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- 저자 : (Yhun Y . Sheen) (검색결과 177 건)
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Mechanism of Action of Estrogen
Sheen, Yhun-Yhong 한국생화학분자생물학회 1990 생화학분자생물학회 소식 Vol.10 No.4
In order to understand the complex of the biology governed by estrogen, the physicochemical properties of estrogen receptor, cDNA cloning of estrogen receptor, estrogen receptor interaction with estrogen responsive element, and estrogen regulation of gene expression were discussed in this review.
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HDAC inhibitors regulate CYP3A4 gene expression in Hepatic cells
Yhun, Yhong Sheen...et al. 이화여자대학교 약학연구소 2003 藥學硏究論文集 Vol.- No.13
Cytochrome P450 3A4 (CYP3A4) is the most abundant CYPs in human liver, comprising approximately 30% of the total liver CYPs contents and is involved in the metabolism of more than 60% of currently used therapeutic drugs. The expression of CYP3A4 is induced by a variety of structurally unrelated xenobiotics including the antibiotic rifampicin and endogenous hormones, and might be mediated through steroid and xenobiotic receptor (SXR) system. The molecular mechanisms underlying regulation of CYP3A4 gene expression have not been understood. In order to gain the insight of the molecular mechanism of CYP3A4 gene expression, study has been undertaken to investigate if the histone deacetylation is involved in the regulation of CYP3A4 gene expression by proximal promoter or not. Also SXR was investigated to see if they were involved in the regulation of CYP3A4 proximal promoter activity. HepG2 or Hepa-I cells were transfected with a plasmid containing ∼1kb of the CYP3A4 proximal promoter region (863 to +64 bp) cloned in front of a reporter gene, luciferase, in the presence or absence of SXR or hERa. Transfected cells were treated with CYP3A4 inducers such as rifampicin, PCN and RU 486, or with estradiol, in order to examine the regulation of CYP3A4 gene expression in the presence or absence of trichostatin A (TSA). In HepG2 cells, CYP3A4 inducers and estradiol increased significantly the luciferase activity by CYP3A4 proximal promoter, only when TSA was co-treated after SXR cotransfection. In the case of Hepa-I cells, CYP3A4 inducers and estradiol increased modestly the luciferase activity when TSA was co-treated, but this incresment was not enhanced by SXR cotransfection in contrast to HepG2 cells. Taken together, these results indicated that the inhibition of histone deacetylation was required to SXR-mediated increase in CYP3A4 proximal promoter region when rifampicin, or PCN was treated. Further a transactivation by SXR may demand other species-specific transcription factors.
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Melphalan Modulates the Expression of E7 Specific Biomarkers in E7-Tg Mice
SHEEN, YHUN YHONG,KIM, EUN JIN,KIM, HEE JONG,LEE, SO JUNG,KANG, JEONG WOO,LEE, DONG HUN,CHOI, HEE SOOK,KIM, JIN MAN,YANG, YOUNG,PARK, SUE NIE,YOON, DO YOUNG 梨花女子大學校 藥學硏究所 2011 藥學硏究論文集 Vol.- No.21
HPV oncoproteins are selectively retained and expressed in HPV infected carcinoma cells. The E7 oncoprotein interacts with the tumour suppressor Rb, and leads to the progression of oncogenesis. In a previous study, E7 biomarkers were identified in E7 Tg mice. In this study, in order to investigate whether a genotoxic carcinogen would modulate carcinogenesis in the E7-Tg mice, an anticancer drug, melphalan, was intraperitoneally injected into E7-Tg mice for eight weeks at two-day intervals and then genes and proteins were analysed using Omics approaches and RT-qPCR. RT-qPCR was performed to confirm whether E7 biomarkers would be modulated by melphalan treatment in E7-Tg mice, revealing that up-regulated E7 markers such as cyclin B1, CD166, and actin alpha1 were down-regulated, whereas expression of down-regulated E7 markers such as vimentin was restored by melphalan treatment. These results suggest that melphalan inhibits carcinogenesis via modulating E7-specific genes and proteins expressed in the lung tissues of E7 Tg mice.
