Chang Gung Memorial Hospital Chiayi

Chiayi, Taiwan

Chang Gung Memorial Hospital Chiayi

Chiayi, Taiwan

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Lee K.-C.,Chang Gung University | Kuo H.-C.,Chang Gung University | Kuo H.-C.,Chronic Diseases and Health Promotion Research Center | Shen C.-H.,Chang Gung Memorial Hospital | And 13 more authors.
Journal of Cellular and Molecular Medicine | Year: 2017

Erinacine A, a major active component of a diterpenoid derivative isolated from Hericium erinaceus mycelium, has been demonstrated to exert anticancer effects. Herein, we present an investigation of the molecular mechanism of erinacine A induction associated with cancer cells’ aggressive status and death. A proteomic approach was used to purify and identify the differentially expressed proteins following erinacine A treatment and the mechanism of its action in apoptotic and the targets of erinacine A. Our results demonstrate that erinacine A treatment of HCT-116 and DLD-1 cells increased cell cytotoxicity and reactive oxygen species (ROS) production as well as decreased cell proliferation and invasiveness. Ten differentially displayed proteins were determined and validated in vitro and in vivo between the erinacine A-treated and untreated groups. In addition, erinacine A time-dependent induction of cell death and inhibitory invasiveness was associated with sustained phosphorylation of the PI3K/mTOR/p70S6K and ROCK1/LIMK2/Cofilin pathways. Furthermore, we demonstrated that erinacine A–induced HCT-116 and DLD-1 cells viability and anti-invasion properties by up-regulating the activation of PI3K/mTOR/p70S6K and production of ROS. Experiments involving specific inhibitors demonstrated that the differential expression of cofilin-1 (COFL1) and profilin-1 (PROF1) during erinacine A treatment could be involved in the mechanisms of HCT-116 and DLD-1 cells death and decreased aggressiveness, which occurred via ROCK1/LIMK2/Cofilin expression, with activation of the PI3K/mTOR/p70S6K signalling pathway. These findings elucidate the mechanism of erinacine A inhibiting the aggressive status of cells by activating PI3K/mTOR/p70S6K downstream signalling and the novel protein targets COF1 and PROF1; this could be a good molecular strategy to limit the aggressiveness of CRC cells. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.


PubMed | Capital Medical University, Lawrence Berkeley National Laboratory, University of California at San Francisco and Chang Gung Memorial Hospital Chiayi
Type: Journal Article | Journal: Thoracic cancer | Year: 2015

Lung cancer is the leading cause of morbidity and death worldwide. Although the available lung cancer animal models have been informative and further propel our understanding of human lung cancer, they still do not fully recapitulate the complexities of human lung cancer. The pathogenesis of lung cancer remains highly elusive because of its aggressive biologic nature and considerable heterogeneity, compared to other cancers. The association of Cul4A amplification with aggressive tumor growth and poor prognosis has been suggested. Our previous study suggested that Cul4A is oncogenic in vitro, but its oncogenic role in vivo has not been studied.Viral delivery approaches have been used extensively to model cancer in mouse models. In our experiments, we used Cre-recombinase induced overexpression of the Cul4A gene in transgenic mice to study the role of Cul4A on lung tumor initiation and progression and have developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A.Here we show that the use of a recombinant adenovirus expressing Cre-recombinase (AdenoCre) to induce Cul4A overexpression in the lungs of mice allows controls of the timing and multiplicity of tumor initiation. Following our mouse models, we are able to study the potential role of Cul4A in the development and progression in pulmonary adenocarcinoma as well.Our findings indicate that Cul4A is oncogenic in vivo, and this mouse model is a tool in understanding the mechanisms of Cul4A in human cancers and for testing experimental therapies targeting Cul4A.


Wang S.-H.,Far Eastern Memorial Hospital | Wang S.-H.,Oriental Institute of Technology | Wang S.-H.,Chang Gung University | Chi C.-C.,Chang Gung Memorial Hospital Chiayi | And 3 more authors.
International Journal of Dermatology | Year: 2014

