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.

Two-step resist-development process of hydrogen silsesquioxane for high-density electron-beam nanopatterning

Lee, Hyo-Sung,Wi, Jung-Sub,Nam, Sung-Wook,Kim, Hyun-Mi,Kim, Ki-Bum American Vacuum Society 2009 JOURNAL OF VACUUM SCIENCE & TECHNOLOGY B - Vol.27 No.1

Thyroid dysfunction associated with follicular cell steatosis in obese male mice and humans.

Lee, Min Hee,Lee, Jung Uee,Joung, Kyong Hye,Kim, Yong Kyung,Ryu, Min Jeong,Lee, Seong Eun,Kim, Soung Jung,Chung, Hyo Kyun,Choi, Min Jeong,Chang, Joon Young,Lee, Sang-Hee,Kweon, Gi Ryang,Kim, Hyun Jin The Endocrine Society 2015 Endocrinology Vol.156 No.3

<P>Adult thyroid dysfunction is a common endocrine disorder associated with an increased risk of cardiovascular disease and mortality. A recent epidemiologic study revealed a link between obesity and increased prevalence of hypothyroidism. It is conceivable that excessive adiposity in obesity might lead to expansion of the interfollicular adipose (IFA) depot or steatosis in thyroid follicular cells (thyroid steatosis, TS). In this study, we investigated the morphological and functional changes in thyroid glands of obese humans and animal models, diet-induced obese (DIO), ob/ob, and db/db mice. Expanded IFA depot and TS were observed in obese patients. Furthermore, DIO mice showed increased expression of lipogenesis-regulation genes, such as sterol regulatory element binding protein 1 (SREBP-1), peroxisome proliferator-activated receptor γ (PPARγ), acetyl coenzyme A carboxylase (ACC), and fatty acid synthetase (FASN) in the thyroid gland. Steatosis and ultrastructural changes, including distension of the endoplasmic reticulum (ER) and mitochondrial distortion in thyroid follicular cells, were uniformly observed in DIO mice and genetically obese mouse models, ob/ob and db/db mice. Obese mice displayed a variable degree of primary thyroid hypofunction, which was not corrected by PPARγ agonist administration. We propose that systemically increased adiposity is associated with characteristic IFA depots and TS and may cause or influence the development of primary thyroid failure.</P>

Crystallinity-Controlled Naphthalene-<i>alt</i>-diketopyrrolopyrrole Copolymers for High-Performance Ambipolar Field Effect Transistors

Lee, Hyo-Sang,Lee, Joong Suk,Cho, Sanghyeok,Kim, Hyunjung,Kwak, Kyung-Won,Yoon, Youngwoon,Son, Seon Kyoung,Kim, Honggon,Ko, Min Jae,Lee, Doh-Kwon,Kim, Jin Young,Park, Sungnam,Choi, Dong Hoon,Oh, Se Yo American Chemical Society 2012 The Journal of Physical Chemistry Part C Vol.116 No.50

<P>We report high-performance of ambipolar organic field-effect transistors (FETs) based on the low band gap copolymers of pDPPT2NAP-HD and pDPPT2NAP-OD. The polymers are composed of electron-rich 2,6-di(thienyl)naphthalene (T2NAP) and electron-deficient diketopyrrolopyrrole (DPP) units with branched alkyl chains of 2-hexyldecyl (HD) or 2-octyldodecyl (OD). The polymers were polymerized via Suzuki coupling, yielding optical band gaps of ∼1.4 eV. In the transistor performance test, we observed good ambipolar transport behavior in both polymer films, and pDPPT2NAP-OD displayed hole and electron mobilities 1 order of magnitude higher than the corresponding properties of pDPPT2NAP-HD. Thermal annealing of the polymer films increased the carrier mobilities. Annealing at 150 °C provided optimal conditions yielding saturated film crystallinity and maximized carrier mobility. The highest hole and electron mobilities achieved in these polymers were 1.3 and 0.1 cm<SUP>2</SUP>/(V s), respectively, obtained from pDPPT2NAP-OD. The polymer structure and thermal annealing affected the carrier mobility, and this effect was investigated by fully characterizing the polymer films by grazing incidence X-ray diffraction (GIXD), atomic force microscopy (AFM), and transmission electron microscopy (TEM) experiments. The GIXD data revealed that both polymers formed highly crystalline films with edge-on orientation. pDPPT2NAP-OD, which included longer alkyl chains, showed a higher tendency to form long-range order among the polymer chains. Thermal annealing up to 150 °C improved the polymer film crystallinity and promoted the formation of longer-range lamellar structures. AFM and TEM images of the films were consistent with the GI-XD data. Theoretical calculations of the polymer structures provided a rationale for the relationship between the torsional angle between aromatic rings and the carrier mobility. From the intensive electrical measurements and full characterizations, we find that the chemical structure of polymer backbone and side alkyl chain has a profound effect on film crystallinity, morphology, and transistor properties.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jpccck/2012/jpccck.2012.116.issue-50/jp309213h/production/images/medium/jp-2012-09213h_0011.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jp309213h'>ACS Electronic Supporting Info</A></P>

