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Novel Methylation Biomarker for Non-invasive Diagnostics in Lung Cancer
오태정,( Chang Hun Lee2 ),( Min Ki Lee ),( Yeul Hong Kim ),( Sang Yull Lee ),( Hyo Sung Jeon ),( Shin Yup Lee ),( Seung Soo Yoo ),( Jae Yong Park ),( Sung Whan An ) 대한결핵 및 호흡기학회 2012 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.114 No.-
To identify aberrantly hypermethylated DNA in lung cancer cells we established a genome-wide analysis for hypermethylation sites, namely Methyl DNA Isolation and Amplification (MeDIA) coupled-CpG microarray analysis. In the comprehensive methyaltion profiling analysis between human lung cancer, A549 cells and normal NHBE cells, we observed that several clusters of genes show a significant level of aberrancy in CpG island methylation pattern in cancer cells compared to normal cells. We further identified PCDHGA12 gene as a new marker of non-invasive diagnostics for lung cancer based on followings. 1) Transcription of PCDHGA12 gene is reactivated after treatment of A549 cells with demethylating agent. 2) Bisulfide clonal-sequencing reveals that CpG island of PCDHGA12 shows a distinctive differential methylation between two cell lines. 3) Pyrosequencing-based quantitative methylation assay for such region in tumor and non-tumorous tissues from lung cancer patients shows aberrant hypermethylation in 37 (92%) of the 40 tumor tissues. In clinical validation by pyrosequencingin induced-sputum of lung cancer patients (n=87) and healthy controls (n=51), we observed aberrant hypermethylation incident at significantly elevated level in samples derived from lung cancer patients. According to the optimal threshold calculated by ROC curve analysis, sensitivity and specificity of PCDHGA12 was 86.2% and 82.4%, respectively. PCDHGA12 methylation status could be a potential methylation biomarker alone or combined with others for the screen and the detection of relapse of lung cancer.
Nursing Effects of Thiols Including Cysteine in Lymph Node Stromal Cells and P388 Cells
Lee, Sang-Han,Ma, Jin-Yeul,Park, Kap-Joo,Kang, Hyunmin,Park, Taekyu,Park, Doo-Sang Korean Society of Life Science 2001 Journal of Life Science Vol.11 No.2
Mouse malignant T-lymphoma CS21 cells can grow when cocultured with CAl2 lymph node stromal cells, but they undergo apoptotic cell death with DNA fragmentation when separated from CA12 stromal cells. In the course of examining the effects of the soluble factor (s) secreted by CAl2 stromal cells on CS2l cell growth, we found that thiols including cysteine promoted CS2l cell growth. P388 cell growth was also promoted by various thiols. These results suggest that thiols including cysteine participate in CA12 and P388 cell growth.
In vitro and vivo assessment of cytochrome P450-mediated herb-drug interaction of Ssang-hwa-tang
( Sang Yoon Lee ),( Ji Yoon Lee ),( Wonku Kang ),( Kwang Il Kwon ),( Soo Jin Oh ),( Jin Yeul Ma ),( Sang Kyum Kim ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0
We have evaluated the herb-drug interaction potential of Ssang-hwa-tang (SHT) mediated by cytochrome P450 (CYP) inhibition/induction. Further, the effects of fermentation on the CYP-mediated herb-drug interaction potential were determined. SHT showed inhibitory activity toward CYP1A2, but not 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4 in human liver microsomes. The results of the enzyme kinetic study suggested that the SHT-induced CYP1A2 inhibition is mixed reversible inhibition. The hepatic CYP expression and activity in rats treated with SHT were examined. The expression/activity of CYP2E1 increased as a result of SHT extract treatment (P<0.005 or P<0.001, respectively), which raises the possibility that SHT may increase the toxicity of environmental toxicants through the elevation of CYP2E1-mediated metabolic activation. SHT fermentation using Lactobacillus fermentum or Lactobacillus gasseri resulted in attenuation of the SHT-induced CYP1A2 inhibition, but not CYP2E1 induction, suggesting that changes in the chemical composition of SHT through fermentation can affect the inhibition of CYP1A2 activity. ⓒ2012 Elsevier Ltd, All rights reserved.ⓒ2012 Elsevier Ltd. All rights reserved.
