Tsai C.-M.,Chung Shan Medical University |
Tsai C.-M.,Tainan Hospital |
Yen G.-C.,National Chung Hsing University |
Sun F.-M.,Health Science University |
And 2 more authors.
Molecular Pharmaceutics | Year: 2013
Patients with lung adenocarcinoma are often diagnosed with metastasizing symptoms and die of early and distal metastasis. Metastasis is made up of a cascade of interrelated and sequential steps, including cell adhesion, extracellular matrix degradation, cell movement, and invasion. Hence, substances carrying the ability to stop one of the metastasis-associated steps could be a potential candidate for preventing tumor cells from metastasizing and prolonging the life of cancer patients. Cinnamic acid (CA) was demonstrated to be such a candidate for human lung adenocarcinoma cells. Nevertheless, the effectiveness of CA derivatives on invasion of lung cancer cells is still unclear. The aims of this study were to explore the mechanisms underlying several select CA derivatives against invasion of human lung adenocarcinoma A549 cells. The results revealed that caffeic acid (CAA), chlorogenic acid (CHA), and ferulic acid (FA) can inhibit phorbol-12-myristate-13-acetate (PMA)-stimulated invasion of A549 cells at a concentration of ≥100 μM. The MMP-9 activity was suppressed by these compounds through regulating urokinase-type plasminogen activator (uPA), tissue inhibitor of metalloproteinase (TIMP)-1, plasminogen activator inhibitor (PAI)-1, and PAI-2; the cell-matrix adhesion was decreased by CAA only. The proposed molecular mechanism involved not only decreasing the signaling of MAPK and PI3K/Akt but also inactivating NF-κB, AP-1, and STAT3. In the present study, we selected CAA, CHA, and FA as potential inhibitors for invasive behaviors of human lung adenocarcinoma cells and disclosed the possible mechanisms. The association between structural features and anti-invasive activity of these compounds cannot be determined here and needs to be further verified. © 2013 American Chemical Society.
Su K.-J.,National Cheng Kung University |
Su K.-J.,Tainan Hospital |
Hwang W.-J.,National Cheng Kung University |
Wu C.-Y.,Chang Gung University |
And 3 more authors.
Gait and Posture | Year: 2014
Research has shown that moving targets help Parkinson's disease (PD) patients improve their arm movement while sitting. We examined whether increasing the speed of a moving ball would also improve standing postural control in PD patients during a virtual reality (VR) ball-catching task. Twenty-one PD patients and 21 controls bilaterally reached to catch slow-moving and then fast-moving virtual balls while standing. A projection-based VR system connected to a motion-tracking system and a force platform was used. Dependent measures included the kinematics of arm movement (movement time, peak velocity), duration of anticipatory postural adjustments (APA), and center of pressure (COP) movement (movement time, maximum amplitude, and average velocity). When catching a fast ball, both PD and control groups made arm movements with shorter movement time and higher peak velocity, longer APA, as well as COP movements with shorter movement time and smaller amplitude than when catching a slow ball. The change in performance from slow- to fast-ball conditions was not different between the PD and control groups. The results suggest that raising the speed of virtual moving targets should increase the speed of arm and COP movements for PD patients. Therapists, however, should also be aware that a fast virtual moving target causes the patient to confine the COP excursion to a smaller amplitude. Future research should examine the effect of other task parameters (e.g., target distance, direction) on COP movement and examine the long-term effect of VR training. © 2013 Elsevier B.V.
