Hu J.-H.,Chang Gung Memorial Hospital |
Chen M.-Y.,Chang Gung University |
Yeh C.-T.,Chang Gung Memorial Hospital |
Lin H.-S.,Chang Gung Memory Hospital |
And 4 more authors.
Medicine (United States) | Year: 2016
The impact of sex on metabolic alterations in individuals with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection remains elusive. A community-based study was performed to assess sex, age, body mass index, the lipid profile, blood pressure, glucose, alanine aminotransferase, HBV surface antigen (HBsAg), and HCV antibody levels, smoking and alcohol drinking habits, and cardiometabolic diseases, incluDing diabetes, hypertension, cardiovascular events, and renal diseases. The HCV-RNA level and genotype were further assessed in HCV antibody-positive subjects, and the hepatitis B e antigen and HBV-DNA levels were further examined in HBsAg-positive subjects. Among the 10,959 adults enrolled, 1949 (17.8%) and 1536 (14.0%) were HBV and HCV-infected, respectively. Univariate and multivariate analyses showed that the lipid profile and hypertension were independently associated with HCV infection (95% confidence intervals of odds ratios [OR 95% CI]: total cholesterol [TC]=0.508-0.677; triglycerides=0.496-0.728; hypertension=0.669-0.937), but not with HBV infection. Consistently, HCV, but not HBV infection, was negatively associated with the TC and triglyceride levels (OR 95% CI for TC: 0.450-0.601; triglycerides: 0.443-0.671). Generalized linear models revealed that HCV infection, sex, and age interactively affected the lipid profile (OR 95% CI TC=1.189-1.385; triglycerides=1.172-5.289). Age-stratification analysis showed that the lipid levels were lower in both the HCV-positive females aged49 years (TC, P<0.001; triglycerides, P=0.001) and males of all ages (TC, P<0.001; triglycerides, P<0.001) compared with their sex and age-matched HCVnegative counterparts. HCV infection was associated with a higher body mass index (49 years, b=0.405, P=0.002) and increased rates of cardiovascular events (<49 years, OR 95% CI 1.23-9.566), diabetes (49 years, OR 95% CI 1.114-1.932), and renal diseases (49 years, OR 95% CI 1.23-9.55), and with a lower rate of hypertension (49 years, OR 95% CI 0.616-0.964) in the females, but not in the males, as determined by multivariate analyses. Only HCV infection was associated with metabolic alterations in this HBV/HCV-hyperendemic area. Females aged 49 years and males of all ages exhibited HCV-associated hypolipidemia. HCV-associated cardiometabolic diseases were evident only in the females. Sex dimorphism in HCV-associated metabolic complications warrants personalized follow-up of HCV-positive patients. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Juang H.-H.,Chang Gung University |
Juang H.-H.,Chang Gung Memorial Hospital |
Lin Y.-F.,Chang Gung University |
Chang P.-L.,Chang Gung Memory Hospital |
And 3 more authors.
Journal of Urology | Year: 2010
Purpose While cardiac glycosides are the mainstay of congestive heart failure treatment, early studies showed that pharmacological doses of cardiac glycosides inhibited prostate cancer cell line proliferation. We evaluated the mechanisms of cardiac glycosides, including digoxin, digitoxin and ouabain (Sigma®), on prostate specific antigen gene expression in vitro. Materials and Methods We cultured LNCaP cells (ATCC®) and used them to determine the effect of cardiac glycosides on prostate derived Ets factor and prostate specific antigen expression. We determined prostate derived Ets factor and prostate specific antigen expression by reverse transcription-polymerase chain reaction, immunoblot, transient gene expression assay or enzyme-linked immunosorbent assay. Results Noncytotoxic doses (100 nM) of cardiac glycosides for 24 hours inhibited prostate specific antigen secretion by LNCaP cells. Reverse transcriptase-polymerase chain reaction and immunoblot revealed that cardiac glycosides significantly down-regulated prostate specific antigen and prostate derived Ets factor expression. Transient gene expression assays showed that prostate derived Ets factor over expression enhanced prostate specific antigen promoter activity. However, prostate specific antigen and prostate derived Ets factor gene promoter activity was attenuated when LNCaP cells were treated with 100 nM cardiac glycosides. When LNCaP cells were treated with 25 nM digitoxin or digoxin for 60 hours, prostate specific antigen secretion decreased by 30%. Conclusions Results suggest that cardiac glycoside inhibition of prostate specific antigen gene expression may be caused by the down-regulation of prostate derived Ets factor gene expression. When cells were chronically treated with digoxin or digitoxin at concentrations close to or at therapeutic plasma levels, prostate specific antigen secretion decreased. This phenomenon merits further study to determine whether it occurs in men on cardiac glycoside therapy. © 2010 American Urological Association Education and Research, Inc.