Lee, Sang-Eok,Lee, Jun-Ho,Ryu, Keun-Won,Nam, Byung-Ho,Cho, Soo-Jeong,Lee, Jong-Yeul,Kim, Chan-Gyoo,Choi, Il-Ju,Kook, Myeong-Cherl,Park, Sook-Ryun,Kim, Young-Woo The Korean Gastric Cancer Association 2012 Journal of gastric cancer Vol.12 No.2
Purpose: The aim of the present study was to assess the association between the pre-operative plasma fibrinogen level and the adjacent organ involvement in advanced gastric cancer. Materials and Methods: A total of 923 pre-operative plasma samples were obtained from 923 patients diagnosed clinically as having advanced gastric cancer, and fibrinogen levels were measured by immunoassay. Associations between fibrinogen levels and clinicopathologic findings (depth of tumor, adjacent organ involvement, and lymph node metastasis), along with survival were examined by univariate and multivariate analyses. Results: Tumor size, tumor depth, and the presence of lymph node metastasis were found to be positively correlated with the preoperative plasma fibrinogen levels (P<0.001). Fifty (5.4%) patients had adjacent organ involvement. Lymphatic invasion (P<0.001), tumor size (P<0.001), clinical T (depth of invasion) stage (P<0.001), and clinical nodal stage (P=0.018) were found to be associated with adjacent organ involvement. Univariate and multivariate regression analyses showed that a preoperatively elevated plasma fibrinogen level was associated with adjacent organ involvement (P<0.001, 0.028), and Kaplan-Meier analysis showed that it was associated with poorer survival (P<0.001). Conclusions: Plasma fibrinogen was found to be a clinically useful marker of adjacent organ involvement and overall survival. When a high fibrinogen level is encountered, preoperatively, adjacent organ involvement should be suspected in clinically advanced gastric cancer.
Lee, Jae-Bok,Woo, Ok Hee,Park, Kyong Hwa,Woo, Sang Uk,Yang, Dae Sik,Kim, Ae-Ree,Lee, Eun Sook,Kim, Yeul Hong,Kim, Jun Suk,Seo, Jae Hong M. Nijhoff ; Kluwer Academic Publishers 2011 Investigational new drugs Vol.29 No.1
<P>Although various new agents have been developed for the treatment of patients with metastatic breast cancer (MBC), overall survival rates have changed little in the last half century. We conducted meta-analysis to verify the clinical efficacy of bevacizumab for the salvage treatment of MBC. Event-based hazard ratios (HR) with 95% confidence intervals (95% CIs) were derived, and a test of heterogeneity was applied. Four studies, with a total of 2,860 patients, met the inclusion criteria for analysis. The pooled results of clinical efficacies were: HR for progression free survival 0.69 (95% CI, 0.58-0.81, z?=?4.54, P?<0.001); HR for overall survival 0.92 (95% CI, 0.82-1.03, z?=1.44, P?=?0.15); and HR for the clinical objective response rate 1.53 (95% CI, 1.37-1.71, z?=?7.37, P?<?0.001). In terms of overall survival, subgroup analysis demonstrated statistically significant improvement for the bevacizumab combination in the initial therapy subgroup (HR, 0.878; 95% CI, 0.771-0.999, z?=?1.98, P?=?0.048). Hypertension and proteinura were more common in the bevacizumab combination arm; however, these toxicities were managed with therapy. In conclusion, meta-analysis suggested benefits of a carefully managed bevacizumab-containing salvage regimen for patients with histologically or cytologically confirmed Her-2 negative MBC who have not received previous cytotoxic therapy. This treatment could improve both progression free survival and overall survival rates.</P>
Influence of planting times on dry matter production and yield of soybean
Sang-Ouk Shin,Hyun-Tae Kim,Tae-Joung Ha,Won-Young Han,Jong-Min Ko,Kyung-Jin Choi,In-Yeul Baek,Keum-Yong Park,Sang-Chul Lee 한국작물학회 2008 한국작물학회 학술발표대회 논문집 Vol.2008 No.10
This experiment was carried out to clear optimum planting time for yield enlargement by comparing yield with dry matter at Miryang from 2005 to 2006. Variety used were Daewon, Daepung, Daol and Cheongja 3. Seeding was performed on April 30 to June 30 with 20day intervals and planting density was 142,857 palnts/ha (70×20㎝, 2plants per hill) with black vinyl mulching. In R2~R4 stages, crop growth rate(CGR) was largest on June 10 seeding. Although net assimilation rate(NAR) increased as seeding date was delayed, NAR on June 10 seeding was the highest throughout the growth period. Positive relationships were observed between NAR from R2 to R4 the ratio of pod to total dry matter weight. The LAI and total dry matter weight at the R4 stage was higher at earlier seeding date. In the case when seeding date was delayed, the ratio of leaf(source) and pod(sink) increased. From the comparison of all factors such as dry weight, optimum LAI, and of source to sink, the optimum planting date for high seed production was June 10. The highest yield was recorded with on June 10 seeding. Also, this seeding date showed high ratio of seed yield to dry matter in R2 stage. Difference between surveyed pod no. and theological pod no. which was calculated by dry matter ratio compared with standard seeding date(June 10) at R2 stage was the smallest in June 10 seeding.
