Diagnostic usefulness of a T cell-based assay for latent tuberculosis infection in kidney transplant candidates before transplantation

Kim, S.-H.,Lee, S.-O.,Park, I.-A.,Park, S.J.,Choi, S.-H.,Kim, Y.S.,Woo, J.H.,Park, S.-K.,Park, J.S.,Kim, S.C.,Han, D.J. Blackwell Publishing Inc 2010 Transplant infectious disease Vol.12 No.2

<P>S.-H. Kim, S.-O. Lee, I.-A. Park, S.J. Park, S.-H. Choi, Y.S. Kim, J.H. Woo, S.-K. Park, J.S. Park, S.C. Kim, D.J. Han. Diagnostic usefulness of a T cell-based assay for latent tuberculosis infection in kidney transplant candidates before transplantation.Transpl Infect Dis 2010: <B>12:</B> 113–119. All rights reserved</P><P>Background</P><P>The presence of latent tuberculosis (TB) infection (LTBI) should be evaluated before kidney transplantation. Although a new T cell-based assay for diagnosing LTBI gave promising results, this assay has not yet been compared with the tuberculin skin test (TST) for diagnosing LTBI in renal transplant candidates before transplantation.</P><P>Patients and methods</P><P>All adult patients admitted to a single institute for renal transplantation over a 1-year period were prospectively enrolled. A clinically predictive risk of LTBI was defined as: (i) recent close contact with a person with pulmonary TB; (ii) abnormal chest radiography; (iii) a history of untreated or inadequately treated TB; or (iv) a new infection (i.e., a recent conversion of TST).</P><P>Results</P><P>Of 209 renal recipients, 47 (22%) had a positive TST≥5 mm, 21 (10%) had a positive TST≥10 mm, 65 (30%) had a positive T-SPOT.<I>TB</I> test, and 25 (12%) had an indeterminate T-SPOT.<I>TB</I> test. The induration size of TST was significantly associated with a high positivity rate on T-SPOT.<I>TB</I> (<I>P</I><0.001). Agreement between T-SPOT.<I>TB</I> test and TST≥10 mm was fair (<I>k</I>=0.24, 95% confidence interval 0.11–0.36). However, neither univariate nor multivariate analysis showed any association between the clinical risk for LTBI and positivity on T-SPOT.<I>TB</I> or TST.</P><P>Conclusion</P><P>T-SPOT.<I>TB</I> test was more frequently positive than TST in renal transplant candidates. However, further longitudinal studies are awaited to determine whether the ability of T-SPOT.<I>TB</I> assay to detect LTBI in renal transplant recipients can better predict the development of TB than can TST after transplantation.</P>

ZNF509S1 downregulates PUMA by inhibiting p53K382 acetylation and p53-DNA binding

Jeon, B.N.,Yoon, J.H.,Han, D.,Kim, M.K.,Kim, Y.,Choi, S.H.,Song, J.,Kim, K.S.,Kim, K.,Hur, M.W. Elsevier Science 2017 Biochimica et biophysica acta. Gene regulatory mec Vol.1860 No.9

Expression of the POK family protein ZNF509L, and -its S1 isoform, is induced by p53 upon exposure to genotoxic stress. Due to alternative splicing of the ZNF509 primary transcript, ZNF509S1 lacks the 6 zinc-fingers and C-terminus of ZNF509L, resulting in only one zinc-finger. ZNF509L and -S1 inhibit cell proliferation by activating p21/CDKN1A and RB transcription, respectively. When cells are exposed to severe DNA damage, p53 activates PUMA (p53-upregulated modulator of apoptosis) transcription. Interestingly, apoptosis due to transcriptional activation of PUMA by p53 is attenuated by ZNF509S1. Thus we investigated the molecular mechanism(s) underlying the transcriptional attenuation and anti-apoptotic effects of ZNF509S1. We show that ZNF509S1 modulation of p53 activity is important in PUMA gene transcription by modulating post-translational modification of p53 by p300. ZNF509S1 directly interacts with p53 and inhibits p300-mediated acetylation of p53 lysine K382, with deacetylation of p53 K382 leading to decreased DNA binding at the p53 response element 1 of the PUMA promoter. ZNF509S1 may play a role not only in cell cycle arrest, by activating RB expression, but also in rescuing cells from apoptotic death by repressing PUMA expression in cells exposed to severe DNA damage.

