benign, premalignant and malignant lesions. The aim of this study was to evaluate the anti-estrogenic effect of metformin on endometrial histology in comparison with progesterone. Materials and Methods: A total of 43 patients who were referred to our center for abnormal uterine bleeding and had a histologic diagnosis were disordered proliferative endometrium or simple endometrial hyperplasia were included and randomly distributed in two groups treated with metformin (500mg Bid) or megestrol (40mg daily), respectively, for three months. After this period the patients were evaluated by another endometrial biopsy to assess the impact of the two drugs in restoring normal endometrial histology. Results: Our findings revealed that metformin could induce endometrial atrophy in 21 out of 22 patients (95.5%) while this positive response was achieved in only 13 out of 21 patients (61.9%) in the megstrol group. In addition two low grade endometrial carcinomas in the metformin group responded very well. Conclusions: We conclude that metformin could be used as an effective antiestrogenic agent in control of abnormal endometrial proliferative disorders.

• The Journal of Korea CHUNA Manual Medicine
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• v.1 no.1
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• pp.125-137
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• 2000

the aim of this study was to investigate whether osteoporosis can be advanced after cerebral infarction Of not and role of female sex hormone. all animals were classified 4 groups; group of ovariectomy (OVXgroup) group of cerebral infarction( INF group), group of combination ovariectomy and cerebral infarction(OVX + INF group), naturally intact group for control data (NOR group ). cerebral infarction was made by Chen,s method with some modification and ovariectomy was performed by Wayforth,s method. experimental data was collected at 15 days, 1 month, 3 months and 6months after starting observation. serum 17 ${{\beta}-estradiol\;(E_2)}$ was determined by radioimmunoassay, for comparision of osteoporosis formation, bone density, serum osteocalcin, Serum total calcium and phosphorus, Serum AST Concentration, Serum ALT Concentration, Creatinine Concentration were also calculated. we have found that cerebral ischemia decreases not only the serum concentration of 17 ${{\beta}-estradiol\;(E_2)}$ and inhibits but also the physiologically compensatory function of the ovariectomized rats and that the decreased estrogen concentration followed by cerebral infarction have not produced osteoporosis, regretfully.

• The Korean Journal of Cytopathology
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• v.6 no.1
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• pp.1-9
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• 1995

This study was carried out to determine the usefulness of imprint cytology for detecting p53 protein in breast carcinoma. NCL-DO7 (Novocastra, U.K.) was used to detect p53 protein immunocytochemically. A total of 33 cases was studied, Immunostaining of imprint cytology with NCL-DO7 was positive in 64% (21/33) and showed relatively high coincident rate (80%) with immunostaining of formalin-fixed, paraffin-embedded specimen p53 protein was related to negative estrogen receptor status, but not to the nuclear grade, lymph node metastasis, or tumor size. The fact that p53 protein expression was not related to nuclear grade might be due to predominance of nuclear grade 3. It was easier to determine the nuclear grade is one of the most important prognostic factors, in imprint cytology than in tissue specimen. p53 protein tended to be stained more strongly in imprint cytology than in tissue. It is concluded that the application of imprint cytology in p53 protein detection can be performed easily, and that it may contribute to the evaluation of prognostic factors in breast carcinoma.

• Korean Journal of Environmental Biology
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• v.22 no.1
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• pp.206-212
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• 2004

In an effort to develop the tools for monitoring the contamination of xenoestrogen in the aquatic environment of Korea, reverse transcription-polymerase chain reaction (RT-PCR) analysis of vitellogenin (VTG) mRNA expression were optimized in Synechogobius hastus. Based on the partial VTG cDNA sequence VTG mRNA level in livers from male fishes was analyzed by RT-PCR. As an internal control beta actin mRNA was amplified. 3 ${\mu}g$ of total RNA was reverse transcribed in 20 $\mu$l reaction using murine leukemia virus 〔MuLV〕 reverse transcriptase. Subsequent PCR using the 1 ${\mu}g$ of cDNA resulted in linear increase in PCR product of VTG in female liver cDNA from 10 to 30 cycles of amplification. On the contrary, in male, PCR product first detected at 28 cycles of amplification and linearly increased during 38 cycles of amplification, suggesting that male S. hastus expresses minute amount of VTG mRNA which is $2^{-18}$ equivalent of female. In conclusion, the optimized protocol of VTG mRNA expression in the liver of male S. hastus will be promising the environmental monitoring the xenoestrogen contamination in the western coast and estuaries in Korea.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2089-2092
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• 2016

Background: The impact of mean platelet volume (MPV) on prognosis, diagnosis and response to therapy in cancer patients has been widely investigated. In the present study, we evaluated whether MPV at diagnosis has predictive value for pathologic complete response (pCR) after neoadjuvant chemotherapy in patients with locally advanced breast cancer (LABC). Materials and Methods: A total of 109 patients with LABC from Akdeniz University and Antalya Research and Training Hospital were evaluated retrospectively. Results: ROC curve analysis suggested that the optimum MPV cut-off point for LABC patients with pCR (+) was 8.15 (AUC:0.378, 95%CI [0.256-0.499], p=0.077). The patients with MPV <8.15 had higher pCR rates (29.2% vs. 13.1%, p=0.038). After binary logistic regression analysis, MPV and estrogen receptor absence were independent predictors for pCR. Conclusions: MPV has an independent predictive value for pCR after neoadjuvant chemotherapy in patients with LABC.