Tri Services General Hospital

Taipei, Taiwan

Tri Services General Hospital

Taipei, Taiwan
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Hung H.-C.,National Health Research Institute | Liu C.-L.,National Chung Hsing University | Hsu J.T.-A.,National Health Research Institute | Hsu J.T.-A.,National Chiao Tung University | And 7 more authors.
Analytical Chemistry | Year: 2012

Recent studies have shown that NP (nucleoprotein), which possesses multiple functions in the viral life cycle, is a new potential anti-influenza drug target. NP inhibitors reliably induce conformational changes in NPs, and these changes may confer inhibition of the influenza virus. The six conserved tryptophan residues in NP can be used as an intrinsic probe to monitor the change in fluorescence of the tryptophan residues in the protein upon binding to an NP inhibitor. In the present study, we found that the fluorescence of recombinant NP proteins was quenched following the binding of available NP inhibitors (such as nucleozin) in a concentration- and time-dependent manner, which suggests that the inhibitor induced conformational changes in the NPs. The minimal fluorescence-quenching effect and weak binding constant of nucleozin to the swine-origin influenza virus H1N1pdm09 (SOIV) NP revealed that the SOIV is resistant to nucleozin. We have used the fluorescence-quenching property of tryptophans in NPs that were bound to ligands in a 96-well-plate-based drug screen to assess the ability of promising small molecules to interact with NPs and have identified one new anti-influenza drug, CSV0C001018, with a high SI value. This convenient method for drug screening may facilitate the development of antiviral drugs that target viruses other than the influenza virus, such as HIV and HBV. © 2012 American Chemical Society.


Chang J.-H.,Tri Services General Hospital | Kuo K.N.,National Taiwan University Hospital | Kuo K.N.,National Health Research Institute | Huang S.-C.,National Taiwan University Hospital
Journal of Surgical Research | Year: 2011

Background: Containment and preservation of hip range of motion have been the principles governing the treatment of Legg-Calvé-Perthes disease. The Staheli's slotted acetabular augmentation (SAA) procedure is an alternative approach for older children with Perthes disease with lateral subluxation, incongruent hip, and abduction hinge. It provides effective coverage, restricts lateral displacement of the femoral head, and achieves containment and congruency in short-term follow-up. Materials and Methods: This study evaluated pre- and postoperative symptoms, range of motion (ROM), and radiographic images in advanced Perthes disease with an incongruent hip or hinge abduction in lateral pillar groups B and C of 21 children who underwent a SAA procedure. Results: Postoperative evaluation showed improved abduction, internal rotation, subluxation ratio, femoral head ratio, and acetabular coverage. At final follow-up, ROM of abduction went from 20° preoperatively to 45° postoperatively, and internal rotation went from 15° preoperatively to 35° postoperatively. The radiographic findings revealed 33% and 38% of patients achieved spherical congruence of the hip and an ovoid or mushroom femoral head, respectively. Conclusion: SAA restricts lateral displacement or subluxation of the femoral head and preserves sphericity, resulting in containment and acetabular coverage. © 2011 Elsevier Inc. All rights reserved.


Hsu C.C.,National Health Research Institute | Hwang S.J.,Kaohsiung Medical University | Tai T.Y.,Taipei Jen Chi Relief Institution | Chen T.,Tulane University | And 11 more authors.
Diabetic Medicine | Year: 2010

