Chang Gung Memorial Hospital Linkou Medical Center

Taoyuan, Taiwan

Chang Gung Memorial Hospital Linkou Medical Center

Taoyuan, Taiwan

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Ye J.-J.,Chang Gung Memorial Hospital | Huang C.-T.,Chang Gung Memorial Hospital | Shie S.-S.,Chang Gung Memorial Hospital | Huang P.-Y.,Chang Gung Memorial Hospital | And 4 more authors.
PLoS ONE | Year: 2010

Background: Multidrug resistant Acinetobacter baumannii (MDRAB) is an important nosocomial pathogen usually susceptible to carbapenems; however, growing number of imipenem resistant MDRAB (IR-MDRAB) poses further clinical challenge. The study was designed to identify the risk factors for appearance of IR MDRAB on patients formerly with imipenem susceptible MDRAB (IS-MDRAB) and the impact on clinical outcomes. Methodology/Principal Findings: A retrospective case control study was carried out for 209 consecutive episodes of ISMDRAB infection or colonization from August 2001 to March 2005. Forty-nine (23.4%) episodes with succeeding clinical isolates of IR-MDRAB were defined as the cases and 160 (76.6%) with all subsequent clinical isolates of IS-MDRAB were defined as the controls. Quantified antimicrobial selective pressure, "time at risk", severity of illness, comorbidity, and demographic data were incorporated for multivariate analysis, which revealed imipenem or meropenem as the only significant independent risk factor for the appearance of IR-MDRAB (adjusted OR, 1.18; 95% CI, 1.09 to 1.27). With selected cases and controls matched to exclude exogenous source of IR-MDRAB, multivariate analysis still identified carbapenem as the only independent risk factor (adjusted OR, 1.48; 95% CI, 1.14 to 1.92). Case patients had a higher crude mortality rate compared to control patients (57.1% vs. 31.3%, p = 0.001), and the mortality of case patients was associated with shorter duration of ''time at risk'', i.e., faster appearance of IR-MDRAB (adjusted OR, 0.9; 95% CI, 0.83 to 0.98). Conclusions/Significance: Judicious use of carbapenem with deployment of antibiotics stewardship measures is critical for reducing IR-MDRAB and the associated unfavorable outcome. © 2010 Ye et al.


Liang C.-C.,Chang Gung Memorial Hospital | Liang C.-C.,Chang Gung University | Liu H.-L.,University of Texas M. D. Anderson Cancer Center | Chang S.-D.,Chang Gung Memorial Hospital | And 4 more authors.
PLoS ONE | Year: 2016

Human umbilical cord blood derived CD34+ stem cells are reported to mediate therapeutic effects in stroke animal models. Estrogen was known to protect against ischemic injury. The present study wished to investigate whether the protective effect of CD34+ cells against ischemic injury can be reinforced with complemental estradiol treatment in female ovariectomized rat and its possible mechanism. Experiment 1 was to determine the best optimal timing of CD34+ cell treatment for the neuroprotective effect after 60-min middle cerebral artery occlusion (MCAO). Experiment 2 was to evaluate the adjuvant effect of 17β-estradiol on CD34+ cell neuroprotection after MCAO. Experiment 1 showed intravenous infusion with CD34+ cells before MCAO (pre-treatment) caused less infarction size than those infused after MCAO (post-treatment) on 7T magnetic resonance T2-weighted images. Experiment 2 revealed infarction size was most significantly reduced after CD34+ + estradiol pre-treatment. When compared with no treatment group, CD34+ + estradiol pre-treatment showed significantly less ADC reduction at 2 h and 2 d, less CBF reduction at 2 h and less hyperperfusion at 2 d. The immunoreactivity of c-Fos, c-Jun and GFAP was attenuated, and BDNF showed significant recovery from 2 h to 2 d after MCAO, especially after CD34+ + estradiol pre-treatment. The present study suggests pre-treatment with CD34+ cells with complemental estradiol can be most protective against ischemic injury, which may act through stabilization of cerebral hemodynamics and normalization of the expressions of immediate early genes and BDNF. © 2016 Liang et al. 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.