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Sheen, Yhun-Y.,Kim, Sun-S.,Yun, Hea-C. The Pharmaceutical Society of Korea 1993 Archives of Pharmacal Research Vol.16 No.4
This study has been undertaken to examine the effect of 3-methylcholanthrene (3MC) on rat uterine growth and to understand the mechanism of action of 3MC in rat uterus. After diethylstilbesterol(DES) or tamoxifen(TAM) or 3MC or DES plus TAM or DES plus 3MC was administered into immature female rats, uterine weight over corn oil-treated uteri. 3MC treatment had no effect on uterine weight but, DES stimulated uterine weight was inhibited by 3MC concomitant tratment. While TAM alone treatment showed slight increase in uterine wieght, inhibited uterine growth simulated by DES when it was adiministrated with DES condirect binding assay with $[^3H]$ estradiol and the relative binding affinities of 3MC and TAM were estimated by competetion assy. Estradiol tumed out to have high affinity for rat uterine estrogen receptor (kd = 0.4 nM). The relative binding affinities of TAM and 3MC were 1% and 4.7% that of DES for rat uterine estrogen receptor, respectively. 3MC was shown to have similar affinity for eat uterine estrogen receptor to that of TAM. Effects of DES 3MC and TAM administration in vivo on rat uterine estrogen recptor level were examined. It was confirmed that the estrogen, DES and antiestrogen, TAM decreased estrogen receptor levels from rat ulterus and also 3MC decreased rat uterine estrogen receptor level when rats were treated with DES, TAM and 3MC in vivo. Data indicates that 3MC acts as an antiestrogen mediated through estrogen receptor system.
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Sheen, Yhun Y.,Kim, Sun S.,Yun Hea C. 梨花女子大學校 藥學硏究所 1994 藥學硏究論文集 Vol.- No.4
This study has been undertaken to examine the effect of 3-methylcholanthrene (3MC) on rat uterine growth and to understand the mechanism of action of 3MC in rat uterus. After diethylstilbesterol(DES) or tamoxifen(TAM) or 3MC or DES plus TAM or DES plus 3MC was administered into immature female rats, uterine weight of each group was measured. DES treatment resulted in 4-fold increase in uterine weight over corn oil-treated uteri. 3MC treatment had no effect on uterine weight but, DES stimulated uterine weight was inhibited by 3MC concomitant treatment While TAM alone treatment showed slight increase in uterine weight, inhibited uterine growth stimulated by DES when it was administrated with DES concomitantly. Affinity of estradiol for estrogen receptor in the rat uterus was detemined via direct binding assay with 〔^3H〕estradiol and the relative binding affinities of 3MC and TAM were estimated by competetion assay. Estradiol turned out to have high affinity for rat uterine estrogen receptor (Kd = 0.4 nM). The relative binding affinities of TAM and 3MC were 1% and 4.7% that of DES for rat uterine estrogen receptor, respectively. 3MC was shown to have similar affinity for rat uterine estrogen receptor to that of TAM. Effects of DES, 3MC and TAM administration in vivo on rat uterine estrogen receptor level were examined. It was confirmed that the estrogen, DES and antiestrogen, TAM decreased estrogen receptor levels from rat uterus and also 3MC decreased rat uterine estrogen receptor level when rats were treated with DES, TAM and 3MC in vivo. Data indicates that 3MC acts as an antiestrogen mediated through estrogen receptor system.
