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>

Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis

Yu, K‐,H.,Hong, K‐,S.,Lee, B‐,C.,Oh, M‐,S.,Cho, Y‐,J.,Koo, J‐,S.,Park, J‐,M.,Bae, H‐,J.,Han, M‐,K.,Ju, Y‐,S.,Kang, D‐,W.,Appelros, P. Blackwell Publishing Ltd 2011 Acta neurologica Scandinavica Vol.123 No.5

<P>Yu K‐H, Hong K‐S, Lee B‐C, Oh M‐S, Cho Y‐J, Koo J‐S, Park J‐M, Bae H‐J, Han M‐K, Ju Y‐S, Kang D‐W, Appelros P, Norrving B, Terent A. Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis. 
Acta Neurol Scand: 2011: 123: 325–331. 
© 2010 John Wiley & Sons A/S.</P><P><B>Background – </B> It has not been clarified whether the disparity in ischemic stroke outcome between populations is caused by ethnic and geographic differences or by variations in case mix. Propensity score matching (PSM) analysis can overcome some analytical problems but is rarely used in stroke outcome research. This study was to compare the ischemic stroke case‐fatality between two PSM cohorts of Sweden and Korea.</P><P><B>Methods – </B> Prognostic variables related to baseline characteristics and stroke care were included in our PSM model. Then, we selected 7675 Swedish and 1220 Korean patients with ischemic stroke from each stroke registers and performed one‐to‐one matching based on propensity scores of each patient.</P><P><B>Results – </B> After PSM, all measured variables were well balanced in 1163 matched subjects, and the 90‐day case‐fatality was identical 6.2% (HR 0.997, 95%CI 0.905–1.099) in Sweden and Korea.</P><P><B>Conclusions – </B> No difference is found in the 90‐day case‐fatality in propensity score‐matched Swedish and Korean patients with ischemic stroke.</P>

Multisite campaign on the open cluster M67 – I. Observations and photometric reductions

Stello, D.,Arentoft, T.,Bedding, T. R.,Bouzid, M. Y.,Bruntt, H.,Csubry, Z.,Dall, T. H.,Dind, Z. E.,Frandsen, S.,Gilliland, R. L.,Jacob, A. P.,Jensen, H. R.,Kang, Y. B.,Kim, S.-L.,Kiss, L. L.,Kjeldsen, Blackwell Publishing Ltd 2006 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.373 No.3

<P>ABSTRACT</P><P>We report on an ambitious multisite campaign aimed at detecting stellar variability, particularly solar-like oscillations, in the red giant stars in the open cluster M67 (NGC 2682). During the six-week observing run, which comprised 164 telescope nights, we used nine 0.6-m to 2.1-m class telescopes located around the world to obtain uninterrupted time series photometry. We outline here the data acquisition and reduction, with emphasis on the optimization of the signal-to-noise ratio of the low-amplitude (50–500 μmag) solar-like oscillations. This includes a new and efficient method for obtaining the linearity profile of the CCD response at ultrahigh precision (∼10 parts per million). The noise in the final time series is 0.50 mmag per minute integration for the best site, while the noise in the Fourier spectrum of all sites combined is 20 μmag. In addition to the red giant stars, this data set proves to be very valuable for studying high-amplitude variable stars such as eclipsing binaries, W UMa systems and δ Scuti stars.</P>

Down-regulation of p21-activated kinase 1 by progestin and its increased expression in the eutopic endometrium of women with endometriosis

Kim, S. H.,Lee, H. W.,Kim, Y. H.,Koo, Y. H.,Chae, H. D.,Kim, C. H.,Lee, P. R.,Kang, B. M. Oxford University Press 2009 Human reproduction Vol.24 No.5