Chen I.-J.,Chang Gung Memorial Hospital Linkou Medical Center | Chen I.-J.,Chang Gung Memorial Hospital | Yen C.-F.,Chang Gung Memorial Hospital Linkou Medical Center | Yen C.-F.,Chang Gung Memorial Hospital | And 6 more authors.
Reproductive Sciences | Year: 2011

Human papillomavirus (HPV) infects large numbers of women worldwide and is present in more than 99% of all cervical cancer. TC-1 cell is a cell line with high expression of E7 antigen of HPV type 16 and its cell lysate has been demonstrated as an ideal inducer of E7-specific, antitumor immunity. OK-432 (Picibanil), a penicillin-killed Streptococcus pyogenes, has been reported with potent immunomodulation properties in cancer treatment by stimulating the maturation of dendritic cells (DCs) and secretion of Th-1 type cytokines. The current study demonstrated that a protocol to immunize the C57BL/6 mice with OK-432 followed by treatment with TC-1 lysate can generate markedly increased immune responses of E7-specific CD4+ T cells and a moderate increase of natural killer (NK) cell, as well as a satisfactorily protective and therapeutic antitumor effect by triggering the DCs to prime T cells. Depletion of lymphocyte subset in vivo suggested that the antitumor effects could be dominantly executed by CD8+ T cells and followed by NK cells, and both of these reactions were induced by the generation of robust E7-specific CD4+ T helper cell response. These findings warrant OK-432 combination with tumor-lysate as an effective and safe vaccine in future clinical application of cervical cancer. © The Author(s) 2011.


Sun N.-K.,Chang Gung University | Huang S.-L.,Chang Gung University | Lu H.-P.,Chang Gung University | Chang T.-C.,Chang Gung Memorial Hospital Linkou Medical Center | Chao C.C.-K.,Chang Gung University
Oncotarget | Year: 2015

A systematic analysis of the genes involved in taxol resistance (txr) has never been performed. In the present study, we created txr ovarian carcinoma cell lines to identify the genes involved in chemoresistance. Transcriptome analysis revealed 1,194 overexpressed genes in txr cells. Among the upregulated genes, more than 12 cryptic transcription factors were identified using MetaCore analysis (including AR, C/EBPß, ER, HNF4a, c-Jun/AP-1, c-Myc, and SP-1). Notably, individual silencing of these transcription factors (except HNF4α)sensitized txr cells to taxol. The androgen receptor (AR) and its target genes were selected for further analysis. Silencing AR using RNA interference produced a 3-fold sensitization to taxol in txr cells, a response similar to that produced by silencing abcb1. AR silencing also downregulated the expression of prominent txr gene candidates (including abcb1, abcb6, abcg2, bmp5, fat3, fgfr2, h1f0, srcrb4d, and tmprss15). In contrast, AR activation using the agonist DHT upregulated expression of the target genes. Individually silencing seven out of nine (78%) AR-regulated txr genes sensitized txr cells to taxol. Inhibition of AKT and JNK cellular kinases using chemical inhibitors caused a dramatic suppression of AR expression. These results indicate that the AR represents a critical driver of gene expression involved in txr.


Liang C.-C.,Chang Gung Memorial Hospital Linkou Medical Center | Liang C.-C.,Chang Gung University | Lee T.-H.,Chang Gung University | Lee T.-H.,Chang Gung Memorial Hospital Linkou Medical Center | And 2 more authors.
Taiwanese Journal of Obstetrics and Gynecology | Year: 2016

Objective To demonstrate the effect of human umbilical cord blood-derived CD34+ cells on bladder dysfunction induced by cerebral ischemia in rats. Materials and Methods Female rats were subjected to either 60 minute middle cerebral artery occlusion (MCAO) or a sham operation. Rats were divided into four groups: sham operation, MCAO without treatment, infusion with 1 × 106 CD34+ cells 30 minutes before MCAO, and infusion with 1 × 106 CD34+ cells 3 hours after MCAO. Bladder function was analyzed by cystometry at 1 day, 3 days, and 7 days after MCAO. Expressions of nerve growth factor (NGF), M2 and M3 muscarinic receptors were measured by immunohistochemistry and real time polymerase chain reaction. Results Cystometric results showed that, following MCAO, rats have a significant increase in peak voiding pressure and residual volume. Conversely, there is a significant decrease in voided volumes and intercontraction intervals. Cystometric variables after pre- and postischemic CD34+ treatment nearly returned to levels found in sham-operated rats. The expression of bladder NGF and M3 was decreased after MCAO, but significantly increased following preischemic CD34+ treatment. There was decreased expression of bladder M2 mRNA despite an increased level of M2 immunoreactivity at 3 days and 7 days after MCAO. Expression of bladder M2 immunoreactivity and mRNA nearly returned to sham group levels after preischemic CD34+ treatment. Conclusion Bladder dysfunction in a rat model caused by MCAO may be restored to normal micturition by treatment with human umbilical cord blood-derived CD34+ cells and may be related to the expressions of NGF, M2, and M3 in the bladder. © 2016