Aims: Cigarette smoking is a well-known risk factor associated with diabetic nephropathy. The objective of this study was to further investigate the dose-response effect of tobacco exposure on proteinuria in males with Type 2 diabetes. Methods: Five hundred and nine males with Type 2 diabetes were selected from a cohort participating in a glucose control study in Taiwan. Pack-years of cigarette smoking were calculated to define tobacco exposure. Proteinuria was identified if albumin-to-creatinine ratio was ≥ 30 mg/g in at least two of three consecutive urine tests. Logistic regression and trend tests were used to delineate the association between smoking status and proteinuria. Results: Compared with non-smokers, those who had smoked 15-30 or more than 30 pack-years were respectively 2.78 (95% CI 1.34-5.76, P < 0.01) and 3.20 (95% CI 1.74-5.86, P < 0.001) times more likely to develop proteinuria. The dose-response effect of tobacco exposure on the development of proteinuria is highly significant in all subjects (P = 0.001) and in subgroups with relatively short duration of diabetes mellitus (P < 0.001), good blood pressure control (P = 0.001) and those of young age (P = 0.007). Conclusions: The current study shows a clear dose-response effect of cigarette smoking on development of proteinuria in male Type 2 diabetic patients. These findings reinforce the urgent need to encourage diabetic patients to stop smoking regardless of age, duration of diabetes mellitus or status of blood pressure control. © 2010 The Authors.


Yu Y.-L.,Graduate Institute of Cancer Biology And | Yu Y.-L.,Medical University and Hospital | Yu Y.-L.,Asia University, Taiwan | Yu S.-L.,Asia University, Taiwan | And 13 more authors.
Journal of Agricultural and Food Chemistry | Year: 2010

Epigenetic alteration of DNA methylation plays an important role in the regulation of gene expression associated with chemosensitivity of human hepatocellular (HCC) carcinoma cells. With the aim of improving the chemotherapeutic efficacy for HCC, the effect of the naturally occurring compound n-butylidenephthalide (BP), which is isolated from a chloroform extract of Angelica sinensis, was investigated. In both HepG2 and J5 HCC cell lines, a synergistic antiproliferative effect was observed when a low dosage of BP was combined with the chemotherapeutic drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). BCNU is an alkylating agent, and it prompts us to examine one of DNA repair genes, O6-methylguanine methyltransferase (MGMT). It was evident from methylation-specific polymerase chain reaction (PCR) analysis that BP/BCNU combined treatment caused a time- and concentration-dependent enhancement of MGMT promoter methylation. Overexpression of MGMT could abolish BP-induced growth inhibition in the J5 tumor cell line as measured by colony formation assay. When BP was combined with BCNU and administered, it showed significant antitumor effects in both HepG2 and J5 xenograft tumors as compared with the use of only one of these drugs. The BCNU-induced apoptosis and inhibited MGMT protein expression in HCC cells, both in vitro and in vivo, resulting from the combination treatment of BP and BCNU suggest a potential clinical use of this compound for improving the prognosis for HCCs. © 2009 American Chemical Society O6-Methylguanine methyltransferase (MGMT), synergistic effect, 1, 3-bis(2-chloroethyl)1-nitrosourea (BCNU), methylation-specific PCR.


Horng C.-T.,Kaohsiung Armed Forces General Hospital | Horng C.-T.,Tajen University | Tsai M.-L.,Tri Services General Hospital | Shiang J.-C.,Kaohsiung Armed Forces General Hospital | And 4 more authors.
Life Science Journal | Year: 2011

Glaucoma is one of the world's leading causes of blindness. Astragalus membranaceus is a well-known traditional Chinese herbal medicine widely used for a long time. The aim of our study is to evaluate the activity of lowering intraocular pressure through the use of Astragalus membranaceus extract (AME) in an experimental glaucoma model. The rats used in the study were divided into six groups: one sham group, two positive control groups with topical brimonidine instillation and oral acetazolamide therapy, and three groups treated with AME (low, medium and high dosage). The antioxidant activity of AME was accessible by MDA and GPx levels. The ability to lower intraocular pressure (IOP) signified the efficiency of treating glaucoma. The results revealed that AME may decrease the MDA production and restore the GPx level in the periocular blood. This extremely beneficial effect may be by the same as that of brimonidine. Furthermore, AME also showed the ability to significantly lower IOP as is the case with brimonidine and acetazolamide. AME is a relatively safe Chinese herbal medicine with no observed side effects such as body-weight loss, or pathological change. In conclusion, the extract of Astragalus membranaceus is beneficial in treating glaucoma during the development of progression of this disease due to its significant IOP and antioxidant activities.