Phase II study of S-1 combined with oxaliplatin as therapy for patients with metastatic biliary tract cancer: influence of the <i>CYP2A6</i> polymorphism on pharmacokinetics and clinical activity

Kim, K-p,Jang, G,Hong, Y S,Lim, H-S,Bae, K-s,Kim, H-S,Lee, S S,Shin, J-G,Lee, J-L,Ryu, M-H,Chang, H-M,Kang, Y-K,Kim, T W Nature Publishing Group 2011 The British journal of cancer Vol.104 No.4

<P><B>Background:</B></P><P>Advanced biliary cancer is often treated with fluoropyrimidine-based chemotherapy. In this study, we evaluated the efficacy and tolerability of a combination of S-1, an oral fluoropyrimidine prodrug, and oxaliplatin in patients with metastatic biliary cancer.</P><P><B>Methods:</B></P><P>Patients with histologically confirmed metastatic biliary cancer and no history of radiotherapy or chemotherapy were enrolled. Oxaliplatin was administered intravenously (130 mg m<SUP>−2</SUP>), followed by 14-day administration of oral S-1 (40 mg m<SUP>−2</SUP> twice daily) with a subsequent 7-day rest period every 21 days. Pharmacokinetic analysis of S-1 was performed at cycle 1. Patients were genotyped for <I>CYP2A6</I> polymorphisms (<SUP>*</SUP>1, <SUP>*</SUP>4, <SUP>*</SUP>7, <SUP>*</SUP>9 or <SUP>*</SUP>10), and pharmacokinetic and clinical parameters compared according to the <I>CYP2A6</I> genotype.</P><P><B>Results:</B></P><P>In total, 49 patients were evaluated, who received a median of four cycles. The overall response rate was 24.5%. Median progression-free and overall survival was 3.7 and 8.7 months, respectively. The most common haematological grade 3 out of 4 toxicity was neutropenia (14%), while non-hematological grade 3 out of 4 toxicities included anorexia (14%), nausea (12%), asthenia (10%), vomiting (10%), and diarrhoea (4%). Biotransformation of S-1 (AUC<SUB>0−24 h</SUB> of 5-fluorouracil/AUC<SUB>0−24 h</SUB> of tegafur) was 1.85-fold higher for the <I>*1/*1</I> group than for the other groups (90% confidence interval 1.37–2.49). Diarrhoea (<I>P</I>=0.0740), neutropenia (<I>P</I>=0.396), and clinical efficacy (response rate, <I>P</I>=0.583; PFS, <I>P</I>=0.916) were not significantly associated with <I>CYP2A6</I> genotype, despite differences in 5-FU exposure.</P><P><B>Conclusion:</B></P><P>The combination of S-1 and oxaliplatin appears to be active and well tolerated in patients with metastatic biliary cancer, and thus is feasible as a therapeutic modality. <I>CYP2A6</I> genotypes are associated with differences in the biotransformation of S-1. However, the impact of the <I>CYP2A6</I> polymorphism on variations in clinical efficacy or toxicity requires further evaluation.</P>

Inflammatory lipid sphingosine-1-phosphate upregulates C-reactive protein via C/EBPβ and potentiates breast cancer progression

Kim, E-S,Cha, Y,Ham, M,Jung, J,Kim, S G,Hwang, S,Kleemann, R,Moon, A Macmillan Publishers Limited 2014 Oncogene Vol.33 No.27

A crucial role of the inflammatory lipid sphingosine-1-phosphate (S1P) in breast cancer aggressiveness has been reported. Recent clinical studies have suggested that C-reactive protein (CRP) has a role in breast cancer development. However, limited information is available on the molecular basis for the expression of CRP and its functional significance in breast cell invasion. The present study aimed to elucidate the molecular link between S1P and CRP during the invasive process of breast epithelial cells. This is the first report showing that transcription of CRP was markedly activated by S1P in breast cells. Our data suggest that not only S1P treatment but also the endogenously produced S1P may upregulate CRP in breast carcinoma cells. Transcription factors CCAAT/enhancer-binding protein beta and c-fos were required for S1P-induced CRP expression. Coupling of S1P<SUB>3</SUB> to heterotrimeric G<SUB>αq</SUB> triggered the expression of CRP, utilizing signaling pathways involving reactive oxygen species (ROS), Ca<SUP>2+</SUP> and extracellular signal-related kinases (ERKs). S1P-induced CRP expression was crucial for the transcriptional activation of matrix metalloproteinase-9 through ERKs, ROS and c-fos, leading to breast cell invasion. Using a xenograft mice tumor model, we demonstrated that S1P induced CRP expression both in vitro and in vivo. Taken together, our findings have revealed a molecular basis for S1P-induced transcriptional activation of CRP and its functional significance in the acquisition of the invasive phenotype of human breast epithelial cells under inflammatory conditions. Our findings may provide useful information on the identification of useful therapeutic targets for inflammatory breast cancer.