Lee Y.-C.,National Cheng Kung University |
Lee Y.-C.,Tainan Hospital |
Hsieh C.-C.,University of Massachusetts Medical School |
Chuang J.-P.,National Cheng Kung University |
Chuang J.-P.,Tainan Hospital
Diseases of the Colon and Rectum | Year: 2013
Background: Complete tumor regression after preoperative chemoradiotherapy for rectal cancer has been associated with better disease-free and overall survival. The survival experience for patients with partial tumor regression is less clear. Objective: The aim of this meta-analysis was to evaluate the prognostic significance of partial response after preoperative chemotherapy on disease-free survival in rectal cancer patients. DATA SOURCES: Relevant studies were identified by a search of MEDLINE and EMBASE databases with no restrictions to October 31, 2012. STUDY SELECTION: We included long-course radiotherapy that reported the association between degree of tumor regression and disease-free survival of rectal cancer. INTERVENTIONS: Direct, indirect, and graph methods were used to extract HRs. Main Outcome Measures: Study-specific HRs on the disease-free survival were pooled using a random-effects model. Eleven articles in total were selected. Analysis was performed first among the 6 studies that separated partial response from the complete response and later among all 11 of the studies. Results: Pooled HR was 0.49 (95% CI, 0.28-0.85) for the 6 studies that compared partial response with poor response. It was 0.41 (95% CI, 0.25-0.67) when all 11 of the studies were analyzed together. Limitations: The studies were limited by not being prospective, randomized trials, and the tumor regression grades were not uniform. Conclusions: Partial tumor response is associated with a 50% improvement in disease-free survival and should be considered as a favorable prognostic factor. © 2013 The ASCRS.
Shen P.-C.,Tainan Hospital |
Lu C.-S.,National Cheng Kung University |
Shiau A.-L.,National Cheng Kung University |
Lee C.-H.,China Medical University at Taichung |
And 2 more authors.
Human Gene Therapy | Year: 2013
Immune cells are involved in the pathogenesis of osteoarthritis (OA). CD4+ T cells were activated during the onset of OA and induced macrophage inflammatory protein (MIP)-1γ expression and subsequent osteoclast formation. We evaluated the effects of local knockdown of MIP-1γ in a mouse OA model induced by anterior cruciate ligament transection. The mouse macrophage cell lines and osteoclast-like cells generated from immature hematopoietic monocyte/macrophage progenitors of murine bone marrow were cocultured with either receptor activator of NFκB ligand (RANKL) or CD4+ T cells. The levels of MIP-1γ and RANKL in cells and mice were examined by enzyme-linked immunosorbent assay (ELISA). The osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase and cathepsin K staining. OA was induced in one hind-leg knee joint of B6 mice. Lentiviral vector encoding MIP-1γ small hairpin RNA (shRNA) and control vector were individually injected intra-articularly into the knee joints, which were histologically assessed for manifestations of OA. The expression of MIP-1γ and matrix metalloproteinase (MMP)-13 and the infiltration of CD4+ T cells, macrophages, and osteoclastogenesis in tissues were examined using immunohistochemistry. CD4+ T cells were involved in OA by inducing MIP-1γ expression in osteoclast progenitors and the subsequent osteoclast formation. Neutralizing MIP-1γ with a specific antibody abolishes RANKL-stimulated and CD4+ T-cell-stimulated osteoclast formation. MIP-1γ levels were significantly higher in synovium and the chondro-osseous junction of joints 90 days postsurgery. The number of infiltrated CD4+ T cells and macrophages and IL-1β expression were reduced in the synovial tissues of mice treated with MIP-1γ shRNA. Histopathological examinations revealed that mice treated with MIP-1γ shRNA had less severe OA than control mice had, as well as decreased osteoclast formation and MMP-13 expression. Locally inhibiting MIP-1γ expression may ameliorate disease progression and provide a new OA therapy. © Copyright 2013, Mary Ann Liebert, Inc.
Shih J.-Y.,Tainan Hospital Sin Hua Branch |
Tsai W.-C.,National Cheng Kung University |
Huang Y.-Y.,National Cheng Kung University |
Liu Y.-W.,National Cheng Kung University |
And 4 more authors.
