<i>CYP2A6</i> and <i>ERCC1</i> polymorphisms correlate with efficacy of S-1 plus cisplatin in metastatic gastric cancer patients

Park, S R,Kong, S-Y,Nam, B-H,Choi, I J,Kim, C G,Lee, J Y,Cho, S J,Kim, Y W,Ryu, K W,Lee, J H,Rhee, J,Park, Y-I,Kim, N K Nature Publishing Group 2011 The British journal of cancer Vol.104 No.7

<P><B>Background:</B></P><P>We evaluated the association between polymorphisms of cytochrome P450 2A6 (<I>CYP2A6</I>)/excision repair cross-complementation group 1 (<I>ERCC1</I>)/X-ray repair cross-complementing group 1(<I>XRCC1</I>) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin.</P><P><B>Methods:</B></P><P>Among MGC patients (<I>n</I>=108), who received S-1 (40 mg m<SUP>−2</SUP> b.i.d., days 1–14) and cisplatin (60 mg m<SUP>−2</SUP>, day 1) every 3 weeks, we analysed the wild-type allele (<I>W</I>) and variants (<I>V</I>) of <I>CYP2A6</I> (<I>*4</I>, <I>*7, *9, *10</I>), and the polymorphisms of <I>ERCC1</I> (rs11615, rs3212986) and <I>XRCC1</I> (rs25487).</P><P><B>Results:</B></P><P>Patients having fewer <I>CYP2A6</I> variants had better response rates (<I>W</I>/<I>W vs W</I>/<I>V</I> other than <I>*1/*4 vs V</I>/<I>V</I> or <I>*1/*4</I>=66.7 <I>vs</I> 58.3 <I>vs</I> 32.3% <I>P</I>=0.008), time to progression (TTP) (7.2 <I>vs</I> 6.1 <I>vs</I> 3.5 months, <I>P</I>=0.021), and overall survival (23.2 <I>vs</I> 15.4 <I>vs</I> 12.0 months, <I>P</I>=0.004). <I>ERCC1 19442C</I>><I>A</I> (rs3212986) was also associated with response rate (<I>C/C</I>, 46.7% <I>vs C/A</I>, 55.3% <I>vs A/A</I>, 87.5%) (<I>P</I>=0.048) and TTP (4.4 <I>vs</I> 7.6 <I>vs</I> 7.9 months) (<I>P</I>=0.012). Patients carrying both risk genotypes of <I>CYP2A6</I> (<I>V</I>/<I>V</I> or <I>1/*4</I>) and <I>ERCC1 19442C</I>><I>A</I> (<I>C/C</I>) <I>vs</I> those carrying none showed an adjusted odds ratio of 0.113 (<I>P</I>=0.004) for response, and adjusted hazard ratios of 3.748 (<I>P</I>=0.0001) for TTP and 2.961 (<I>P</I>=0.006) for death.</P><P><B>Conclusion:</B></P><P>Polymorphisms of <I>CYP2A6</I> and <I>ERCC1 19442C</I>><I>A</I> correlated with the efficacy of S-1/cisplatin.</P>

Adenosine triphosphate-based chemotherapy response assay-guided chemotherapy in unresectable colorectal liver metastasis

Hur, H,Kim, N K,Kim, H G,Min, B S,Lee, K Y,Shin, S J,Cheon, J H,Choi, S H Nature Publishing Group 2012 The British journal of cancer Vol.106 No.1

<P><B>Background:</B></P><P>This study aims to evaluate the effectiveness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided neoadjuvant chemotherapy for increasing resectability in patients with unresectable colorectal liver metastasis.</P><P><B>Patients and methods:</B></P><P>Patients were randomised into two groups: Group A was treated by conventional chemotherapy regimen and Group B was treated by chemotherapy regimen according to the ATP-CRA. Three chemotherapeutic agents (5-fluorouracil, oxaliplatin and irinotecan) were tested by ATP-CRA and more sensitive agents were selected. Either FOLFOX or FOLFIRI was administered. Between Group A and B, treatment response and resectability were compared.</P><P><B>Results:</B></P><P>Between November 2008 and October 2010, a total 63 patients were randomised to Group A (<I>N</I>=32) or Group B (<I>N</I>=31). FOLFOX was more preferred in Group A than in Group B (26 out of 32 (81.3%) <I>vs</I> 20 out of 31 (64.5%)). Group B showed better treatment response than Group A (48.4% <I>vs</I> 21.9%, <I>P</I>=0.027). The resectability of hepatic lesion was higher in Group B (35.5% <I>vs</I> 12.5%, <I>P</I>=0.032). Mean duration from chemotherapy onset to the time of liver resection was 11 cycles (range 4–12) in Group A and 8 cycles (range 8–16) in Group B.</P><P><B>Conclusion:</B></P><P>This study showed that tailored-chemotherapy based on ATP-CRA could improve the treatment response and resectability in initially unresectable colorectal liver metastasis.</P>

한국의 HIV-1 감염의 분자역학

이주실,김은영,남정구,기미경,최병선,김성순,강춘,구본기,신영오 국립보건연구원 1998 국립보건원보 Vol.35 No.-

한국인 Long Term Non Progressors로부터 분리된 HIV-1 env 및 nef 유전자와 이들의 면역 유전학적 특성 분석에 의한 질병진전 요인 규명

이주실,강춘,김성순,박근용,고운영,기미경,최병선,남정구,서순덕,이성래,구본기,박혜경,도경미,김태규,최희백,조현일,김요숙,김지영,이해정,안수진 국립보건연구원 1999 국립보건원보 Vol.36 No.-

국내 HIV/AIDS 발견이후 HIV 유행주의 분자역학적 변이 분석

이주실,김성순,남정구,전수경,변승옥,최병선,박미선,김옥진,서순덕 국립보건연구원 2000 국립보건원보 Vol.37 No.-

Clinical and histopathological study of Charcot-Marie-Tooth neuropathy with a novel S90W mutation in BSCL2.

