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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.
Morin Protects Acute Liver Damage by Carbon Tetrachloride ($CCl_4$) in Rat
Lee, Hee-Seung,Jung, Kyung-Hee,Hong, Sang-Won,Park, In-Sub,Lee, Chong-Mu,Han, Hyo-Kyung,Lee, Don-Haeng,Hong, Soon-Sun 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.9
The purpose of this study was to investigate possible beneficial effects of morin on $CCl_4$-induced acute hepatotoxicity in rats. Rats received a single dose of $CCl_4$ ($150{\mu}L$/100 g 1:1 in corn oil). Morin treatment (20 mg/kg) was given at 48, 24, and 2 h before $CCl_4$ administration. $CCl_4$ challenge elevated serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) levels, but these effects were prevented by the pretreatment of rats with morin. To identify the mechanism of protective activity of morin in $CCl_4$-induced hepatotoxicity in rats, we investigated expressions of tumor necrosis factor alpha (TNF-$\alpha$), interleukin-$1{\beta}$ (IL-$1{\beta}$), interleukin-6 (IL-6), and inducible nitric oxide (iNOS). The expressions of TNF-$\alpha$, IL-$1{\beta}$, IL-6, and iNOS were increased by $CCl_4$ treatment and increased expressions of those were decreased by morin. These findings suggest that morin prevents acute liver damage by inhibiting the production of TNF-$\alpha$, IL-$1{\beta}$, IL-6, and iNOS.
Reduced Mitochondrial Properties in Putative Progenitor/Stem Cells of Human Keratinocytes
( Sung Eun Chang ),( Young Mi Kim Pak ),( Hae Woong Lee ),( Jee Ho Choi ),( Eun Jeong Jeong ),( Seung Ho Choi ),( Hyo Won Chang ),( Yoo Sam Chung ),( Sang Yoon Kim ) 대한피부과학회 2009 Annals of Dermatology Vol.21 No.4
Background: The characterization of progenitor/keratinocyte stem cells (KSC) remains an unachieved goal. A previous study showed that rapid adhering cells to collagen IV had the characteristics of putative progenitor/KSCs. Objective: The purpose of this study was to investigate the genetic expression of rapid adhering cells compared to non adhering cells to determine the characteristic of KSCs. Methods: We isolated rapid adhering cells representative of KSCs from non adhering cells representative of transient amplifying cells. In addition, we differentiated cells from human tonsilar keratinocytes utilizing the adhering capability of the KSCs to collagen IV. Annealing control primer based differentially displayed polymerase chain reaction (PCR) was performed as well as Western blot analysis. Results: The levels of mitochondria- related gene expression were low in the rapid adhering cells compared to the non adhering cells. Mitochondrial complex I, COX IV, peroxiredoxins (I, II and IV) and mitochondrial membrane potential were all low in the rapid adhering cells compared to the non adhering cells. Conclusion: Using an adhesion method on human collagen IV-coated plates, our results suggest that reduced mitochondrial function may be an important characteristic of KSCs. (Ann Dermatol 21(4) 364~368, 2009)
Lee, Do-Nam,Park, Hee-Sang,Kim, Eun-Hwa,Jun, Young-Moo,Lee, Ja-Young,Lee, Won-Yong,Kim, Byeong-Hyo Korean Chemical Society 2006 Bulletin of the Korean Chemical Society Vol.27 No.1
Polyamine dendrimers functionalized with electrochemiluminescent (ECL) polypyridyl Ru(II) complexes, dend-$[CO-(CH_2)_3-mbpy{\cdot}Ru(L)_2]_3(PF_6)_6$ (dend: N$(CH_2CH_2NH)_3$-, L: bpy, o-phen, phen-Cl, DTDP), were synthesized through the complexation of dendritic polypyridyl ligands to Ru(II) complexes. Their electrochemical redox potentials, photoluminescence (PL), and relative ECL intensities were studied. The ECL emissions produced by the reaction between the electro-oxidized $Ru^{3+}$ species of polyamine dendrimers and tripropylamine as a coreactant were measured in a static system with potential cycles between 0.8 and 1.3 V or through flow injection analysis with a potential of +1.3 V, and were compared to that of $[Ru(o-phen)_3](PF_6)_2{\cdot}Dend-[CO-(CH_2)_3-mbpy{\cdot}Ru(bpy)_2]_3(PF_6)_6$ showed an ECL intensity that was two-fold greater than that of the reference complex $[Ru(o-phen)_3](PF_6)_2$.
