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Hou C.-H.,National Taiwan University Hospital | Lin F.-L.,Sijhih Cathay General Hospital | Hou S.-M.,Shin Kong Wu Ho Su Memorial Hospital | Liu J.-F.,Shin Kong Wu Ho Su Memorial Hospital
Molecular Cancer | Year: 2015

Background: Osteosarcoma is the most common primary malignant tumor in children and young adults, and its treatment requires effective therapeutic approaches because of a high mortality rate for lung metastasis. Epithelial to mesenchymal transition (EMT) has received considerable attention as a conceptual paradigm for explaining the invasive and metastatic behavior during cancer progression. The cysteine-rich angiogenic inducer 61 (Cyr61) gene, a member of the CCN gene family, is responsible for the secretion of Cyr61, a matrix-associated protein that is involved in several cellular functions. A previous study showed that Cyr61 expression is related to osteosarcoma progression. In addition, Cyr61 could promote cell migration and metastasis in osteosarcoma. However, discussions on the molecular mechanism involved in Cyr61-regulated metastasis in osteosarcoma is poorly discussed. Results: We determined that the expression level of Cyr61 induced cell migration ability in osteosarcoma cells. The Cyr61 protein promoted the mesenchymal transition of osteosarcoma cells by upregulating mesenchymal markers (TWIST-1 and N-cadherin) and inhibiting the epithelial marker (E-cadherin). Moreover, the Cyr61-induced cell migration was mediated by EMT. The Cyr61 protein elicited a signaling cascade that included αvβ5 integrin, Raf-1, mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase (ERK), and Elk-1. The reagent or gene knockdown of these signaling proteins could inhibit Cyr61-promoted EMT in osteosarcoma. Finally, the knockdown of Cyr61 expression obviously inhibited cell migration and repressed mesenchymal phenotypes, reducing lung metastasis. Conclusion: Our results indicate that Cyr61 promotes the EMT of osteosarcoma cells by regulating EMT markers via a signal transduction pathway that involves αvβ5 integrin, Raf-1, MEK, ERK, and Elk-1. © 2014 Hou et al.; licensee BioMed Central Ltd.


Hou C.-H.,National Taiwan University Hospital | Lin F.-L.,Sijhih Cathay General Hospital | Tong K.-B.,Shin Kong Wu Ho Su Memorial Hospital | Hou S.-M.,Shin Kong Wu Ho Su Memorial Hospital | Liu J.-F.,Shin Kong Wu Ho Su Memorial Hospital
Biochemical Pharmacology | Year: 2014

Osteosarcoma is the most common primary malignancy of bone and is characterized by a high malignant and metastatic potential. Transforming growth factor alpha (TGF-α) is classified as the EGF (epidermal growth factor)-like family, which is involved in cancer cellular activities such as proliferation, motility, migration, adhesion and invasion abilities. However, the effect of TGF-α on human osteosarcoma is largely unknown. We found that TGF-α increased the cell migration and expression of intercellular adhesion molecule-1 (ICAM-1) in human osteosarcoma cells. Transfection of cells with ICAM-1 siRNA reduced TGF-α-mediated cell migration. We also found that the phosphatidylinositol 3′-kinase (PI3K)/Akt/NF-κB pathway was activated after TGF-α treatment, and TGF-α-induced expression of ICAM-1 and cell migration was inhibited by the specific inhibitors and siRNAs of PI3K, Akt, and NF-κB cascades. In addition, knockdown of TGF-α expression markedly decreased cell metastasis in vitro and in vivo. Our results indicate that TGF-α/EGFR interaction elicits PI3K and Akt activation, which in turn activates NF-κB, resulting in the expression of ICAM-1 and contributing the migration of human osteosarcoma cells. © 2014 Elsevier Inc.


Lai Y.-T.,Sijhih Cathay General Hospital | Lai Y.-T.,National Taiwan University Hospital | Dai Y.-S.,National Taiwan University Hospital | Yen M.-F.,Taipei Medical University | And 4 more authors.
British Journal of Dermatology | Year: 2013

