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>

Changes in the Ångstrom Exponent during Aerosol Coagulation and Condensation

Jung, Chang H.,Lee, Ji Yi,Kim, Yong P. Korean Society for Atmospheric Environment 2012 Asian Journal of Atmospheric Environment (AJAE) Vol.6 No.4

In this study, the ${\AA}$ngstrom exponent for polydispersed aerosol during dynamic processes was investigated. Log-normal aerosol size distribution was assumed, and a sensitivity analysis of the ${\AA}$ngstrom exponent with regards the coagulation and condensation process was performed. The ${\AA}$ngstrom exponent is expected to decrease because of the particle growth due to coagulation and condensation. However, it is difficult to quantify the degree of change. In order to understand quantitatively the change in the ${\AA}$ngstrom exponent during coagulation and condensation, different real and imaginary parts of the refractive index were considered. The results show that the ${\AA}$ngstrom exponent is sensitive to changes in size distribution and refractive index. The total number concentration decreases and the geometric mean diameter of aerosols increase during coagulation. On the while, the geometric standard deviation approaches monodispersed size distribution during the condensation process, and this change in size distribution affects the ${\AA}$ngstrom exponent. The degree of change in the ${\AA}$ngstrom exponent depends on the refractive index and initial size distribution, and the size parameter changes with the ${\AA}$ngstrom exponent for a given refractive index or chemical composition; this indicates that the size distribution plays an important role in determining the ${\AA}$ngstrom exponent as well as the chemical composition. Subsequently, this study shows how the ${\AA}$ngstrom exponent changes quantitatively during the aerosol dynamics processes for a log-normal aerosol size distribution for different refractive indices; the results showed good agreement with the results for simple analytic size distribution solutions.

Prognostic value of chronic total occlusions detected on coronary computed tomographic angiography

Opolski, Maksymilian P,Gransar, Heidi,Lu, Yao,Achenbach, Stephan,Al-Mallah, Mouaz H,Andreini, Daniele,Bax, Jeroen J,Berman, Daniel S,Budoff, Matthew J,Cademartiri, Filippo,Callister, Tracy Q,Chang, Hy BMJ Group 2019 Heart Vol.105 No.3

<P><B>Objective</B></P><P>Data describing clinical relevance of chronic total occlusion (CTO) identified by coronary CT angiography (CCTA) have not been reported to date. We investigated the prognosis of CTO on CCTA.</P><P><B>Methods</B></P><P>We identified 22 828 patients without prior known coronary artery disease (CAD), who were followed for a median of 26 months. Based on CCTA, coronary lesions were graded as normal (no atherosclerosis), non-obstructive (1%–49%), moderate-to-severe (50%–99%) or totally occluded (100%). All-cause mortality, and major adverse cardiac events defined as mortality, non-fatal myocardial infarction and late coronary revascularisation (≥90 days after CCTA) were assessed.</P><P><B>Results</B></P><P>The distribution of patients with normal coronaries, non-obstructive CAD, moderate-to-severe CAD and CTO was 10 034 (44%), 7965 (34.9%), 4598 (20.1%) and 231 (1%), respectively. The mortality rate per 1000 person-years of CTO patients was non-significantly different from patients with moderate-to-severe CAD (22.95; 95% CI 12.71 to 41.45 vs 14.46; 95% CI 12.34 to 16.94; p=0.163), and significantly higher than of those with normal coronaries and non-obstructive CAD (p<0.001 for both). Among 14 382 individuals with follow-up for the composite end point, patients with CTO had a higher rate of events than those with moderate-to-severe CAD (106.56; 95% CI 76.51 to 148.42 vs 65.45; 95% CI 58.01 to 73.84, p=0.009). This difference was primarily driven by an increase in late revascularisations in CTO patients (27 of 35 events). After multivariable adjustment, compared with individuals with normal coronaries, the presence of CTO conferred the highest risk for adverse cardiac events (14.54; 95% CI 9.11 to 23.20, p<0.001).</P><P><B>Conclusions</B></P><P>The detection of CTO on non-invasive CCTA is associated with increased rate of late revascularisation but similar 2-year mortality as compared with moderate-to-severe CAD.</P><P><B>Trial registration number</B></P><P> NCT01443637.</P>

