Chang Gung Memorial Hospital Linkou

Taoyuan, Taiwan

Chang Gung Memorial Hospital Linkou

Taoyuan, Taiwan
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Lin H.-H.,Chang Gung University | Lin H.-H.,Chang Gung Memorial Hospital Linkou | Hsiao C.-C.,University of Amsterdam | Pabst C.,Martin Luther University of Halle Wittenberg | And 4 more authors.
Advances in Immunology | Year: 2017

The adhesion family comprises one of the five major clades of G protein-coupled receptors (GPCRs). Unlike conventional GPCRs, adhesion GPCRs (aGPCRs) have extended ectodomains with various protein folds that facilitate protein-protein interactions and, hence, putative cellular adhesive functions. Juxtaposed to the seven-pass transmembrane domain is a GPCR autoproteolysis-inducing domain that enables autoproteolytic cleavage of the receptor, resulting in a bipartite structure of many aGPCRs. aGPCRs are widely distributed and play critical roles in many developmental processes; yet, the underlying mechanisms of activation and signal transduction have emerged only recently. About one-third of the 33 human aGPCRs are expressed in hematopoietic stem, progenitor, or mature cells, where they define distinct cellular populations. Recent studies have demonstrated roles of aGPCR in the control of innate effector functions and the susceptibility for and onset of (auto)inflammatory conditions. We here discuss the current knowledge about aGPCRs in the regulation of immune responses and inflammation. © 2017 Elsevier Inc.

Hsu C.,National Taiwan University Hospital | Yang T.-S.,Chang Gung Memorial Hospital Linkou | Huo T.-I.,Taipei Veterans General Hospital | Hsieh R.-K.,Mackay Memorial Hospital | And 7 more authors.
Journal of Hepatology | Year: 2012

Background & Aims: Inhibitors of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) have shown anti-tumor activities in advanced hepatocellular carcinoma (HCC). The present study evaluated the efficacy and safety of vandetanib, an oral inhibitor of both VEGFR and EGFR, in patients with unresectable advanced HCC. Methods: Eligible patients were randomized 1:1:1 to receive vandetanib 300 mg/day, vandetanib 100 mg/day, or placebo. Upon disease progression, all patients had the option to receive open-label vandetanib 300 mg/day. The primary objective was to evaluate tumor stabilization rate (complete response + partial response + stable disease ≥4 months). Secondary assessments included progression-free survival (PFS), overall survival (OS) and safety. Biomarker studies included circulating pro-angiogenic factors and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Results: Sixty-seven patients were randomized to vandetanib 300 mg (n = 19), vandetanib 100 mg (n = 25) or placebo (n = 23) groups. Twenty-nine patients entered open-label treatment. Vandetanib induced a significant increase in circulating VEGF and decrease in circulating VEGFR levels. In both vandetanib arms, tumor stabilization rate was not significantly different from placebo: 5.3% (vandetanib 300 mg), 16.0% (vandetanib 100 mg) and 8.7% (placebo). DCE-MRI did not detect significant vascular change after vandetanib treatment. Although trends of improved PFS and OS after vandetanib treatment were found, they were statistically insignificant. The most common adverse events were diarrhea and rash, whose incidence did not differ significantly between treatment groups. Conclusions: Vandetanib has limited clinical activity in HCC. The safety profile was consistent with previous studies. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Yu H.-J.,National Taiwan University Hospital | Lin A.T.-L.,Taipei Veterans General Hospital | Yang S.S.-D.,Buddhist Tzu Chi General Hospital | Tsui K.-H.,Chang Gung Memorial Hospital Linkou | And 5 more authors.
BJU International | Year: 2011