Late Respiratory Infection after Lung Transplantation

( Sang Young Kim ),( Jung Ar Shin ),( Eun Na Cho ),( Min Kwang Byun ),( Hyung Jung Kim ),( Chul Min Ahn ),( Suk Jin Haam ),( Doo Yun Lee ),( Hyo Chae Paik ),( Yoon Soo Chang ) 대한결핵 및 호흡기학회 2013 Tuberculosis and Respiratory Diseases Vol.74 No.2

Background: Aiming to improve outcome of lung transplantation (LTx) patients, we reviewed risk factors and treatment practices for the LTx recipients who experienced respiratory infection in the late post-LTx period (>1 month after LTx). Methods: We analyzed the clinical data of 48 recipients and donors from 61 LTx, who experienced late respiratory infections. Late respiratory infections were classified according to the etiology, time of occurrence, and frequency of donor-to-host transmission or colonization of the recipient prior to transplantation. Results: During the period of observation, 42 episodes of respiratory infections occurred. The organisms most frequently involved were gram (-) bacteria: Acinetobacter baumannii (n=13, 31.0%), Pseudomonas aeruginosa (n=7, 16.7%), and Klebsiella pneumoniae (n=4, 10.0%). Among the 42 episodes recorded, 14 occurred in the late post-LTx period. These were bacterial (n=6, 42.9%), fungal (n=2, 14.3%), viral (n=4, 28.5%), and mycobacterial (n=2, 14.3%) infections. Of 6 bacterial infections, 2 were from multidrug-resistant (MDR) A. baumannii and one from each of MDR P. aeruginosa, extended spectrum β-lactamase (+) K. pneumoniae, methicillin-resistant Staphylococcus aureus and Streptococcus pneumoniae. Infection-related death occurred in 6 of the 14 episodes (43%). Conclusion: Although the frequency of respiratory infection decreased sharply in the late post-LTx period, respiratory infection was still a major cause of mortality. Gram (-) MDR bacteria were the agents most commonly identified in these infections.

Bone and joint infection as a predictor of community-acquired methicillin-resistant <i>Staphylococcus aureus</i> bacteraemia: a comparative cohort study

Lee, Ju Young,Chong, Yong Pil,Kim, Tark,Hong, Hyo-Lim,Park, Su-Jin,Lee, Eun-Sook,Kim, Mi-Na,Kim, Sung-Han,Lee, Sang-Oh,Choi, Sang-Ho,Woo, Jun Hee,Kim, Yang Soo Oxford University Press 2014 The Journal of antimicrobial chemotherapy Vol.69 No.7