Changes in the Angstrom Exponent during Aerosol Coagulation and Condensation

Chang H. Jung,Ji Yi Lee,Yong P. Kim,김용표 한국대기환경학회 2012 Asian Journal of Atmospheric Environment (AJAE) Vol.6 No.4

In this study, the Ångstrom exponent for polydispersed aerosol during dynamic processes was investigated. Log-normal aerosol size distribution was assumed,and a sensitivity analysis of the Ångstrom exponent with regards the coagulation and condensation process was performed. The Ångstrom exponent is expected to decrease because of the particle growth due to coagulation and condensation. However, it is difficult to quantify the degree of change. In order to understand quantitatively the change in the Ångstrom exponent during coagulation and condensation,different real and imaginary parts of the refractive index were considered. The results show that the Ångstrom exponent is sensitive to changes in size distribution and refractive index. The total number concentration decreases and the geometric mean diameter of aerosols increase during coagulation. On the while, the geometric standard deviation approaches monodispersed size distribution during the condensation process, and this change in size distribution affects the Ångstrom exponent. The degree of change in the Ångstrom exponent depends on the refractive index and initial size distribution, and the size parameter changes with the Ångstrom exponent for a given refractive index or chemical composition; this indicates that the size distribution plays an important role in determining the Ångstrom exponent as well as the chemical composition. Subsequently, this study shows how the Ångstrom exponent changes quantitatively during the aerosol dynamics processes for a log-normal aerosol size distribution for different refractive indices; the results showed good agreement with the results for simple analytic size distribution solutions.

Ribonucleotide reductase small subunit p53R2 suppresses MEK–ERK activity by binding to ERK kinase 2

Piao, C,Jin, M,Kim, H B,Lee, S M,Amatya, P N,Hyun, J -W,Chang, I -Y,You, H J Macmillan Publishers Limited 2009 Oncogene Vol.28 No.21

The p53-dependent RR small subunit (p53R2) protein, a newly identified member of the ribonucleotide reductase family, plays a key role in the p53-dependent cellular response to DNA. Several recent studies have suggested that p53R2 also plays an important role in suppressing the invasive potential of human cancer cells. However, the cellular mechanism that regulates invasiveness remains largely unknown. In this study, we show that p53R2 interacts with MEK2 (extracellular signal-regulated kinase (ERK) kinase 2–mitogen-activated protein kinase (MAPK) kinase 2), the molecule immediately upstream of ERK in the Ras–Raf–MAPK signaling cascade. In co-immunoprecipitation and immunofluorescence analyses, we found that p53R2 and MEK2 interact physically in cultured mammalian cells, and that the p53R2 segment comprising amino acids 161–206 is critical for this interaction. Moreover, serum-induced phosphorylation of MEK1/2 and ERK1/2 was greatly augmented in human cancer cells expressing small-interfering RNA against p53R2. On the other hand, phosphorylation of MEK1/2 and ERK1/2 in human cancer cells was markedly attenuated by overexpression of p53R2. Furthermore, MEK2 was required for p53R2 knockdown-induced enhancement of the invasive ability and anchorage-independent growth of human lung cancer H1299 cells. Taken together, these findings show that p53R2 negatively modulates serum-induced MEK–ERK activity and inhibits the MEK–ERK-mediated malignancy potential of human cancer cells.Oncogene (2009) 28, 2173–2184; doi:10.1038/onc.2009.84; published online 27 April 2009