Optimal Dietary Ratio of Spray Dried Plasma Protein (SDPP) and Dried Porcine Solubles (DPS) in Improving Growth Performance and Immune Status in Pigs Weaned at 21 Days of Age

Kim, J.D.,Hyun, Y.,Sohn, K.S.,Kim, T.J.,Woo, H.J.,Han, In K. Asian Australasian Association of Animal Productio 2001 Animal Bioscience Vol.14 No.3

An experiment was conducted to determine the optimal inclusion ratio of spray dried plasma protein (SDPP) and dried porcine solubles (DPS) for maximizing growth and improving immunity in weaned pigs. One hundred-fifty male (barrow) pigs were allotted in a completely randomized block design. Treatments were as follows: 1) control (6% SDPP), 2) S6D6 (6% SDPP+6% DPS), 3) S6D3 (6% SDPP+3% DPS), 4) S3D6 (3% SDPP+6% DPS) and 5) S3D3 (3% SDPP+3% DPS). Each treatment has 6 replicates with 5 pigs per replicate. Average daily gain (ADG) and average daily feed intake (ADFI) were highest, but not significantly different when pigs were fed a diet contained 6% SDPP and DPS from d 0 to 7 after weaning. Pigs fed the S6D3 diet showed better weight gain and feed intake than other treatments, especially compared with pigs fed S3D6 diet (p<0.05) from d 8 to 21 after weaning. For the overall experimental period, pigs fed the S6D3 diet showed the best improvement in ADG and ADFI. The digestibilities of dry matter (DM) and crude protein (CP) were higher in pigs fed the S6D6 diet than other diets from d 0 to 7 after weaning. However, pigs fed S6D3 diet showed higher DM, CP and essential amino acids (except methionine and arginine) digestibilities than pigs fed other diets from d 8 to 21 after weaning, although there was no significant difference. From d 8 to 21 after weaning, threonine, valine, isoleucine and leucine digestibilites were higher in S6D6 group, and phenyalanine, histidine, lysine and arginine digestibility were higher in S6D3 group than other groups. The ratio of CD4 and CD8 positive lymphocytes during the overall experimental period was independent of the ratio of SDPP and DPS. However, CD4+:CD8+ ratio was numerically lowered in pigs fed diet the S6D3 diet. Therefore, the present study suggests that an optimal inclusion ratio for maximizing growth performance and maintaining low immune status is 6% of SDPP and 3% of DPS in weaned pigs.

Production of (S)-3-hydroxybutyrate by metabolically engineered Saccharomyces cerevisiae

Yun, E.J.,Kwak, S.,Kim, S.R.,Park, Y.C.,Jin, Y.S.,Kim, K.H. Elsevier Science Publishers 2015 Journal of biotechnology Vol.209 No.-

(S)-3-Hydroxybutyrate (S-3HB) can be used as a precursor for the synthesis of biodegradable polymers such as polyhydroxyalkanoate and stereo-specific fine chemicals such as antibiotics, pheromones, and drugs. For the production of S-3HB in yeast, the biosynthetic pathway of S-3HB from acetyl-CoA, consisting of the three enzymes, acetyl-CoA C-acetyltransferase (ACCT), acetoacetyl-CoA reductase (ACR), and 3-hydroxybutyryl-CoA thioesterase (HBT), was introduced into Saccharomyces cerevisiae. An engineered yeast strain overexpressing ERG10, hbd, and tesB genes not only exhibited enzyme activities of AACT, ACR, and HBT, but also produced S-3HB from ethanol. In order to increase the titer of S-3HB, a fed-batch fermentation based on pulse feeding of ethanol as a carbon source was performed, and a final S-3HB titer of 12.0g/L was achieved. This is the first report on the production of 3HB by engineered yeast, utilizing ethanol as the carbon source, suggesting that the industrially preferred S. cerevisiae can be a promising host for producing S-3HB.

Reply to ''Comment on ''Facile chemical bath deposition of CuS nano peas like structure as a high efficient counter electrode for quantum-dot-sensitized solar cells'' by H.-J. Kim, J.-H. Kim, CH. S. S. Pavan Kumar, D. Punnoose, S.-K. Kim, C. V. V. M. Gop

Kim, H.J.,Kim, J.H.,Pavan Kumar, C.H.S.S.,Punnoose, D.,Kim, S.K.,Gopi, C.V.V.M.,Rao, S.S. Elsevier Sequoia 2015 Journal of Electroanalytical Chemistry Vol.756 No.-

<i>S100A9</i> and <i>EGFR</i> gene signatures predict disease progression in muscle invasive bladder cancer patients after chemotherapy

Kim, W. T.,Kim, J.,Yan, C.,Jeong, P.,Choi, S. Y.,Lee, O. J.,Chae, Y. B.,Yun, S. J.,Lee, S. C.,Kim, W. J. Oxford University Press 2014 Annals of Oncology Vol.25 No.5