Study Type - Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Silodosin administered by 4 mg twice daily is as effective as tamsulosin 0.2 mg daily in treating patients with LUTS associated with BPH. Relative to tamsulosin, silodosin has less cardiovascular side effects as judged by the minimal changes of blood pressure and pulse rats after treatment. OBJECTIVE • To test the hypothesis that the efficacy of silodosin would not be inferior to tamsulosin in treating patients with lower urinary tract symptoms associated with benign prostate hyperplasia (BPH). PATIENTS AND METHODS • At nine medical centres, 209 patients with an International Prostate Symptom Score (IPSS) of ≥13 were randomized to silodosin (4 mg twice daily) or tamsulosin (0.2 mg once daily) for 12 weeks. • The primary efficacy measure was the mean change from baseline to endpoint in IPSS. • The non-inferiority margin of the IPSS change was set at 1.0. • Secondary efficacy measures included change in maximal urinary flow rate (Q max) and health-related quality of life (HRQL) score. RESULTS • Of the 170 (81.3%) patients who completed the study, 86.2% in the silodosin group vs 81.9% in the tamsulosin group achieved a ≥25% decrease in IPSS (P= 0.53). • The mean difference (silodosin minus tamsulosin) in IPSS change from baseline was -0.60 (95% confidence interval -2.15, 0.95), inferring the non-inferiority of silodosin to tamsulosin. • The mean changes in the Q max and HRQL score from baseline were comparable between the groups (both, P > 0.05). Although patients receiving silodosin had a significantly higher incidence of abnormal ejaculation (9.7% vs tamsulosin 1.0%, P= 0.009), only 1.9% discontinued treatment. • Tamsulosin treatment resulted in a significant reduction in mean systolic blood pressure (-4.2 mmHg, within-group P= 0.004) relative to the negligible change of silodosin (-0.1 mmHg, within-group P= 0.96) CONCLUSION • The trial shows the non-inferiority of silodosin 4 mg twice daily to tamsulosin 0.2 mg once daily in patients with symptoms of BPH. © 2011 BJU INTERNATIONAL.

Chen F.-H.,National Tsing Hua University | Fu S.-Y.,National Tsing Hua University | Yang Y.-C.,National Taiwan University Hospital | Wang C.-C.,Chang Gung Memorial Hospital LinKou | And 5 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2013

Purpose: To investigate vascular responses during fractionated radiation therapy (F-RT) and the effects of targeting pericytes or bone marrow-derived cells (BMDCs) on the efficacy of F-RT. Methods and Materials: Murine prostate TRAMP-C1 tumors were grown in control mice or mice transplanted with green fluorescent protein-tagged bone marrow (GFP-BM), and irradiated with 60 Gy in 15 fractions. Mice were also treated with gefitinib (an epidermal growth factor receptor inhibitor) or AMD3100 (a CXCR4 antagonist) to examine the effects of combination treatment. The responses of tumor vasculatures to these treatments and changes of tumor microenvironment were assessed. Results: After F-RT, the tumor microvascular density (MVD) was reduced; however, the surviving vessels were dilated, incorporated with GFP-positive cells, tightly adhered to pericytes, and well perfused with Hoechst 33342, suggesting a more mature structure formed primarily via vasculogenesis. Although the gefitinib+F-RT combination affected the vascular structure by dissociating pericytes from the vascular wall, it did not further delay tumor growth. These tumors had higher MVD and better vascular perfusion function, leading to less hypoxia and tumor necrosis. By contrast, the AMD3100+F-RT combination significantly enhanced tumor growth delay more than F-RT alone, and these tumors had lower MVD and poorer vascular perfusion function, resulting in increased hypoxia. These tumor vessels were rarely covered by pericytes and free of GFP-positive cells. Conclusions: Vasculogenesis is a major mechanism for tumor vessel survival during F-RT. Complex interactions occur between vessel-targeting agents and F-RT, and a synergistic effect may not always exist. To enhance F-RT, using CXCR4 inhibitor to block BM cell influx and the vasculogenesis process is a better strategy than targeting pericytes by epidermal growth factor receptor inhibitor. © 2013 Elsevier Inc.

Lee C.-H.,Chang Gung Memorial Hospital Linkou | Lee C.-H.,Chang Gung University | Chiang C.-L.,Chang Gung University | Liu S.-J.,Chang Gung University
Separation and Purification Technology | Year: 2013

In this study we developed rhodanine loaded nanofibrous membranes for the removal of heavy metal ions. Rhodanine and polymethylmethacrylate dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) were electrospun into nanofibrous membranes via an electrospinning process. The morphology of as-spun rhodanine/polymethylmethacrylate nanofibers was examined by scanning electron microscopy. The average diameter of electrospun nanofibers ranged from 840 nm to 1440 nm. The adsorption capability of nanofibrous rhodanine/ polymethylmethacrylate membranes was measured and compared with that of bulk rhodanine. The influence of various process conditions on adsorption efficiency was also examined. The experimental results suggested that the electrospun nanofibrous membranes exhibit good Ag (I) and Pb (II) ion uptake capabilities. The metal uptake of nanofibrous membranes increased with the initial metal ion concentrations and decreased with the filtering rate of the solutions. Furthermore, the electrospun membrane could be reused after the recovery process. The empirical results in this study suggested that electrospun rhodanine/polymethylmethacrylate nanofibrous membranes can be a good candidate for the removal of heavy metal ions. © 2013 Elsevier B.V. All rights reserved.

