Sphingosine-1-phosphate-induced Flk-1 transactivation stimulates mouse embryonic stem cell proliferation through S1P₁/S1P₃-dependent β-arrestin/c-Src pathways

Ryu, J.M.,Baek, Y.B.,Shin, M.S.,Park, J.H.,Park, S.H.,Lee, J.H.,Han, H.J. Elsevier 2014 Stem cell research Vol.12 No.1

Although recent findings showed that the bioactive lipid metabolites can regulate the ES cell functions, the physiological relevance of interaction between sphingosine-1-phosphate (S1P) and Flk-1 and its related signaling molecules are not yet clear in ES cell proliferation. In the present study, S1P<SUB>1-5</SUB> receptors were expressed in mouse ES cells and S1P increased S1P<SUB>1-3</SUB> receptor expression level. S1P treatment stimulated the cellular proliferation in S1P<SUB>1/3</SUB>-dependent manner, located in lipid rafts. In response to S1P, β-arrestin was recruited to S1P<SUB>1/3</SUB> receptor and c-Src was activated. S1P also increased the binding of S1P<SUB>1/3</SUB> receptor with Flk-1. Similar to responses for VEGF, S1P increased Flk-1 phosphorylation, which was blocked by β-arrestin siRNA, and PP2, but not by VEGF-A<SUB>164</SUB> antibody or VEGF siRNA. In addition, S1P induced VEGF expression and VEGFR2 kinase inhibitor (SU1498) blocked the S1P-induced cellular proliferation. However, VEGF-A<SUB>164</SUB> antibody or VEGF siRNA partially blocked S1P-induced cellular proliferation, suggesting that both VEGF-dependent Flk-1 activation and VEGF-independent Flk-1 activation are involved in S1P-induced ES cell proliferation. S1P and VEGF-induced phosphorylation of ERK and JNK were blocked by pretreatment with SU1498. Moreover, inhibition of ERK and JNK blocked S1P-induced cellular proliferation. In conclusion, S1P-elicited transactivation of Flk-1 mediated by S1P<SUB>1/3</SUB>-dependent β-arrestin/c-Src pathways stimulated mouse ES cell proliferation.

충청지역에서 발생한 쭈쭈가무시병의 임상상, 원인균의 혈청형 및 혈청역학적 연구

김선영,김윤성,박장규,윤태영,강재승,송인숙,최명식,최인학,차창룡,이우곤,박종우,이증훈,장우현,유영해,윤광혁,송계용 대한감염학회 1989 감염 Vol.21 No.2

From September to december 1987, eighty-six cases of tsutsugamushi disease were diagnosed by indirect immunofluorecent test or by isolating the causative agent in Chungcheung area. Their clinical features and patterns of antibody response to R. tsutsugamushi were analyzed. For the indenfication of prevalent antigenic types of R. tsutsugamushi in Chungcheung area, twenty-seven strains isolated were tested by indirect immunofluorescent test. To assess the extent of exposure to R.tsutsugamushi of a general population in Korea, the prevalence of antibody was investigated in 6,572 sera obtained from the residents of Chungcheung area by indirect immunofluorescent test. The female patients slightly outnumbered the male patients. More cases (68%) were older than 40 years of age. The epidemic peaked in October. The mean incubation period estimated was about 8 days. The major clinical features were fever and chill, headache, rash, eschar, and lymphadenopathy. Increased serm transaminase was the most singificant laboratory findings. Abnormalities in the chest roentgenography were often observed. The antibody titer rose rapidly 5 days after the onset, reached its peak at 20 days (1:640), and then declined agradually until 7 months(1:20). The seroype of 23 out of the 27 isolates wase found to be karp, one was Gilliam, and 3 isolates could not be classified by using polyclonal mouse hyperimmune sera. The prevalence of antibody to R.tsutsugamushi in the residents of Chungcheung area was 4.8%. The prevalence of antibody was higher in the female than in the male. The prevalence was higher in the residents of age above 40 years than below 40 years, and was the lowest in the children less than 10 years of age. Of the 318 positive sera from normal residents, only 2 sera showed the titers higher than 1:80.

여대생의 월경시 불편감과 삶의 질에 대한 연구

김지선,노자민,류진영,오정연,이서주,정미영,조재실,주한별 이화여자대학교 간호과학대학 2011 이화간호학회지 Vol.- No.45

The purpose of this study was to investigate the aspect and degree of female university students' menstruation discomfort and to study how the menstruation discomfort affects their quality of life The subjects consisted of 315 female university students in Seoul City by convenience sampling from July 22 to August 3, 2010. The data was collected by structured questionnaire that included general characteristics, Menstrual Distress Questionnaire and Smith Kline Beecham 'Quality of Life' Scale. To analyze the data, used the following methods: frequency, mean, standard deviation, t-test, ANOVA, Pearson's correlation coefficients with the SPSS program 15.0. The Results as follows: The participants indicated water accumulation, the ache, negative emotion, conduct change and attention intensive obstacle order to show the women's menstrual discomforts and the quality of life was high competent feeling, body and mental stability, vitality and stability order. The correlation of the women's menstrual discomforts and the quality of life was r=-.605 and p=.000, the women's menstrual discomforts and the quality of life show considerably negative correlation. In the event that the women's menstrual discomforts was high comes to be low appeared the quality of life. As a result, this study showed that the women's menstrual discomforts and the quality of life have negative correlation, and discovered various factors which effect to the menstrual discomforts and the quality of life for the women's college students. Thus in the future, do a research for the middle school girls, the maiden and married women, and the repetition research of the women's college student is necessary. The nursing arbitration program development for relaxation of the women's menstrual discomforts is necessary as well.

