The Association of Acquired T790M Mutation with Clinical Characteristics after Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma

Yen-Hsiang Huang,Kuo-Hsuan Hsu,Jeng-Sen Tseng,Kun-Chieh Chen,Chia-Hung Hsu,Kang-Yi Su,Jeremy J. W. Chen,Huei-Wen Chen,Sung-Liang Yu,Tsung-Ying Yang,Gee-Chen Chang 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

Purpose The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)mutant lung adenocarcinoma patients with acquired resistance after firstline EGFRtyrosine kinase inhibitor (TKI) treatment. Materials and Methods We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFRmutation status. Results A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression- free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). Conclusion PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746- A750 mutation are associated with the frequency of T790M mutation.

Magnetic Property and Structure of Electrodeposited Nickel on a Thin Niobium Film

Huei-Ying Ho,Shih-Jia Chen,Wei-Yan Lin,Hong-Wen Cheng 한국물리학회 2013 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.62 No.12

Cyclic voltammetry, chronopotentiometry, atomic force microscopy (AFM), the magneto-opticalKerr effect (MOKE), and X-ray diffraction were used to investigate the magnetic property and thestructure of thin Ni films electrodeposited onto thin Nb films. A constant-current method was usedto grow the Ni films in this study. We found that -Ni(OH)2 coexists with the Ni deposits. The Nigrains favor growing along the polar direction the very early deposition stage; they tend to growin the lateral direction during the steady-state deposition process. The preferred orientations ofthe Ni deposits are fcc (111) and fcc (200); however, the easy axis of the magnetization of the Nideposits is in the in-plane direction. Increasing the deposition current can decrease the coercivity. We used the AFM and MOKE results to determine the mechanism of the growth of the Ni deposits. We found that the growth modes of the Ni deposits in the polar and the lateral directions largelycorresponded to the direct reduction of Ni and the decomposition of -Ni(OH)2, respectively.

Deficiency or activation of peroxisome proliferator-activated receptor ⍺ reduces the tissue concentrations of endogenously synthesized docosahexaenoic acid in C57BL/6J mice

Wen-Ting Hsiao,Hui-Min Su,Kuan-Pin Su,Szu-Han Chen,Hai-Ping Wu,Yi-Ling You,Ru-Huei Fu,Pei-Min Chao 한국영양학회 2019 Nutrition Research and Practice Vol.13 No.4

BACKGROUND/OBJECTIVES: Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of α-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha (PPARα). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by PPARα. MATERIALS/METHODS: The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among PPARα homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate (PPARα agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA. RESULTS: PPARα ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, PPARα activation increased hepatic Acox, Fads1, Fads2, and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex. CONCLUSIONS: LCPUFA enzyme expression was altered by PPARα. Either PPARα deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.

New Time-Domain Decoder for Correcting both Errors and Erasures of Reed-Solomon Codes

Erl-Huei Lu,Tso-Cho Chen,Chih-Wen Shih 한국전자통신연구원 2016 ETRI Journal Vol.38 No.4

A new time-domain decoder of Reed-Solomon (RS) codes is proposed. Because this decoder can correct both errors and erasures without computing the erasure locator, the errata locator, or errata evaluator polynomial, the computational complexity can be substantially reduced. Herein, to demonstrate the benefit, the (255, 223) and the (63, 39) RS codes are used as examples for the comparisons of computational complexity of the proposed decoder with two well-known related decoders. The comparisons show that the proposed decoder always has lower computational requirement to decode all combination of u erasures and v errors than both the well-known related decoders on the condition of 2v+u<=d_min -1 where d_min denotes the minimum distance of the RS code. Moreover, the benefit is more evident if u becomes larger.