Huang S.-T.,Chang Gung Memorial Hospital Linkou | Huang S.-T.,Chang Gung University | Jiann B.-P.,Kaohsiung Veterans General Hospital | Jiann B.-P.,National Yang Ming University
International Journal of Impotence Research | Year: 2013

The Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) and its partner version questionnaire were used to assess couples' satisfaction with the use of phosphodiesterase type 5 (PDE5) inhibitors to treat erectile dysfunction (ED) over a 3-month period. Of 161 ED patients, who together with their female partners were invited to answer separate questionnaires at home, 111 patients (68.9%; mean age 61.8 (23-87) years) and female partners (mean age 52.8 (22-77) years) returned completed questionnaires. Patients reported a substantially higher treatment satisfaction score and level of satisfaction with ED treatment than their female partners (P<0.001). Patients with milder severity of ED at baseline and better erectile function after treatment were more likely to be satisfied with the outcome of the treatment. Of the different aspects of satisfaction that patients were asked about, they reported the lowest level of satisfaction about their partners' feeling about continued treatment for ED. Our study shows that more patients than their female partners are more satisfied with medical treatment for ED. To maintain long-term therapy for ED, it is important to include female partners in the assessment and management of the therapy. © 2013 Macmillan Publishers Limited All rights reserved.

Chen C.-H.,Chang Gung Memorial Hospital Linkou | Chen C.-H.,Chang Gung University
PLoS ONE | Year: 2016

Genetic polymorphisms of apolipoprotein E (APOE) are associated with various health conditions and diseases, such as Alzheimer's disease, cardiovascular diseases, type 2 diabetes, etc. Hence, genotyping of APOE has broad applications in biomedical research and clinical settings, particularly in the era of precision medicine. The study aimed to develop a convenient and accurate method with flexible throughput to genotype the APOE polymorphisms. A melting curve-based allele-specific PCR method was developed to genotype two single nucleotide polymorphisms (SNPs) of APOE, i.e. rs429358 at codon 112 and rs7412 at codon 158. These two SNPs determine the genotype of APOE2, E3, and E4. PCR-based Sanger sequencing was used as the reference method for APOE genotyping. A 100% concordance rate was obtained in 300 subjects between the melting curve-based allele-specific PCR method and the Sanger sequencing method. This method was applied to a genetic association analysis of APOE and schizophrenia consisting of 711 patients with schizophrenia and 665 control subjects from Taiwan. However, no significant differences in the allele and genotype frequencies were detected between these two groups. Further experiments showed that DNA dissolved from blood collected on Guthrie filter paper and total blood cell lysate without DNA extraction can be used in the melting curve-based allele-specific PCR method. Thus, we suggest that this is a fast, accurate and robust APOE genotyping method with a flexible throughput and suitable for DNA template from different preparations. This convenient method shall meet the different needs of various research and clinical laboratories. © 2016 Chia-Hsiang Chen. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Wang L.-J.,Chang Gung University | Chen C.-K.,Chang Gung Memorial Hospital at Keelung | Chen C.-K.,Chang Gung University | Huang Y.-S.,Chang Gung University | Huang Y.-S.,Chang Gung Memorial Hospital Linkou
Journal of Child and Adolescent Psychopharmacology | Year: 2015

