<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 Feeding Cyanidin 3-glucoside (C3G) High Black Rice Bran on Nutrient Digestibility, Blood Measurements, Growth Performance and Pork Quality of Pigs

Kil, D.Y.,Ryu, S.N.,Piao, L.G.,Kong, C.S.,Han, S.J.,Kim, Y.Y Asian Australasian Association of Animal Productio 2006 Animal Bioscience Vol.19 No.12

Two experiments were conducted to investigate the effect of feeding cyanidin 3-glucoside (C3G) high black rice bran on nutrient digestibility, blood measurements, growth performance and pork quality of pigs. In Exp. I, a total of fifteen pigs (19.91${\pm}$1.80 kg, average initial body weight) were used in assay of nutrient digestibility and blood measurements. All pigs were allotted to 5 treatments with 3 replicates according to a completely randomized design (CRD) in an individual metabolic crate. Treatments included 1) CON: basal diet, 2) BRB-2: basal+brown rice bran 2%, 3) BRB-4: basal+brown rice bran 4%, 4) CRB-2: basal+C3G high black rice bran 2% and 5) CRB-4: basal+C3G high black rice bran 4%. The digestibility of dry matter (DM), crude protein (CP), crude fat (CF), crude ash (CA) and crude fiber (CF) was not affected by dietary treatments. Serum triglyceride (TG) and high density lipoprotein (HDL) cholesterol concentrations were not affected by addition of C3G high black rice bran. However, at the end of experiment, pigs fed rice bran showed decreased tendency in total cholesterol concentration. Especially pigs fed C3G high black rice bran showed significantly lower total cholesterol concentration compared to pigs fed brown rice bran (p<0.03). There was numerically lower total cholesterol concentration with increasing levels of black rice bran in the diet. In terms of serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), there were no significant differences among treatments, even though pigs fed CRB-4 showed the lowest GOT concentration compared to other pigs. In Exp. II, sixteen finishing pigs (average initial body weight 89.96${\pm}$0.35 kg) were divided into 4 treatments to investigate the effect of feeding C3G high black rice bran on growth performance and pork quality. There were no significant differences in average daily gain (ADG), average daily feed intake (ADFI) and feed conversion ratio (FCR) among the treatments. Pigs fed C3G high black rice bran showed numerical decrease in ADG and increase in FCR while not effecting feed intake. There was no significant difference in live weight, carcass weight, carcass rate, backfat thickness and carcass grade. However, pigs fed C3G high black rice bran tended to show lower backfat thickness than pigs fed basal diet. Pigs fed C3G high black rice bran showed a tendency of decreased TBA value than pigs fed basal diet, although there was no overall significant difference among treatments. In conclusion, nutrient digestibility, blood measurements, growth performance and pork quality were not significantly affected by feeding C3G high black rice bran to pigs. However, C3G high black rice bran might have an effect on lowering serum total cholesterol and decrease the TBA value in pork compared to control group and these effects might be due to high concentration of antioxidative compounds in C3G high black rice bran.

LCD 공정용 C₃F₆ 가스를 이용한 Si₃N₄박막 식각공정 및 배출가스에 관한 연구

전성찬(S. C. Jeon),공대영(D. Y. Kong),표대승(D. S. Pyo),최호윤(H. Y. Choi),조찬섭(C. S. Cho),김봉환(B. H. Kim),이종현(J. H. Lee) 한국진공학회(ASCT) 2012 Applied Science and Convergence Technology Vol.21 No.4

SF? 가스는 반도체 및 디스플레이 제조공정 중 건식식각 공정에서 널리 사용되는 가스이다. 하지만 SF? 가스는 대표적인 온실가스로서 지구 온난화에 큰 영향을 끼치기 때문에 반도체 및 디스플레이 공정에서 SF? 가스를 대체할 수 있는 가스의 연구가 필요한 상황이다. 그 후보군으로 떠오르고 있는 가스 중의 하나가 바로 C₃F? 가스이다. 이 가스를 이용하여 Si3N4 박막을 건식식각 방법인 Reactive Ion Etching 공정을 수행하여 식각 특성에 관하여 연구하였으며, 흡착제 Zeolite 5A를 이용하여 식각공정 중 배출되는 가스 성분을 감소시켰다. Plasma Enhanced Chemical Vapor Deposition 장비를 이용하여 500 ㎚ 두께의 Si₃N₄ 박막을 증착하였으며, 노광 공정을 통해 패터닝을 한 후 Reactive Ion Etching 공정을 수행하였다. 그리고 Scanning Electron Microscope 장비를 이용하여 Si₃N₄ 박막의 식각된 단면과 식각율을 확인하였다. 또한 공정 후 흡착제 Zeolite 5A를 통과하기 전과 후에 배출되는 가스를 포집하여 Gas Chromatograph-Mass Spectrophotometry 장비를 이용하여 가스 성분을 측정 및 비교하였다. SF? gas is widely used for dry etching process of semiconductor and display fabrication process. But SF? gas is considered for typical greenhouse gas for global warming. So it is necessary to research relating to SF? alternatives reducing greenhouse effect in semiconductor and display. C₃F? gas is one of the promising candidates for it. We studied about etch characteristics by performing Reactive Ion Etching process of dry etching and reduced gas element exhausted on etching process using absorbent Zeolite 5A. Si₃N₄ thin film was deposited to 500 ㎚ with Plasma Enhanced Chemical Vapor Deposition and we performed Reactive Ion Etching process after patterning through photolithography process. It was observed that the etch rate and the etched surface of Si₃N₄ thin film with Scanning Electron Microscope pictures. And we measured and compared the exhausted gas before and after the absorbent using Gas Chromatograph-Mass Spectrophotometry.