산삼배양액 이용에 관한 반추위 미생물 대사 연구

배귀석,남경표,김혜숙,이상구,최행석,민우기,주종원,맹원재,장문백 한국동물자원과학회 2003 한국축산학회지 Vol.45 No.6

This study was conducted to determine the effects of the artificial culture medium of wild-ginsengs on in vitro fermentation characteristics. NH_(3)-N concentration was showed the highest in 3% WGM treatment among all treatments and control. In addition, microbila protein synthesis was significantly different in all treatments throughout the incubation time, and WGM 3% tratment was the highest at the 9 h incubation(P<0.05). Protozoa numbers within rumen were decreased in all WGM treatments a t9h incubation time, whereas WGM 3% treatment was always decreased throughtout the incubation(P<0.05). NDF and ADF digestibility showed no significantly increased as the incubation time in both control and treatments. NDF digestibility showed no significantly increased as the incubation time in both control and treatments. NDF digestibility showed no significantly difference between contro and the 3% treatment, and ADF digestibility was similar in all. Total volatile fatty acid(VFA) concentrations of WGM treatments without 5% were significantly higher than control(P<0.05). No differences were observed in total VFA, acetate, propionate and butyrate concentration among the WGM treatments. Acetate/Propionate roatio of WGN treatments was higher than control after 12 h incubation(P<0.05). As a result of the artificial culture medium of wild-ginseng on rumen fermentation characteristics in vitro, microbial protein synthesis of WGM treatment was higher than control, and WGM 3% was the highest in all treatments(P<0.05). The effect of saponin in artificaial culture medium of wild-ginseng tended to decrease NH_(3)-N concentration, while it increases the microbial synthesis in early incubation. Therefor, artificial cultures medium of wild-ginseng ca increase utilization of feed by microbial and anti-protozoal effects of saponin, which may enhance microbial synthesis capacity in early fernentation period in rumen.

Prevalences of Clonorchiasis and Metagonimiasis along Rivers in Jeonra-Nam-Do, Korea

Soh, C.T.,Lee, K.T.,Cho, K.M.,Ahn, Y.K.,Kim, S.J.,Chung, P.R.,Im, K.I.,Min, D.Y.,Lee, J.H.,Chang, J.K. INSTITUTE OF TROPICAL MEDICINE YONSEI UNIVERSITY 1976 YONSEI REPORTS ON TROPICAL MEDICINE Vol.7 No.1