Objective: This study investigated the trends in neurocognitive function and behavioral symptoms among patients with attention-deficit/hyperactivity disorder (ADHD) during 24 months of treatment with methylphenidate in a clinical setting. Methods: Study participants consisted of 181 ADHD patients with a mean age of 13.4±2.5 years (ages ranged from 8 to 18 years; 151 boys and 30 girls) who were prescribed oral short-acting methylphenidate two or three times daily, with each dose ranging between 0.3 and 1.0mg/kg. At baseline and 6, 12, 18, and 24 months from baseline, neurocognitive function was assessed using the Test of Variables of Attention (TOVA) on the day the patient was off medication, and behavioral symptoms were evaluated using the Swanson, Nolan, and Pelham Version IV Scale for ADHD (SNAP-IV) parent form, the SNAP-IV teacher form, and the ADHD-Rating Scale (completed by a child psychiatrist). Results: Of the 181 ADHD patients at the initial visit, 103 (56.9%) completed the study. During the 24-month methylphenidate treatment, only the commission errors in TOVA significantly improved; however, the omission errors, response time, response time variability, response sensitivity, and ADHD score did not. The behavioral symptoms of ADHD, observed by various informants, all declined substantially, and were significantly correlated with each other during the long-term follow-up. The severity of teacher ratings was lower than that of parent and psychiatrist ratings. However, the teacher-rated inattention symptoms showed the strongest correlations with TOVA performance. Conclusions: Findings suggest that neurocognitive deficits in ADHD patients, except inhibition ability, might be long lasting in realistic settings. In addition, obtaining behavior profile assessments from multiple informants, especially from teachers, is vital for establishing a complete understanding of ADHD patients. © Copyright 2015, Mary Ann Liebert, Inc.

Hsiao C.-C.,Chang Gung University | Hsiao C.-C.,University of Amsterdam | Wang W.-C.,Chang Gung University | Kuo W.-L.,Chang Gung University | And 4 more authors.
FEBS Journal | Year: 2014

CD97 is a tumor-associated adhesion-class G-protein-coupled receptor involved in modulating cell migration. Adhesion-class G-protein-coupled receptors are characterized by proteolytic cleavage at a G-protein-coupled receptor proteolysis site (GPS) into an N-terminal fragment (NTF) and a C-terminal fragment (CTF), which remain associated noncovalently. The molecular mechanism and the role of GPS proteolysis in CD97-modulated cell migration are not completely understood. We report here that CD97 expression in HT1080 fibrosarcoma cells enhanced tissue inhibitor of metalloproteinase-2 secretion, leading to reduced membrane type 1 matrix metalloproteinase and matrix metalloproteinase 2 activities. This, in turn, impaired cell migration and invasion in vitro and lung macrometastasis in vivo. CD97 expression also upregulated the expression of integrins, promoting cell adhesion. Importantly, these cellular functions absolutely required the presence of both the NTF and the CTF of CD97, confirming functional cooperation between the two receptor subunits. CD97 gene knockdown reversed these phenotypic changes. We conclude that GPS proteolysis and the functional interplay between the NTF and the CTF are indispensible for CD97 to inhibit HT1080 cell migration by suppressing matrix metalloproteinase activity. © 2014 FEBS.

Chen C.-H.,Chang Gung Memorial Hospital Linkou | Chen C.-H.,Chang Gung University | Huang C.-C.,Tzu Chi University | Liao D.-L.,Bali Psychiatric Center
PLoS ONE | Year: 2014

GABRB3 encoding the b3 subunit of GABAA receptor has been implicated in multiple neuropsychiatric disorders, including substance abuse. Previous studies reported that SNPs at the 5′ regulatory region of GABRB3 could regulate GABRB3 gene expression and associated with childhood absence epilepsy (CAE). The study aimed to investigate whether SNPs at the 5′ regulatory region of GABRB3 were associated with heroin dependence in our population. We first re-sequenced 1.5 kb of the 5′regulatory region of GABRB3 gene to examine the SNP profile in the genomic DNA of 365 control subjects. Then, we conducted a case-control association analysis between 576 subjects with heroin dependence (549 males, 27 females) and 886 controls (472 males, 414 females) by genotyping the rs4906902 as a tag SNP. We also conducted a reporter gene assay to assess the promoter activity of two major haplotypes derived from SNPs at this region. We detected 3 common SNPs (rs4906902, rs8179184 and rs20317) at this region that had strong pair-wise linkage disequilibrium. The C allele of rs4906902 was found to be associated with increased risk of heroin dependence (odds ratio:1.27, p = 0.002). Two major haplotypes (C-A-G and T-G-C) derived from these 3 SNPs accounted for 99% of this sample, and reporter gene activity assay showed that haplotype C-A-G that contained the C allele of the tag SNP rs4906902 had higher activity than haplotype T-G-C. Our data suggest that GABRB3 might be associated with heroin dependence, and increased expression of GABRB3 might contribute to the pathogenesis of heroin dependence. © 2014 Chen et al.

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