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한국여성에서 자궁내막증의 발생위험도와 Estrogen Receptor-α 유전자 다형성과의 관련성에 관한 연구
이사라,허성은,문혜성,김형래,정혜원 이화여자대학교 의과대학 2003 EMJ (Ewha medical journal) Vol.26 No.2
Objectives: To investigate whether polymorphism of gene encoding estrogen receptor-a is asso-ciated with the risk of endometriosis in Korean women. Material and Methods :We investigated 136 patients with histopathologically confirmed endo-metriosis rAFS stage III/IV and 251 control group women who were surgically proven to have no endometriosis. Polymerase chain reaction(PCR) and restriction fragment length polymorphism (RFLP) of PCR products were done to determine each participant's estrogen receptor-a genotype. Results : The distridution according to PvuII genetic polymorphism of estrogen receptor-a were as follows. PP, Pp and pp were 14.7%(20 women), 39.0%(53 women) and 46.3%(63 women) in the study group and 13.9%(35 women), 38.6%(98 women) and 47.4%(119 women) in the con-trol group, respectively. There was no significant difference between the study group and the control group. Conclusion : The results suggest that estrogen receptor-a genetic polymorphism may not be associated with the development of endometriosis in Korean women. 목적: 자궁내막증은 에스트로겐에 의존적인 질환이므로 에스트로겐의 합성, 대사 및 작용에 관여하는 유전자의 다형성이 자궁내막증의 발생기전에 중요한 역할을 할 수 있다. 이에 본 연구에서는 한국인 여성에서 에스트로겐 수용체-a의 유전자 다형성이 자궁내막증의 발생 위험도를 증가시키는 지에 대해 연구하고자 하였다. 방법: 1996년 9월부터 2003년 8월가지 본원 산부인과에서 수술을 통해 병리조직학적으로 자궁내막증 III기와 IV기를 확인한 한국인 여성 136명을 대상으로 하였다. 대조군은 자궁내막증 환자군과 연령이 비슷한 만삭 산모에서 제왕절개술을 시행하거나 양성 난소낭종으로 수술을 시행 하였을 때, 자궁내막증이 없음을 확인한 여성 251명 으로 하였다. 결과: ER-a 유전자의 PvuII 다형성의 분포는 자궁내막증 환자군에서 PP군이 20명(14.7%), Pp군이 53명(39.0%), pp군이 63명(46.3%) 이었고 대조군에서의 분포는 각각 35명(13.9%), 97명(38.7%), 119명(47.4%)으로 나타났으며 자궁내막증 환자군과 대조군 사이의 유의한 차이는 없었다. Pp, pp형을 가지는 경우가 자궁 내막증 환자의 85.3%(116명), 대조군의 86.1%(216명)로 나타났으며, 이 경우 자궁내막증이 발생할 odds ratio가 0.904(95% CI, 0.519~1.702)로 통계적으로 유의한 차이가 없었다. 결론: 이상의 결과로 볼 때, 한국인 여성에서 자궁내막증의 발생위험과 에스트로겐 수용체 a 유전자 다형성간에 연관성은 없는 것으로 나타났다.
( Sung Woo Hong ),( Won Hee Hur ),( Yong Ki Lee ),( Jung Eun Choi ),( Sung Woo Kim ),( Tian Zhu Li ),( Jung Hee Kim ),( Sung Min Kim ),( Eun Byul Lee ),( Seung Kew Yoon ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1
Background: Recent studies have described that cancer stem cell plays a key role radioresistance. The aim of this study is to investigate the molecular and cellular mechanisms of liver cancer stem cell in metastasis after irradiation in HCC. In addition, we found ADAM17 genes associated with liver metastasis that can be used to suppress liver metastasis effectively by molecular regulation. Methods: Both CD133+ and CD133- sorted cells were exposed to γ-irradiation. We investigated the key gene/pathway responsible for metastasis in post-irradiated liver cancer stem cells, CD133+ and CD133- cells using cDNA microarray. Metastatic activities in sorted cells were analyzed by cell migration assay. Also the expressions of the typical genes related metastasis MMP-2 and MMP-9 were also measured by gelatin zymography. Stable cell lines expressing shRNA against human ADAM17 were produced by lentiviral transductions. CD133+ and CD133- cells which were suppressed ADAM17 gene expression were analyzed migration activity. Results: After cDNA microarray analysis, eighty nine metastasis- related genes were up-regulated. Specifically we found that the ADAM17 gene was more increased in CD133+ cells than CD133- cells treated with γ-irradiation. In addition CD133+ cells from radiation exposure were consistently expressed higher levels of vascular endothelial growth factor by ELISA. After irradiation, CD133+ cells migrated more actively, and showed an increased invasion rate compared to CD133- cell. Gelatin zymography showed that MMP-2, -9 proteins expression are significantly higher in CD133+ cells media samples than CD133- cells. Suppression of ADAM17 in CD133+ cells reduced migration activity in treating radiation condition. Conclusions: These results suggest that CD133+ cells have more metastatic capacity than CD133- cells after irradiation. In addition, inhibition of cancer stem cells migration through targeting ADAM17 may be promising the therapeutic against of radiotherapy for HCC.
