S-1 plus irinotecan and oxaliplatin for the first-line treatment of patients with metastatic colorectal cancer: a prospective phase II study and pharmacogenetic analysis

Kim, S Y,S Hong, Y,K Shim, E,Kong, S-Y,Shin, A,Baek, J Y,Jung, K H Nature Publishing Group 2013 The British journal of cancer Vol.109 No.6

<P><B>Background:</B></P><P>S-1 is an oral fluoropyrimidine that mimics infusional 5-fluorouracil. The aim of this phase II trial was to explore the clinical efficacy of the triplet regimen TIROX, which consists of S-1, irinotecan and oxaliplatin.</P><P><B>Methods:</B></P><P>Forty-two chemo-naive patients with metastatic colorectal cancer (mCRC) were planned to be enrolled and be treated with irinotecan 150 mg m<SUP>−2</SUP> followed by oxaliplatin 85 mg m<SUP>−2</SUP> on day 1 and S-1 80 mg m<SUP>−2</SUP> per day from day 1 to 14 every 3 weeks. Polymorphisms in the <I>UGT1A1</I>, <I>UGT1A6</I>, <I>UGT1A7</I> and <I>CYP2A6</I> genes were analysed.</P><P><B>Results:</B></P><P>Between July 2007 and February 2008, 43 patients were enrolled. An objective response was noted in 29 patients (67.4%, 95% confidence interval: 53.4–81.4), of which 2 achieved durable complete responses. The median progression-free survival was 10.0 months and the median overall survival was 19.2 months. Significant grade 3 or 4 adverse events were neutropenia (45.2%), febrile neutropenia (9.5%), diarrhoea (7.1%) and vomiting (9.5%). Increased gastrointestinal toxicities were associated with the presence of <I>UGT1A6*2</I> or <I>UGT1A7*3</I> and an improved tumour response was noted in those without variant alleles of <I>CYP2A6</I> or <I>UGT1A1*60</I>.</P><P><B>Conclusion:</B></P><P>The combination of S-1, irinotecan and oxaliplatin showed favourable efficacy and tolerability in untreated patients with mCRC.</P>

<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>

Effect of Follicle Stimulation Hormone and Luteinizing Hormone on Cumulus Cell Expansion and <i>In Vitro</i> Nuclear Maturation of Canine Oocytes

Lee, H-S,Seo, Y-I,Yin, X-J,Cho, S-G,Lee, S-S,Kim, N-H,Cho, S-K,Kong, I-K KOCH NEFF UND OETINGER 2007 REPRODUCTION IN DOMESTIC ANIMALS Vol.42 No.6

<P>Contents</P><P>In general, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play important roles in the regulation of cumulus cell expansion and oocyte maturation. We investigated the effects of supplementation of FSH or LH in <I>in vitro</I> maturation (IVM) medium on the incidence of cumulus cell expansion and nuclear maturation in canine oocytes. Cumulus–oocyte complexes (COCs) were cultured in TCM-199 supplemented with 10% foetal bovine serum (FBS), 1 mg/ml cysteine, 0.2 m<SMALL>M</SMALL> pyruvic acid and different concentrations of FSH or LH (control, 0.5, 5 or 50 <I>μ</I>g/ml) at 38.5°C, 5% CO<SUB>2</SUB> in air for 72 h. The cumulus cell expansion was measured by microscopic visualization, and nuclear maturation of denuded oocytes was determined by staining with 10 <I>μ</I>g/ml Hoechst33342 for 30 min. The cumulus cell expansion in the 5 <I>μ</I>g/ml FSH group (397.2 ± 64.3 <I>μ</I>m) was significantly higher than those in the control, 0.5, and 50 <I>μ</I>g/ml FSH groups (168.3 ± 19.1, 286.0 ± 69.7 and 300.0 ± 84.3 <I>μ</I>m, respectively; p < 0.05). However, there was no difference in cumulus cell expansion among the control, 0.5, 5 and 50 <I>μ</I>g/ml LH groups (165.6 ± 20.2, 160 ± 26.5, 172 ± 20.5 and 168 ± 23.1 <I>μ</I>m, respectively; p > 0.05). After 72 h of IVM, the proportion of nuclear development to the MI–MII stage in the 0.5 <I>μ</I>g/ml FSH group (15.1%) was higher than those in the control, 0.5 and 50 <I>μ</I>g/ml FSH groups (0.9%, 6.5% and 8.0%, respectively; p < 0.05). However, there was no significant difference in nuclear maturation to the MI-MII stage among control, 0.5, 5 and 50 <I>μ</I>g/ml LH groups (4.6%, 2.3%, 5.4% and 8.6%, respectively; p > 0.05). This study indicated that a FSH supplement in IVM medium can increase cumulus cell expansion and nuclear maturation, while the nuclear maturation rate remained low. Further studies are required to improve the nuclear development to the MI–MII stages in canine oocytes.</P>