Identification of Novel SNPs with Effect on Economic Traits in Uncoupling Protein Gene of Korean Native Chicken

Oh, J.D.,Kong, H.S.,Lee, J.H.,Choi, I.S.,Lee, S.J.,Lee, S.G.,Sang, B.D.,Choi, C.H.,Cho, B.W.,Jeon, G.J.,Lee, H.K. Asian Australasian Association of Animal Productio 2006 Animal Bioscience Vol.19 No.8

The avian uncoupling protein (avUCP) is a member of the mitochondrial transporter superfamily that uncouples proton entry in the mitochondrial matrix from ATP synthesis. The sequencing analysis method was used to identify nucleotide polymorphisms within the avUCP gene in Korean native chicken (KNC). This study identified ten single nucleotide polymorphisms (SNPs) in the avUCP gene. We analyzed the SNPs of the avUCP gene to investigate whether polymorphism in the gene might be responsible for quantitative variations in economic traits in KNC. Three significant polymorphic sites for economic traits were avUCP C+282T (mean body weight, p<0.05), avUCP C+433T (daily percent lay, p<0.05), and avUCP T+1316C (daily percent lay, p<0.05). The frequency of each SNP was 0.125 (C+282T in avUCP gene exon 1 region), 0.150 (C+433T in avUCP gene intron 1 region), and 0.15 (T+1316C in avUCP gene exon 3 region), respectively. Among the identified SNPs, one pair of SNPs (genotype CC, C+282T and TT, avUCP C+433T) showed the highest daily percent lay (p<0.05) and mean body weight (p<0.05) and the frequency was 0.067. This study of the avUCP gene could be useful for genetic studies of this gene and selection on economic traits for KNC.

한국 재래 닭의 Uncoupling Protein 유전자 Exon 3에서의 +1316 T/T 유전자형이 산란율에 미치는 효과 분석

오재돈,이제현,홍윤숙,이성진,이승규,공홍식,상병돈,최철환,조병욱,전광주,이학교,Oh J. D.,Lee J. H.,Hong Y. S.,Lee S. J.,Lee S. G.,Kong H. S.,Sang B. D.,Choi C. H.,Cho B. W.,Jeon G. J.,Lee H. K. 한국가금학회 2005 韓國家禽學會誌 Vol.32 No.4

Uncoupling protein(UCP)은 갈색 지방세포에서 특이적으로 발현하고 있으며 복잡한 세포의 열 생산 작용에 관여한다고 알려져 있다. 본 연구는 한국 재래 닭 집단의 UCP 유전자 내에 존재하는 SNP를 검출하였다. 한국 재래 닭 집단의 UCP유전자 exon 3지역의 염기서열 분석 결과 1316 bp에서 T염기가 C염기로 치환되어짐을 확인하였다. T+11316C 지역의 PCR-RFLP 분석을 위해 제한효소 Afl III를 사용하였다. 한국 재래닭 집단내 유전자형 빈도는 TT가 0.7875, TC가 0.1875 그리고 CC가 0.025로 검출되었으며 대립유전자의 빈도는 T가 0.881 그리고 C가 0.119로 나타났다. 또한 검출된 SNP가 경제형질에 미치는 영향을 분석한 결과 한국 재래 닭 집단의 T/T 유전자형과 C/C유전자형에서 일당 산란율에서 통계적으로 유의한 차이가 있음을 확인하였다. 본 연구의 결과는 향후 더 많은 UCP 유전자와 관련된 연구와 한국 재래 닭의 육종 전략에 도움이 될 것으로 사료된다. Uncoupling protein(UCP) is expressed exclusively in brown adipose tissue(BAT). It is blown to uncouple phosphorylation from oxidation and hence to be involved in energy metabolism and heat production, especially under cold exposure. In the present study, we identified single nucleotide polymorphism(SNP) in exon 3 of avUCP gene in Korean native chicken(KNC) population. It was detected a SNP T+1316C in exon 3 of avUCP gene by sequence analysis in KNC population. For PCR-RFLP analysis of the SNP T+1316C, used by AP III restriction enzyme. The result of PCR-RFLP analysis showed that allele T has two fragments of 255 bp and 86 bp, and allele C has only one fragment of 341 bp. The genotype frequencies were TT type, 0.7875; TC type, 0.1875 and CC type, 0.025; and the frequencies of allele T and C were 0.881 and 0.119, respectively in KNC population. Next study was conducted to investigate the effect of the SNP in avUCP gene on economic traits in the KNC population. The TT genotype had a significant higher daily percent lay(84.61) than CC genotype(p<0.05) in KNC population. This study may be useful for genetic studies of avCUP gene and selection on daily percent lay of KNC.