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EW-7195, a novel inhibitor of ALKS kinase inhibits EMT and breast cancer metastasis to lung
Yhun Yhong, Sheen,Chul-Yong, Park,Jee-Yeon, Son,Cheng Hua, Jin,Jeong-Suk, Nam,Dae-Kee, Kim 梨花女子大學校 藥學硏究所 2012 藥學硏究論文集 Vol.- No.22
Recently, researchers are actively pursuing efforts to develop potent and selective ALK5 (TβRI) kinase inhibitors for clinical development. In this study, the authors examined a novel small molecule inhibitor of ALK5, 3-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methylamino)benzonitrile (EW-7195) to determine if it has potential for cancer treatment. The inhibitory effects of EW-7195 on TGF-β-induced Smad signaling and epithelial-to-mesenchymal transition (EMT) were investigated in mammary epithelial cells using luciferase reporter assays, immunoblotting, confocal microscopy and wound healing assays. In addition, the suppressive effects of EW-7195 on mammary cancer metastasis to lung were examined using a Balb/c xenograft and MMTV/cNeu transgenic mice model system. The novel ALK5 inhibitor, EW-7195, inhibited the TGF-β(1)-stimulated transcriptional activations of p3TP-Lux and pCAGA(12)-Luc. In addition, EW-7195 decreased phosphorylated Smad2 levels and the nuclear translocation of Smad2 increased by TGF-β(1). In addition, EW-7195 inhibited TGF-β(1)-induced EMT and wound healing of NMuMG cells. Furthermore, in xenografted Balb/c and MMTV/cNeu mice, EW-7195 inhibited metastasis to lung from breast tumours. The novel ALK5 inhibitor, EW-7195, efficiently inhibited TGF-β(1)-induced Smad signaling, EMT and breast tumour metastasis to the lung in vivo, demonstrating that EW-7195 has therapeutic potential for the breast cancer metastasis to the lung.
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Yhun Yhang, Sheen,Minjung, Cho,Wan-Seob, Cho,Mina, Choi,Sueng Jun, Kim,Beam Seak, Han,Sheen Hee, Kim,Hyoung Oak, Kim,Ja Young, Jeong 이화여자대학교 약학연구소 2010 藥學硏究論文集 Vol.- No.20
Many approaches for the application of nano-sized particles to the human body as nanotechnology have been recently developed. The size of nanoparticles is related to their useful character and also plays a key role in toxicity. Since this surface area can interact with biological components of cells, nanoparticles can be more reactive in than larger particles. In the present study, a fluorescence dye-labeled 50, 100 and 200 nm-sized silica particle suspension was intravenously injected into mice to identify the toxicity, tissue distribution and excretion of silica nanoparticles in vivo. Incidence and severity of inflammatory response was transiently increased with injection of 200 and 100 nm silica nanoparticles within 12h. But there was no significant response related to injection of 50 nm particles. The silica particles of 50, 100 and 200 nm were cleared via urine and bile. The 50 nm silica anoparticles cleared to urine and bile than 100 nm and particles of 200 nm existed at lower concentration than other two smaller particles in urine and feces. Silica nanoparticles were trapped by macrophages in the spleen and liver and remained there until 4 weeks after the single injection.
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Sheen, Yhun Y.,Kim, Sun S.,Yun, Hea C. 이화여자대학교 생명과학연구소 1993 생명과학연구논문집 Vol.4 No.-
This stydy has been undertaken to examine the effect of 3-methylcholanthrene (3MC) on rat uterine growth and to undertstand the mechanism of action of 3MC in rat uterus. After diethylstilbesterol(DES) or tamoxifen(TAM) or 3MC or DES plus TAM or DES plus 3MC was administered into immature female rats, uterine weight of each group was measured. DES treatment resulted in 4-fold increase in uterine weight over com oil-treated uteri. 3MC treatment had no effect on uterine weight but, DES stimulated uterine weight was inhibited by 3MC concomitant treatment. While TAM alone treatment showed slight increase in uterine weight, inhibited uterine growth stimulated by DES when it was administrated with DES concomitantly. Affinity of estradiol for estrogen receptor in the rat uterus was determined via direct binding assay with [^3H]estradiol and the relative binding affinities of 3MC and TAM were estimated by competetion assay. Estradiol tumed out to have high affinity for rat uterine estrogen receptor (Kd=0.4nM). The relative binding affinities of TAM and 3MC were 1% and 4.7% that of DES for rat uterine estrogen receptor, respectively. 3MC was shown to have similar affinity for rat uterine estrogen receptor to that of TAM. Effects of DES, 3MC and TAM administration in vivo on rat uterine estrogen receptor level were examined. It was confirmed that the estrogen, DES and antiestrogen, TAM decreased estrogen receptor levels from rat uterus and also 3MC decreased rat uterine estrogen receptor level when rats were treated with DES, TAM and 3MC in vivo. Data indicates that 3MC acts as an antiestrogen mediated through estrogen receptor system.
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