• Korean Journal of Animal Reproduction
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• v.23 no.4
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• pp.365-369
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• 1999

Interferon tau (IFN$\tau$), the pregnancy recognition signal in ruminants, suppresses transcription of the estrogen receptor (ER) gene in the endometrial luminal (LE) and superficial glandular epithelium (sGE) to prevent oxytocin receptor (OTR) expression and pulsatile release of luteolytic prostaglandin $F_{2{\alpha}}$ (PGF), Interferon regulatory factors one (IRF-l) and two (IRF-2) are transcription factors induced by IFN$\tau$ that activate and silence gene expression, respectively. Available results suggest that IFN$\tau$ acts directly on LE and sGE during pregnancy to induce sequentially IRF-l and then IRF-2 gene expression to silence transcription of ER and OTR genes, block the luteolytic mechanism to maintenance a functional corpus luteum (CL) and, signal maternal recognition of pregnancy. The theory for maternal recognition of pregnancy in pigs is that the uterine endometrium of cyclic gilts secretes PGF in an endocrine direction, toward the uterine vasculature for transport to the CL to exert its luteolytic effect. However, in pregnant pigs, estrogens secreted by the conceptuses are responsible, perhaps in concert with effects of prolactin and calcium, for exocrine secretion of PGF into the uterine lumen where it is sequestered to exert biological effects and / or be metabolized to prevent luteolysis.

• Development and Reproduction
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• v.15 no.2
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• pp.179-185
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• 2011

Some phytoestrogens in soy and red wine, for example, might have beneficiary rather than adverse effects. In particular, dietary soy intake seems to be highly correlated with protection of breast cancer, osteoporosis and cardiovascular disorders. However, questions persist on the potential adverse effects of the main soy constituent genistein (GS) on female reproductive physiology. Previously we found that prepubertal exposure to GS could activate the reproductive system of immature female rats leading to precocious puberty onset, and intracerebroventricularly (ICV) injected GS could directly activate hypothalamic kisspeptin-GnRH neuronal circuits in adult female rats. The present study was performed to examine the hypothalamus-specific GS effects in prepubertal female rats and which subtype of estrogen receptor is mediated in this GS effect. Prepubertal female rats (PND 30) were anaesthetized, treated with single dose of GS (3.4 ${\mu}g$/animal), and sacrificed at 2 hrs post-injection. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus, total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). ICV infusion of GS significantly lowered the transcriptional activities of mTOR (1:$0.361{\pm}0.058$ AU, p<0.001) but increased that of GAD67 (1:$1.285{\pm}0.099$ AU, p<0.05), which are known to act as an upstream modulator of kisspeptin and GnRH neuronal activities in the hypothalamus, respectively. GS administration enhanced significantly the mRNA levels of KiSS-1(1:$1.458{\pm}0.078$ AU, p<0.001), and exerted no effect on the mRNA level of kisspeptin receptor GPR-54 (1:$1.29{\pm}0.08$ AU). GnRH gene expression was significantly decreased in GS-treated group compared to control group (1:$0.379{\pm}0.196$ AU, p<0.05). There was no difference in the mRNA level of $ER{\alpha}$ in the GS-treated group compare to control group (1:$1.180{\pm}0.390$ AU, Fig. 3A). However, icv infusion of GS significantly increased the transcriptional activities of $ER{\beta}$ (1:$4.209{\pm}0.796$ AU, p<0.01, Fig. 3B). Taken together, the present study indicated that the acute exposure to GS could directly alter the hypothalamic GnRH modulating system in prepubertal female rats. Our study strongly suggested the involvement of $ER{\beta}$ pathway in GS's hypothalamus-specific action, and this idea is consistent with the GS's well-known $ER{\beta}$-mediated protective action in breast cancer.

• Journal of radiological science and technology
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• v.36 no.4
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• pp.305-311
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• 2013

The purpose of this study was to evaluate the Pathological Diagnosis associated with pSUV uptake of $^{18}F$-FDG PET/CT. We had enrolled 39 women that underwent $^{18}F$-FDG PET/CT before operative. We evaluated whether there was correlation between the pSUV of $^{18}F$-FDG PET/CT and prognostic factors. As a results, pSUV level increase according to tumor size but pSUV had no significant association with tumor size. pSUV of high histologic grade was higher than low histologic grade, and pSUV showed positive correlations with histologic grade. The ER and PR showed significant negative correlations with the pSUV of $^{18}F$-FDG PET/CT. Therefore, our results demonstrated that an correlation exists between pSUV and prognostic factors such as histologic grade, ER and PR.