Tseng J.-C.,Chang Gung Memory Hospital |
Tseng J.-C.,Chang Gung University |
Chang L.-C.,Chang Gung Memory Hospital |
Jiang B.-Y.,Cardinal Tien Hospital |
And 4 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2014
Purpose: Microvesicles (MV) in the blood stream are associated with distant metastasis in cancer. Platelet or endothelial cell-related MV actively participate in thrombogenesis, which is an important step in cancer metastasis. This study investigated the correlations between MV levels of platelet-poor plasma and distant metastasis in lung cancer. Methods: Platelet-poor plasma from 44 treatment-naive lung cancer (23 with distant metastasis) and 19 normal subjects was used to determine the levels of glycoprotein Iβ (CD42) + platelet MV (PMV), P-selectin (CD62P) + PMV, VE-cadherin (CD144) + endothelial MV (EMV), tissue factor (CD142) + MV, thrombin-antithrombin complex and vascular endothelial growth factor (VEGF). Results: The level of CD142 + MV was significant (odds ratio 5.86, 95 % confidence interval 1.31-38.3) in predicting distant metastasis in lung cancer, and a cutoff value of 2.668 (after logarithm transformation) in the ROC curve had a specificity of 90 % and a sensitivity of 59 %. The presence of distant metastasis showed a significant correlation between CD144 + EMV and VEGF, but not between CD144 + EMV and CD42 + PMV or CD62P + PMV in lung cancer subjects. Conclusions: The finding of CD142 + MV in platelet-poor plasma may be useful for suggesting distant metastasis in lung cancer. In addition to thrombogenesis, interaction between VE-cadherin and VEGF may be needed for successful metastasis in lung cancer. © 2013 Springer-Verlag Berlin Heidelberg.
Tsui K.-H.,Chang Gung Memory Hospital |
Lin Y.-F.,Chang Gung University |
Chen Y.-H.,Chang Gung University |
Chang P.-L.,Chang Gung Memory Hospital |
And 2 more authors.
Journal of Andrology | Year: 2011
Interleukin-6 (IL-6) is involved in regulation of cell growth and survival of prostate carcinoma cells. Previous studies suggest that IL-6 promotes prostate cancer progression through the induction of an androgen-independent response. In this study, we evaluated the mechanisms by which IL-6 regulates the gene expression of prostate-specific antigen (PSA) in human prostate LNCaP carcinoma cells. 3H-thymidine incorporation assays revealed that IL-6 treatment inhibited the proliferation of LNCaP cells. Results of enzyme-linked immunosorbent assay (ELISA) and immunoblot assays indicated that IL-6 treatment enhanced PSA gene expression. Similar results were found in LNCaP cells that had been engineered to stably overexpress IL-6. Although forced overexpression of c-Myc-associated zinc finger protein (MAZ) induced PSA promoter activity, mutation of the MAZ response elements had little effect on IL-6-induced PSA promoter activity. Results from 59-deletion reporter assays revealed that the effects of IL-6 appear to be mediated via an androgen enhancer region (24801 to 23933), which is dependent on the signal transducer and activator of the transcription 3 (STAT3) pathway, and a region located at 2193 to 241 base pairs upstream of the translational initiation site of the human PSA gene, which did not respond to androgen or STAT3. Results of reporter assays, immunoblot assays, and ELISA revealed that the heat shock protein 90 (Hsp90) inhibitors 17-allyamino-17-demethoxygeldanamycin and geldanamycin blocked IL-6-induced PSA gene expression. Those results suggest that IL-6 upregulates PSA gene expression and that Hsp90 plays a novel role in the activation of IL-6 on PSA gene expression in an androgenindependent manner. © American Society of Andrology.
