Feasibility of proposed single-nucleotide polymorphisms as predictive markers for targeted regimens in metastatic colorectal cancer

Kim, J C,Ha, Y J,Roh, S A,Choi, E Y,Yoon, Y S,Kim, K P,Hong, Y S,Kim, T W,Cho, D H,Kim, S Y,Kim, Y S Nature Publishing Group 2013 The British journal of cancer Vol.108 No.9

<P><B>Background:</B></P><P>Surrogate biomarkers for metastatic colorectal cancer (mCRC) are urgently needed to achieve the best outcomes for targeted therapy.</P><P><B>Methods:</B></P><P>A clinical association analysis was performed to examine the three single-nucleotide polymorphisms (SNPs) that were previously proposed as markers of chemosensitivity to the cetuximab (124 patients) and bevacizumab regimens (100 patients) in mCRC patients. In addition, biological correlations were examined for the candidate SNPs in terms of their regulatory pathway.</P><P><B>Results:</B></P><P>For cetuximab regimens, patients homozygous for the wild-type alleles (<I>GG</I>) of <I>LIFR rs3729740</I> exhibited a 1.9 times greater overall response rate (ORR) and 1.4 months longer progression-free survival (PFS) than those homozygous or heterozygous for the mutant allele (<I>GA</I> and <I>AA</I>; <I>P</I>=0.022 and 0.027, respectively). For bevacizumab regimens, patients homozygous for the minor alleles (<I>TT</I>) of <I>ANXA11 rs1049550</I> exhibited an ORR twice as high as those homozygous or heterozygous for the ancestral allele (<I>CC</I> and <I>CT</I>; <I>P</I>=0.031). Overall response rate gain was achieved up to 10% in patients with wild-type <I>LIFR rs3729740</I> patients either with wild-type <I>KRAS</I> or skin toxicity (<I>P</I>=0.001) respectively. Specifically in clones treated with cetuximab and bevacizumab regimens, active p-ERK and MMP-9 expressions were significantly reduced in clones expressing wild-type <I>LIFR rs3729740</I> (<I>P</I>=0.044) and in those expressing minor-type <I>ANXA11 rs1049550</I> (<I>P</I>=0.007), respectively.</P><P><B>Conclusion:</B></P><P><I>LIFR rs3729740</I> and possibly <I>ANXA11 rs1049550</I> may be useful as biomarkers for predicting whether mCRC patients are sensitive to relevant target regimens, although further validation in large cohorts is needed.</P>

P. C 강선에서 Patenting 열처리에 미치는 인장응력의 영향

이찬규,신평우,홍종휘 고려대학교 공학기술연구소 1982 고려대학교 생산기술연구소 연구보고 Vol.17 No.1

Optimum heat treatment producing P.C. wire is the most important for the further drawing. Drawability depends on the metallic microstructure and mechanical properties. Mechanical properties depend on the amount of pro-eutctoid ferrite and the fineness of pearlite. The amount of ferrite and the fineness of pearlite are dominated by the solid solution treatment and the cooling velocity from the sutenitizing temperature to the patenting temperature. Basides the above, the tension stress is very effective for ausenitizing and eutectoid reaction. The results obtained from this investigation could be summarized as follows. 1. Drawabdity was lowered by the precipitation of pro-eutectoid ferrite as the solid solution treating time was longer. 2. Slow cooling velocity from solid solution treating temperature to the isothermal transformation temperature made the drawability poor. 3. Solid solution treatment under tension stress was very effective for reducing the solid solution treating time and for refining the pearlite. 4. Solid solution treatment under tension stress and rapid cooling from 950 % to 540 % made the pearlite fine and increased drawability.

Polarization and Space-Charge-Limited Current in III-Nitride Heterostructure Nanowires

Mastro, M. A.,Hong-Youl Kim,Jaehui Ahn,Simpkins, B.,Pehrsson, P.,Jihyun Kim,Hite, J. K.,Eddy, C. R. IEEE 2011 IEEE transactions on electron devices Vol.58 No.10

<P>An undoped AlGaN/GaN nanowire (NW) demonstrated p-type conductivity solely based on the formation of hole carriers in response to the negative polarization field at the (000-1) AlGaN/GaN facet. A transistor based on this NW displayed a low-voltage transition from ohmic to space-charge-limited conduction. A numerical simulation showed that a highly asymmetric strain exists across the triangular cross section, which creates a doublet peak in the piezoelectric-induced polarization sheet charge at the (000-1) facet. Additionally, there is a strong interplay between the charge at the (000-1) AlGaN/GaN interface with depletion from the three surfaces, as well as an interaction with the opposing polarization fields at two semipolar {- 110-1} facets. The charge distribution and resultant conduction regime is highly interdependent on the configuration of the multilayer structure, and it is not amenable to an analytical model.</P>