<P>BACKGROUND: P21-activated kinase 1 (Pak1) integrates various signaling pathways that are vital to cell survival and function. This study was performed to evaluate whether sex steroids may regulate the expression of Pak1 in endometrial cells as well as whether its expression is increased in the eutopic endometrium of women with endometriosis. METHODS: Following in vitro estradiol (E(2)) and/or medroxyprogesterone acetate (MPA) treatment of Ishikawa cells and endometrial stromal cells (ESCs), Pak1 protein was analyzed utilizing western blot analysis and immunocytochemistry. Immunohistochemistry was performed to evaluate Pak1 immunoreactivity semiquantitatively in women with endometriosis and in controls. To assess the role of Pak1 on endometrial cell viability, crystal violet assay was performed following transfection of Ishikawa cells with Pak1 small interfering RNA (siRNA). RESULTS: In vitro treatment with E(2) plus MPA or MPA alone led to a significant decrease of Pak1 protein in Ishikawa cells and ESCs (both P < 0.05 versus control). Immunohistochemistry also revealed that Pak1 protein is significantly decreased during the secretory phase in both epithelial and stromal cells in the control subjects (P < 0.001 and P < 0.01, respectively). The immunoreactivity of Pak1 in glandular cells was significantly increased in the eutopic endometrium of women with endometriosis compared with the controls during the secretory phase (P < 0.01). Crystal violet assay has shown that transfection of Ishikawa cells with Pak1 siRNA led to a significant decrease of cellular viability (P < 0.05). CONCLUSIONS: These findings suggest that Pak1 is down-regulated by progesterone during the secretory phase in normal endometrium and increased Pak1 activity during the secretory phase might lead to establishment of endometriosis.</P>

Effects of Lacquer (Rhus verniciflua) Meal on Carcass Traits, Fatty Acid Composition and Meat Quality of Finishing Pigs

Song, C.H.,Choi, J.Y.,Yoon, S.Y.,Yang, Y.X.,Shinde, P.L.,Kwon, I.K.,Kang, S.M.,Lee, S.K.,Chae, B.J. Asian Australasian Association of Animal Productio 2008 Animal Bioscience Vol.21 No.8

This experiment was conducted to evaluate the effects of feeding different levels of lacquer (Rhus verniciflua Stokes) meal on the growth performance, carcass traits, fatty acid profile and meat quality of longissmuss dorsi (LD) muscle in finishing pigs. Pigs (n = 117; Landrace$\times$Yorkshire$\times$Duroc; initial body weight $80{\pm}0.4kg$) were allotted to three dietary treatments and fed lacquer at 0, 2 and 4% of the diet for five weeks. Inclusion of lacquer meal in the diets of pigs had no influence on their growth performance, carcass yield, loin eye area and fat free lean; however, pigs fed lacquer diets had lower backfat (linear, p = 0.006; quadratic, p = 0.004). Pigs fed increasing levels of lacquer meal had lower moisture (linear, p<0.001; quadratic, p = 0.008), crude fat (linear, p<0.001) and crude protein (linear, p<0.001; quadratic, p = 0.002) in LD muscle. The LD muscle of pigs fed lacquer meal had lower pH (linear and quadratic, p<0.05) at 6, 8 and 10 days, and linearly lower thio-barbituric acid reactive substances (TBARS, p<0.01) at 8 and 10 days and water holding capacity (WHC, p<0.05) at 3, 6, 8 and 10 days. The fatty acid composition of LD muscle revealed linearly lower stearic (p = 0.034) and total saturated fatty acid (p = 0.049) with increasing dietary lacquer meal levels. In general, higher lightness, redness and yellowness values were observed in LD muscle of pigs fed 2% lacquer meal on day 0 and subsequently on 3, 6, 8 and 10 days of refrigerated storage. The results of the current study suggest that lacquer meal can be incorporated up to 4% in the diet of finishing pigs without any adverse effects on performance; moreover, improvements in the meat quality during refrigerated storage can be obtained by inclusion of lacquer meal in the diet of finishing pigs.

Alpha-lipoic acid attenuates cisplatin-induced acute kidney injury in mice by suppressing renal inflammation

Kang, K. P.,Kim, D. H.,Jung, Y. J.,Lee, A. S.,Lee, S.,Lee, S. Y.,Jang, K. Y.,Sung, M. J.,Park, S. K.,Kim, W. Oxford University Press 2009 Nephrology, dialysis, transplantation Vol.24 No.10

