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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.
Lee, Hyo-Jung,Yang, Il-Hyung,Kim, Seong-Kyun,Yeo, In-Sung,Kwon, Taek-Ka Korean Academy of Periodontology 2015 Journal of Periodontal & Implant Science Vol.45 No.3
Purpose: The aim of this study was to investigate the combined effects of physical and chemical surface factors on in vivo bone responses by comparing chemically modified hydrophilic sandblasted, large-grit, acid-etched (modSLA) and anodically oxidized hydrophobic implant surfaces. Methods: Five modSLA implants and five anodized implants were inserted into the tibiae of five New Zealand white rabbits (one implant for each tibia). The characteristics of each surface were determined using field emission scanning electron microscopy, energy dispersive spectroscopy, and confocal laser scanning microscopy before the installation. The experimental animals were sacrificed after 1 week of healing and histologic slides were prepared from the implant-tibial bone blocks removed from the animals. Histomorphometric analyses were performed on the light microscopic images, and bone-to-implant contact (BIC) and bone area (BA) ratios were measured. Nonparametric comparison tests were applied to find any significant differences (P<0.05) between the modSLA and anodized surfaces. Results: The roughness of the anodized surface was $1.22{\pm}0.17{\mu}m$ in Sa, which was within the optimal range of $1.0-2.0{\mu}m$ for a bone response. The modSLA surface was significantly rougher at $2.53{\pm}0.07{\mu}m$ in Sa. However, the modSLA implant had significantly higher BIC than the anodized implant (P=0.02). Furthermore, BA ratios did not significantly differ between the two implants, although the anodized implant had a higher mean value of BA (P>0.05). Conclusions: Within the limitations of this study, the hydrophilicity of the modSLA surface may have a stronger effect on in vivo bone healing than optimal surface roughness and surface chemistry of the anodized surface.
UMONS: Ubiquitous monitoring system in smart space
Hyo-nam Lee,Sung-hwa Lim,Jai-hoon Kim IEEE 2009 IEEE TRANSACTIONS ON CONSUMER ELECTRONICS - Vol.55 No.3
<P>Ubiquitous smart space consists of various ubiquitous objects (devices and applications) and their collaborations that provide convenient and intelligent services for users. Many studies have focused on developing convenient ubiquitous systems and their applications. However, to provide smooth and satisfactory services to users, a ubiquitous system must be aware of the real-time context of its ubiquitous objects and their collaborations during execution. Therefore, monitoring and analyzing must be provided, not only for the status of the functions and performance of individual ubiquitous objects, but also for their collaborative status. This paper discusses the challenges of monitoring systems for ubiquitous smart space, and proposes seven prerequisites for a monitoring system that examines and diagnoses ubiquitous smart space. We also developed a monitoring system for a ubiquitous smart space scenario, to verify our proposal.</P>
Lee, Hyo-Jeong,Jung, Deok-Beom,Sohn, Eun Jung,Kim, Hanna Hyun,Park, Moon Nyeo,Lew, Jae-Hwan,Lee, Seok Geun,Kim, Bonglee,Kim, Sung-Hoon Hindawi Publishing Corporation 2012 Evidence-based Complementary and Alternative Medic Vol.2012 No.-
<P>Although cryptotanshinone (CT) was known to exert antitumor activity in several cancers, its molecular mechanism under hypoxia still remains unclear. Here, the roles of AEG-1 and HIF-1<I><I>α</I></I> in CT-induced antitumor activity were investigated in hypoxic PC-3 cells. CT exerted cytotoxicity against prostate cancer cells and suppressed HIF-1<I><I>α</I></I> accumulation and AEG-1 expression in hypoxic PC-3 cells. Also, AEG-1 was overexpressed in prostate cancer cells. Interestingly, HIF-1<I><I>α</I></I> siRNA transfection enhanced the cleavages of caspase-9,3, and PAPR and decreased expression of Bcl-2 and AEG1 induced by CT in hypoxic PC-3 cells. Of note, DMOG enhanced the stability of AEG-1 and HIF-1<I><I>α</I></I> during hypoxia. Additionally, CT significantly reduced cellular level of VEGF in PC-3 cells and disturbed tube formation of HUVECs. Consistently, ChIP assay revealed that CT inhibited the binding of HIF-1<I><I>α</I></I> to VEGF promoter. Furthermore, CT at 10 mg/kg suppressed the growth of PC-3 cells in BALB/c athymic nude mice by 46.4% compared to untreated control. Consistently, immunohistochemistry revealed decreased expression of Ki-67, CD34, VEGF, carbonic anhydrase IX, and AEG-1 indices in CT-treated group compared to untreated control. Overall, our findings suggest that CT exerts antitumor activity via inhibition of HIF-1<I><I>α</I></I>, AEG1, and VEGF as a potent chemotherapeutic agent.</P>
<i>TP53</i> Mutations in Korean Patients with Non-small Cell Lung Cancer
Lee, Eung Bae,Jin, Guang,Lee, Shin Yup,Park, Ji Young,Kim, Min Jung,Choi, Jin Eun,Jeon, Hyo Sung,Cha, Seung Ick,Cho, Sukki,Kim, Chang Ho,Park, Tae-In,Jung, Tae Hoon,Son, Ji-Woong,Park, Jae Yong The Korean Academy of Medical Sciences 2010 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.25 No.5
<P>Although <I>TP53</I> mutations have been widely studied in lung cancer, the majority of studies have focused on exons 5-8 of the gene. In addition, <I>TP53</I> mutations in Korean patients with lung cancers have not been investigated. We searched for mutations in the entire coding exons, including splice sites of the gene, in Korean patients with non-small cell lung cancer (NSCLC). Mutations of the gene were determined by direct sequencing in 176 NSCLCs. Sixty-nine mutations (62 different mutations) were identified in 65 tumors. Of the 62 mutations, 12 were novel mutations. <I>TP53</I> mutations were more frequent in males, ever-smokers and squamous cell carcinomas than in females, never-smokers and adenocarcinomas, respectively (all comparisons, <I>P</I><0.001). Missense mutations were most common (52.2%), but frameshift, nonsense, and splice-site mutations were frequently observed at frequencies of 18.8%, 15.9% and 10.1%, respectively. Of the 69 mutations, 9 (13.0%) were found in the oligomerization domain. In addition, the proportion of mutations in the oligomerization domain was significantly higher in adenocarcinomas than in squamous cell carcinomas (23.5% vs. 2.9%, <I>P</I>=0.01). Our study provides clinical and molecular characteristics of <I>TP53</I> mutations in Korean patients with NSCLCs.</P>