Effects of Timing of Initial Cutting and Subsequent Cutting on Yields and Chemical Compositions of Cassava Hay and Its Supplementation on Lactating Dairy Cows

Hong, N.T.T.,Wanapat, M.,Wachirapakorn, C.,Pakdee, P.,Rowlinson, P. Asian Australasian Association of Animal Productio 2003 Animal Bioscience Vol.16 No.12

Two experiments were conducted to examine the production and quality of cassava hay and its utilization in diets for dairy cows. In experiment I, a $2{\times}2$ Factorial arrangement in a randomized complete block design with 4 replications was carried out to determine the effects of different initial (IC) and subsequent cutting (SC) on yield and composition of cassava plant. The results revealed that cassava could produce from 4 to 7 tonne of DM and 1.2 to 1.6 tonne of CP for the first six months after planting. CP content in cassava plant ranged from 20.8 to 28.5% and was affected by different SC regimes. Condensed tannin in cassava foliage ranged from 4.9 to 5.5%. Initial cutting at 2 months with subsequent cutting at 2 month intervals was the optimal to obtain high dry matter and protein yield. In the second experiment, five crossbred Holstein-Friesian cows in mid lactation with an initial live-weight of 505${\pm}6.1kg$ and average milk yield of 10.78${\pm}1.2kg/d$ were randomly assigned in a $5{\times}5$ Latin square design to study the effects of 2 levels of CH (1 and 2 kg/hd/d) and concentrate (1 to 2 kg of milk and 1 to 3 kg of milk) on milk yield and milk composition. The results showed that cassava hay increased rumen $NH_3-N$ and milk urea nitrogen (MUN) (p<0.05). Cassava hay tended to increase milk production and 4% FCM. Milk protein increased in cows fed cassava hay (p<0.05). Moreover, cassava hay could reduce concentrate levels in dairy rations thus resulting in increased economic returns. Cassava hay can be a good source of forage to reduce concentrate supplementation and improve milk quality.

Gut-Specific Delivery of T-Helper 17 Cells Reduces Obesity and Insulin Resistance in Mice

Hong, C.P.,Park, A.,Yang, B.G.,Yun, C.H.,Kwak, M.J.,Lee, G.W.,Kim, J.H.,Jang, M.S.,Lee, E.J.,Jeun, E.J.,You, G.,Kim, K.S.,Choi, Y.,Park, J.H.,Hwang, D.,Im, S.H.,Kim, J.F.,Kim, Y.K.,Seoh, J.Y.,Surh, C. Elsevier North Holland [etc.] 2017 Gastroenterology Vol.152 No.8

<P>BACKGROUND & AIMS: Obesity and metabolic syndrome have been associated with alterations to the intestinal microbiota. However, few studies examined the effects of obesity on the intestinal immune system. We investigated changes in subsets of intestinal CD4(+) T-helper (T-H) cells with obesity and the effects of gut-tropic T(H)17 cells in mice on a high-fat diet (HFD). METHODS: We isolated immune cells from small intestine and adipose tissue of C57BL/6 mice fed a normal chow diet or a HFD for 10 weeks and analyzed the cells by flow cytometry. Mice fed a vitamin A-deficient HFD were compared with mice fed a vitamin A-sufficient HFD. Obese RAG1-deficient mice were given injections of only regulatory T cells or a combination of regulatory T cells and T(H)17 cells (wild type or deficient in integrin beta 7 subunit or interleukin 17 [IL17]). Mice were examined for weight gain, fat mass, fatty liver, glucose tolerance, and insulin resistance. Fecal samples were collected before and after T cell transfer and analyzed for microbiota composition by metagenomic DNA sequencing and quantitative polymerase chain reaction. RESULTS: Mice placed on a HFD became obese, which affected the distribution of small intestinal CD4(+) T-H cells. Intestinal tissues from obese mice had significant reductions in the proportion of T(H)17 cells but increased proportion of T(H)1 cells, compared with intestinal tissues from nonobese mice. Depletion of vitamin A in obese mice further reduced the proportion of T(H)17 cells in small intestine; this reduction correlated with more weight gain and worsening of glucose intolerance and insulin resistance. Adoptive transfer of in vitro-differentiated gut-tropic T(H)17 cells to obese mice reduced these metabolic defects, which required the integrin beta 7 subunit and IL17. Delivery of T(H)17 cells to intestines of mice led to expansion of commensal microbes associated with leanness. CONCLUSIONS: In mice, intestinal T(H)17 cells contribute to development of a microbiota that maintains metabolic homeostasis, via IL17. Gut-homing T(H)17 cells might be used to reduce metabolic disorders in obese individuals.</P>