Associations between CYP2A6 polymorphisms and outcomes of adjuvant S-1 chemotherapy in patients with curatively resected gastric cancer

Jeong, J. H.,Park, S. R.,Ahn, Y.,Ryu, M. H.,Ryoo, B. Y.,Kong, S. Y.,Yook, J. H.,Yoo, M. W.,Kim, B. S.,Kim, B. S. Springer Science + Business Media 2017 GASTRIC CANCER Vol.20 No.1

<P>CYP2A6 polymorphisms are not associated with toxicity of S-1 chemotherapy, but correlate with the efficacy of S-1 in the adjuvant setting for gastric cancer.</P>

Comparative studies on steam gasification of ash-free coals and their original raw coals

Kong, Y.,Kim, J.,Chun, D.,Lee, S.,Rhim, Y.,Lim, J.,Choi, H.,Kim, S.,Yoo, J. Pergamon Press ; Elsevier Science Ltd 2014 INTERNATIONAL JOURNAL OF HYDROGEN ENERGY - Vol.39 No.17

Catalytic gasification of raw coals at mild condition is not realized yet mainly due to deactivation of catalysts via their irreversible interaction with mineral matters in coal. As a means to achieve repeated use of catalysts, four different ash-free coals (AFCs) containing less than 0.2 wt% ash are produced in this work. Steam gasification of ash-free coals (AFCs) and their parent raw coals of various ranks ranging from lignite (Eco) to coking coal (Posco) is performed in a fixed bed reactor at 700-900 <SUP>o</SUP>C. Regardless of the rank of the parent raw coals, all the AFCs behave like a highly carbonized coal such that their gasification rate are similarly slow and they exhibit relatively low H<SUB>2</SUB>/CO ratio. The steam gasification and associated CO to CO<SUB>2</SUB> conversion of the AFCs are, however, significantly enhanced by K<SUB>2</SUB>CO<SUB>3</SUB>, resulting in the higher H<SUB>2</SUB>/CO and CO<SUB>2</SUB>/CO molar ratio.