Evaluation of a furochromone from the halophyte Corydalis heterocarpa for cytotoxic activity against human gastric cancer (AGS) cells

Kong, C. S.,Kim, Y.,Kim, H.,Seo, Y. Royal Society of Chemistry 2016 Food & Function Vol.7 No.12

<P>A furochromone, heterocarpin (1), was isolated from the halophyte Corydalis heterocarpa, along with four known compounds (25), which were obtained for the first time from this genus. The chemical structures of these compounds were determined by extensive 2-D NMR experiments and by comparison with the data reported in the literature. Compound 1 showed significant cytotoxic activities against four human cancer cells, AGS (human gastric cancer), HT29 (human colon cancer), HT1080 (human fibrosarcoma) and MCF7 (human breast carcinoma). According to the cytotoxicity results, the mechanism behind the cytotoxic presence of compound 1 on AGS cells was investigated through the mRNA and protein levels of apoptotic pathway factors such as p21, p53, Bax, Bcl-2, XIAP, and caspases-3 and -9. The results indicated that heterocarpin (1) showed the cytotoxic effect on cancer cells by inducing apoptosis via regulated BaxBcl- 2 ratio, overproduced caspases and suppressed XIAP. The inhibition of NF kappa B and activation of JNK and ERK pathways were also observed in the presence of heterocarpin (1). Therefore, heterocarpin and its source C. heterocarpa were suggested to be utilized as a functional food with potential proapoptotic activity against cancer cells.</P>

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>

Characterization of the flounder IL-6 promoter and its regulation by the p65 NF-κB subunit

Kong, H.J.,Nam, B.H.,Kim, Y.O.,Kim, W.J.,Cho, H.K.,Lee, C.H.,Lee, S.J.,Kim, K.K. Academic Press 2010 Fish & Shellfish Immunology Vol. No.

Interleukin (IL)-6 plays important roles in the regulation of the immune response and inflammation in many cell types and its induction by bacterial endotoxins or cytokines is regulated at the transcriptional level. The present study demonstrates the isolation and characterization of the flounder IL-6 promoter sequence and its transcriptional regulation in olive flounder (hirame) natural embryo (HINAE) cells. The promoter region (-400 to +79 bp from the transcription initiation site) of the flounder IL-6 gene contains putative cis-regulatory elements for CCAAT-enhancer-binding proteins (C/EBP; -346 to -355 bp and -166 to -160 bp), cAMP response element binding (CREB; -81 to -85 bp), the activator protein 1 (AP-1; -56 to -62 bp), and NF-κB (-39 to -48 bp). Transfection of p65 stimulated the PoIL-6-luc-WT reporter, but not the PoIL-6-luc-κB mt reporter, and treatment with LPS augmented p65-stimulated reporter activity in HINAE cells. In contrast, transfection of C/EBPβ or c-Jun failed to induce synergistic effects in the LPS-driven PoIL-6-luc-WT reporter activity. These results give us new insight into the regulation of flounder IL-6 transcription by the p65 NF-κB subunit.

A C-type lectin like-domain (CTLD)-containing protein (PtLP) from the swimming crab Portunus trituberculatus

Kong, H.J.,Park, E.M.,Nam, B.H.,Kim, Y.O.,Kim, W.J.,Park, H.J.,Lee, C.H.,Lee, S.J. Academic Press 2008 FISH AND SHELLFISH IMMUNOLOGY Vol.25 No.3

C-type lectins play important roles in the non-self innate immune system of invertebrates. In this study, we isolated the full-length cDNA of the C-type lectin like-domain (CTLD)-containing protein, designated PtLP, from the hepatopancreas of the swimming crab Portunus trituberculatus, one of the most common edible crabs of East Asia. The PtLP cDNA consists of 923bp and encodes a polypeptide of 164 amino acids containing a well-conserved C-type lectin like-domain (CTLD). The deduced amino acid sequence of PtLP shows 29-36% amino acid sequence identity to other crustacean C-type lectin sequences. A phylogenetic analysis revealed that PtLP is in a large cluster together with black tiger shrimp PmAV, a gene involved in virus resistance of shrimp, and all of the C-type lectins from the various shrimps. Quantitative RT-PCR analysis showed that the PtLP mRNA was expressed highly in hepatopancreas and moderately in gills, hemocytes, and ovary of normal swimming crabs.

Phase II study of a triplet regimen of S-1 combined with irinotecan and oxaliplatin in patients with metastatic gastric cancer: clinical and pharmacogenetic results

Park, S.R.,Kong, S.-Y.,Rhee, J.,Park, Y.-I.,Ryu, K.W.,Lee, J.H.,Kim, Y.-W.,Choi, I.J.,Kim, C.G.,Lee, J.Y.,Cho, S.-J.,Kim, N.K. Elsevier 2011 Annals of oncology Vol.22 No.4