<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>

Phase I/II study of S-1 combined with weekly docetaxel in patients with metastatic gastric carcinoma

Park, S R,Kim, H K,Kim, C G,Choi, I J,Lee, J S,Lee, J H,Ryu, K W,Kim, Y-W,Bae, J-M,Kim, N K Cancer Research UK 2008 The British journal of cancer Vol.98 No.8

We designed a phase I/II trial of S-1 combined with weekly docetaxel to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in metastatic gastric carcinoma (MGC). Patients with measurable disease received S-1 orally b.i.d. on days 1–14 and docetaxel intravenously on days 1 and 8 every 3 weeks. In phase I (n=30), each cohort received escalating doses of S-1 (30–45 mg m<SUP>−2</SUP> b.i.d.) and docetaxel (25–40 mg m<SUP>−2</SUP>); MTD was 45 mg m<SUP>−2</SUP> b.i.d. S-1/35 mg m<SUP>−2</SUP> docetaxel and RD was 40 mg m<SUP>−2</SUP> b.i.d. S-1/35 mg m<SUP>−2</SUP> docetaxel. Dose-limiting toxicities included grade 3 elevated liver enzymes, gastric perforation, grade 3 diarrhoea/fatigue, febrile neutropenia with grade 3 anorexia/fatigue, and neutropenic infection with grade 3 stomatitis/anorexia. In phase II (n=52), the overall response rate was 66.7% (95% confidence interval (CI): 53.8–79.6%) and the median time to progression and overall survival were 6.5 months (95% CI: 4.9–8.1) and 13.7 months (95% CI: 9.9–17.5), respectively. The most common grade 3/4 toxicity was neutropenia (29.4%), and febrile neutropenia/neutropenic infection occurred in 19.6% of patients. Non-haematological toxicities were generally mild. There was one treatment-related death due to pneumonitis. S-1 combined with weekly docetaxel is active in MGC with moderate toxicities.British Journal of Cancer (2008) 98, 1305–1311. doi:10.1038/sj.bjc.6604312 www.bjcancer.com Published online 25 March 2008

다운증후군의 산전진단을 위한 다양한 선별검사의 기여율 비교 - 산전 및 신생아때 진단된 96 례 분석 -

한정열(J . Y . Han),김문영(Y. M . Kim),조준형(J . H . Cho),안현경(H . K . Ahn),류현미(H . M . Ryu),김진미(J . M . Kim),김영미(Y . M . Kim),박소연(S . Y . Park),한혜경(H . K . Han),이영호(Y . H . Lee),양재혁(J . H . Yang) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.10