Background While the chronic inflammation related to autoimmune diseases is known to be associated with an increased cardiovascular risk, much less is known about cerebrovascular risks. Objectives The present population-based, age- and sex-matched follow-up study was undertaken to investigate the risks of acute myocardial infarction (AMI) and ischaemic stroke in patients with dermatomyositis (DMS). Methods In total 907 patients with DMS were enrolled and compared with a non-DMS control group consisting of 4535 age- and sex-matched, randomly sampled subjects without DMS. The AMI-free and ischaemic stroke-free survival curves were generated using the Kaplan-Meier method. Cox proportional hazard regression was used to estimate the DMS-associated risks of AMI and ischaemic stroke. Results During the 2-year follow-up period, 14 patients with DMS (1·5%) and 18 patients in the non-DMS control group (0·4%) suffered AMIs. The crude hazard ratio (HR) for suffering an AMI in patients with DMS compared with subjects in the non-DMS group was 3·96 [95% confidence interval (CI) 1·97-7·96, P = 0·0001], while the adjusted HR was 3·37 (95% CI 1·67-6·80, P = 0·0007), after taking into account demographic characteristics and cardiovascular comorbidities. During the same follow-up period, 46 patients (5·1%) and 133 subjects in the control group (2·9%) developed ischaemic strokes. The crude HR for developing an ischaemic stroke in patients with DMS compared with subjects in the non-DMS group was 1·78 (95% CI 1·27-2·49, P = 0·0007), and the adjusted HR was 1·67 (95% CI, 1·19-2·34, P = 0·0028). Conclusions These findings suggest that DMS is associated with an increased risk of cardiovascular and cerebrovascular events. © 2013 The Authors. BJD © 2013 British Association of Dermatologists.


Hou C.-H.,National Taiwan University Hospital | Lin F.-L.,Sijhih Cathay General Hospital | Hou S.-M.,Shin Kong Wu Ho Su Memorial Hospital | Liu J.-F.,Shin Kong Wu Ho Su Memorial Hospital
International Journal of Molecular Sciences | Year: 2014

Osteosarcoma (OS) is a relatively rare form of cancer, but OS is the most commonly diagnosed bone cancer in children and adolescents. Chemotherapy has side effects and induces drug resistance in OS. Since an effective adjuvant therapy was insufficient for treating OS, researching novel and adequate remedies is critical. Hyperthermia can induce cell death in various cancer cells, and thus, in this study, we investigated the anticancer method of hyperthermia in human OS (U-2 OS) cells. Treatment at 43 °C for 60 min induced apoptosis in human OS cell lines, but not in primary bone cells. Furthermore, hyperthermia was associated with increases of intracellular reactive oxygen species (ROS) and caspase-3 activation in U-2 OS cells. Mitochondrial dysfunction was followed by the release of cytochrome c from the mitochondria, and was accompanied by decreased anti-apoptotic Bcl-2 and Bcl-xL, and increased pro-apoptotic proteins Bak and Bax. Hyperthermia triggered endoplasmic reticulum (ER) stress, which was characterized by changes in cytosolic calcium levels, as well as increased calpain expression and activity. In addition, cells treated with calcium chelator (BAPTA-AM) blocked hyperthermia-induced cell apoptosis in U-2 OS cells. In conclusion, hyperthermia induced cell apoptosis substantially via the ROS, ER stress, mitochondria, and caspase pathways. Thus, hyperthermia may be a novel anticancer method for treating OS. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


Hanafy D.A.,Taipei Veterans General Hospital | Chang S.-L.,Taipei Veterans General Hospital | Lu Y.-Y.,Taipei Medical University | Lu Y.-Y.,Sijhih Cathay General Hospital | And 6 more authors.
Journal of Cardiovascular Electrophysiology | Year: 2014