Biologic therapies are more effective than conventional therapies in the treatment of psoriasis, but they are also more costly. Objectives: The aim of this study was to compare the cost-efficacy of etanercept, adalimumab, and ustekinumab therapies in the treatment of moderate to severe psoriasis in a Taiwanese setting. Methods: We conducted a meta-analysis of randomized, placebo-controlled trials to calculate the incremental efficacy of etanercept, adalimumab, and ustekinumab, respectively, in affecting a reduction of ≥75% in score on the Psoriasis Area and Severity Index (PASI 75). The base, best case, and worst case incremental cost-effectiveness ratios (ICERs) for one subject to achieve PASI 75 were calculated for the purposes of economic analysis. Results: One-year ICERs per PASI 75 responder were US$ 39,709 (best scenario US$ 36,400; worst scenario US$ 43,680), US$ 23,711 (best scenario US$ 22,633; worst scenario US$ 25,319), and US$ 26,329 (best scenario US$ 24,780; worst scenario US$ 27,623) for etanercept, adalimumab, and ustekinumab, respectively. Two year ICERs per PASI 75 responder were US$ 71,973 (best scenario US$ 65,975; worst scenario US$ 79,170), US$ 62,665 (best scenario US$ 59,817; worst scenario US$ 66,914), and US$ 52,657 (best scenario US$ 49,560; worst scenario US$ 55,427) for etanercept, adalimumab, and ustekinumab, respectively. Conclusions: In a Taiwanese setting, adalimumab and ustekinumab had lower 1-year costs per PASI 75 responder than etanercept, and ustekinumab had the lowest 2-year cost per PASI 75 responder. © 2014 The International Society of Dermatology.


Wang C.-P.,Chang Gung Memorial Hospital Chiayi | Huang E.J.-C.,Chang Gung Memorial Hospital Chiayi | Huang E.J.-C.,Chang Gung University | Kuo C.-N.,Chang Gung Memorial Hospital Chiayi | And 3 more authors.
Taiwan Journal of Ophthalmology | Year: 2016

In March 2014, a 56-year-old woman without previous underlying disease underwent encircling scleral buckling, 20-gauge pars plana vitrectomy, cryotherapy around a retinal tear, and gas-fluid exchange with 15% perfluoropropane flush for upper rhegmatogenous retinal detachment of the left eye. However, she developed progressive left leg swelling, pain, warmth, and redness, associated with difficulty in elevating her left leg after continuously maintaining a prone head position when either lying down or sitting for 2 days. When she arrived at the emergency room, she had an elevated d-dimer level. After undergoing Doppler ultrasound imaging, she was diagnosed as having deep vein thrombosis of the left leg. She received anticoagulation therapy with enoxaparin and warfarin overlapping for 7 days. The edema, pain, and paresthesia of her left leg were relieved. However, because of the risk of bleeding with anticoagulation drug usage, the patient needed to be monitored for 6 months. Prone positioning for gas tamponade is important for anatomic and functional success in retinal detachment surgery; however, timely walking and rest between periods of continuous prone positioning should be encouraged to prevent deep vein thrombosis and other impaired circulation-related complications. © 2015.


Huang E.J.-C.,Chang Gung Memorial Hospital Chiayi | Huang E.J.-C.,Chang Gung University | Wu S.-H.,Chang Gung Memorial Hospital Chiayi | Wu S.-H.,Chang Gung University | And 13 more authors.
Eye (Basingstoke) | Year: 2014

AimThis study aimed to ascertain the prevalence of and the risk factors associated with early and late age-related macular degeneration (AMD) among Chinese individuals aged ≥65 years residing in Puzih, Taiwan.MethodsThis population-based cross-sectional study graded digital colour photographs of the ocular fundus of 673 individuals using the Wisconsin Age-Related Maculopathy Grading System. We compared the characteristics of individuals with early and late AMD using χ 2 -analyses and described risk factors for early and late AMD using odds ratios and 95% confidence intervals.ResultsIndividuals with late AMD were significantly older and more likely to have hypertension. Further, their sunlight exposure time was longer than that of those with early AMD, only drusen, or no AMD lesions (P<0.01). A history of hyperlipidaemia for >10 years was a significant risk factor for early AMD, while old age, hypertension for >10 years, and exposure to sunlight for >8 h per day were associated with late AMD.ConclusionsThe prevalence rate of early AMD in the present study was 15.0%, which is similar to that reported for Caucasians and Japanese included in the European Eye Study and the Hisayama Study, respectively. The late AMD prevalence rate of 7.3% found among our study participants was comparable to that reported by the Greenland Inuit Eye Study and Reykjavik Study, but considerably lower than that reported for Caucasians, indicating that late AMD might be less prevalent among Asians than Caucasians. © 2014 Macmillan Publishers Limited.