전라남도 영산강 및 섬진강유역 주민의 간디스토마와 요꼬가와흡충 감염율의 조사 및 이들 패류매개성 기생충의 제1, 제2 중간숙주를 조사한 바 그 성적을 요약하면 다음과 같다(조사기간: 1975년 8,9월, 1976년 7,8월). 영산강 유역 영산강을 상류(YU), 중류(YM), 하류(YD)로 삼분하여 10개 표본지역을 선정, 조사하였다(표 1 참조). 상류는 광산군 송정읍의 상부지역으로 장성군과 담양군이 이에 해당되며 중류는 송정읍과 나주군 영산포읍 사이의 지역으로 광산군 일부와 나주군이 이에 해당되며 하류는 영산포읍이하의 나주군 일부와 함평군이 이에 해당된다. 1. 주민의 감열율 : 상류 3개지역, 중류 1개지역 그리고 하류 2개지역 등 6개지역 주민 359명을 대상으로 조사하였다. 상류지역의 간디스토마 감염율은 29.9%(69/231), 중류 38.5%(20/52), 하류 21.1%(16/76)이었다. 전체적으로는 29.2%(105/359)의 감염율을 나타내었으며 남자는 39.3%(79/201), 여자 15.4%(21/136)로 전자가 2.5배 이상의 감염상을 보였다. 2. 제 1 중간숙주 : 간디스토마의 제 1 중간숙주인 왜우렁(Parafossarulus manchouricus)의 조사는 상류 2개지역, 중류 4개지역, 하류 1개지역등 7개지역에서 채집한 980개를 검사하였으며 그 중 11개(1.1%)에서 간디스토마셀카리아를 검출하였다. 지역별로는 상류 1.8%(6/333), 중류 0.9%(5/553)가 양성이었으나 하류지역의 94개에서는 모두 음성이었다. 요꼬가와흡충의 제 1 중간숙주인 다슬기(Semisulcospira libertina)를 상, 중, 하류의 각 1개지역씩 3개지역에서 모두 179개를 채집하여 검사하였으나. 요꼬가와흡충 또는 페디스토마의 셀카리아는 검출할 수 없었다. 3. 제 2 중간숙주 : 전지역에서 9종의 담수어 263마리를 포획하여 검사한바 간디스토마메타셀카리아의 양성율은 참붕어에서 62.9%(22/35), 피리 5.7%(3/53), 납지리류 21.9%(7/32), 돌고기 17.6%(3/17), 그리고 끄리에서 14.3%(1/7)이었으나 붕어, 모래무지, 버들붕어 및 꺽지 등에서는 검출할 수 없었다. 요꼬가와흡충의 제2중간숙주인 은어는 채집 또는 포획할 수 없었다. 섬진강유역 전라남도 관내의 섬진강을 상, 중, 하류로 구분하여 각 유역별로 2개지역씩 선정, 6개지역에서 조사하였다(표 1 참조). Soh, C.T. et al. 표 1. 영산강 및 섬진강 유역 조사대상 지역 =================================================================================== 영산강 유역 ∥ 섬진강 유역 ------------------------------------------∥--------------------------------------- 지 역 *조사내용 ∥ 지 역 *조사내용 ------------------------------------------∥--------------------------------------- 상류 1. 장성군 황룡면 황룡리 P. 1.2. ∥상류 1. 곡성군 곡성면 동산리 P. 1. 2. 담양군 봉산면 삼지리 P. 1.2. ∥ 2. 곡성군 곡성면 석곡리 P. 1.2. 3. 담양군 금성면 금월리 P. ∥ 중류 1. 나주군 영산포읍 1. ∥중류 1. 구례군 구례읍 신월리 P. 1.2. 2. 나주군 산포면 산제리 1.2. ∥ 2. 곡성군 곡성면 압록리 2. 3. 나주군 남평면 남평리 1.2. ∥ 4. 광산군 동곡면 복용리 P. 1.2. ∥ 하류 1. 함평군 엄다면 학교리 P. 1.2. ∥하류 1. 광양군 다압면 신원리 2. 2. 나주군 다시면 신풍리 P. ∥ 2. 광양군 다압면 고사리 P. 1.2. 3. 나주군 문평면 용문리 2. ∥ ------------------------------------------------------------------------------------ *(주) P: 주민 감염율조사. 1: 제1 중간숙주조사. 2: 제2 중간 숙주조사. 상류는 전라북도와 전라남도의 경계선 이하에서 곡성군 곡성읍 상부와 섬진강의 지류인 보성강유역이 해당되며 중류지역은 섬진강과 보성강이 합류되는 곳에서부터 광양군 다압면의 상류지역으로 곡성군 일부와 구례군이 이에 해당되며 하류는 다압면이하로 광양군이 해당된다. 1. 주민의 감염율 : 상류 2개지역, 중하류 각 1개지역 등 4개지역에서 296명을 대상으로 조사하였던바 전체적으로 간디스토마 충란양성자는 21명(7.1%)인데 비해 요꼬가와흡충충란 양성자는 123명(41.6%)이었으며 지역별 간디스토마의 감염율은 상류 5.6%(7/124), 중류 7.4%(6/81), 하류 8.8%(8/91)이었으며 요꼬가와흡충은 상류29.0%(36/124), 중류 58.0%(47/81), 하류 44.0%(40/91)이었다. 요꼬가와흡충충란양성자의 경우 남자는 55.5%(81/146)로 여자의 28.0%(42/150)보다 약 2배 가량 높은 감염율을 보였다. 요꼬가와흡충충란은 전 연령층에서 검출되었으나 간디스토마는 19세이하에서는 검출되지 않았다. 한편 두 흡충의 혼합감염율은 5.7%(17/296)이었다. 2. 제 1 중간숙주 : 왜우렁은 중류지방에서만 채집되었으나 간디스토마셀카리아를 검출치 못하였고 다슬기는 모두 663개를 채집하여 검사한바 62개(9.4%)에서 요꼬가와흡충셀카리아를 검출하였다. 이를 지역별로 보면 상류 9.2%(39/427), 중류 4.8%(3/62), 하류 11.5%(20/174)의 양성율을 보였다. 3. 제 2 중간숙주 : 전지역에서 10종의 담수어 175마리를 포획하여 검사하였으나 간디스토마메타셀카리아는 검출치 못 하였다. 그러나 그중 은어에서는 35마리 전부에서 요꼬가와흡충메타셀카리아를 검출하였다. 이상의 성적으로 보아 영산강유역은 간디스토마의 만연지역이나 요꼬가와흡충의 만연은 볼 수 없었다. 그러나 섬진강유역은 요꼬가와흡충 및 간디스토마의 만연지역이라고 볼 수 있으나 이 지역의 간디스토마감염이 토착성인지는 더 추구되어야 할 과제라고 본다.