Electromechanical Effects of 1,25-Dihydroxyvitamin D on the LA Introduction Treatment with 1,25-dihydroxyvitamin D (1,25[OH]2D) has several cardiovascular benefits. 1,25[OH]2D has direct cellular effects, but its effects on the atrium are not clear. We evaluated the effects of 1,25[OH]2D on the atrial electrophysiology and atrial fibrillation (AF). Methods Conventional microelectrodes were used to record action potentials (APs) and contractility in isolated rabbit left atrium (LA) tissue preparations before and after the administration of 0.01, 0.1, and 1 nM 1,25[OH] 2D with and without rapid atrial pacing (RAP) and acetylcholine (5 mM)-induced AF. Surface ECG and intracardiac electrograms were recorded before and after the intravenous administration of 4 units/kg of 1,25[OH]2D in heart failure (HF) rabbits (4 weeks after coronary artery ligation) with RAP and acetylcholine-induced AF. Results 1,25[OH]2D dose-dependently increased the AP duration in the LA, which was abolished by pretreatment with 0.1 μM ryanodine. RAP and 5 mM acetylcholine-induced fewer (64.3% vs 100%, P < 0.05) AF occurrences in the presence (n = 14) of 1,25[OH]2D than those (n = 14) in the absence of 1,25[OH]2D. The LA treated with 1,25[OH]2D (n = 9) had a slower maximal AF rate (10.9 ± 2.4 Hz vs 13.3 ± 2.7 Hz, P < 0.05) than the LA (n = 14) without 1,25[OH]2D. Moreover, 1,25[OH]2D caused a lower AF inducible percentage (11.0 ± 1.9% vs 100 ± 0%, P < 0.001) and a shorter duration (4 ± 0.4 seconds vs 309 ± 26 seconds, P < 0.001) with a prolonged LA 90% monophasic AP duration (94.1 ± 0.2 milliseconds vs 98.5 ± 0.1 milliseconds, P < 0.05) in 5 rabbits with HF. 1,25[OH]2D did not prolong the QT interval or 90% of the AP duration in isolated Purkinje fibers. Conclusion 1,25[OH]2D has direct electromechanical effects on the LA and can prevent or terminate AF. © 2013 Wiley Periodicals, Inc.


Hung S.-H.,Taipei Medical University Hospital | Lin C.-Y.,Chen An Otolaryngology Clinic | Lee J.-Y.,Sijhih Cathay General Hospital | Tseng H.,Taipei Medical University
Auris Nasus Larynx | Year: 2012

Objective: Metastatic neck nodes are commonly described as "heterogenous" or "inhomogenous" on computed tomographic (CT) images, and this remains a highly subjective issue. The purpose of this study is to justify classical criteria and to develop novel supplemental methods for diagnosing a positive neck node on CT scans. Methods: Fifty-four patients with H&N SCC were separated into two groups according to their neck nodal status. CT scan digital images were used and the lymph node borders were selected by a radiologist. Lymph node images from the pathologically proven N- (negative for cervical metastases) group were compared to the N+ (positive for cervical metastases) group. Image-analysis software, ImageJ, was used to record and compare various characteristics collected from the images. Results: The image-analysis comparisons shows, the area (size) of the lymph node in the N+ group is much larger than the N- group (474.02 VS.81.55mm2) (P<0.01). There are no significant differences with regards to distribution of pixel values between the two groups (P=0.79). The lacunarity, a parameter used to describe gappiness or inhomogeneity, of the N+ group was significantly higher than the N- group (P=0.026). Conclusions: While size of the lymph node remains an important factor in the interpretation of a clinically suspicious lymph node metastasis on CT scan images, the distribution of pixel values could not clarify a heterogeneous state. Nevertheless, 'lacunarity' proves to be a more accurate parameter which correlates better to the subjective heterogeneity. © 2012 Elsevier Ireland Ltd.


Lin J.-L.,Hsinchu Cathay General Hospital | Lin Y.-H.,Sijhih Cathay General Hospital | Chueh K.-H.,Fu Jen Catholic University
Journal of Clinical Nursing | Year: 2014

Aims and objectives: To explore sleep quality in infertile women and examine the factors that contribute to sleep disturbances during intrauterine insemination treatment. Background: Sleep disturbance is an important factor of human health and well-being. Sleep disturbances tend to occur among infertile women during intrauterine insemination treatment. Although many studies have focused on the high percentage of somatic symptoms and psychological distress in infertile women associated with their treatment, few studies have investigated factors linked to their sleep disturbances. Design: A cross-sectional study. Methods: The study was conducted during the period of September 2010-January 2011 in a teaching hospital in Taiwan. Infertile women (n = 117) who received assisted reproduction with intrauterine insemination treatment completed a questionnaire. Demographic data, somatic symptoms, psychological distress and perceived sleep quality were collected. Results: More than one-third (35%) of the infertile women reported having sleep disturbances. Their nausea symptoms and psychological distress were risk factors that contributed to sleep disturbance. Conclusions: The variables of nausea and psychological distress significantly explained 30% of the sleep disturbances in the infertile women. The evaluation of nausea symptoms and/or psychological distress among infertile women is an important area of future research; such research should aim to identify the best compromise between infertility treatment and sleep quality. Relevance to clinical practice: Clinical obstetrics and gynaecology nurses should develop strategies to help infertile women reduce their nausea symptoms and psychological distress during intrauterine insemination treatment to promote healthy sleep. © 2013 John Wiley & Sons Ltd.


