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( Sol Lee ),( Miyoung Nam ),( Ah-reum Lee ),( Jaewoong Lee ),( Jihye Woo ),( Nam Sook Kang ),( Anand Balupuri ),( Minho Lee ),( Seon-young Kim ),( Hyunju Ro ),( Youn-woong Choi ),( Dong-uk Kim ),( Kwa 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.2
We used a heterozygous gene deletion library of fission yeasts comprising all essential and non-essential genes for a microarray screening of target genes of the antifungal terbinafine, which inhibits ergosterol synthesis via the Erg1 enzyme. We identified 14 heterozygous strains corresponding to 10 non-essential [7 ribosomal-protein (RP) coding genes, spt7, spt20, and elp2] and 4 essential genes (tif302, rpl2501, rpl31, and erg1). Expectedly, their erg1 mRNA and protein levels had decreased compared to the control strain SP286. When we studied the action mechanism of the non-essential target genes using cognate haploid deletion strains, knockout of SAGA-subunit genes caused a down-regulation in erg1 transcription compared to the control strain ED668. However, knockout of RP genes conferred no susceptibility to ergosterol-targeting antifungals. Surprisingly, the RP genes participated in the erg1 transcription as components of repressor complexes as observed in a comparison analysis of the experimental ratio of erg1 mRNA. To understand the action mechanism of the interaction between the drug and the novel essential target genes, we performed isobologram assays with terbinafine and econazole (or cycloheximide). Terbinafine susceptibility of the tif302 heterozygous strain was attributed to both decreased erg1 mRNA levels and inhibition of translation. Moreover, Tif302 was required for efficacy of both terbinafine and cycloheximide. Based on a molecular modeling analysis, terbinafine could directly bind to Tif302 in yeasts, suggesting Tif302 as a potential off-target of terbinafine. In conclusion, this genome-wide screening system can be harnessed for the identification and characterization of target genes under any condition of interest.
마우스 대장암 모델 구축 및 항암제 활성 평가를 위한 예비 연구
김예솔,강봉석,이상은,이은주,이경록,정상헌,박정숙 충남대학교 약학대학 의약품개발연구소 2014 藥學論文集 Vol.29 No.-
Abstract – Aberrant crypt foci (ACF) are early imorphological changes observed in rodents after administration of colon-specific carcinogen such as azoxymethane (AOM). ACF are considered to be putative preneoplastic lesions and are widely used as a surrogate biomarker to rapidly evaluate chemopreventive potential of compounds. The size of colorectal cancer was evaluated after administration of three anticancer drugs, 1 parent drug and 2 prodrugs. The body weights of mice were measured daily and considered as a surrogate for evaluation of general wellbeing. Colons were removed, cut along the longitudinal axis and flushed with phosphate-buffered saline. Each colon was cut into three equal lengths and fixed flat between filter papers. The fixed colon sections were stained with methylene blue. The number of ACF per colon, the number of aberrant crypts observed in each focus and the location of each focus were recorded. After single administration of AOM and multiple doses of anticancer drugs, no significant changes in the body weights of the mice was observed which was recorded for 52 days. However, an expected ACF was not observed in any treated groups. These findings suggest the induction of ACF in mice requires the promotion by dextran sulfate sodium as well as the initiation by AOM.
Sol Ji Ahn,Chang Ik Yoon,Pill Sun Paik,Tae-Kyung Yoo,Namsun Park,Eun Sook Lee,Jung Eun Choi,Joon Jeong,Hyun Jo Youn,Woo-Chan Park 대한외과학회 2021 Annals of Surgical Treatment and Research(ASRT) Vol.101 No.6
Purpose: This study was performed to identify the risk of mortality in patients diagnosed with human epidermal growth factor receptor 2 (HER2)-positive ductal carcinoma in situ (DCIS). Methods: We selected 2,592 patients with HER2-positive DCIS from Korean Breast Cancer Society (KBCS) database between January 1997 and December 2019. Patients who received neoadjuvant chemotherapy were excluded. Logistic regression analysis was used to determine the association between clinical factors and overall death after adjusting for tumor and clinical characteristics. Mortality data were modified using the Statistics Korea data. Results: Thirty deaths (1.2%) were identified out of 2,592 patients in the KBCS database. In the univariate logistic regression analysis, older age, higher body mass index (BMI), type of breast surgery (mastectomy), estrogen receptor-negative, progesterone receptor-negative, and exposure to endocrine therapy were significant clinical factors associated with death. In the multivariate analysis, age (hazard ratio [HR], 1.062; 95% confidence interval [CI], 1.015–1.111; P = 0.006), BMI (HR, 1.179; 95% CI, 1.032–1.347, P = 0.016), breast surgery type (mastectomy vs. lumpectomy; HR, 0.285; 95% CI, 0.096–0.844; P = 0.024), and endocrine therapy (HR, 0.314; 95% CI, 0.099–0.995; P = 0.049) were significant risk factors for mortality. Conclusion: Advanced age, higher BMI, mastectomy, and the absence of endocrine therapy were factors associated with poor survival of patients with HER2-positive DCIS. This finding requires further validation combined with additional analysis of large databases.