Liao G.-S.,Tri Services General Hospital | Chou Y.-C.,National Defense Medical Center | Golshan M.,Dana-Farber Cancer Institute | Hsu H.-M.,Tri Services General Hospital | And 3 more authors.
American Journal of Surgery | Year: 2015

Background Several studies indicate that lymph node (LN) ratio (LNR) is more predictive than the traditional LN-positive stratification (pNs). We assessed whether LNR can provide additional prognostic information on node-positive breast cancer patients, particularly with breast cancer subtypes (BCS). Methods We retrospectively reviewed the medical records of 2,049 patients with primary breast cancer treated between January 2006 and December 2011 and identified 511 subjects with positive axillary LN. Clinicopathological findings, types of treatment, and the 5-year overall survival (OS) were included. Results The results of multivariate analysis of the cohort showed that the correlations of pNs and LNR in regard to OS were P <.001 and P <.001, respectively, with adjustment for tumor characteristics and treatment factors. Moreover, our data revealed that LNR was more predictive in luminal A, luminal B, and luminal human epidermal growth factor receptor 2 in a comparison of pNs and LNR with regard to OS among BCS. Conclusion LNR and pNs are important prognostic factors with regard to OS for patients with node-positive breast cancer, but LNR has a more correlated value in BCS. © 2015 Elsevier Inc.All rights reserved.


Chang T.-H.,Tri Services General Hospital | Hsu H.-H.,National Defense Medical Center | Chou Y.-C.,National Defense Medical Center | Yu J.-C.,Tri Services General Hospital | And 3 more authors.
PLoS ONE | Year: 2015

Background and Objectives The Breast Imaging Reporting and Data System (BI-RADS) of Mammography (MG) and Ultrasonography (US) were equivalent to the "5-point score" and applied for combined and sub-stratified imaging assessments. This study evaluated the value of combined and sub-stratified imaging assessments with MG and US over breast cancer subtypes (BCS). Materials and Methods Medical records of 5,037 cases having imaging-guided core biopsy, performed from 2009 to 2012, were retrospectively reviewed. This study selected 1,995 cases (1,457 benign and 538 invasive cancer) having both MG and US before biopsy. These cases were categorized with the "5-point score" for their MG and US, and applied for combined and sub-stratified imaging assessments. Invasive cancers were classified on the basis of BCS, and correlated with combined and sub-stratified imaging assessments. Results These selected cases were evaluated by the "5-point score." MG, US, and combined and sub-stratified imaging assessments all revealed statistically significant (P 0.001) incidence of malignancy. The sensitivity was increased in the combined imaging score (99.8%), and the specificity was increased in the sub-stratified combined score (75.4%). In the sub-stratified combined imaging assessment, all BCS can be classified with higher scores (abnormality hierarchy), and luminal B subtype showed the most salient result (hierarchy: higher, 95%; lower, 5%). Conclusions Combined and sub-stratified imaging assessments can increase sensitivity and specificity of breast cancer diagnosis, respectively, and Luminal B subtype shows the best identification by sub-stratified combined imaging scoring. © 2015 Chang 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.