Shao I.-H.,Chang Gung University |
Shao I.-H.,Lotung Poh Ai Hospital |
Lin Y.-H.,Chang Gung University |
Hou C.-P.,Chang Gung University |
And 7 more authors.
Drug Design, Development and Therapy | Year: 2014
Purpose: Radical nephroureterectomy (RNU) is a standard treatment for upper urinary tract urothelial carcinoma. However, RNU can result in decreased renal function and cannot be treated with adjuvant chemotherapy. We performed a risk group stratification analysis to determine the preoperative factors that are predictive of diminished renal function after RNU.Materials and methods: We retrospectively evaluated the medical records of all patients who underwent nephroureterectomy for upper urinary tract urothelial carcinoma at the Chang Gung Memorial Hospital from 2001 to 2008. We analyzed the association between perioperative glomerular filtration rate and preoperative parameters including cancer characteristics, serum creatinine level, and kidney size measured on computed tomographic images.Results: A total of 242 patients fulfilled the inclusion criteria. The average decrease in renal function 1 month after RNU was 19.7%. Using 60 mL/min/1.73 m2 as the eligibility cutoff for cisplatin-based chemotherapy, 42.1% of the population was eligible prior to nephroureterectomy, whereas following surgery only 15.2% remained eligible. Using a cutoff of 45 mL/min/1.73 m2, 59.9% of the cohort was eligible for fractionated cisplatin dosing preoperatively, whereas only 32.6% remained above the cutoff postoperatively. The most significant predictors of poor postoperative renal function were body mass index >25 kg/m2, age >65 years, contralateral kidney length less than 10 cm, and absence of ipsilateral hydronephrosis.Conclusion: Our results suggest that older age, higher body mass index, smaller contralateral renal length, and absence of ipsilateral hydronephrosis are predictive of decreased renal function after RNU. © 2014 Shao et al.
Gateno J.,Methodist Hospital |
Gateno J.,Cornell University |
Cookston C.,Institute of Orthopedic Research and Education |
Hsu S.S.-P.,Methodist Hospital |
And 12 more authors.
Journal of Oral and Maxillofacial Surgery | Year: 2013
Purpose Current mandibular plating systems contain a wide range of plates and screws needed for the treatment of mandibular reconstruction and mandibular fractures. The authors' hypothesis was that a single diameter screw could be used in all applications in a plating system. Therefore, the purpose of this study was to test if the 2.0-mm locking screws could replace the 2.4-mm screws to stabilize a 2.5-mm-thick reconstruction plate in the treatment of mandibular discontinuity. Materials and Methods Thirty-six fresh human cadaveric mandibles were used: 18 were plated using 2.0-mm locking screws (experimental) and the other 18 were plated using 2.4-mm locking screws (control). Each group was further divided into 3 subgroups based on the site of loading application: the ipsilateral (right) second premolar region, the central incisal region, and the contralateral (left) first molar region. The same ipsilateral (right) mandibular angular discontinuity was created by the same surgeon. The mandible was mounted on a material testing machine. The micromotions between the 2 segments, permanent and elastic displacements, were recorded after incremental ramping loads. The magnitude of screw back-out and the separation between plate and bone were recorded using a laser scanner (resolution, 0.12 mm) before and after the loading applications. The data were processed. Descriptive analyses and a general linear model for repeated measures analysis of variance were performed. Results There was no statistically significant difference in permanent displacement (mean, 1.16 and 0.82 mm, respectively) between the 2.0-mm and 2.4-mm screw groups. There also was no statistically significant difference in elastic displacement between the 2 groups (mean, 1.48 and 1.21 mm, respectively). Finally, there were no statistically significant differences in screw back-out or separation between plate and bone between the 2 groups. All means for screw back-out and separation between screw and bone for each group were judged within the error of the laser scanning system (<0.12 mm). Conclusion One may anticipate that the mechanical functions of the 2.0-mm locking screws are not different from those of the 2.4-mm screws when a 2.5-mm-thick reconstruction plate is used to reconstruct mandibular angular discontinuity. However, further biomechanical studies (ie, fatigue of screws) are warranted before a randomized clinical trial can be conducted to definitively prove that the 2.4-mm screws can be replaced by 2.0-mm screws. © 2013 American Association of Oral and Maxillofacial Surgeons.