Huang E.J.-C.,Chang Gung University | Huang E.J.-C.,Chang Gung Memorial Hospital Chiayi
Eye (London, England) | Year: 2014

AIM: This study aimed to ascertain the prevalence of and the risk factors associated with early and late age-related macular degeneration (AMD) among Chinese individuals aged ≥65 years residing in Puzih, Taiwan.METHODS: This population-based cross-sectional study graded digital colour photographs of the ocular fundus of 673 individuals using the Wisconsin Age-Related Maculopathy Grading System. We compared the characteristics of individuals with early and late AMD using χ(2)-analyses and described risk factors for early and late AMD using odds ratios and 95% confidence intervals.RESULTS: Individuals with late AMD were significantly older and more likely to have hypertension. Further, their sunlight exposure time was longer than that of those with early AMD, only drusen, or no AMD lesions (P<0.01). A history of hyperlipidaemia for >10 years was a significant risk factor for early AMD, while old age, hypertension for >10 years, and exposure to sunlight for >8 h per day were associated with late AMD.CONCLUSIONS: The prevalence rate of early AMD in the present study was 15.0%, which is similar to that reported for Caucasians and Japanese included in the European Eye Study and the Hisayama Study, respectively. The late AMD prevalence rate of 7.3% found among our study participants was comparable to that reported by the Greenland Inuit Eye Study and Reykjavik Study, but considerably lower than that reported for Caucasians, indicating that late AMD might be less prevalent among Asians than Caucasians.


PubMed | Chang Gung University, Taipei Medical University and Chang Gung Memorial Hospital Chiayi
Type: | Journal: World neurosurgery | Year: 2016

Cerebral infarction is a common cause of disability. Malignant large infarction (MLI) is a catastrophic event, and there is no effective medical treatment. This study aimed to assess the outcome predictors of MLI and to analyze the impact of decompressive craniectomy (DC) on the functional outcome of survivors.This study comprised 213 MLI cases. Outcome was evaluated with modified Rankin Scale (mRS) at 1-year follow-up, and various parameters were tested for MLI outcome predictors. The impact of DC on functional outcome was examined after being further stratified into good survival (mRS score= 0, 1, 2, 3), poor survival (mRS score= 4, 5), and mortality (mRS score= 6) groups.Standard medical treatment only was used in 106 cases, and both medical treatment and DC were used in 107 cases. With multiple logistic regression analysis, age, motor response at deterioration/operation, and DC were identified as independent outcome predictors of MLI (P= 0.027, P < 0.001, P < 0.001). Compared with the sole standard medical treatment, additional DC resulted in a better outcome (odds ratio [OR]=19.95; 95% confidence interval [CI], 7.61-52.27; P < 0.001). Further analysis of functional outcome revealed that DC significantly increased the chance of good survival as opposed to poor survival (OR= 20.04; 95% CI, 6.05-66.32; P < 0.001) and death (OR= 43.72; 95% CI, 13.21-144.72; P < 0.001).In this study, DC performed on a young patient with motor response of localizing pain or better was linked with a better outcome. DC not only reduced mortality and increased the number of good survivals but also, most importantly, decreased the number of poor functional outcome survivals.


Wang T.-Y.,Chang Gung Memorial Hospital Chiayi | Lee K.-D.,Chang Gung Memorial Hospital Chiayi | Chen P.-T.,Chang Gung Memorial Hospital Chiayi | Chen M.-C.,Chang Gung Memorial Hospital Chiayi | And 5 more authors.
Journal of the Formosan Medical Association | Year: 2015

Background/Purpose: Cytotoxic chemotherapy via central venous access ports is an important part of the standard treatment for most cancers, but it is accompanied with the risk of infections. This study aimed to analyze the incidence and risk factors for central venous access port-related infection (CPI) among Chinese patients receiving cytotoxic chemotherapy. Methods: Between January 1, 2002 and December 31, 2005 a total of 1391 cancer patients with 1449 totally implantable central venous access ports were evaluated. The log-rank test and Cox proportional hazards model were used for the analyses of risk factors. Results: The overall CPI incidence rate was 0.21 per 1000 catheter-days. Hematological malignancies and head and neck cancer were associated with an increased risk of CPI (hazard ratio 4.00 and 4.11, respectively, both p < 0.001) and less infection-free catheter longevity (p < 0.001) compared with other cancer types. Chemotherapy in an adjuvant setting was associated with a lower risk of infection than for patients in a nonadjuvant setting (p < 0.001). The most common pathogens isolated from CPI were Pseudomonas aeruginosa and Candida. Conclusion: Infection remains to be a challenging issue for totally implantable central venous ports. Implementation of an insertion bundle for the prevention of central line-associated bloodstream infections is warranted, especially for those patients with hematological and head and neck cancers, as well as for patients receiving chemotherapy in the metastatic settings. © 2015.

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