Ru nanoparticles supported graphene oxide catalyst for hydrogenation of bio-based levulinic acid to cyclic ethers

Upare, P.P.,Lee, M.,Lee, S.K.,Yoon, J.W.,Bae, J.,Hwang, D.W.,Lee, U.H.,Chang, J.S.,Hwang, Y.K. Elsevier Science Publishers 2016 CATALYSIS TODAY - Vol.265 No.-

<P>Ruthenium nanoparticles supported on graphene oxide (GO) catalysts have been evaluated for bio-based levulinic acid (LA) hydrogenation to produce vapor-phase cyclic ethers in a fixed-bed reactor. It was found that using the GO supported Ru nanoparticles (Ru/GO) produced additional hydrogenation products cyclic ethers (54%) and gamma-valerolactone (GVL; 41%), while Ru on carbon (Ru/C) catalysts gave only GVL with 100% LA conversion. To improve the yield of cyclic ethers, an additional two-step hydrogenation of LA via GVL was successfully carried out. This provided GVL as a second feedstock from which the Ru/GO catalyst could produce cyclic ethers such as methyltetrahydrofuran (MTHF) and tetrahydrofuran (THF). Ru on GO catalysts showed a 92% selectivity of predominantly cyclic ethers, including a 77% selectivity of MTHF through two steps process. Such a remarkable enhancement in activity and selectivity of LA hydrogenation over Ru/GO can be attributed to the well-dispersion of Ru nanoparticles, as well as favorable interaction with GO in the presence of oxy-functional groups of GO. In order to evaluate the active sites on the catalyst, they were characterized using different characterization techniques such as Raman, XRD, X-ray photoelectron spectroscopy (XPS), temperature-programmed reduction (TPR), temperature-programmed desorption of NH3 (TPD), electron microscopy (TEM and SEM) and H-2-chemisorption and N-2 adsorption. (C) 2015 Elsevier B.V. All rights reserved.</P>

Safety assessment of trans-tympanic photobiomodulation

Moon, T. H.,Lee, M. Y.,Jung, J. Y.,Ahn, J. C.,Chang, S. Y.,Chung, P. S.,Rhee, C. K.,Kim, Y. H.,Suh, M. W. Springer Science + Business Media 2016 Lasers in medical science Vol.31 No.2

<P>We evaluated functional and morphological changes after trans-tympanic laser application using several different powers of photobiomodulation (PBM). The left (L) ears of 17 rats were irradiated for 30 min daily over 14 days using a power density of 909.1 (group A, 5040 J), 1136.4 (group B, 6300 J), and 1363.6 (group C, 7560 J) mW/cm(2). The right (N) ears served as controls. The safety of PBM was determined by endoscopic findings, auditory brainstem response (ABR) thresholds, and histological images of hair cells using confocal microscopy, and light microscopic images of the external auditory canal (EAC) and tympanic membrane (TM). Endoscopic findings revealed severe inflammation in the TM of C group; no other group showed damage in the TM. No significant difference in ABR threshold was found in the PBM-treated groups (excluding the group with TM damage). Confocal microscopy showed no histological difference between the AL and AN, or BL and BN groups. However, light microscopy showed more prominent edema, inflammation, and vascular congestion in the TM of BL ears. This study found a dose-response relationship between laser power parameters and TM changes. These results will be useful for defining future allowance criteria for trans-tympanic laser therapies.</P>

오리고기에 있어서 저장기간에 따른 보수성과 지방산 조성변화

박구부,김영환,장판형 경상대학교 축산진흥연구소 1986 畜産振興硏究所報 Vol.13 No.1

This experiment was carried out to investigate changes in WHC, lipid contents and fatty acid composition from duck muscles(9 months) during postmortem storage. Experimental animals were normally slaughted to produce sample from leg, breast and gizzard muscles. And the samples were stored for 0, 8, 48, 96 and 168hrs at 4℃. Fatty acid compositions were analysed by GLC. The results obtained were as follows: WHC of duck muscles at right after slaugutering 71.7-74.0%, respectively. WHC decreased rapidly at 8hrs, but increased only slightly at 48hrs and increased a little at 168hrs postmortem storage. As the storage time passed the means of total lipid contents were 1-3% duck muscles, respectively. Fatty acid was identified to ten from myristic acid to arachidonic acid in duck muscles by GLC. The highest composition of fatty acids was oleic acid(38-44%) in duck muscles. The next higher compositions of fatty acid were linoleic(26-27%) and palmitic acid(19-22%) in breast and leg muscles. Although saturated fatty acids increased as the storage time passed, unsaturated fatty acids relatively decreased in experimental animals, the composition of unsaturated fatty acids was higher than that of saturated fatty acids.