Chen P.-C.,Taipei Medical University | Tseng T.-C.,Sijhih Cathay General Hospital | Hsieh J.-Y.,Min Sheng General Hospital | Lin H.-W.,National Yang Ming University | Lin H.-W.,Taipei Medical University
Stroke | Year: 2011

Background and Purpose- The aim of this study is to estimate the risk of stroke in a 3-year period after pelvic inflammatory disease (PID) using a nationwide population-based study. Methods- Our study cohort consisted of all patients with a diagnosis of PID (N=64 515) between 2004 and 2005 with a control cohort (1:2) of age-matched controls (N=129 030). Each patient was tracked from hospitalization until the end of 2006. Cox regressions were performed to compute the 3-year stroke-free survival rates after adjusting for possible confounding factors. Results- We found that women with PID were more likely to have strokes than the control population. After adjusting for potential confounding factors, the adjusted hazard ratio of stroke was 1.63 (95% CI, 1.45-1.85) for PID patients as compared to the general population cohort. Sensitivity analysis using a bootstrap approach further ensured the validity of the results of our study. Conclusions- We concluded that patients with PID have an association with stroke. Further research is necessary to investigate the pathophysiology between PID and stroke. Copyright © 2011 American Heart Association. All rights reserved.


Tasi C.K.,Sijhih Cathay General Hospital
International journal of surgical pathology | Year: 2012

Lymph node status is pivotal in the staging process of cancer. With regards to colorectal cancer, lymph node retrieval is always laborious. Sometimes, it is also a challenge to recover a minimum of 12 lymph nodes from the pericolorectal tissue. Among many proposed adjunctive solutions, GEWF solution (glacial acetic acid, ethanol, distilled water, and formaldehyde) has been introduced recently and suggested to be superior. To further evaluate its efficiency, the pericolorectal tissue, which has been reexamined extensively in the conventional condition, was refixed into GEWF solution in this study. More lymph nodes were found in 75% (n = 6) of the 8 experimental cases, and 50% (n = 4) of them had 12 or more yielded lymph nodes eventually. In addition, no adverse influences on the expressions of immunohistochemical and special stains were seen. These data support the reliability and effectiveness of GEWF solution in improvement of lymph node yield.


Chung C.-C.,Taipei Medical University | Hsu R.-C.,Taipei Medical University | Kao Y.-H.,Taipei Medical University | Liou J.-P.,Taipei Medical University | And 3 more authors.
International Journal of Cardiology | Year: 2014

Background: Androgen deficiency produces heart failure, which can be ameliorated by testosterone supplementation. Cardiac fibrosis plays a critical role in the pathophysiology of heart failure. This study aimed to evaluate whether testosterone can attenuate cardiac fibroblast activity through modulating transforming growth factor (TGF)-β and angiotensin (Ang) II signaling. Methods:Migration, proliferation, myofibroblast differentiation, collagen production, and transcription signaling were evaluated in adult male rat (weighing 300-350 g) cardiac fibroblasts with and without incubation with testosterone (10 nM) and co-administration of TGF-β1 (10 ng/ml) or Ang II (100 nM) by cell migration analysis, proliferation assay, soluble collagenmeasurement, zymographic analysis, immunofluorescence microscopy, realtime PCR and Western blot. Results: Compared to thosewithout testosterone, testosterone-treated fibroblasts exhibited less collagen production. Testosterone-treated fibroblasts also had less migration, proliferation, myofibroblast differentiation, and collagen production in the presence of TGF-β1, or had less collagen production with Ang II. Testosteronetreated fibroblasts had decreased phosphorylated Akt, mammalian target of rapamycin, and 4E binding protein-1 irrespective of TGF-β1 treatment and had increased matrix metalloproteinase (MMP)-2 in the presence of TGF-β1 treatment, and had decreased phosphorylated P38 and Smad 2/3 levels in the presence of Ang II. Cardiac fibroblasts with and without testosterone had similar mRNA and protein expressions of total Akt and total Smad 2/3 irrespective of TGF-β1 or Ang II treatment. Conclusion: Physiological level of testosterone attenuated Akt and Smad 2/3 phosphorylation mediated by TGF- β1 and angiotensin II respectively, which can result in decreased cardiac fibroblast activation and potentially contribute to beneficial effects in heart failure. © 2014 Elsevier Ireland Ltd. All rights reserved.

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