PubMed | Tri Services General Hospital, National Defense Medical Center and Kang Ning General Hospital
Type: Journal Article | Journal: PloS one | Year: 2015

The Breast Imaging Reporting and Data System (BI-RADS) of Mammography (MG) and Ultrasonography (US) were equivalent to the 5-point score and applied for combined and sub-stratified imaging assessments. This study evaluated the value of combined and sub-stratified imaging assessments with MG and US over breast cancer subtypes (BCS).Medical records of 5,037 cases having imaging-guided core biopsy, performed from 2009 to 2012, were retrospectively reviewed. This study selected 1,995 cases (1,457 benign and 538 invasive cancer) having both MG and US before biopsy. These cases were categorized with the 5-point score for their MG and US, and applied for combined and sub-stratified imaging assessments. Invasive cancers were classified on the basis of BCS, and correlated with combined and sub-stratified imaging assessments.These selected cases were evaluated by the 5-point score. MG, US, and combined and sub-stratified imaging assessments all revealed statistically significant (P < 0.001) incidence of malignancy. The sensitivity was increased in the combined imaging score (99.8%), and the specificity was increased in the sub-stratified combined score (75.4%). In the sub-stratified combined imaging assessment, all BCS can be classified with higher scores (abnormality hierarchy), and luminal B subtype showed the most salient result (hierarchy: higher, 95%; lower, 5%).Combined and sub-stratified imaging assessments can increase sensitivity and specificity of breast cancer diagnosis, respectively, and Luminal B subtype shows the best identification by sub-stratified combined imaging scoring.


Jan H.-J.,Taipei Medical University | Lee C.-C.,Shin Kong Memorial Hospital | Shih Y.-L.,Shin Kong Memorial Hospital | Hueng D.-Y.,Tri services General Hospital | And 5 more authors.
Neuro-Oncology | Year: 2010

Human malignant glioma cells are characterized by local invasion. In the present study, we investigated the role of osteopontin (OPN) in the invasiveness of human glioma cells isolated from grade IV tumors. We found that the expression levels of OPN in these cell lines paralleled matrix metalloproteinase-2 (MMP-2) expression and cell invasiveness potential. When U87MG glioma cells (with a high-OPN expression level) were stably transformed with specific small hairpin RNA to knock down OPN expression, MMP-2 secretion, cell invasiveness, and tumor growth in implanted brains were dramatically reduced. Conversely, forced expression of OPN in GBM-SKH glioma cells (which expressed OPN at a low level) increased MMP-2 secretion, enhanced cell invasiveness, and increased tumor growth in a rodent xenograft model. Expression of OPN was associated with increased expression of vimentin and decreased expression of glial fibrillary acidic protein. Treatment of glioma cells with 5-aza-2'-deoxycytidine (5-aza-dC) suppressed OPN expression in a concentration-dependent manner. Suppression of OPN expression by 5-aza-dC was associated with reductions in MMP-2 secretion, vimentin expression, cell invasion, intravasation, and tumor growth. These data suggest that OPN may play important roles in regulating cell invasion in glioma cells and that 5-aza-dC may serve as a therapeutic agent for human gliomas. © The Author(s) 2009.


PubMed | Tri Services General Hospital
Type: Journal Article | Journal: The Journal of surgical research | Year: 2011

Containment and preservation of hip range of motion have been the principles governing the treatment of Legg-Calv-Perthes disease. The Stahelis slotted acetabular augmentation (SAA) procedure is an alternative approach for older children with Perthes disease with lateral subluxation, incongruent hip, and abduction hinge. It provides effective coverage, restricts lateral displacement of the femoral head, and achieves containment and congruency in short-term follow-up.This study evaluated pre- and postoperative symptoms, range of motion (ROM), and radiographic images in advanced Perthes disease with an incongruent hip or hinge abduction in lateral pillar groups B and C of 21 children who underwent a SAA procedure.Postoperative evaluation showed improved abduction, internal rotation, subluxation ratio, femoral head ratio, and acetabular coverage. At final follow-up, ROM of abduction went from 20 preoperatively to 45 postoperatively, and internal rotation went from 15 preoperatively to 35 postoperatively. The radiographic findings revealed 33% and 38% of patients achieved spherical congruence of the hip and an ovoid or mushroom femoral head, respectively.SAA restricts lateral displacement or subluxation of the femoral head and preserves sphericity, resulting in containment and acetabular coverage.

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