Wu H.-M.,University of British Columbia | Wu H.-M.,Chang Gung Memorial Hospital Linkou Medical Center | Wu H.-M.,Chang Gung University | Schally A.V.,University of Miami | And 4 more authors.
Cancer Letters | Year: 2010

The growth hormone-releasing hormone (GHRH) antagonists have been shown to inhibit growth of human cancer cells, but the underlying molecular mechanisms and their actions have not been fully investigated. In this study, we first showed that GHRH-R splice variant 1 (SV1) was expressed in two human endometrial cancer cell lines, Ishikawa and ECC-1. By using MTT assay, immunoblotting for cleaved caspase-3 and TUNEL assays, we found that cell growth inhibition and apoptosis were induced in GHRH antagonist, JMR-132-treated cells by activating PKCδ and could be inhibited by treatment with PKC inhibitor, GF109203X. In addition, activation and protein expression of p53 as well as the expression of its downstream effector, p21, were increased by JMR-132 treatment. Moreover, JMR-132-induced p53 and p21 expression were diminished by treatment with PKC inhibitor. Knockdown of endogenous p53 and p21 by siRNAs abolished the JMR-132-induced cell growth inhibition and apoptosis. This study demonstrates a novel mechanism in which GHRH antagonist-induced cell growth inhibition and apoptosis through PKCδ-mediated activation of p53/p21 in human endometrial cancer cells. These findings may suggest the feasibility of GHRH antagonists as a therapeutic approach for human cancer. © 2010 Elsevier Ireland Ltd.


PubMed | Chang Gung University and Chang Gung Memorial Hospital Linkou Medical Center
Type: Journal Article | Journal: Oncotarget | Year: 2015

A systematic analysis of the genes involved in taxol resistance (txr) has never been performed. In the present study, we created txr ovarian carcinoma cell lines to identify the genes involved in chemoresistance. Transcriptome analysis revealed 1,194 overexpressed genes in txr cells. Among the upregulated genes, more than 12 cryptic transcription factors were identified using MetaCore analysis (including AR, C/EBP, ER, HNF4, c-Jun/AP-1, c-Myc, and SP-1). Notably, individual silencing of these transcription factors (except HNF4`)sensitized txr cells to taxol. The androgen receptor (AR) and its target genes were selected for further analysis. Silencing AR using RNA interference produced a 3-fold sensitization to taxol in txr cells, a response similar to that produced by silencing abcb1. AR silencing also downregulated the expression of prominent txr gene candidates (including abcb1, abcb6, abcg2, bmp5, fat3, fgfr2, h1f0, srcrb4d, and tmprss15). In contrast, AR activation using the agonist DHT upregulated expression of the target genes. Individually silencing seven out of nine (78%) AR-regulated txr genes sensitized txr cells to taxol. Inhibition of AKT and JNK cellular kinases using chemical inhibitors caused a dramatic suppression of AR expression. These results indicate that the AR represents a critical driver of gene expression involved in txr.


Dahiya D.,Chang Gung Memorial Hospital Linkou Medical Center | Wu T.-J.,Chang Gung Memorial Hospital Linkou Medical Center | Wu T.-J.,Chung Gung University | Lee C.-F.,Chang Gung Memorial Hospital Linkou Medical Center | And 3 more authors.
Surgery | Year: 2010

Background: The choice between minor versus major resection or anatomic versus nonantatomic resection for small (<5 cm) solitary hepatocellular carcinoma (HCC) in patients with cirrhosis is controversial. The aim of our study was to evaluate the long-term disease-free survival (DFS) and overall survival (OS) after minor or major hepatic resection for small solitary HCC in cirrhotic patients. Methods: Between January 1983 and December 2002, patients with solitary HCC of ≤5 cm in size who had histologically proven liver cirrhosis and microscopically tumor-free margin were included. These selected patients underwent either minor (≤2 segments) or major (≥3 segments) hepatectomy. Results: In 373 patients, 259 underwent minor and 114 underwent major hepatectomy. Patients in the minor resection group had more severe underlying liver disease (P = .005). Therefore, only 29.3% received anatomic resection in the minor resection group in comparison with 72.8% in the major hepatectomy group (P = .0001). No difference was found in postoperative morbidity (P = .105), mortality (P =.222), intrahepatic recurrence (P = .742), and 5-year DFS and OS (31.6% vs 31.8%, P = .932 and 50.7% vs 44.0%, P = .114) in both groups. The type of operative resection was not found to be a significant factor affecting survival in univariate analysis, but the preoperative liver function (alanine aminotransferase [AST] or alanine aminotransferase [ALT], serum albumin, or Child-Pugh status), tumor characteristics (alpha-feto protein, size, and presence of daughter nodules), and blood transfusion were found to be independent factors that affect the DFS and OS in a multivariate analysis. Conclusion: The severity of cirrhosis and tumor characteristics depicts long-term survival rather than the type of resection in HCC. Crown Copyright © 2010.


