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>

Serine palmitoyltransferase inhibitor myriocin induces growth inhibition of B16F10 melanoma cells through G₂/M phase arrest

Lee, Y.‐,S.,Choi, K.‐,M.,Choi, M.‐,H.,Ji, S.‐,Y.,Lee, S.,Sin, D.‐,M.,Oh, K.‐,W.,Lee, Y.‐,M.,Hong, J.‐,T.,Yun, Y.‐,P.,Yoo, H.‐,S. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.4

<P><B>Abstract</B></P><P><B>Objectives: </B> Melanoma is the most aggressive form of skin cancer, and it resists chemotherapy. Candidate drugs for effective anti‐cancer treatment have been sought from natural resources. Here, we have investigated anti‐proliferative activity of myriocin, serine palmitoyltransferase inhibitor, in the <I>de novo</I> sphingolipid pathway, and its mechanism in B16F10 melanoma cells.</P><P><B>Material and methods: </B> We assessed cell population growth by measuring cell numbers, DNA synthesis, cell cycle progression, and expression of cell cycle regulatory proteins. Ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate levels were analysed by HPLC.</P><P><B>Results: </B> Myriocin inhibited proliferation of melanoma cells and induced cell cycle arrest in the G<SUB>2</SUB>/M phase. Expressions of cdc25C, cyclin B1 and cdc2 were decreased in the cells after exposure to myriocin, while expression of p53 and p21<SUP>waf1/cip1</SUP> was increased. Levels of ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate in myriocin‐treated cells after 24 h were reduced by approximately 86%, 57%, 75% and 38%, respectively, compared to levels in control cells.</P><P><B>Conclusions: </B> Our results suggest that inhibition of sphingolipid synthesis by myriocin in melanoma cells may inhibit expression of cdc25C or activate expression of p53 and p21<SUP>waf1/cip1</SUP>, followed by inhibition of cyclin B1 and cdc2, resulting in G<SUB>2</SUB>/M arrest of the cell cycle and cell population growth inhibition. Thus, modulation of sphingolipid metabolism by myriocin may be a potential target of mechanism‐based therapy for this type of skin cancer.</P>

Search for Λc+→ϕpπ0 and branching fraction measurement of Λc+→K−π+pπ0

Pal, B.,Schwartz, A. J.,Adachi, I.,Aihara, H.,Al Said, S.,Asner, D. M.,Aushev, T.,Ayad, R.,Badhrees, I.,Bakich, A. M.,Bansal, V.,Behera, P.,Berger, M.,Bhardwaj, V.,Biswal, J.,Bobrov, A.,Bozek, A.,Bra& American Physical Society 2017 Physical review. D Vol.96 No.5

<P>We have searched for the Cabibbo-suppressed decay Lambda(+)(c) -> pi p(0) in e(+) e(-) collisions using a data sample corresponding to an integrated luminosity of 915 fb(-1). The data were collected by the Belle experiment at the KEKB e(+) e(-) asymmetric-energy collider running at or near the (4S) and (5S) resonances. No significant signal is observed, and we set an upper limit on the branching fraction of B(Lambda(+)(c) -> phi p(0)) < 15.3 x 10(-5) at 90% confidence level. The contribution of nonresonant Lambda(+)(c) -> K+ K- p pi(0) decays is found to be consistent with zero, and the corresponding upper limit on its branching fraction is set to be B(Lambda(+)(c) ->. K+ K- p pi(0))(NR) < 6.3 x 10(-5) at 90% confidence level. We also search for an intermediate hidden-strangeness pentaquark decay P-s(+) -> phi p. We see no evidence for this intermediate decay and set an upper limit on the product branching fraction of B(Lambda(+)(c) -> P-s(+) pi(0)) x B(P-s(+) -> phi p) < 8.3 x 10(-5) at 90% confidence level. Finally, we measure the branching fraction for the Cabibbo-favored decay Lambda(+)(c) -> K- pi(+) p pi(0); the result is B(Lambda(+)(c) -> K- pi(+) p pi(0)) = (4.42 +/- 0.05(stat)+/- 0.12(syst)+/- 0.16(norm))%, which is the most precise measurement to date.</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>

MINIMAL P-SPACES

Arya, S.P.,Bhamini, M.P. Department of Mathematics 1987 Kyungpook mathematical journal Vol.27 No.1