Journal of the American Society of Echocardiography | Year: 2011
Background: The objective of this study was to investigate myocardial deformation of the left atrium (LA) assessed by two-dimensional speckle tracking echocardiography in patients with permanent atrial fibrillation (AF) and its value for risk stratification for stroke. Methods: We recruited 66 consecutive patients with permanent AF who were referred to our echocardiography laboratory for evaluation. These patients were divided into two groups according to the presence of previous stroke or not. Results: Peak positive longitudinal strain (LASp) during atrial filling, peak strain rate in the reservoir phase of LA (LASRr), and peak strain rate in the conduit phase (LASRc) were identified from LA strain and strain rate curves. The ratio of peak early filling velocity (E) of mitral inflow to early diastolic annulus velocity (E') of the medial annulus (E/E') was calculated. LASp (10.44% ± 4.2% vs. 15.69% ± 5.1%, P < .001), LASRr (1.09 ± 0.27 1/s vs. 1.37 ± 0.32 1/s, P = .001), and LASRc (-1.28 ± 0.38 1/s vs. -1.62 ± 0.43 1/s, P = .002) were significantly lower in patients with AF with stroke than those without stroke. By multivariate analysis controlling for age, LA volume index, and left ventricular ejection fraction, LASp (OR 0.787, 95% CI, 0.639-0.968, P = .023) and LASRr (OR 0.019, 95% CI, 0.001-0.585, P = .023) were independently associated with stroke but not LASRc, E', and E/E' ratio. Conclusion: Decreased LASp and LASRr were independently associated with stroke in patients with permanent AF. © 2011 by the American Society of Echocardiography.
Wu Y.-H.,National Cheng Kung University |
Chen P.-L.,National Cheng Kung University |
Hung Y.-P.,Tainan Hospital |
Hung Y.-P.,National Cheng Kung University |
Ko W.-C.,National Cheng Kung University
Journal of Microbiology, Immunology and Infection | Year: 2014
Background: Gram-negative bacilli causing community-onset urinary tract infections (CoUTIs) are getting increasingly resistant to antimicrobial agents. Clinical significance and risk factors of the acquisition of antimicrobial-nonsusceptible pathogens are still under investigation. Methods: A prospective study was performed in the medical wards of two hospitals in southern Taiwan between August 2009 and January 2012. Patients were enrolled if they were aged >18, admitted through the emergency department, and had CoUTI due to Enterobacteriaceae isolates. Results: Overall 136 adults with CoUTI were enrolled. Their mean age was 67 years and females were predominant (68.4%). Comorbidities, such as diabetes mellitus (30.1%) and hypertension (54.4%), were common. Escherichia coli (111, 81.6%) was the predominant species, followed by Klebsiella pneumoniae (11, 8.1%), and Proteus mirabilis (7, 5.1%). Nine (8.0%) of E. coli isolates and 5 (45%) of K. pneumoniae isolates had extended-spectrum β-lactamase (ESBL) production. Out of 122 non-ESBL producing isolates, 35 (28.7%) and 31 (25.4%) were nonsusceptible to levofloxacin and cefazolin, respectively. In the multivariate analysis, several clinical characters were found to be independently associated with CoUTIs due to levofloxacin-nonsusceptible (i.e. males, recent hospitalization, underlying old stroke, diabetes mellitus, and altered consciousness, or absence of chills, pyuria, or tachycardia), cefazolin-nonsusceptible (i.e. males, recent hospitalization, underlying old stroke, absence of fever or chills), or ESBL-producing isolates (i.e. recent hospitalization or antimicrobial therapy). All patients survived and discharged. However, the patients with CoUTIs due to levofloxacin-nonsusceptible (16.1 vs. 7.5 days, p < 0.01), cefazolin-nonsusceptible (15.4 vs. 8.4 days, p < 0.01) or ESBL-producing (16.7 vs. 9.6 days; p < 0.01) pathogens had a longer hospitalization stay than those due to their susceptible comparators. Conclusion: Several host factors were recognized to be independently associated with the acquisition of UTIs due to levofloxacin- or cefazolin- nonsusceptible, or ESBL-producing Gram-negative bacilli. The clinical impact of UTIs due to nonsusceptible uropathogens is that they result in the prolongation of hospital stays. © 2012.