<P>In our previous gene expression profile analysis, IL1B, S100A8, S100A9, and EGFR were shown to be important mediators of muscle invasive bladder cancer (MIBC) progression. The aim of the present study was to investigate the ability of these gene signatures to predict disease progression after chemotherapy in patients with locally recurrent or metastatic MIBC. Patients with locally advanced MIBC who received chemotherapy were enrolled. The expression signatures of four genes were measured and carried out further functional analysis to confirm our findings. Two of the four genes, S100A9 and EGFR, were determined to significantly influence disease progression (P = 0.023, 0.045, respectively). Based on a receiver operating characteristic curve, a cut-off value for disease progression was determined. Patients with the good-prognostic signature group had a significantly longer time to progression and cancer-specific survival time than those with the poor-prognostic signature group (P < 0.001, 0.042, respectively). In the multivariate Cox regression analysis, gene signature was the only factor that significantly influenced disease progression [hazard ratio: 4.726, confidence interval: 1.623-13.763, P = 0.004]. In immunohistochemical analysis, S100A9 and EGFR positivity were associated with disease progression after chemotherapy. Protein expression of S100A9/EGFR showed modest correlation with gene expression of S100A9/EGFR (r = 0.395, P = 0.014 and r = 0.453, P = 0.004). Our functional analysis provided the evidence demonstrating that expression of S100A9 and EGFR closely associated chemoresistance, and that inhibition of S100A9 and EGFR may sensitize bladder tumor cells to the cisplatin-based chemotherapy. The S100A9/EGFR level is a novel prognostic marker to predict the chemoresponsiveness of patients with locally recurrent or metastatic MIBC.</P>

Spitz naevus is rare in Korea

Kim, Y. C.,Do, J. E.,Bang, D.,Cho, B. K.,Cho, K. H.,Choi, J. C.,Kim, M. B.,Kim, M. H.,Kim, S. Y.,Kim, S. N.,Lee, J. H.,Lee, S. J.,Shin, D. H.,Shin, J. H.,Son, S. J.,Suh, K. S.,Yoon, T. Y.,Park, C. K. Blackwell Publishing Ltd 2010 Clinical and experimental dermatology Vol.35 No.2

<P>Summary</P><P>Background. </P><P>Spitz naevi have not been widely studied in Asians.</P><P>Aim. </P><P>To compare the epidemiology and clinicopathological features of Spitz naevi in Koreans with lesions in western countries.</P><P>Methods. </P><P>In total, 80 Spitz naevi in 77 patients diagnosed over 10 years at 17 university hospitals in Korea were analysed.</P><P>Results. </P><P>The relative incidence of Spitz naevus vs. MM was 1 vs. 10.9. In most patients (75%) the Spitz naevi had been present for > 6 months. The size of the lesion was relatively large. Histologically, most of the lesions (54%) were the dermal type and pigmentation was common (49% of lesions). Immunohistochemical study found that all of the 34 lesions were positive for S-100 protein but only 14 (47%) were positive for HMB-45.</P><P>Conclusion. </P><P>Spitz naevus is rare in Korea. The lesions were more commonly larger, pigmented, and of the dermal type than reported in western countries.</P>

Status of the KSTAR superconducting magnet system development

Kim, K.,Park, H.K.,Park, K.R.,Lim, B.S.,Lee, S.I.,Chu, Y.,Chung, W.H.,Oh, Y.K.,Baek, S.H.,Lee, S.J.,Yonekawa, H.,Kim, J.S.,Kim, C.S.,Choi, J.Y.,Chang, Y.B.,Park, S.H.,Kim, D.J.,Song, N.H.,Kim, K.P.,So International Atomic Energy Agency 2005 Nuclear fusion Vol.45 No.8

<P>The aim of the Korea superconducting tokamak advanced research (KSTAR) project is to develop a steady-state-capable advanced superconducting tokamak for establishing a scientific and technological basis for an attractive fusion reactor. Since the KSTAR mission includes the achievement of a steady-state-capable operation, the use of superconducting coils is an obvious choice for the magnet system. The KSTAR superconducting magnet system consists of 16 toroidal field (TF) and 14 poloidal field (PF) coils which include 8 central solenoid coils. Both the TF and PF coil systems use internally-cooled cable-in-conduit conductors (CICC). The TF coil system provides a magnetic field of 3.5 T at the plasma centre and the PF coil system provide a flux swing of 17 V s. The major achievement in the KSTAR magnet system development includes the development of CICC, a full size TF model coil, a background magnetic field generation coil system and the construction of a large scale superconducting magnet and the CICC test facility. TF and PF coils are at the stage of fabrication for the KSTAR completion in the year 2007.</P>