Minimal s-Urysohn and minimal s-regular spaces are studied. An s-Urysohn (respectively, s-regular) space (X, $\mathfrak{T}$) is said to be minimal s-Urysohn (respectively, minimal s-regular) if for no topology $\mathfrak{T}^{\prime}$ on X which is strictly weaker than $\mathfrak{T}$, (X, $\mathfrak{T}^{\prime}$) is s-Urysohn (respectively s-regular). Several characterizations and other related properties of these classes of spaces have been obtained. The present paper is a study of minimal P-spaces where P refers to the property of being an s-Urysohn space or an s-regular space. A P-space (X, $\mathfrak{T}$) is said to be minimal P if for no topology $\mathfrak{T}^{\prime}$ on X such that $\mathfrak{T}^{\prime}$ is strictly weaker than $\mathfrak{T}$, (X, $\mathfrak{T}^{\prime}$) has the property P. A space X is said to be s-Urysohn [2] if for any two distinct points x and y of X there exist semi-open set U and V containing x and y respectively such that $clU{\bigcap}clV={\phi}$, where clU denotes the closure of U. A space X is said to be s-regular [6] if for any point x and a closed set F not containing x there exist disjoint semi-open sets U and V such that $x{\in}U$ and $F{\subseteq}V$. Throughout the paper the spaces are assumed to be Hausdorff.

Seasonal and geographical toxicity of Indoxacarb against Helicoverpa armigera and influence of different host plants against Indoxacarb in India, 2005–2007

Basweshwar S. GHODKI,Shivcharan M. THAKARE,Mangesh P. MOHARIL,Nagarjuna G. V. RAO 한국곤충학회 2009 Entomological Research Vol.39 No.1

Indoxacarb, an oxadiazine insecticide, was evaluated for its effectiveness against Helicoverpa armigera collected from selected locations in India. Determination of Indoxacarb efficacy was done using a log-dose probit (LDP) bioassay against third instars collected from cotton (Gossypium arborium) fields near Akola, India. Monthly levels of toxicity of Indoxacarb were determined from July 2005 to March 2007. The maximum tolerance level of Indoxacarb was reported for the Amaravati strain (5.09 p.p.m.) and the minimum tolerance level for the Fatehbad strain (0.22 p.p.m.). Seasonal monitoring of Indoxacarb toxicity revealed an increased trend in tolerance from July 2005 to February 2006, which decreased from March 2006. The LC50 of Indoxacarb was 2.71 p.p.m. in July 2005 and 17.14 p.p.m. in February 2006. During 2006–007, the LC50 was 3.84 p.p.m. at the start of the season and in March 2007 it was 13.51 p.p.m. The minimum LC50 of Indoxacarb was reported for H. armigera larvae fed on Legasca spp. (1.62 p.p.m.) and the maximum LC50 was reported for H. armigera reared on chickpea (Cicer arietium) (8.45 p.p.m.). LC50 of 2.73 and 4.56 p.p.m. were reported for H. armigera fed on cotton (Gossypium arborium) and pigeonpea (Cajanus cajan), respectively.

放射菌을 利用한 異種間 原形質體 融合과 그 融合體의 安定性에 관한 硏究(Ⅱ)

閔洪基,金昌珉,孫麗源,韓惠勝,崔英珠,丁大映,韓康玄,李相燮,李欽淑,元奉必 국립보건연구원 1992 국립보건원보 Vol.29 No.2

Balanced intake of protein and carbohydrate maximizes lifetime reproductive success in the mealworm beetle, Tenebrio molitor (Coleoptera: Tenebrionidae)

Rho, M.S.,Lee, K.P. Pergamon Press 2016 Journal of insect physiology Vol.91 No.-

<P>Recent developments in insect gerontological and nutritional research have suggested that the dietary protein:carbohydrate (P:C) balance is a critical determinant of lifespan and reproduction in many insects. However, most studies investigating this important role of dietary P:C balance have been conducted using dipteran and orthopteran species. In this study, we used the mealworm beetles, Tenebrio molitor L. (Coleoptera: Tenebrionidae), to test the effects of dietary P:C balance on lifespan and reproduction. Regardless of their reproductive status, both male and female beetles had the shortest lifespan at the protein-biased ratio of P:C 5:1. Mean lifespan was the longest at P:C 1:1 for males and at both P:C 1:1 and 1:5 for females. Mating significantly curtailed the lifespan of both males and females, indicating the survival cost of mating. Age-specific egg laying was significantly higher at P:C 1:1 than at the two imbalanced P:C ratios (1:5 or 5:1) at any given age throughout their lives, resulting in the highest lifetime reproductive success at P:C 1:1. When given a choice, beetles actively regulated their intake of protein and carbohydrate to a slightly carbohydrate-biased ratio (P:C 1:1.54-1:1.64 for males and P:C 1:1.31:1.36 for females). The self-selected P:C ratio was significantly higher for females than males, reflecting a higher protein requirement for egg production. Collectively, our results add to a growing body of evidence suggesting the key role played by dietary macronutrient balance in shaping lifespan and reproduction in insects. (C) 2016 Elsevier Ltd. All rights reserved.</P>