Tsai Y.-C.,National Cheng Kung University |
Tsai Y.-C.,Tainan Hospital |
Hsiao W.-H.,National Cheng Kung University |
Yang H.-B.,National Cheng Kung University |
And 5 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2013
Background To eradicate Helicobacter pylori before the occurrence of precancerous changes is important to prevent gastric carcinogenesis. Aim To validate whether the corpus-predominant gastritis index (CGI) can serve as an early marker to identify the H. pylori-infected patients at risk of gastric carcinogenesis. Methods This study enrolled 188 subjects, including 43 noncardiac gastric cancer patients, 63 of their first-degree relatives and 82 sex- and age-matched duodenal ulcer patients as controls. All received endoscopy to provide topographic gastric specimens to test for H. pylori infection and its related histological features, translated into the operative link on gastritis assessment (OLGA), operative link on gastric intestinal metaplasia assessment (OLGIM) stages, and the presence of CGI. Spasmolytic polypeptide-expressing metaplasia (SPEM) was assessed by immunohistochemistry staining of trefoil factor 2. Results Gastric cancer patients had higher prevalence of CGI and OLGIM stage II-IV, but not OLGA stage II-IV, than the controls (P = 0.001, OR = 3.4[95% CI: 1.4-8.1] for CGI; OR = 5.0[95% CI: 2.0-12.8] for OLGIM). In patients with the combined presence of CGI and OLGIM stage II-IV, the risk of gastric cancer increased to 9.8 (P < 0.001). The first-degree relatives of the gastric cancer patients had a higher rate of the presence of CGI, but not OLGA or OLGIM stage II-IV than the duodenal ulcer controls (P = 0.001). Of the first-degree relatives, the presence of CGI increased the risk of SPEM (P = 0.003, OR = 5.5[95% CI: 1.8-17.0]). Conclusion The corpus-predominant gastritis index, which is highly correlated to SPEM, may serve as an early marker to identify the H. pylori-infected patients at a higher risk of gastric cancer. © 2013 Blackwell Publishing Ltd.
Avila N.A.,Washington Dc Veterans Affairs Medical Center |
Avila N.A.,Warren gnuson Clinical Center |
Dwyer A.J.,Warren gnuson Clinical Center |
Rabel A.,U.S. National Institutes of Health |
And 3 more authors.
Radiology | Year: 2010
Purpose: To determine if sclerotic bone lesions evident at body computed tomography (CT) are of value as a diagnostic criterion of tuberous sclerosis complex (TSC) and in the differentiation of TSC with lymphangioleiomyomatosis (LAM) from sporadic LAM. Materials and Methods: Informed consent was signed by all patients in this HIPAA-compliant study approved by the institutional review board. Retrospective analysis was performed of the body CT studies of 472 patients: 365 with sporadic LAM, 82 with TSC/LAM, and 25 with TSC. The images were reviewed by using a picture archiving and communication system workstation with bone settings (window width, 1500 HU; window level, 300 HU) and fit-to-screen option. CT image characteristics assessed included shape, size, and distribution of sclerotic bone lesions with subsequent calculation of differences in the frequency of these lesions. Results: Most commonly the sclerotic bone lesions were round, measured 0.3 cm (range, 0.2-3.2), and were distributed throughout the spine. The frequencies differed among the three patient groups Four or more sclerotic bone lesions were detected in all 25 (100%) of those with TSC, with a sensitivity of .89 (72 of 82) and specificity of .97 (355 of 367) in the differentiation of sporadic LAM from TSC/LAM (P < .01). Conclusion: The number of sclerotic bone lesions at body CT is of potential value in the diagnosis of TSC and in the differentiation of patients with sporadic LAM from those with TSC/LAM. © RSNA, 2010.