전신 골밀도와 기능 상실 치율 및 하악골 골소주 흡수 양상의 상관 관계

공선애,송용준,노재형,안종인,고영규,김종화,이희철 인제대학교 1996 仁濟醫學 Vol.17 No.1

1993년 3월부터 1995년 6월까지 부산백병원 치과에 내원한 40세 이상 65세 이하의 연령층에 속하는 여성 환자를 대상으로 임상 검사 및 방사선학적 검사를 시행한 결과 치주병에 이환된 치아의 비율이 20% 이하인 30명을 선정하여 이화학적 검사, 치아 파노라마 단층 촬영을 이용한 방사선학적 검사 및 LUNAR DPX 골밀도 측정기를 이용한 전신 골밀도 측정을 시행하였다. 이를 통한 검사 결과를 분석하면서 전신 골밀도 수준과 기능 상실치율 및 하악골 내 골소주의 흡수 양상 간의 상관 관계를 평가하여 다음과 같은 결과를 얻었다. 1.골대사의 지표인 칼슘, 무기인, 알칼리성 인산화효소를 측정하여 전신 골밀도와의 상관 관계를 검증하였으나 유의한 상관 관계는 없었다 (P>0.05). 2.전신 골밀도 분석 결과는 기능 상실치수 및 기능 상실치율에 유의한 상관 관계를 가지고 있었다 (연령에 의한 영향을 보정함)(P=0.0050). 3.30명 환자의 기능 상실치율은 평균 33.7%였으며 치아 파노라마 단층 촬영을 분석한 결과 이공 주변부의 골소주 흡수양상은 현저하여 Diffuse resorption type, Moth-eaten type, Limited(round) resorption type으로 분류 가능하였으나 각 군별로 전신 골밀도 분석 평균의 차이는 없었다(P>0.05). The author selected 30 women whose periodontal disease rate was no more than 20%. They were the patients who have visited at the Dept. of Dentistry in Paik hospital from 1993 to 1995. Biochemical examination, dental panoramic tomogram check and toal body bone density check were done using LUNAR DPX bone densitometer. The results were analysed by total body bone density level, function loss teeth rate and mandibular trabeculi resorption pattern. Then, the author accessed the correlation on the basis of their results. The following observations were made ; 1.Calcium, phosphorus and alkaline phosphatase levels were not correlated with tonal body bone density (P>0.05) 2.There was a good correlation between function loss teeth rate and total body bonedensi ty(corrected by age) (P = 0.0050) 3.We analysed dental panoramic tomograms of 30 women whose periodontal disease rate was no more than 20%. The mean function loss teeth rate in 30 patients was 33.7%. So we could divide mandibular trabeculi resorption pattern into 3-types ; Diffuse resorption type, Moth-eaten type, Limited (round) resorption type. But, there was no correlation between each resorption pattern and total body bonedensity (P>0.05).

Metabolic engineering of the Stevia rebaudiana ent-kaurene biosynthetic pathway in recombinant Escherichia coli

Kong, M.K.,Kang, H.J.,Kim, J.H.,Oh, S.H.,Lee, P.C. Elsevier Science Publishers 2015 Journal of biotechnology Vol.214 No.-

<P>The ent-kaurene is a dedicated precursor pool and is responsible for synthesizing natural sweeteners such as steviol glycosides. In this study, to produce ent-kaurene in Escherichia coli, we modularly constructed and expressed two ent-kaurene genes encoding ent-copalyl diphosphate synthase (CPPS) and ent-kaurene synthase (KS) from Stevia rebaudiana known as a typical plant producing steviol glycoside. The CPPS and KS from S. rebaudiana were functionally expressed in a heterologous host E. coli.,Furthermore, in order to enhance ent-kaurene production in E. coli, six geranylgeranyl diphosphate synthases (GGPPS) from various microorganisms and eight strains of E. coli as host were compared by measuring ent-kaurene production. The highest ent-kaurene production of approximately 41.1 mg/L was demonstrated in E. coli. strain MG1655 co-expressing synthetic CPPS-KS module and GGPPS from Rhodobacter sphaeroides. The ent-kaurene production was further increased up to 179.6 mg/L by overexpression of the three key enzymes for isoprenoid precursor, 1-deoxyxylulose-5-phosphate synthase (DXS), farnesyl diphosphate synthase (IspA) and isopentenyl diphosphate isomerase (IDI) from E. colt. Finally, the highest titer of ent-kaurene (578 mg/L) with a specific yield of ent-kaurene of 143.5 mg/g dry cell weight was obtained by culturing E. coli strain MG1655 co-expressing the ent-kaurene module, DXS, IDI and IspA in 1 L bioreactor containing 20 g/L glycerol. (C) 2015 Elsevier B.V. All rights reserved.</P>

POSTERS / PT-002 : SITE - DIRECTED MUTAGENESIS STUDY OF AMINO ACID RESIDUES INVOLVED IN THE SUBSTRATE BINDING OF HUMAN GLUTATHONE S-TRANSFERASE P1-1