<P>BACKGROUND: Cisplatin is a chemotherapeutic agent used in treatment of malignant tumours. However, cisplatin produces various side effects, such as nephrotoxicity, neurotoxicity, emetogenesis and ototoxicity. Inflammation is an important mechanism of cisplatin nephrotoxicity. Alpha-lipoic acid (alpha-LA) has anti-inflammatory effects that inhibit both adhesion molecule expression in human endothelial cells and monocyte adhesion by suppressing the nuclear factor-kappaB (NF-kappaB) signalling pathway. The goals of this study were to investigate the anti-inflammatory effects of alpha-LA during cisplatin-induced renal injury and to examine the mechanisms of protection. METHODS: C57BL/6 mice were given cisplatin (20 mg/kg) with or without alpha-LA treatment (100 mg/kg for 3 days). Renal function, histological changes, adhesion molecule expression and inflammatory cell infiltration were examined. The effect of alpha-LA on NF-kappaB activity was evaluated by examining nuclear translocation and phosphorylation of NF-kappaB p65 subunits in kidney tissue. RESULTS: Cisplatin-induced decreases in renal function, measured by blood urea nitrogen, serum creatinine level and renal tubular injury scores, were attenuated by alpha-LA treatment. alpha-LA decreased the tissue levels of tumour necrosis factor-alpha, the expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), and suppressed the infiltration of CD11b-positive macrophages. alpha-LA also attenuated the cisplatin-induced increases in the phosphorylation and nuclear translocation of NF- kappaB p65 subunits in kidney tissue. CONCLUSIONS: These results suggest that alpha-LA treatment ameliorates cisplatin-induced acute kidney injury by reducing inflammatory adhesion molecule expression and NF-kappaB activity.</P>

Circulating TNF receptors predict cardiovascular disease in patients with chronic kidney disease

Bae, Eunjin,Cha, Ran-Hui,Kim, Yong C.,An, Jung N.,Kim, Dong K.,Yoo, Kyung D.,Lee, Su M.,Kim, Myoung-Hee,Park, Jung T.,Kang, Shin-Wook,Park, Jae Y.,Lim, Chun S.,Kim, Yon S.,Yang, Seung H.,Lee, Jung P. Williams & Wilkins Co 2017 Medicine Vol.96 No.19

<P>We prospectively recruited 984 patients with CKD from 11 centers between 2006 and 2012. The levels of cTNFR1 and cTNFR2 were determined by performing an enzyme-linked immunosorbent assay. During the mean follow-up period of 4 years, 36 patients experienced a CVD event. The median serum concentrations of cTNFR1 and cTNFR2 were 2703.4 (225.6-13,057.7) and 5661.0 (634.9-30,599.6) pg/mL, respectively, and the cTNFR1 level was closely correlated with the cTNFR2 level (r=0.86, P < .0001). The urinary protein-to-creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) were significantly correlated with the cTNFR2 level (r=0.21 for UPCR, r=-0.67 for eGFR; P<.001 for all). Similar correlations were observed for serum cTNFR1 (r=0.21 for UPCR, r=-0.75 for eGFR; P < .001 for all). In the Cox proportional hazard analyses, cTNFR1 (hazard ratio [HR] 2.506, 95% confidence interval [CI] 1.186-5.295, P=.016) and cTNFR2 (HR4.156, 95% CI 1.913-9.030, P < .001) predictedCVDrisk even after adjustment for clinical covariates, such as UPCR, eGFR, and high-sensitivity C-reactive protein. cTNFR1 and 2 are associated with CVD and other risk factors in CKD, independently of eGFR and UPCR. Furthermore, cTNFRs could be relevant predictors of CVD in CKD patients.</P>

Validity of a commercial wearable sleep tracker in adult insomnia disorder patients and good sleepers

Kang, S.G.,Kang, J.M.,Ko, K.P.,Park, S.C.,Mariani, S.,Weng, J. Pergamon Press 2017 Journal of psychosomatic research Vol.97 No.-