Su B.-H.,National Cheng Kung University |
Tseng Y.-L.,National Cheng Kung University |
Shieh G.-S.,Tainan Hospital |
Chen Y.-C.,National Cheng Kung University |
And 3 more authors.
Journal of Pathology | Year: 2016
Emphysema, a major consequence of chronic obstructive pulmonary disease (COPD), is characterized by the permanent airflow restriction resulting from enlargement of alveolar airspace and loss of lung elasticity. Transforming growth factor-β (TGFβ) signalling regulates the balance of matrix metalloproteinase (MMP)/tissue inhibitor of matrix metalloproteinase (TIMP) to control matrix homeostasis. Patients with COPD have dysregulated TGFβ signalling and reduced histone deacetylase (HDAC) activity through epigenetic up-regulation of histone acetylation in the promoters of pro-inflammatory genes. However, the potential link between decreased HDAC activity and dysregulated TGFβ signalling in emphysema pathogenesis remains to be determined. Prothymosin α (ProT), a highly conserved acidic nuclear protein, plays a role in the acetylation of histone and non-histone proteins. The aim of this study was to test the hypothesis that ProT inhibits TGFβ-Smad signalling through Smad7, thereby contributing to emphysema pathogenesis. We show that ProT enhances Smad7 acetylation by decreasing its association with HDAC and thereby down-regulates TGFβ-Smad signalling. ProT caused an imbalance between MMP and TIMP through acetylated Smad7 in favour of MMP expression. In addition to interfering with R-Smad activation and targeting receptors for degradation in the cytoplasm, acetylated Smad7 potentiated by ProT competitively antagonized binding of the pSmad2/3-Smad4 complex to the TIMP-3 promoter, resulting in reduced TIMP-3 expression. These effects were detected in ProT-over-expressing cells, lungs of ProT transgenic mice displaying an emphysema phenotype and in emphysema patients. Importantly, increased Smad7 and reduced TIMP-3 were found in the lungs of emphysema patients and mice with cigarette smoke extract (CSE)-induced emphysema. Such effects could be abrogated by silencing endogenous ProT expression. Collectively, our results uncover acetylated Smad7 regulated by ProT as an important determinant in dysregulated TGFβ signalling that contributes to emphysema pathogenesis. © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Tabbada K.A.,University of the Philippines at Diliman |
Tabbada K.A.,University of Cambridge |
Trejaut J.,Mackay Memorial Hospital |
Loo J.-H.,Mackay Memorial Hospital |
And 5 more authors.
Molecular Biology and Evolution | Year: 2010
Relatively little is known about the genetic diversity of the Philippine population, and this is an important gap in our understanding of Southeast Asian and Oceanic prehistory. Here we describe mitochondrial DNA (mtDNA) variation in 423 Philippine samples and analyze them in the context of the genetic diversity of other Southeast Asian populations. The majority of Philippine mtDNA types are shared with Taiwanese aboriginal groups and belong to haplogroups of postglacial and pre-Neolithic origin that have previously been identified in East Asian and Island Southeast Asian populations. Analysis of hypervariable segment I sequence variation within individual mtDNA haplogroups indicates a general decrease in the diversity of the most frequent types (B4a1a, E1a1a, and M7c3c) from the Taiwanese aborigines to the Philippines and Sulawesi, although calculated standard error measures overlap for these populations. This finding, together with the geographical distribution of ancestral and derived haplotypes of the B4a1a subclade including the Polynesian Motif, is consistent with southward dispersal of these lineages Out of Taiwan via the Philippines to Near Oceania and Polynesia. In addition to the mtDNA components shared with Taiwanese aborigines, complete sequence analyses revealed a minority of lineages in the Philippines that share their origins-possibly dating back to the Paleolithic-with haplogroups from Indonesia and New Guinea. Other rare lineages in the Philippines have no closely related types yet identified elsewhere.