Liao C.-H.,Chang Gung University |
Chen J.-J.,Ta jen University |
Lin J.E.,Thomas Jefferson University |
Liu C.-H.,Chang Gung University |
And 2 more authors.
Journal of Cellular Physiology | Year: 2011
Respiratory burst mediates crucial bactericidal mechanism in neutrophils. However, undesirable respiratory burst leads to pathological inflammation and tissue damage. This study investigates the effect and the underlying mechanism of 5-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3,7-dimethoxy-4H-chromen-4-one (MSF-2), a lignan extracted from the fruit of Melicope Semecarprifolia, on fMLP-induced respiratory burst in human neutrophils and suggests a possible therapeutic approach to ameliorate disease associated with neutrophil hyperactivation. MSF-2 inhibited fMLP-induced neutrophil superoxide anion production, cathepsin G release and migration in human neutrophils isolated from healthy volunteers, reflecting inhibition of phosphatidylinositol 3-kinase (PI3K) activation. Specifically, PI3K/AKT activation results in migration, degranulation and superoxide anion production in neutrophils. MSF-2 suppresses PI3K activation and phosphatidylinositol (3,4,5)-trisphosphate (PIP3) production, and consequently inhibits downstream activation of PDK1 and AKT. Further, PI3K also stimulates respiratory burst via PLC-dependent elevation of intracellular calcium. MSF-2 reduces fMLP-mediated PLCγ2 activation and intracellular calcium accumulation notably through extracellular calcium influx in a PI3K and PLC-dependent manner. However, MSF-2 is not a competitive or allosteric antagonist of fMLP. Additionally, in an in vivo study, MSF-2 prevents fMLP-induced neutrophil infiltration and inflammation in mice. In conclusion, MSF-2 opposes fMLP-mediated neutrophil activation and inflammation by inhibiting PI3K activation and subsequent activation of AKT and PLCγ2. © 2010 Wiley-Liss, Inc.
PubMed | Chang Gung Memory Hospital
Type: Journal Article | Journal: Journal of cancer research and clinical oncology | Year: 2014
Microvesicles (MV) in the blood stream are associated with distant metastasis in cancer. Platelet or endothelial cell-related MV actively participate in thrombogenesis, which is an important step in cancer metastasis. This study investigated the correlations between MV levels of platelet-poor plasma and distant metastasis in lung cancer.Platelet-poor plasma from 44 treatment-naive lung cancer (23 with distant metastasis) and 19 normal subjects was used to determine the levels of glycoprotein I (CD42)+platelet MV (PMV), P-selectin (CD62P)+PMV, VE-cadherin (CD144)+endothelial MV (EMV), tissue factor (CD142)+MV, thrombin-antithrombin complex and vascular endothelial growth factor (VEGF).The level of CD142+MV was significant (odds ratio 5.86, 95% confidence interval 1.31-38.3) in predicting distant metastasis in lung cancer, and a cutoff value of 2.668 (after logarithm transformation) in the ROC curve had a specificity of 90% and a sensitivity of 59%. The presence of distant metastasis showed a significant correlation between CD144+EMV and VEGF, but not between CD144+EMV and CD42+PMV or CD62P+PMV in lung cancer subjects.The finding of CD142+MV in platelet-poor plasma may be useful for suggesting distant metastasis in lung cancer. In addition to thrombogenesis, interaction between VE-cadherin and VEGF may be needed for successful metastasis in lung cancer.