Selective production of 1-monocaprin by porcine liver carboxylesterase-catalyzed esterification: Its enzyme kinetics and catalytic performance

Park, K.M.,Lee, J.H.,Hong, S.C.,Kwon, C.W.,Jo, M.,Choi, S.J.,Kim, K.,Chang, P.S. IPC Science and Technology Press ; Elsevier Scienc 2016 Enzyme and microbial technology Vol.82 No.-

<P>Porcine liver carboxylesterase (PLE) belongs to carboxylesterase family (EC 3.1.1.1) as a serine-type esterase. The PLE-catalyzed esterification of capric acid with glycerol in reverse micelles was investigated on the catalytic performance and enzyme kinetics. The most suitable structure of reverse micelles was comprised of isooctane (reaction medium) and bis(2-ethylhexyl) sodium sulfosuccinate (AOT, anionic surfactant) with 0.1 of R-value ([water]/[surfactant]) and 3.0 of G/F-value ([glycerol]/[fatty acid]) for the PLE-catalyzed esterification. In the aspect of regio-selectivity, the PLE mainly produced 1-monocaprin without any other products (di- and/or tricaprins of subsequent reactions). Furthermore, the degree of esterification at equilibrium state (after 4 h from the initiation) was 62.7% under the optimum conditions at pH 7.0 and 60 degrees C. Based on Hanes-Woolf plot, the apparent K-m and V-max values were calculated to be 16.44 mM and 38.91 mu M/min/mg protein, respectively. (C) 2015 Elsevier Inc. All rights reserved.</P>

Bioaccessibility of AhR-active PAHs in sediments contaminated by the Hebei Spirit oil spill: Application of Tenax extraction in effect-directed analysis

Hong, S.,Yim, U.H.,Ha, S.Y.,Shim, W.J.,Jeon, S.,Lee, S.,Kim, C.,Choi, K.,Jung, J.,Giesy, J.P.,Khim, J.S. Pergamon Press 2016 CHEMOSPHERE - Vol.144 No.-

Bioaccessibility of toxic substances in sedimentary residual oil is a crucial factor that needs to be considered for accurate risk assessments posed by oil spills. However, information on oil weathering processes and bioaccessibility of residual oil is often not sufficient and clear. In the present study, bioaccessibility of aryl hydrocarbon receptor (AhR)-active polycyclic aromatic hydrocarbons (PAHs) in coastal sediments near the site of the Hebei Spirit oil spill (Korea, 2007) was assessed by Tenax extraction in effect-directed analysis (EDA). Sediment samples collected 6 years after the oil spill were extracted using Soxhlet or Tenax, and EDA was performed using a battery of H4IIE-luc bioassay and GC/MSD analysis. Concentrations of PAHs and alkyl-PAHs in Soxhlet extracts ranged from 210 to 53,000 μg kg<SUP>-1</SUP> dry mass. However, concentrations of PAHs and alkyl-PAHs in Tenax extracts were approximately 20-fold less compared to those in Soxhlet extracts. In Soxhlet and Tenax extracts, the major AhR-active PAHs were identified as C1-chrysene, C3-chrysene, and C4-phenanthrene. Concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TEQ<SUB>PAHs</SUB>) explained 31% and 60% of the bioassay-derived TCDD-EQ concentrations in Soxhlet and Tenax extracts, respectively. Overall, bioaccessibility of PAHs and alkyl-PAHs in sedimentary residual oils depended on hydrophobicity (log K<SUB>ow</SUB>) and degree of weathering of crude oil. The results of the present study provide further evidence in support of the biological and ecological recoveries of oil spill sites.