• Genomics & Informatics
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• v.21 no.2
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• pp.20.1-20.10
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• 2023

Aromatase inhibitors (AI) are drugs that are widely used in treating estrogen receptor (ER)-positive breast cancer patients. Drug resistance is a major obstacle to aromatase inhibition therapy. There are diverse reasons behind acquired AI resistance. This study aims at identifying the plausible cause of acquired AI resistance in patients administered with non-steroidal AIs (anastrozole and letrozole). We used genomic, transcriptomic, epigenetic, and mutation data of breast invasive carcinoma from The Cancer Genomic Atlas database. The data was then separated into sensitive and resistant sets based on patients' responsiveness to the non-steroidal AIs. A sensitive set of 150 patients and a resistant set of 172 patients were included for the study. These data were collectively analyzed to probe into the factors that might be responsible for AI resistance. We identified 17 differentially regulated genes (DEGs) among the two groups. Then, methylation, mutation, miRNA, copy number variation, and pathway analyses were performed for these DEGs. The top mutated genes (FGFR3, CDKN2A, RNF208, MAPK4, MAPK15, HSD3B1, CRYBB2, CDC20B, TP53TG5, and MAPK8IP3) were predicted. We also identified a key miRNA - hsa-mir-1264 regulating the expression of CDC20B. Pathway analysis revealed HSD3B1 to be involved in estrogen biosynthesis. This study reveals the involvement of key genes that might be associated with the development of AI resistance in ER-positive breast cancers and hence may act as a potential prognostic and diagnostic biomarker for these patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.459-462
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• 2012

Expression of estrogen-receptor (ER), progesterone-receptor (PR) and HER-2 has recently been linked with various breast cancer subtypes identified by gene microarray. This study aimed to document breast cancer subtypes based on ER, PR and HER-2 status in Thai women, where expression of these subtypes may not be similar to those evident in Western women. During 2009 to 2010, histological findings from 324 invasive ductal carcinomas (IDC) at Siriraj Hospital were studied. Various subtypes of IDC were identified according to expression of ER, PR and HER-2: luminal-A (ER+;PR+/-;HER-2-), luminal-B (ER+;PR+/-;HER-2 +), HER-2 (ER-;PR- ;HER-2+) and basal-like (ER-;PR-;HER-2-). As well, associations of tumor size, tumor grade, nodal status, angiolymphatic invasion (ALI), multicentricity and multifocality with different breast cancer subtypes were studied. Of 324 IDCs, 143 (44.1%), 147 (45.4%), 15 (4.6%) and 12 (3.7%) were T1, T2, T3 and T4, respectively. Most tumors were grade 2 (54.9%) and had no nodal involvement (53.4%). According to ER, PR and HER-2 status, 192 (59.3%), 40 (12.3%), 43 (13.3%) and 49 (15.1%) tumors were luminal-A, luminal-B, HER-2 and basal-like subtypes. HER-2 subtype presented with large tumor (p=0.04, ANOVA). Luminal-A IDC was associated with single foci (p<0.01, ${\chi}^2$). HER-2 and basal-like subtypes were likely to have high tumor grade (p<0.01, ${\chi}^2$). In addition, HER-2 subtype had higher number of nodal involvement (p=0.048, ${\chi}^2$). In conclusion, the luminal-A subtype accounted for the majority of IDCs in Thai women. Percentages of HER-2 and basal-like IDCs were high, compared with a recent study from the USA. The HER-2 subtype was related with high nodal invasion. The findings may highlight biological differences between IDCs occurring in Asian and Western women.

• Korean Journal of Food Science and Technology
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• v.51 no.4
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• pp.361-368
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• 2019

The present study aimed to evaluate the effect of Dendropanax morbifera (DM) extract on postmenopausal syndrome and to develop DM extract as an alternative for hormonal therapy. The following seven groups of rats; normal control (sham), ovariectomized (OVX) control, Punica granatum (PG)-treated group (770 mg/kg), estradiol treated group (0.5 mg/kg), and three DM-treated groups (200, 500, 1000 mg/kg) were compared. Indicated compounds were administrated once a day for eight weeks. To evaluate the estrogenic effect of DM extract, western blot analysis was performed on the liver tissue to confirm the expression of estrogen receptor ($ER-{\alpha}$, $ER-{\beta}$). Our analysis showed that after DM administration, collagen cross-linked C-telopeptide (CTX) value decreased while $ER-{\alpha}$ protein expression increased in a dose-dependent manner through the MAPK/ERK pathway in OVX rats. These results suggest that Dendropanax morbifera exerts estrogenic effect by inducing estrogen receptor expression and activating MAPK/ERK pathway.