Objectives: To compare the accuracy of the commercial Fitbit Flex device (FF) with polysomnography (PSG; the gold-standard method) in insomnia disorder patients and good sleepers. Methods: Participants wore an FF and actigraph while undergoing overnight PSG. Primary outcomes were intraclass correlation coefficients (ICCs) of the total sleep time (TST) and sleep efficiency (SE), and the frequency of clinically acceptable agreement between the FF in normal mode (FFN) and PSG. The sensitivity, specificity, and accuracy of detecting sleep epochs were compared among FFN, actigraphy, and PSG. Results: The ICCs of the TST between FFN and PSG in the insomnia (ICC=0.886) and good-sleepers (ICC=0.974) groups were excellent, but the ICC of SE was only fair in both groups. The TST and SE were overestimated for FFN by 6.5min and 1.75%, respectively, in good sleepers, and by 32.9min and 7.9% in the insomnia group with respect to PSG. The frequency of acceptable agreement of FFN and PSG was significantly lower (p=0.006) for the insomnia group (39.4%) than for the good-sleepers group (82.4%). The sensitivity and accuracy of FFN in an epoch-by-epoch comparison with PSG was good and comparable to those of actigraphy, but the specificity was poor in both groups. Conclusions: The ICC of TST in the FFN-PSG comparison was excellent in both groups, and the frequency of agreement was high in good sleepers but significantly lower in insomnia patients. These limitations need to be considered when applying commercial sleep trackers for clinical and research purposes in insomnia.

Multisite campaign on the open cluster M67 – III. δ Scuti pulsations in the blue stragglers

Bruntt, H.,Stello, D.,Suá,rez, J. C.,Arentoft, T.,Bedding, T. R.,Bouzid, M. Y.,Csubry, Z.,Dall, T. H.,Dind, Z. E.,Frandsen, S.,Gilliland, R. L.,Jacob, A. P.,Jensen, H. R.,Kang, Y. B.,Kim, S.-L. Blackwell Publishing Ltd 2007 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.378 No.4

<P>ABSTRACT</P><P>We have made an asteroseismic analysis of the variable blue stragglers in the open cluster M67. The data set consists of photometric time-series from eight sites using nine 0.6–2.1 m telescopes with a time-baseline of 43 d. In two stars, EW Cnc and EX Cnc, we detect the highest number of frequencies (41 and 26) detected in δ Scuti stars belonging to a stellar cluster, and EW Cnc has the second highest number of frequencies detected in any δ Scuti star. We have computed a grid of pulsation models that take the effects of rotation into account. The distribution of observed and theoretical frequencies shows that in a wide frequency range a significant fraction of the radial and non-radial low-degree modes are excited to detectable amplitudes. Despite the large number of observed frequencies we cannot constrain the fundamental parameters of the stars. To make progress we need to identify the degrees of some of the modes from either multicolour photometry or spectroscopy.</P>

Optimal Poultry Litter Management through GIS-based Transportation Analysis System

Kang, M.S.,Srivastava, P.,Fulton, J.P.,Tyson, T.,Owsley, W.F.,Yoo, K.H. The Korean Society of Agricultural Engineers 2006 한국농공학회논문집 Vol.48 No.7

Concentrated poultry production in the State of Alabama, U.S.A. results in excessive poultry litter. Application of poultry litter to pastures and row crops serves as a cheap alternative to commercial fertilizer. However, over the years, poultry litter application to perennial forage crops in the Appalachian Plateau region of North Alabama has resulted in phosphorus (P) buildup in soils. Phosphorus index (P-index) and comprehensive nutrient management plans (CNMP) are often used as a best management practice (BMP) for proper land application of litter. Because nutrient management planning is often not done for small animal feeding operations (AFOs), and also because, in case of excess litter, litter transportation infrastructure has not been developed, over application of poultry litter to near by area is a common practice. To alleviate this problem, optimal poultry litter management and transportation infrastructure needs to be developed. This paper presents a methodology to optimize poultry litter application and transportation through efficient nutrient management planning and transportation network analysis. The goal was accomplished through implementation of three important modules, a P-Index module, a CNMP module, and a transportation network analysis module within ArcGIS, a Geographic Information System (GIS). The CNMP and P-Index modules assist with land application of poultry litter at a rate that is protective of water quality, while the transportation network analysis module helps transport excess litter to areas requiring litter in the Appalachian Plateau and Black Belt (a nutrient-deficient area) regions. Once fully developed and implemented, such a system will help alleviate water quality problems in the Appalachian Plateau region and poor soil fertility problems in the Black Belt region by optimizing land application and transportation. The utility of the methodology is illustrated through a hypothetical case study.