Synthesis of Obovatol Derivatives and Their Preliminary Evaluation as Antitumor Agents
Lee, Mi-Sung,Yang, Jung-Eun,Choi, Eun-Hwa,In, Jin-Kyung,Lee, So-Yong,Lee, Hee-Soon,Hong, Jin-Tae,Lee, Hyo-Won,Suh, Young-Ger,Jung, Jae-Kyung Korean Chemical Society 2007 Bulletin of the Korean Chemical Society Vol.28 No.9
Lee, Jeong-Mi,Choi, Ji-Yoon,Kim, Jong-Moon,Lee, Sang-Yong,Lee, Hyo-Sun,Kim, Seog-K.,Cho, Tae-Sub Korean Chemical Society 2007 Bulletin of the Korean Chemical Society Vol.28 No.6
The spectral properties, namely the circular dichroism, electric absorption and luminescence properties, of Λ- and Δ-[Ru(II)(1,10-phenanthroline)2benzodipyrido[b:3,2-h:2',3'-j]phenazine]2+ ([Ru(phen)2BDPPZ]2+) in the presence and absence of single stranded poly(dA) and poly(dT) were compared in this work. In the presence of single stranded DNAs, hypochromism in the absorption spectrum and significant changes in the circular dichroism spectrum in the ligand absorption band were apparent, indicating the strong interaction of the [Ru(phen)2BDPPZ]2+ complex with the single stranded DNAs. The luminescence intensity of the Ru(II) complex decreased stoichiometrically with increasing concentrations of the single stranded DNAs. All of these spectral changes were independent of the configuration of the Ru(II) complex and the nature of the DNA bases. Therefore, it is conceivable that both enantiomers of the [Ru(phen)2BDPPZ]2+ complex interact electrostatically with the negatively charged phosphate groups of DNA. However, the spectral properties of [Ru(II)(1,10-phenanthroline)3]2+ were not altered even in the presence of single stranded DNAs. Therefore, the size of the ligand involved in the interaction of the metal complex with the phosphate group of DNA may play an important role, even when the nature of the interaction is electrostatic.
Lee, Hae-Kyung,Choi, Myung-Gil,Yu, Hyo-Yeon,Ahn, Sang-Doo,Chang, Suk-Kyu Korean Chemical Society 2010 Bulletin of the Korean Chemical Society Vol.31 No.12
Selective mercuration at the 1,6-positions of 2-hydroxy derivative of Nile Red and its application towards $Hg^{2+}$-selective signaling was investigated. The 2-hydroxy Nile Red exhibited a selective UV-vis absorption and fluorescent signaling behavior towards $Hg^{2+}$ ions over common coexisting physiologically important metal ions in aqueous environment. $^1H$ NMR studies revealed that the mercuration was selectively effected at the 1,6-positions of 2-hydroxy Nile Red, which is quite different from that at the 6,8-positions for the parent Nile Red.
S-29 : Peritoneal Mesothelioma Detected on Follow-up of Endoscopic Resection for Colon Cancer
( Hyo Deok Lee ),( Joung Ho Han ),( Sung Soo Koong ),( Hye Suk Han ),( Sung Nam Lim ) 대한내과학회 2013 대한내과학회 추계학술대회 Vol.2013 No.1
A 72-year-old male was transferred for colonic polypectomy. He had a history of nephrectomy for cancer of left kidney 17 years ago and resection for squamous cell carcinoma on the left middle finger a year ago. Resected colon polyp confirmed the presence of moderately differentiated adenocarcinoma, with Haggitt level 3, submucosal invasion depth of 0.8 mm. So, we decided scheduled follow up without additional surgery. 4 months later, a 2.0 cm sized nodule with peripheral enhancing pattern at the recto-vesical pouch was observed on the abdomen and pelvic CT scan. PET-CT scan showed irregular shaped small soft tissue lesions with focal FDG uptake (SUVmax=3.8) at the recto-vesical pouch. Early stage colorectal cancer shows a low recurrence and metastasis rates; moreover recto-vesical pouch is not sentinel lymph nodes of sigmoid colon cancer. So our multidisciplinary care team cannot exclude other primary neoplasm. And then laparoscopic biopsy was performed at department of surgery. Grossly, white protruded multiple peritoneal and omental nodules were detected during the laparoscopy and pathologic findings of peritoneal nodules differed completely from colonic adenocarcinoma that previously diagnosed. Conclusively, a diagnosis of primary malignant peritoneal mesothelioma was made based on immunohistochemical staining. We suggest that histological confirmation should be considered when newly appeared intra-peritoneal nodule detected on follow up period of early stage colorectal cancer surveillance, due to possibility of other primary neoplasm.