• 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.

• Nutrition Research and Practice
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• v.3 no.2
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• pp.77-83
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• 2009

Retinoic acids (RAs) modulate growth, differentiation, and apoptosis in normal, pre-malignant & malignant cells. In the present study, the effects of RA isomers (all-trans RA, 13-cis RA, and 9-cis RA) on the cell signal transduction of human breast cancer cells have been studied. The relationship between RAs and an enzymatic antioxidant system was also determined. Estrogen-receptor (ER) positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cells were treated with different doses of each RA isomers, all-trans RA, 13-cis RA, or 9-cis RA. Treatment of RA isomers inhibited cell viability and induced apoptosis of MCF-7 cells as a result of increased caspase activity in cytoplasm and cytochrome C released from mitochondria. All-trans RA was the most effective RA isomer in both cell growth inhibition and induction of apoptosis in MCF-7 cells. However, no significant effect of RA isomers was observed on the cell growth or apoptosis in ER-negative MDA-MB-231 cells. In addition, activities of antioxidant enzymes such as catalase and glutathione peroxidase were decreased effectively after treatment of RA in MCF-7 cells, whereas SOD activity was rarely affected. Thus, the present data suggest that all-trans RA is the most potential inducer of apoptosis and modulator of antioxidant enzymes among RA isomers in MCF-7 human breast cancer cells.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2004.11a
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• pp.29-35
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• 2004

유방암 환자의 임상정보(clinical features)와 cDNA microarray 기술을 이용하여 얻은 유전자 발현 프로파일은 유방암 예후 인자를 찾는 데에 매우 중요하다. 본 논문에서는 임상정보와 유전자 발현 정보를 접목해서 분석하는 방법으로써 주성분 분석(Principal Component Analysis)을 이용하였다. 이 방법은 다변량 자료의 차원을 줄이는 방법으로써, 대용량 실험 데이터로 인해 발생하는 문제점을 해결하기 위하여 많이 쓰이고 있다. 본 연구에서는 주성분 분석을 이용하여 먼저 한국인 유방암 환자 73명의 cDNA microarray 데이터 차원을 줄이고, 이를 통해 얻어진 주성분(Principal Components)과 임상정보 데이터와의 상관관계를 보았다. One-way ANOVA를 이용한 상관관계 분석 결과의 P-value는 permutation test를 통해 검증하였다. 동일한 방법을 estrogen receptor(ER)(+) 환자 20명과 ER(-) 환자 31명에 적용해본 결과, ER(-) 환자 중에서 재발과 관련된 유전자를 찾을 수 있었다. 주성분 분석을 molecular phenotypic profiles of clinical features에 이용한 결과 발견된 유전자는 유방암의 재발과 관련된 예후 인자로서 의미가 있다.

• Journal of Environmental Health Sciences
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• v.47 no.5
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• pp.462-471
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• 2021

Background: The number of synthesized chemicals has rapidly increased over the past decade. For many chemicals, there is a lack of information on toxicity. With the current movement toward reducing animal testing, the use of toxicity big data and deep learning could be a promising tool to screen potential toxicants. Objectives: This study identified potential chemicals related to reproductive and estrogen receptor (ER)-mediated toxicities for 1135 cleaning products and 886 laundry products. Methods: We listed chemicals contained in cleaning and laundry products from a publicly available database. Then, chemicals that potentially exhibited reproductive and ER-mediated toxicities were identified using the European Union Classification, Labeling and Packaging classification and ToxCast database, respectively. For chemicals absent from the ToxCast database, ER activity was predicted using deep learning models. Results: Among the 783 listed chemicals, there were 53 with potential reproductive toxicity and 310 with potential ER-mediated toxicity. Among the 473 chemicals not tested with ToxCast assays, deep learning models indicated that 42 chemicals exhibited ER-mediated toxicity. A total of 13 chemicals were identified as causing reproductive toxicity by reacting with the ER. Conclusions: We demonstrated a screening method to identify potential chemicals related to reproductive and ER-mediated toxicities utilizing chemical toxicity big data and deep learning. Integrating toxicity data from in vivo, in vitro, and deep learning models may contribute to screening chemicals in consumer products.