<P><B>Background</B></P><P>A new clone of community-acquired methicillin-resistant <I>Staphylococcus aureus</I> (CA-MRSA), sequence type (ST) 72-staphylococcal chromosomal cassette <I>mec</I> (SCC<I>mec</I>) type IV/IVA without the Panton–Valentine leucocidin (PVL) genes, has been the major clonal type in Korea since 2007. However, there have been no evaluations of the clinical features, risk factors and outcomes associated with CA-MRSA bacteraemia in Korea.</P><P><B>Methods</B></P><P>Adult patients with community-acquired <I>S. aureus</I> bacteraemia (SAB) were enrolled between 1 January 2004 and 31 September 2012. We compared the clinical features and outcomes of CA-MRSA bacteraemia with those of community-acquired methicillin-susceptible <I>S. aureus</I> (CA-MSSA) bacteraemia and evaluated the risk factors for CA-MRSA infection. A microbiological study of the CA-MRSA isolates was also conducted.</P><P><B>Results</B></P><P>In total, 169 patients were included, i.e. 31 (18%) patients with CA-MRSA bacteraemia and 138 (82%) patients with CA-MSSA bacteraemia. Bone and joint infection [45.2% (14/31) versus 22.5% (31/138); adjusted OR, 2.61; 95% CI, 1.09–6.21] was an independent predictor of CA-MRSA bacteraemia. There were no significant differences in relapse of bacteraemia and mortality within 12 weeks after SAB between the two groups. ST72-SCC<I>mec</I> type IV/IVA without the PVL genes was the most common genotype, especially among bone and joint infections (64%, 9/14) as well as among the CA-MRSA isolates (71%, 22/31).</P><P><B>Conclusions</B></P><P>CA-MRSA accounted for 18% of community-acquired SAB and was significantly associated with bone and joint infection. Our study suggests that CA-MRSA should be considered in patients with bone and joint infection and that empirical therapy against MRSA should be included.</P>

Differential protein expression and novel biomarkers related to 5-FU resistance in a 3D colorectal adenocarcinoma model

LEE, SANG-HAK,NAM, JAE KOOK,PARK, JONG-KOOK,LEE, JOO-HO,MIN, DO SIK,KUH, HYO-JEONG Spandidos Publications 2014 ONCOLOGY REPORTS Vol.32 No.4

<P>The multicellular spheroid (MCS) is an in?vitro model which is highly representative of the avascular region of solid tumors by reflecting microenvironmental conditions in?vivo. Hence, it is considered the most appropriate model for studying drug resistance. We compared chemosensitivity to 5-fluorouracil (5-FU) and differential protein expression between the 3D MCS model and the 2D monolayers using DLD-1 cells. We analyzed several significant signaling molecules through western blot analysis. Although various changes in the expression level were observed depending on the samples, we did not obtained remarkable findings. Notably, the level of p-mTOR decreased upon 5-FU exposure in the monolayers, while its level was higher in the MCSs. Nine novel proteins were identified by 2-DE and MALDI-TOF analysis for exhibiting differential expression between the MCS model and the monolayers. Among these, collapsin response mediator protein?2 (CRMP-2), DNA replication complex GINS protein PSF2 (PSF-2) and selenium-binding protein?1 (SBP-1) were notable not only for their differential expression but also for decreased expression following 5-FU exposure, indicating their possible roles as novel biomarkers for sensitivity (CRMP-2, PSF-2) as well as resistance (SBP-1) to 5-FU. Overall, the present study demonstrated greater 5-FU resistance in human colorectal cancer cells grown as MCSs compared to monolayers and identified p-mTOR, CRMP-2, PSF-2 and SBP-1 as novel potential biomarkers of 5-FU chemosensitivity/resistance for human colorectal cancer, findings which warrant further investigation.</P>

<i>Ramlibacter solisilvae</i> sp. nov., isolated from forest soil, and emended description of the genus Ramlibacter

Lee, Hyo Jung,Lee, Se Hee,Lee, Sang-Suk,Lee, Joon Seon,Kim, Yongseong,Kim, Seung-Chul,Jeon, Che Ok International Union of Microbiological Societies 2014 International journal of systematic and evolutiona Vol.64 No.4

<P>A Gram-staining-negative, strictly aerobic, white-colony-forming bacterium, designated strain 5-10<SUP>T</SUP>, was isolated from forest soil of Bac Kan Province in Vietnam. Cells were non-motile rods or coccoids, showing oxidase- and catalase-positive reactions. Growth was observed at 10–37 °C (optimum, 30 °C), at pH 5.0–9.0 (optimum, pH 7.0) and in the presence of 0–1.0 % (w/v) NaCl (optimum, 0–0.5 %). The major cellular fatty acids were summed feature 3 (comprising C<SUB>16 : 1</SUB>ω6<I>c</I> and/or C<SUB>16 : 1</SUB>ω7<I>c</I>), C<SUB>16 : 0</SUB>, C<SUB>10 : 0</SUB> 3-OH and summed feature 8 (comprising C<SUB>18 : 1</SUB>ω6<I>c</I> and/or C<SUB>18 : 1</SUB>ω7<I>c</I>). The G+C content of the genomic DNA was 69.9 mol% and the only respiratory quinone detected was ubiquinone 8 (Q-8). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 5-10<SUP>T</SUP> formed a tight phyletic lineage with members of the genus <I>Ramlibacter</I>. Strain 5-10<SUP>T</SUP> was most closely related to <I>Ramlibacter tataouinensis</I> TTB310<SUP>T</SUP> (97.3 %), but the DNA–DNA relatedness level between the two strains was 38.2±1.8 %. Based on phenotypic, chemotaxonomic and molecular features, strain 5-10<SUP>T</SUP> was shown to represent a novel species of the genus <I>Ramlibacter</I>, for which the name <I>Ramlibacter solisilvae</I> sp. nov. is proposed. The type strain is 5-10<SUP>T</SUP> ( = KACC 17567<SUP>T</SUP> = JCM 19319<SUP>T</SUP>). An emended description of the genus <I>Ramlibacter</I> is also proposed.</P>