연구의 목적은 다운증후군을 산전진단하기 위한 다양한 산전선별검사 (나이; 35세 이상, 임산부 혈청 marker를 이용한 triple test, 초음파; 비정상 소견, 후경부 투명대 (nuchal translucency), 후경부두께 (nuchal fold thickness))의 기여율를 비교하기 위한 것이다. 1990년 1월부터 1999년 9월까지 본원에서 산전 및 산후에 진단된 례는 총 96례 이었다. 산전 및 신생아기에 진단된 다운증후군의 빈도는 각각 68례 (71 %), 28례 (29 %)였다. 다운증후군 태아를 임신했던 임산부의 평균연령은 33±5.7세이다. 다운증후군의 1,000분만당 연도별 빈도율은 1990년부터 1999년까지 각각 0.4, 1.3, 0.7, 0.7, 1.6, 0.7, 1.2, 2.2, 2.0, 그리고 2.3 (Y=0.28±0.18 year, P=0.01)이었다. 산전진단된 다운증후군의 비율 (%)은 지난 10년간 각각 0 (0/2), 43 (3/7), 50 (2/4), 25 (1/4), 56 (5/9), 100 (5/5), 71 (5/7), 78 (14/18), 78 (14/18), 그리고 89 (17/19) (Y=12.9±8.9 year, P=0.000) 이었다. 다운증후군을 산전진단하기 위한 다양한 산전선별 검사에 따른 기여율은 35세이상의 연령에 의하면 30.2±5.6 %, triple test의 경우 18.2±3.4 %, 초음파에 의한 경우 51.7±6.3 % 이며, 초음파에 의한 산전 선별 검사가 통계적으로 유의하게 연령이나 triple test에 의한 경우 보다 다운증후군의 산전진단에 기여율이 높았다. (P=0.008) 결론적으로 본 연구에 의하면 지난 10년 동안 다운증후군을 산전 진단하기 위한 여러 선별 검사방법의 적용은 효율적이었으며, 특히 초음파에서 다양한 소견을 이용한 다운증후군의 산전선별검사는 연령이나 triple test 보다는 더욱더 의미가 있다고 추론된다. Objective : The purpose of this study was comparison of the contribution rate for prenatal diagnosis of Down syndrome using various screening methods (Age: greater than or equal to 35 years old, Serum markers: Triple test, Ultrasonography: abnormal sonographic findings, nuchal translucency, nuchal fold thickness).Methods : Total 96 cases of Down syndrome, prenatally or postnatally diagnosed between Jan. 1990 and Sept. 1999, made up the study population. We got the contribution rate of various prenatal screening methods of down syndrome, and obtained the efficiency of various screening program applied for last 10 years. Results : The frequencies of Down syndrome confirmed in prenatal and postnatal were 68 (71%) and 28 (29%) in respectively. The mean age of mother of Down syndrome fetus was 33.0±5.7 years old. The frequency rate of Down syndrome was 0.4, 1.3, 0.7, 0.7, 1.6, 0.7, 1.2, 2.2, 2.0 and 2.3 a 1,000 deliveries from 1990 to 1999 (Y= 0.28+0.18 year, P=0.01). The percentage of Down syndrome diagnosed prenatally was 0 (0/2), 43 (3/7), 50 (2/4), 25 (1/4), 56 (5/9), 100 (5/5), 71 (5/7), 78 (14/18), 78 (14/18) and 89 (17/19) from 1990 to 1999 (Y= 12.9+8.9 year, P=0.000). The contribution rate of prenatal diagnosis for Down syndrome was 30.2±5.6% by age, 18.2±3.4% by triple test and 51.7±6.3% by ultrasonography, and was significantly difference among each screen methods (P=0.008). Conclusions : This study shows that our prenatal screening program is highly effective to detect Down syndrome and especially ultrasonographic findings (abnormal sono findings, Nuchal translucency, Nuchal fold thickness) may be more important than that of age or Triple test to detect the Down syndrome prenatally.

혈청 LDH 효소분석 검사의 효준화에 관한 연구(Ⅴ)

이창규,이승관,조경진,박종성,정수경,유병서,박상숙,류정록,남현철,김석수,김상섭,김재영,이국성 高麗大學校 倂設 保健大學 保健科學硏究所 1998 保健科學論集 Vol.24 No.1

Since the Korean Association of Quality Assurance for Clinical Laboratory was established in 1976, the numbers of the participating hospitals nowadays were increased from 40 to 450 or more hospitals all over the country. In the early day the both internal and external quality control programs were started at the same time, however, the external QC programs prevailed over the internal ones putting the cart before the horse. The accuracy and the precision of the data are not satisfying in spite of the 20 years experiences of quality control programs. All the daily data should be reported after the validity is assured by the self-evaluation not by third party evaluation. It is regret that the CVs of enzymatic tests in external QC are exceeding 10% and there is no sign of diminishing CVs. One of the major reasons is that the types of anaytical instrurments and reagents are diverisified. Moreover, most of them are subject to the standards of the respective country of manufacturer. Accordingly, we can make a suggestion that the reagents and instruments should be imported or supplied meeting the established requirements for Korean standardization.

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>

Kurarinol, tyrosinase inhibitor isolated from the root of Sophora flavescens

Ryu, Y.B.,Westwood, I.M.,Kang, N.S.,Kim, H.Y.,Kim, J.H.,Moon, Y.H.,Park, K.H. G. Fischer 2008 Phytomedicine Vol.15 No.8

It is well known that flavanones, sophoraflavanone G 1, kurarinone 2, and kurarinol 3, from the root of Sophora flavescens, have extremely strong tyrosinase inhibitory activity. This study delineates the principal pharmacological features of kurarinol 3 that lead to inhibition of the oxidation of l-tyrosine to melanin by mushroom tyrosinase (IC<SUB>50</SUB> of 100nM). The inhibition kinetics analyses unveil that compounds 1 and 2 are noncompetitive inhibitors. However similar analysis shows kurarinol 3 to be a competitive inhibitor. Compounds 1 and 2 exhibited potent antibacterial activity with 10μg/disk against Gram-positive bacteria, whereas kurarinol 3 did not ostend any antibacterial activity. Interestingly, kurarinol 3 inhibits production of melanin in S. bikiniensis without affecting the growth of microorganism. It is thus distinctly different from the other tyrosinase inhibitors 1 and 2. In addition, kurarinol 3 manifests relatively low cytotoxic activity (EC<SUB>50</SUB>>30μM) compared to 1 and 2. To account for these observations, we conducted molecular modeling studies. These suggested that the lavandulyl group within 3 is instrumental in the interaction with the enzyme. More specifically, the terminal hydroxy function within the lavandulyl group is most important for optimal binding.

식물공장용 포트묘 로봇 이식기 개발

류관희,김기영,류영선,한재성 한국농업기계학회 1998 바이오시스템공학 Vol.23 No.3