Variable number of tandem repeats of 9 Plasmodium vivax genes among Southeast Asian isolates

Wang, B.,Nyunt, M.H.,Yun, S.G.,Lu, F.,Cheng, Y.,Han, J.H.,Ha, K.S.,Park, W.S.,Hong, S.H.,Lim, C.S.,Cao, J.,Sattabongkot, J.,Kyaw, M.P.,Cui, L.,Han, E.T. Verlag fur Recht und Gesellschaft 2017 Acta tropica Vol.170 No.-

<P>The variable number of tandem repeats (VNTRs) provides valuable information about both the functional and evolutionary aspects of genetic diversity. Comparative analysis of 3 Plasmodium falciparum genomes has shown that more than 9% of its open reading frames (ORFs) harbor VNTRs. Although microsatellites and VNTR genes of P. vivax were reported, the VNTR polymorphism of genes has not been examined widely. In this study, 230 P. vivax genes were analyzed for VNTRs by SERV, and 33 kinds of TR deletions or insertions from 29P. vivax genes (12.6%) were found. Of these, 9 VNTR fragments from 8 P. vivax genes were used for PCR amplification and sequence analysis to examine the genetic diversity among 134 isolates from four Southeast Asian countries (China, Republic of Korea, Thailand, and Myanmar) with different malaria endemicity. We confirmed the existence of extensive polymorphism of VNTR fragments in field isolates. This detection provides several suitable markers for analysis of the molecular epidemiology of P. vivax field isolates. (C) 2017 Elsevier B.V. All rights reserved.</P>

Formulation and Evaluation of a Self-microemulsifying Drug Delivery System Containing Bortezomib

Hong, E.-P.,Kim, J.-Y.,Kim, S.-H.,Hwang, K.-M.,Park, C.-W.,Lee, H.-J.,Kim, D.-W.,Weon, K.-Y.,Jeong, S. Y.,Park, E.-S. PHARMACEUTICAL SOCIETY OF JAPAN 2016 Chemical & pharmaceutical bulletin Vol.64 No.8

<P>The purposes of the present study were to develop a self-microemulsifying drug delivery system (SMEDDS) containing bortezomib, a proteasome inhibitor. The solubility of the drug was evaluated in 15 pharmaceutical excipients. Combinations of oils, surfactants and cosurfactants were screened by drawing pseudo-ternary phase diagrams. The system exhibiting the largest region of microemulsion was considered optimal. Bortezomib SMEDDS spontaneously formed a microemulsion when diluted with an aqueous medium with a median droplet size of approximately 20-30 nm. In vitro release studies showed that the SMEDDS had higher initial release rates for the drug when compared with the raw drug material alone. Measurement of the viscosity, size, and ion conductivity indicated that a phase inversion from water in an oil system to oil in a water system occurred when the weight ratio of the water exceeded 30% of the entire microemulsion system. In a pharmacokinetics study using rats, the bortezomib microemulsion failed to improve the bioavailability of the drug. The reason was assumed to be degradation of the drug in the microemulsion in the gastrointestinal tract. However, bortezomib in Labrasol (R) solution (an aqueous solution containing 0.025% Labraso (R)) showed significantly increased area under the curve from 0-24h (AUC(0-24h)) and maximum plasma concentration (C-max) values compared to the drug suspension. The findings of this study imply that oral delivery of a bortezomib and colloidal system containing Labrasol (R) could be an effective strategy for the delivery of bortezomib.</P>

C?H bond arylation of anilides inside copper-exchanged zeolites

Mathew, B.P.,Yang, H.J.,Jeon, H.,Lee, J.H.,Kim, J.C.,Shin, T.J.,Myung, K.,Kwak, S.K.,Kwak, J.H.,Hong, S.Y. Elsevier 2016 Journal of molecular catalysis Chemical Vol.417 No.-

<P>Syntheses of fine-chemicals using heterogeneous catalysts have tremendous industrial potentials, yet C-H functionalization studies have been largely focused on homogeneous catalysis. We report here the first meta-selective C-H bond arylation of anilides inside copper-exchanged zeolites. Mid- or large-pore zeolite frameworks are selected as supports to access large organic molecules, and atomically distributed copper catalysts exhibit high activities (84-90% conversions) toward direct arylation of anilides with diphenyliodonium salt on 0.5 mol% copper concentration. Computational studies indicate the well fitted copper-aryl complexes inside zeolite frameworks. Electron micrographs, elemental analyses, and reusability study show no observable leaching of catalytically active copper species during the reactions tested. These results demonstrate the practical synthetic potential of copper-exchanged zeolites as promising supported molecular catalysts to afford biaryl motifs-containing compounds with high catalytic activity, chemical stability, and recyclability. (C) 2016 Elsevier B.V. All rights reserved.</P>