( Eun Byul Lee ),( Jung Eun Choi ),( Jung Hee Kim ),( Wonhee Hur ),( Tian Zhu Li ),( Sung Woo Kim ),( Sung Woo Hong ),( Young Ki Lee ),( Sung Min Kim ),( Joon Ho Lee ),( Seung Kew Yoon ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1
Background: Hepatitis E virus (HEV) is a hepatotropic virus and has shown the ability of self-assembly through its N-terminally truncated ORF2 (Nt-ORF2). Recently, many researchers have attempted to use the virus like particles (VLPs) as a gene delivery vehicle. In this study, we established the liver specific delivery system using HEV-LP produced in Huh7 cells by recombinant baculovirus expression system. Methods: To produce HEV-LP in mammalian cells, the recombinant baculovirus containing the CMV promoter derived Nt-ORF2 gene was generated in the insect cells, Sf21. Subsequently, the baculovirus was used to infect into the human hepatoma cell line, Huh7 cells. The expression of Nt-ORF2 in Huh7 cells was confirmed by western blot analysis. In addition, the formation of HEV-LP particle was observed by electron microscopy. Next, to determine the liver-specific entrance of HEV-LP, FITC-conjugated HEV-LP infected into the cancer cell lines derived from various organs. After infection, the fluorescence existed in infected cells was detected by confocal microscopy. Results: Nt-ORF2 was highly expressed in Huh7 cells infected with recombinant baculoviruses. Nt-ORF2 expressed in the cells showed the ability of self-assembly and release from the cells. The HEV-LPs produced from Huh7 cells was observed 25 nm in diameter. Furthermore, HEV-LP could enter into the hepatoma cell lines within 4 hr post-infection. Conclusions: These results suggest that HEV-LP was efficiently produced and infected in hepatoma cells and established HEV-LP system could be used as the valuable liver specific transporter to deliver the therapeutic agents.
( Sung Eun Hur ),( Ji Young Lee ),( Hye Sung Moon ),( Hye Won Chung ) 대한산부인과학회 2008 Journal of Womens Medicine Vol.1 No.1
Objective: To investigate the expression of vascular endothelial growth factors (VEGFs) and VEGF receptor 1 and 2 in eutopic endometrium of patients with advanced endometriosis and to understand the role of VEGFs and VEGF receptors in the development of endometriosis. Methods: Endometrial samples were obtained from 65 premenopausal women, 29~44 years of age, undergoing laparoscopic surgery or hysterectomy for non-malignant lesions. Sufficient samples were collected from 33 patients with endometriosis (stages III or IV) and 32 controls without endometriosis, as confirmed by laparoscopic surgery. Expression of VEGFs mRNA and protein and their receptors in the eutopic endometrium were analyzed by RT-QC PCR and Western blotting. The quantitative expression of VEGF-A, -B, and -C in eutopic endometrium from patients with endometriosis was examined throughout the menstrual cycle, and was compared to eutopic endometrial expression in control patients without endometriosis. Results: VEGF-A expression in healthy controls was lower in the secretory phase than in the proliferative phase. In patients with endometriosis, VEGF-A expression was not lower in the secretory phase than in the proliferative phase and was higher than in the secretory phase of healthy controls. The expression of VEGF-B and -C was similar to VEGF-A. The mRNA of VEGF receptors 1 and 2 was expressed at the same level in eutopic endometrium from patients with endometriosis and in healthy controls throughout the menstrual cycle. All eutopic endometrial samples from women with and without endometriosis in both the proliferative and secretory phases of the menstrual cycle showed clear bands at the expected molecular weights for VEGF-A and -B. Conclusions: These results suggest that specific angiogenic factors (VEGF-A, -B, and -C) play important roles in the pathogenesis of endometriosis.