(H . J . Park),(H . Jegal),(H . S . Noh),(K . H . Kong) 한국생화학분자생물학회 (구 한국생화학회) 1999 6th IUBMB SEOUL CONFERENCE Vol.- No.-

Effect of Warming Temperature on the Viability of Bovine IVP Blastocyst Cryopreserved by Glass Micropipette (GMP) Vitrification

W.S. Moon,S.R. Jeong,S.H. Jung,B.H. Son,Lee, J. W.,I.K. Kong 한국수정란이식학회 2002 한국수정란이식학회 학술대회 Vol.2002 No.1

The purpose of this study was to investigate the warming temperature and exposed time on the post-thaw survival rate and viability of bovine blastocyst cryopreserved by GMP vitrification. Groups of three bovine IVP blastocysts were sequentially placed into vitrification solution before being loaded into the GMP straws and immersed into LNwithin 20 to 25 sec. The warming rate was increased 2 times of warming temperature for improvement of post-thaw survival rates. The frozen embryos were warmed either at 35 or 70 for 1 or 2 sec and then diluted in sucrose solution. Post-thaw blastocysts were serially washed in 0.25 and 0.15 M sucrose in holding medium (HM: TCM199 supplemented with 10% FCS) and TCM-199 for each 5 min, respectively, and then cultured in TCM199 for 24 h. The rate of re-expanded blastocyst was significantly different fer 35 and 70 warming temporature (76.4 vs. 89.3%; P<0.05). The rate of re-expanded blastocyst at 70 for 1 sec was significantly higher than that for 2 sec (91.1 vs. 70.9%; P<0.05). The number of nuclei counted were significantly different among control, 35 and 70 (1218.5 vs. 10411.7 vs. 11410.3; P<0.05). These results indicated that the increasing of warming rate can provide high survival rates of bovine IVP blastocysts. Especially, the best viability of post-thaw blastocyst could be thaw at 70 for 1 sec. The warming temperature and exposed time far warming was considered to be limiting factors to the viability of bovine IVP embryos. he purpose of this study was to investigate the warming temperature and expose.

Two novel phospholipid hydroperoxide glutathione peroxidase genes of <i>Paragonimus westermani</i> induced by oxidative stress

KIM, S.-H.,CAI, G.-B.,BAE, Y.-A.,LEE, E.-G.,LEE, Y.-S.,KONG, Y. Cambridge University Press 2009 Parasitology Vol.136 No.5

<B>SUMMARY</B><P>Phospholipid hydroperoxide glutathione peroxidase (PHGPx; GPx4) plays unique roles in the protection of cells against oxidative stress by catalysing reduction of lipid hydroperoxides. We characterized 2 novel <I>GPx</I> genes from a lung fluke, <I>Paragonimus westermani</I> (designated <I>PwGPx1</I> and <I>PwGPx2</I>). These single copy genes spanned 6559 and 12 371 bp, respectively, and contained each of 5 intervening introns. The <I>PwGPx2</I> harboured a codon for Sec and a Sec insertion sequence motif. Proteins encoded by the <I>Paragonimus</I> genes demonstrated a primary structure characteristic to the PHGPx family, including preservation of catalytic and glutathione-binding domains and absence of the subunit interaction domain. Expression of <I>PwGPx1</I> increased gradually as the parasite matured, whereas that of <I>PwGPx2</I> was temporally regulated. <I>PwGPx2</I> was expressed at the basal level from the metacercariae to the 3-week-old juveniles; however, the expression was significantly induced in the 7-week-old immature worms and reached a plateau in the 12-week-old adults and eggs. PwGPx1 and PwGPx2 were largely localized in vitellocytes within vitelline glands and eggs. Oxidative stress-inducible paraquat, juglone and H2O2 substantially augmented the <I>PwGPx1</I> and <I>PwGPx2</I> expressions in viable worms by 1·5- to 11-fold. Our results strongly suggested that PwGPxs may actively participate in detoxification of oxidative hazards in <I>P. westermani</I>.</P>