Atypical teratoid/rhabdoid tumors: the need for more active therapeutic measures in younger patients.

Lee, Ji Yeoun,Kim, In-Kyeong,Phi, Ji Hoon,Wang, Kyu-Chang,Cho, Byung-Kyu,Park, Sung-Hye,Ahn, Hyo Seop,Kim, Il Han,Kim, Seung-Ki M. Nijhoff ; Kluwer Academic Publishers 2012 Journal of neuro-oncology Vol.107 No.2

<P>Despite active and aggressive therapeutic measures, atypical teratoid/rhabdoid tumors (AT/RTs) are without doubt one of the most malignant brain tumors that occur during childhood. These tumors are more prevalent in children less than 3 years of age, and the prognosis is worse in these young children. Medical records of 14 patients diagnosed at our institution were reviewed. Patients diagnosed with AT/RT at our institution between 1997 and 2009 were identified. Clinical data for those patients with pathologic confirmation of AT/RTs were reviewed regarding surgery, adjuvant treatment, and survival. A total of 14 patients were identified. One patient who died 3 days after initial surgery was excluded, and 13 patients were recruited. Of the 13 patients, 7 were less than 1 year of age, and only 2 were over 3 years of age. Nine patients showed dissemination at diagnosis. Four patients were treated with radiation therapy (RTx), and 2 of these were less than 3 years of age. Ten patients had chemotherapy (CTx), and 3 of these underwent high dose chemotherapy and autologous peripheral blood stem cell transplantation. The median progression-free survival (PFS) was 4 months, and the median overall survival (OS) was 9 months. Univariable analysis revealed age more than 1 year, CTx, and RTx to be significant factors for better PFS and OS. None of the variables were significant in multivariable analysis. Young patients with AT/RT have a bad prognosis. An aggressive therapeutic strategy needs to be profiled for this age group.</P>

Capillary Force-Induced Glue-Free Printing of Ag Nanoparticle Arrays for Highly Sensitive SERS Substrates

Lee, Jaehong,Seo, Jungmok,Kim, Dayeong,Shin, Sera,Lee, Sanggeun,Mahata, Chandreswar,Lee, Hyo-Sung,Min, Byung-Wook,Lee, Taeyoon American Chemical Society 2014 ACS APPLIED MATERIALS & INTERFACES Vol.6 No.12

<P>The fabrication of well-ordered metal nanoparticle structures onto a desired substrate can be effectively applied to several applications. In this work, well-ordered Ag nanoparticle line arrays were printed on the desired substrate without the use of glue materials. The success of the method relies on the assembly of Ag nanoparticles on the anisotropic buckling templates and a special transfer process where a small amount of water rather than glue materials is employed. The anisotropic buckling templates can be made to have various wavelengths by changing the degree of prestrain in the fabrication step. Ag nanoparticles assembled in the trough of the templates via dip coating were successfully transferred to a flat substrate which has hydrophilic surface due to capillary forces of water. The widths of the fabricated Ag nanoparticle line arrays were modulated according to the wavelengths of the templates. As a potential application, the Ag nanoparticle line arrays were used as SERS substrates for various probing molecules, and an excellent surface-enhanced Raman spectroscopy (SERS) performance was achieved with a detection limit of 10<SUP>–12</SUP> M for Rhodamine 6G.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/aamick/2014/aamick.2014.6.issue-12/am5000382/production/images/medium/am-2014-000382_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/am5000382'>ACS Electronic Supporting Info</A></P>