해독화 효소 유전자 (GSTM1, GSTT1 and CYP1A1) 다형성과 한국인 여성의 자궁내막증의 연관성에 관한 연구
심성신 ( Sung Shin Shim ),허성은 ( Sung Eun Hur ),이경순 ( Kyung Soon Lee ),문혜성 ( Hye Sung Moon ),안정자 ( Jung Ja Ahn ),유한기 ( Han Ki Yu ),김형래 ( Hyung Rae Kim ),정혜원 ( Hye Won Chung ) 대한산부인과학회 2003 Obstetrics & Gynecology Science Vol.46 No.2
목적 : 한국인 여성에 있어 자궁내막증의 감수성을 예측하는데 유전자의 다형성이 관련되어 있는지를 알아보기 위하여 CYP1A1, GSTT1과 GSTM1의 유전자형을 분석하였다. 연구 방법 : 이화여자대학교 산부인과를 방문한 Ⅲ, Ⅳ기의 자궁내막증 환자 74명과 자궁내막증이 없는 환자 93명을 대조군으로 하여 각각의 유전자형을 PCR 등을 이용해서 분석하였다. 결과 : 1. CYP1A1 MspI 다형성에서 wt/wt은 대조군에서 45.1%, 자궁내막증 환자 Objective : Enzymes belonging to the Glutathione S transferase and cytochrome P450 families are involved in the two-stage detoxification process of a number of pro-carcinogens. We genotyped each 74 women with moderate or severe endometriosis and a control
허성은 ( Sung Eun Hur ),정혜원 ( Hye Won Chung ) 대한폐경학회 2003 대한폐경학회지 Vol.9 No.3
요골 말단 부위의 골밀도는 Colles` fracture를 예견하는데 도움이 되며, 다른 axial bone보다 변형이 덜 일어나고 axial bone과의 상관 관계도 비교적 높게 나타나는 부위이면서 손쉽게 측정을 할 수 있다는 장점을 가지고 있다. 본 연구에서는 한국 여성에서 요골 말단 부위의 골밀도를 측정하여, 각 연령군의 골밀도 값과 연령에 따른 관계를 조사하여 다음과 같은 결과를 얻었다. 1. 한국 여성의 요골 말단부위의 골밀도는 40-49세 사이에서 가장 높게 나타났다. 2. 한국 여성의 요골 말단부위의 골밀도는 연령이 증가함에 따라 50세 까지는 골밀도가 약간 증가하거나 유지되는 정도으 기울기를 가지고 있고, 50세 이후부터는 현저히 감소되는 양상이 보인다. 3. 폐경 전의 요골 말단부위의 골밀도는 년간 0.75% 즉, 10년간 7.5%의 골밀도의 증가를 보여주었고, 폐경 후의 요골 말단부위의 골밀도는 10년간 15.9%의 감소를 보여주어 폐경 후 골밀도의 감소가 증가하였다. 4. 요골 말단 부위의 골밀도를 연령별과 더불어 신장과, 체중 그리고, 연령과 BMI와의 상관 관계를 다중회귀 분석 하였을 때 신장보다는 연령과 체중이 골밀도에 미치는 영향이 크게 나타났다. 결론적으로 요골말단 부위의 골밀도는 폐경을 전후로 연령과의 상관관계가 다르게 나타났으며 비교적 이동이 간편하며 측정이 용이하여 지역사회 폐경여성의 골다공증 유병을 연구에 활용할 수 있을 것으로 사료된다. Objective : The objective of this study was to clarify the age related difference in bone mineral densitv(BMD) of distal forearm in Korean women. Method: Distal forearm BMD were measured by dual energy X-ray absorptiometry in women who visited Ewha Woman`s Universtiy Mock-dong Hospital. The mean age, height and weight were measured, and there was no statistically significant difference in the group of aged over 50 years old and group of aged under 50 years old. Results: The relationship between age and distal forearm BMD is different before and after the age of around 50 years. For the persons of under 50 years of age, BMD slightly increased with age. In contrast, after the 50 years old, BMD steeply decreased with age. The mean age, height and weight and there was no statistically significant difference in the group of aged over 50 years old and group of aged under 50 years old. Conclusion: The BMDs of over 50 years old age group were decreased with age compared to the group of age under the 50 years olds.