Deficiency or activation of peroxisome proliferator-activated receptor α reduces the tissue concentrations of endogenously synthesized docosahexaenoic acid in C57BL/6J mice

Hsiao, Wen-Ting,Su, Hui-Min,Su, Kuan-Pin,Chen, Szu-Han,Wu, Hai-Ping,You, Yi-Ling,Fu, Ru-Huei,Chao, Pei-Min The Korean Nutrition Society 2019 Nutrition Research and Practice Vol.13 No.4

BACKGROUND/OBJECTIVES: Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of ${\alpha}$-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha ($PPAR{\alpha}$). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by $PPAR{\alpha}$. MATERIALS/METHODS: The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among $PPAR{\alpha}$ homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate ($PPAR{\alpha}$ agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA. RESULTS: $PPAR{\alpha}$ ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, $PPAR{\alpha}$ activation increased hepatic Acox, Fads1, Fads2, and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex. CONCLUSIONS: LCPUFA enzyme expression was altered by $PPAR{\alpha}$. Either $PPAR{\alpha}$ deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.

Cilostazol ameliorates diabetic nephropathy by inhibiting highglucose-induced apoptosis

Chien-Wen Chian,Yung-Shu Lee,Yi-Ju Lee,Ya-Hui Chen,Chi-Ping Wang,Wen-Chin Lee,Huei-Jane Lee 대한생리학회-대한약리학회 2020 The Korean Journal of Physiology & Pharmacology Vol.24 No.5

Diabetic nephropathy (DN) is a hyperglycemia-induced progressive development of renal insufficiency. Excessive glucose can increase mitochondrial reactive oxygen species (ROS) and induce cell damage, causing mitochondrial dysfunction. Our previous study indicated that cilostazol (CTZ) can reduce ROS levels and decelerate DN progression in streptozotocin (STZ)-induced type 1 diabetes. This study investigated the potential mechanisms of CTZ in rats with DN and in high glucose-treated mesangial cells. Male Sprague-Dawley rats were fed 5 mg/kg/day of CTZ after developing STZ-induced diabetes mellitus. Electron microscopy revealed that CTZ reduced the thickness of the glomerular basement membrane and improved mitochondrial morphology in mesangial cells of diabetic kidney. CTZ treatment reduced excessive kidney mitochondrial DNA copy numbers induced by hyperglycemia and interacted with the intrinsic pathway for regulating cell apoptosis as an antiapoptotic mechanism. In high-glucose-treated mesangial cells, CTZ reduced ROS production, altered the apoptotic status, and down-regulated transforming growth factor beta (TGF-β) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). Base on the results of our previous and current studies, CTZ deceleration of hyperglycemia-induced DN is attributable to ROS reduction and thereby maintenance of the mitochondrial function and reduction in TGF-β and NF-κB levels.

Apple Polyphenol Suppresses Indomethacin-Induced Gastric Damage in Experimental Animals by Lowering Oxidative Stress Status and Modulating the MAPK Signaling Pathway

Yi-Chen Lee,Chun-Wen Cheng,Huei-Jane Lee,Huei-Chuien Chu 한국식품영양과학회 2017 Journal of medicinal food Vol.20 No.11

Indomethacin is a nonsteroid anti-inflammatory drug (NSAID) that is used to alleviate pain and inflammation in clinical medicine. Previous studies indicated that NSAIDs can cause gastrointestinal mucosal complications, and it is associated with mucosal lipid peroxidation and oxidative damage. Based on the evidences, decreasing oxidative stress may be an ideal therapeutic strategy for preventing gastrointestinal ulcer. Apple (Rosaceae Malus sp.) is one of the most commonly consumed fruits worldwide. The abundant polyphenolic constituents have received increasing attention for decades. In both in vivo and in vitro studies, the reports showed that apple polyphenol (AP) seems to provide an indirect antioxidant protection by activating cellular antioxidant enzymes to defend against oxidative stress. To address this issue and develop AP into a healthy improvement supplement, we studied the effect and potential mechanisms of AP in indomethacin-treated animal. The results showed AP can decelerate the gastric lesion, significantly suppress lipid peroxidation, increase the level of glutathione and the activity of catalase, and regulate the MAPK signaling proteins. These findings imply that AP protects the gastric mucosa from indomethacin-caused lesions and the protection is at least partially attributable to its antioxidative properties. This alternative medical function of AP may be a safe and effective intervention for preventing indomethacin-induced gastric complications.