PubMed | Chang Gung Memorial Hospital Linkou Medical Center
Type: Journal Article | Journal: Human reproduction (Oxford, England) | Year: 2012

The impact of gonadotrophin-releasing hormone (GnRH) antagonists used in IVF protocols on endometrial tissue remodeling, embryo implantation and the programming of early pregnancy is still unclear. Pregnancy and infant outcomes after treatment with GnRH antagonist for IVF are particular causes of concern. The purpose of this study was to investigate the mechanisms of GnRH antagonist-induced apoptosis of human decidual stromal cells and the effects of GnRH antagonist on the activation of ERK1/2, JNK and GADD45 signaling.Human decidual stromal cells were isolated from decidual tissue. The expression of GnRH-I receptor (GnRH-IR) was examined by immunoblot analysis and immunohistochemistry. The cells were treated with the GnRH antagonist, Cetrorelix. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay was used to examine cell viability. Cleaved caspase-3 and terminal deoxynucleotidyl transferase-mediated dUDP nick-end labeling assay were used as indicators for cell apoptosis. Mitogen-activated protein kinase function was tested for the elucidation of intracellular signalings through the pre-treatment of stromal cells with ERK1/2 (U0126) and JNK (SP600125) inhibitors prior to the Cetrorelix treatment. To characterize the signaling pathway of GnRH antagonist, the endogenous GnRH-IR and GADD45 were knocked down by specific small-interfering RNA (siRNA).The GnRH-IR is expressed in human decidual stromal cells. Treatment with GnRH antagonist decreased cell viability, induced apoptosis and increased the phosphorylation of ERK1/2 and JNK. Cells pre-treated with U0126 and SP600125 were rescued from the GnRH antagonist-mediated inhibition of cell growth and did not exhibit GnRH antagonist-induced apoptosis and downstream GADD45 signaling. GnRH antagonist-mediated cell growth inhibition and apoptosis were also abolished by the knockdown of the endogenous GnRH-IR or GADD45 with siRNAs.The GnRH antagonist suppresses the growth of decidual stromal cells by inducing apoptosis through the GnRH-IR and through the ERK1/2 and JNK phosphorylation-dependent induction of GADD45 signaling. These results indicate that ERK1/2, JNK and GADD45 are coordinately regulated by the GnRH antagonist through the GnRH-IR to induce apoptosis in human decidual stromal cells, suggesting that the GnRH antagonist may play a role in decidual programming in human pregnancy.


PubMed | Chang Gung Memorial Hospital LinKou Medical Center
Type: Journal Article | Journal: Radiology | Year: 2011

To examine the usefulness of diffusion kurtosis imaging for the diagnosis of Parkinson disease (PD).Examinations were performed with the understanding and written consent of each subject, with local ethics committee approval, and in compliance with national legislation and Declaration of Helsinki guidelines. Diffusion-weighted magnetic resonance imaging was performed in 30 patients with idiopathic PD (mean age, 64.5 years 3.4 [standard deviation]) and 30 healthy subjects (mean age, 65.0 years 5.1). Mean kurtosis, fractional anisotropy, and mean, axial, and radial diffusivity of the basal ganglia were compared between the groups. Disease severity was assessed by using Hoehn and Yahr staging and the motor section of the Unified Parkinsons Disease Rating Scale (mean scores, 2.0 and 33.6, respectively). Receiver operating characteristic (ROC) analysis was used to compare the diagnostic accuracies of the indexes of interest. Pearson correlation coefficient analysis was used to correlate imaging findings with disease severity.Mean kurtosis in the putamen was higher in the PD group (0.93 0.15) than in the control group (0.71 0.09) (P < .000416). The area under the ROC curve (AUC) was 0.95 for both the ipsilateral putamen and the ipsilateral substantia nigra. The mean kurtosis for the ipsilateral substantia nigra had the best diagnostic performance (mean cutoff, 1.10; sensitivity, 0.92; specificity, 0.87). In contrast, AUCs for the tensor-derived indexes ranged between 0.43 (axial and radial diffusivity in substantia nigra) and 0.65 (fractional anisotropy in substantia nigra).Diffusion kurtosis imaging in the basal ganglia, as compared with conventional diffusion-tensor imaging, can improve the diagnosis of PD.

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