MOA-2011-BLG-293Lb: A TEST OF PURE SURVEY MICROLENSING PLANET DETECTIONS

Yee, J. C.,Shvartzvald, Y.,Gal-Yam, A.,Bond, I. A.,Udalski, A.,Kozłowski, S.,Han, C.,Gould, A.,Skowron, J.,Suzuki, D.,Abe, F.,Bennett, D. P.,Botzler, C. S.,Chote, P.,Freeman, M.,Fukui, A.,Furusawa, K. IOP Publishing 2012 The Astrophysical journal Vol.755 No.2

<P>Because of the development of large-format, wide-field cameras, microlensing surveys are now able to monitor millions of stars with sufficient cadence to detect planets. These new discoveries will span the full range of significance levels including planetary signals too small to be distinguished from the noise. At present, we do not understand where the threshold is for detecting planets. MOA-2011-BLG-293Lb is the first planet to be published from the new surveys, and it also has substantial follow-up observations. This planet is robustly detected in survey+follow-up data (Delta chi(2) similar to 5400). The planet/host mass ratio is q = (5.3 similar to 0.2) x 10(-3). The best-fit projected separation is s = 0.548 +/- 0.005 Einstein radii. However, due to the s <-> s(-1) degeneracy, projected separations of s-1 are only marginally disfavored at Delta chi(2) = 3. A Bayesian estimate of the host mass gives M-L = 0.43(-0.17)(+0.27) M-circle dot, with a sharp upper limit of M-L < 1.2 M-circle dot from upper limits on the lens flux. Hence, the planet mass is m(p) = 2.4(-0.9)(+1.5) M-Jup, and the physical projected separation is either r(perpendicular to) similar or equal to 1.0 AU or r(perpendicular to) similar or equal to 3.4 AU. We show that survey data alone predict this solution and are able to characterize the planet, but the Delta chi(2) is much smaller (Delta chi(2) similar to 500) than with the follow-up data. The Delta chi(2) for the survey data alone is smaller than for any other securely detected planet. This event suggests a means to probe the detection threshold, by analyzing a large sample of events like MOA-2011-BLG-293, which have both follow-up data and high-cadence survey data, to provide a guide for the interpretation of pure survey microlensing data.</P>

Local structures and electronic band states of α−Fe2O3 polycrystalline particles in the glazes of the HIZEN celadons produced in the Edo period of Japan, by means of X-ray absorption spectra (II)

Hidaka, M.,Ohashi, K.,Wijesundera, R. P.,Kumara, L. S. R.,Sugihara, S.,Momoshima, N.,Kubuki, S.,Sung, N. E. SciELO 2011 Cerâmica Vol.57 No.342

<▼1><P>HIZEN celadon glazes produced in 1630's to 1790's (Edo period, Japan) have been investigated by means of X-ray absorption spectra (XAS) near a Fe-K edge by using synchrotron radiation and a Mössbauer spectrum. The XAS suggest that the local structure around Fe2O3 fine powders is slightly different between the Izumiyama ceramics of mainly the Quartz-SiO2 and Ohkawachi ceramics of mainly the feldspar of (K,Na)Si3O8 (Sanidine), and that the glazes of the HIZEN celadons include the Fe2O3 fine powders in the glassy state, though the X-ray diffraction patterns of the glassy celadon glazes do not show any peaks of the Fe2O3 structure. The Mössbauer spectrum suggests that the celadon glaze of Seiji (m) includes only Fe3+ ions, but not Fe2+ ions. This indicates the existence of Fe2O3 in the celadon glaze. It is interpreted that the colored brightness of the HIZEN celadons is induced by the structural properties of the used raw celadon ceramics and the other transition-metal ions of Cr, Cu, Zn in the celadon glazes, but not by the chemical reaction from Fe2O3 to FeO under the deoxidizing thermal treatment at higher temperature in a kiln.</P></▼1><▼2><P>Esmaltes de celadon Hizen produzidos dos anos 1630 a 1790 (período Edo, Japão) foram investigados por meio de espectros de absorção de raios X (XAS) próximos da linha Fe-K usando radiação síncrotron e espectro Mossbaues. Os resultados de XAS sugerem que a estrutura local em pós finos de Fe2O3 é levemente diferente entre as cerâmicas Izumiyama principalmente o quartzo e cerâmicas Ohkawachi principalmente do feldspato (K,Na)Si3O8 (Sanidine), e que os esmaltes dos celadons Hizen incluem finos pós de Fe2O3 no estado vítreo, embora os difratogramas de raios X dos esmaltes celadon não mostrem picos da estrutura do Fe2O3. O espectro Mossbauer sugere que os esmaltes celadon de Seiji (m) incluem somente íons Fe3+, mas não Fe2+. Isto indica a existência de Fe2O3 no esmalte celadon. É feita a interpretação que o brilho nas cores dos celadons Hizen é induzido pelas propriedades estruturais das cerâmicas básicas de celadon e os outros metais de transição Cr, Cu, Zn nos esmaltes celadon, mas não pela reação química entre Fe2O3 para FeO sob tratamento térmico desoxidante em forno a altas temperaturas.</P></▼2>