Preparation of Carotenoids and Chlorophylls from Gynostemma pentaphyllum (Thunb.) Makino and Their Antiproliferation Effect on Hepatoma Cell

Yu-Chian Tsai,Wen-Bin Wu,Bing-Huei Chen 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.6

A preparative column chromatographic method for isolation of carotenoids and chlorophylls from Gynostemma pentaphyllum, a traditional Chinese herb, was developed to evaluate their antiproliferative effects on the hepatoma cell Hep3B. An open column containing 70g of magnesium oxide–diatomaceous earth (1:2.5, wt/wt) was used to elute carotenoid with 2% ethanol in ethyl acetate and chlorophyll with 50% ethanol in acetone. After high-performance liquid chromatography–mass spectrometry analysis, the carotenoid fraction was composed of all-trans- and cis-isomers of lutein, α-carotene, and β-carotene as well as epoxy-containing carotenoids, while the chlorophyll fraction consisted of chlorophylls a and b and their derivatives. Both carotenoid and chlorophyll fractions as well as lutein and chlorophyll a standards at 50–100μg/mL were effective against Hep3B cells with a dose-dependent response with the following order: carotenoid fraction>chlorophyll fraction>lutein>chlorophyll a. For all treatments, the cell cycle was arrested in the G0/G1 phase, with Hep3B cells undergoing necrosis or apoptosis.

Application of Arbuscular Mycorrhizal Fungi on the Growth and Production of Several Horticultural Seedlings

Chun-Li Wang,Ting-Yen Chen,Wen-Huei Tsai 한국원예학회 2006 한국원예학회 기타간행물 Vol.- No.-

Abstract : Arsenic sequestration in iron plaque and its effect on As uptake by rice plants grown in paddy soils with high contents of As, iron oxides, and organic matter

( Chien Hui Syu ),( Pei Yu Jiang ),( Hsuan Han Huang ),( Wen Ting Chen ),( Tzu Huei Lin ),( Dar Yuan Lee ) 한국환경농학회 2012 한국환경농학회 워크샵자료 Vol.2012 No.2

The iron plaque formed on rice root has been confirmed to be a barrier on the uptake of arsenic in many hydroponic experiments. However, few studies provide the information about the relationship between soil characteristics, iron plaque formation and As uptake by rice in Ascontaminated soils. Therefore, the aim of this study is to investigate the effect of the rice root`s iron plaques on the As uptake by rice plants grown in geologically As-contaminated soils with high contents of iron oxides and organic matter from the Guandu Plain of northern Taiwan. A soil flooding incubation study was performed and a pot experiment was conducted. The rice seedling was pre-cultivated in solution cultures and then transplanted in three level As-contaminated soils for growing 39 days. The amounts of iron plaque on rice root were determined by extraction using dithionite-citrate-bicarbonate (DCB). The As species on iron plaque and the concentrations of As and Fe in iron plaque, root, root base and shoot of rice plants were determined. The results of the soil incubation study showed that both As and Fe concentrations in the soil solutions increased with flooding time due to reductive dissolution of iron oxides induced by high contents of organic matter in soils. High amounts of iron plaque were deposited on rice roots and large amounts of As were sequestrated in these iron plaques. Results of the As K-edge X-ray absorption nearedge spectroscopy (XANES) indicated that arsenate was the main species of arsenic sorbed on iron plaque of rice roots. About 74.0 to 93.2 % of total As released from soils were distributed in the iron plaques and only small proportion was distributed in the rice plants. This study provides evidence that the iron plaques of the rice roots was the main controlling factor in limiting the uptake and accumulation of As into the rice plants grown in paddy soils with high contents of iron oxides and organic matter, meanwhile, it suggests that enhancement of iron plaque formation could be the approach used for reducing the uptake of As by paddy rice grown in As-contaminated soils.