Sang-Ouk Shin,Sea-Gyu Lim,Tae-Joung Ha,Seong-Hyu Shin,Kyung-Jin Choi,In-Yeul Baek,Keum-Yong Park,Sang-Chul Lee 한국작물학회 2008 한국작물학회 학술발표대회 논문집 Vol.2008 No.10
This study was carried out to obtain general agronomic characteristics and identify its relationship with seeding date for high quality soybean seed production. One hundred(100) domestic soybean varieties were used and seeding date were scheduled at April 30 and May 30. This experiment was carried out at YARI, NICE situated at Miryang from 2005 to 2006. Maturity Group(MG) was classified by Kweon et al's method (1974). Correlation analysis of major agronomic characters showed positive relationship between days to flowering and growth days, seed weight and lodging in MG ,seed crack and growth days in Ⅳ~Ⅴ MG0~Ⅲ,seed crack and days to flowering in MGⅣ~Ⅴ and MGⅥ~Ⅶ, seed crack and lodging in MGⅣ~Ⅴ and MGⅥ~Ⅶ, seed crack and seed weight in MGⅣ~Ⅴ and MGⅥ~Ⅶ, purple seed and growth days in MGⅣ~Ⅴ , purple seed and seed weight in MGⅥ~Ⅶ, phomopsis and growth days in MGⅣ~Ⅴ and MGⅥ~Ⅶ, and phomopsis and purple seed in MGⅣ~Ⅴ and MGⅥ~Ⅶ. In contrast, a negative relationship was observed between seed weight and lodging in MG0~Ⅲ. Correlating yield and major characters revealed negative relationship between days to flowering and growth days in MG0~Ⅲ and MGⅣ~Ⅴ, whereas positive relationships were obtained on MGⅥ~Ⅶ seeded on April 30. Lodging, seed weight and seed crack were all negatively correlated with yield in MGⅣ~Ⅴ and MGⅥ~Ⅶ
Classification of maturity group in 100 Korea soybean varieties
Sang-Ouk Shin,Tae-Joung Ha,Seong-Hyu Shin,Sea-Gyu Lim,Kyung-Jin Choi,In-Yeul Baek,Keum-Yong Park,Sang-Chul Lee 한국작물학회 2008 한국작물학회 학술발표대회 논문집 Vol.2008 No.10
This study was carried out to classify Korean soybean varieties based maturity group. One hundred (100) domestic soybean varieties ( 56 for fermentation, 26 for sprouting, 17 for mixed with rice) were used and seeding date was scheduled at April 30. This experiment carried out at Yeongnam Agricultural Research Institute, NICE situated at Miryang from 2005 to 2006. Classification of maturity group in 100 soybeans was followed by Kweon et al's method (1974) The main difference between this experiment and that of Kweon et al's method (1974) were the planting region and planting date. This experiment was conducted on April 30 at Miryang while Kweon et al. was conducted on May 23 in Seoul. Results of maturity grouping of Korean soybean varieties showed that Keunol, which was represented among 3 varieties, belonged to Group 0, Seonnok and Danmi in GroupⅡ, Shinrok in GroupⅢ, Seonyu, represented by 17 cultivars, in GroupⅣ, Taekwang, having 44 cultivars in GroupⅤ, Daewon, represented by 25 cultivars in GroupⅥ, and Kwangdu and Keumdu in GroupⅦ.