Choi, B-O,Park, M-H,Chung, K W,Woo, H-M,Koo, H,Chung, H-K,Choi, K-G,Park, K D,Lee, H J,Hyun, Y S,Koo, S K Oxford University Press 2013 Neurogenetics Vol.14 No.1

<P>The objective of the study was to investigate the disease-causing mutation in an autosomal dominant Charcot-Marie-Tooth disease type 2 family and examine the clinical and histopathological evaluation. We enrolled a family of Korean origin with axonal Charcot-Marie-Tooth disease neuropathy (FC305; 13 males, six females) and applied genome-wide linkage analysis. Whole exome sequencing was performed for two patients. In addition, sural nerve biopsies were obtained from two patients. Through whole exome sequencing, we identified an average of 20,336 coding variants from two patients. We also found evidence of linkage mapped to chromosome 11p11-11q13.3 (LOD score of 3.6). Among these variants in the linkage region, we detected a novel p.S90W mutation in the Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene, after filtering 31 Korean control exomes. Our p.S90W patients had frequent sensory disturbances, pyramidal tract signs, and predominant right thenar muscle atrophy in comparison with reported p.S90L patients. The phenotypic spectra were wide and demonstrated intrafamilial variability. Two patients with different clinical features underwent sural nerve biopsies; the myelinated fiber densities were increased slightly in both patients, which differed from two previous case reports of BSCL2 mutations (p.S90L and p.N88S). This report expands the variability of the clinical spectrum associated with the BSCL2 gene and describes the first family with the p.S90W mutation.</P>

S-BRT 운행행태를 고려한 저상버스의 정차시간 예측모형

신소명,이수범,김영찬,박신형,유연승,최정훈,Shin, S.M.,Lee, S.B.,Kim, Y.C.,Park, S.H.,Yu, Y.S.,Choi, J.H. 한국안전학회 2021 한국안전학회지 Vol.36 No.1

This basic study introduces the concept of S-BRT and develops dwell time estimation models that consider road geometry and S-BRT characteristics for a signal operation strategy to meet the S-BRT's operational goal of high speed and punctuality. Field surveys of low-floor buses similar in shape to S-BRTs and data collection of passengers, station elements, vehicle elements, and other factors that can affect stop times were used in a regression analysis to establish statistically significant dwell time estimation models. These dwell time estimation models are developed by categorizing according to the locations of the signal or sidewalk that have the most impact on the dwell time. In this way, the number of people boarding and alighting the bus at the crowded door and the number of people boarding and alighting the bus at the front door considering the internal congestion was analyzed to affect the dwell time. The estimation dwell time models in this study can be used in the establishment of strategies that provide priority signals to S-BRTs.

Role of the Meckel’s Cartilage in Embryonic Mandibular Development of Mice

J. W Choi,S. B Han,J. H Sung,H. I Shin 대한구강악안면병리학회 2005 대한구강악안면병리학회지 Vol.29 No.5

Mecke!'s car t ilage is one of the ea rliest structu re to appear in a mandible derived from the lï rst branchi a l a rch and serves as the primorclium I"or the formation 01‘ mandible‘ mall eus. incus. and sphenomandibular li gament However. its direct role a nd the mechanism in mandibular clevelopment a re not well elucidated. 1'0 address t his Issue‘ we observed morphol ogical and histological changes and gene expression patterns in the Mecke!'s cart ilage 01" a cleveloping mouse. I"rom E13.5 to E18.5 embryos. using skeletal preparation samples a ncl routinely prepa red s lide secti ons for light mi croscopic observation in various sectional planes. The following methods were per |‘ ormecl : H&E staining I"or general hi st이 og i cal observation ‘ Von Kossafor detection of minerali zation. TRAP activ ity staining for locali zaLion 01’ osteoclastic cell s. immunohistochemistry for !Iα@-1 a ncl -9 forevaluati on of enzy matic activity 01" osteoclasLic cell s. a ncl in situ hybricli zation for detection of collagen type 1. Il. ancl X mRNA ex presslon‘ respecLively. AL E1 3.5 Mec kel's cartilage appeared as a V-shaped rod fused a t the micl line and thin minera li zed ma ndibular buccal plaLe was I"ormed lateral to. and at some clistance from. Meckel’s carti lage in an intramembranous ossi lïcation mocle. WiLh the progression of tooth development. t he Meckel’s in carti lage adjacent incisors revealecl hyperLrophi c chonclrocyte di ff"er entiation with minerali zation of the chondroid matrix. The Meckel’s car Li lage was replacecl with bone by o~ L eoc l asLs . showing strong immunoreact ivity for MMP- l ancl -9 from E16 5 Wi Lh ti me‘ Lhis bony replacement of Meckel's cartilage in an endochondral ossification mode was ex Lenclecl up Lo the mid-porLion of Lhe molar sockets til l EI8.5. The bony replacement of minera li zed hypertrophic chondrocyte zone expressing X collagen mHNA conLri buted to the formation of thick mandibular lingual plate . 1'hese f"i ndings suggesL LhaL mandibular formalion and development is closely relatecl with not only Mecke!'s carLi lage. buL also wiLh Lhc developing LooLh. and thaL C'erLai n in f"l uence from the developing tooth may play a role in detcrmin in g Lhe faLc of Meckel’s ca rLi lage cluring ma ndi bular development.

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.

<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>