이솔(Sol Lee),이윤복(Yoon bok Lee),김향숙(Hyang Sook Kim) 한국식품영양과학회 2013 한국식품영양과학회지 Vol.42 No.8
본 연구는 검정콩 2호, 대원콩, 선흑콩, 소명콩, 신팔달콩 2호, 진품콩 2호, 태광콩, 푸른콩에 대해 이화학적 특성과 기능성 성분에 대한 기초 자료를 얻기 위하여 실시하였다. 일반성분 분석 결과, 수분함량은 5.50~6.16% 범위였고, 조단백 함량은 40% 내외로 시료 간 큰 차이는 없었다. 조지방 함량은 푸른콩, 대원콩, 소명콩 및 검정콩 2호가 20% 내외로 비교적 높은 편이었고, 진품, 선흑, 신팔달콩 2호, 태광콩는 15% 내외로 비교적 낮은 편이었다. 회분 함량은 4.89~5.86%로 나타내어 품종 간의 큰 차이를 보이지 않고, 탄수화물 함량은 26.20~35.45%로 분포하였다. 무기질의 함량에서 콩나물용 칼슘 함량은 소명콩이 406.36 mg/100 g으로 가장 높았고, 마그네슘 함량은 신팔달 2호가 247.79 mg/100 g으로 가장 높았다. 이에 반해 진품콩은 칼슘이 199.51mg/100 g으로 가장 낮았고, 선흑콩은 가장 낮은 마그네슘함량(90.03 mg/100 g)을 나타냈다. 총 이소플라본 함량은97.54~402.00 mg/100 g으로 품종 간 차이를 보였다. 시료중 가장 높은 함량을 나타낸 것은 콩나물용 소명콩이었고, 가장 낮은 함량을 나타낸 것은 밥밑용 선흑콩이었다. 총 올리고당 함량은 5.84~9.35 mg/100 g이었다. 총 올리고당 중 sucrose의 함량이 약 50% 정도로 나타났다. Raffinose는 0.52~0.81 mg/100 g으로 함량이 나타났고, stachyose의 함량은 2.05~3.45 mg/100 g으로 나타났다. Bracassisterol, campesterol, stigmasterol, β-sitosterol을 분석한 것으로 β-sitosterol이 평균적으로 식물성 sterol의 50%를 차지하였고, 그 다음으로 campesterol, stigmasterol 순서였으며 bracassisterol은 소량이 분석되었다. Phytic acid 함량은 신팔달콩 2호와 진품콩 2호가 0.86%, 1.65%로 이를 제외한 시료들은 약 2% 정도를 함유한 것으로 분석되었다. 식이섬유소 함량은 24.20~29.20% 범위로 나타났다. The objective of this study was to analyze the general and functional components of various soybeans, used for producing soy sauce, tofu, bean sprouts, and for cooking with rice. The moisture, crude protein, crude fat, and ash content of soybeans were in the ranges of 5.50~6.16%, 38.49~41.08%, 14.89~21.89%, and 4.89~5.86%, respectively. Mineral and functional components varied by sample and showed no relationship with usage type. Somyeong for bean sprouts had the highest level of Ca (406.36 mg/100 g), and Sinpaldal for soy sauce and tofu had the highest level of Mg (247.79 mg/100 g). However, Jinpum No. 2 for soy sauce and tofu had the lowest level of Ca (199.51 mg/100 g), and Seonhuk had the lowest level of Mg (90.03 mg/100 g) among the soybeans tested. The isoflavone content in soybeans was in the range of 97.54~402.00 mg/100 g. Somyeong for bean sprouts had the highest level and Seonheuk for cooking with rice had the lowest level. Total oligosaccharides were in the range of 5,838.52~9,345.90 μg/100 g. Sucrose content was approximately 50% of total oligosaccharides in all samples. Raffinose content was 516.28~806.95 μg/100 g, and stachyose content was 2,047.13~3,454.10 μg/100 g. Phytosterols including bracassisterol, campesterol, stigmasterol, and β-sitosterol ranged from 19.25~35.34 mg/100 g. β-sitosterol represented 50% of total phytosterols in almost all samples, followed by campesterol, stigmasterol and bracassisterol. The phytic acid content in soybeans tested was around 2%, except for Sinpaldal No. 2 and Jinpum No. 2 at 0.86% and 1.65%, respectively. The dietary fiber of soybeans was in the ranges of 24.20%~29.20%.