Yang C.-C.,Armed Forces Hualien General Hospital |
Yang C.-C.,Mennonite Christian Hospital |
Chang S.-F.,National Yang Ming University |
Chao J.-K.,Taipei Veterans General Hospital |
And 6 more authors.
BMC Cancer | Year: 2014
Background: Resistin, adipocyte-secreting adipokine, may play critical role in modulating cancer pathogenesis. The aim of this study was to investigate the effects of resistin on HCC adhesion to the endothelium, and the mechanism underlying these resistin effects.Methods: Human SK-Hep1 cells were used to study the effect of resistin on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions as well as NF-κB activation, and hence cell adhesion to human umbilical vein endothelial cells (HUVECs). 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, was used to determine the regulatory role of AMPK on HCC adhesion to the endothelium in regard to the resistin effects.Results: Treatment with resistin increased the adhesion of SK-Hep1 cells to HUVECs and concomitantly induced NF-κB activation, as well as ICAM-1 and VCAM-1 expressions in SK-Hep1 cells. Using specific blocking antibodies and siRNAs, we found that resistin-induced SK-Hep1 cell adhesion to HUVECs was through NF-κB-regulated ICAM-1 and VCAM-1 expressions. Moreover, treatment with AICAR demonstrated that AMPK activation in SK-Hep1 cells significantly attenuates the resistin effect on SK-Hep1 cell adhesion to HUVECs.Conclusions: These results clarify the role of resistin in inducing HCC adhesion to the endothelium and demonstrate the inhibitory effect of AMPK activation under the resistin stimulation. Our findings provide a notion that resistin play an important role to promote HCC metastasis and implicate AMPK may be a therapeutic target to against HCC metastasis. © 2014 Yang et al.; licensee BioMed Central Ltd.
Hsu W.-H.,Armed Forces Taichung General Hospital |
Chen C.-N.,National Chiayi University |
Huang H.-I.,Central Taiwan University of Science and Technology |
Lai Y.-L.,Armed Forces Taichung General Hospital |
And 4 more authors.
Journal of Cellular Physiology | Year: 2012
Both the urokinase-type plasminogen activator (uPA) and the uPA receptor (uPAR) play important roles with regard to hepatocellular carcinoma (HCC) progression and metastasis. Notably, the stromal cell-derived factor-1 (SDF-1) is an important chemokine involved in HCC pathology. However, the influence of uPA on SDF-1 expression in human HCC cells remains unknown. We investigated the mechanisms underlying the modulation of SDF-1 expression through uPA stimulation in human HCC SK-Hep-1 cells. SK-Hep-1 cells stimulation with uPA induced increases in the expression and secretion of SDF-1. By using specific inhibitors and small interfering RNA, we have demonstrated that the activation of extracellular signal-related kinase (ERK) and c-Jun-NH 2-terminal kinase (JNK) pathways are critical for uPA-induced SDF-1 expression. Transcription factor ELISA and chromatin immunoprecipitation assays suggest that uPA increase Sp1- and AP-1-DNA-binding activities in SK-Hep-1 cells. Inhibition of Sp1 and AP-1 activations by specific siRNAs blocked the uPA-induced SDF-1 promoter activity and expression. The effect of uPA on SK-Hep-1 signaling and SDF-1 expression is mediated by uPAR. In summary, our findings serve to elucidate the uPA/uPAR downstream signaling, providing new insight into the function of uPA in HCC cells. © 2011 Wiley Periodicals, Inc.
Wu M.H.,China Medical University at Taichung |
Lo J.-F.,National Yang Ming University |
Kuo C.-H.,Taipei Physical Education College |
Lin J.A.,China Medical University at Taichung |
And 7 more authors.
Journal of Cellular Physiology | Year: 2012
Tumor malignancy is associated with several cellular properties including proliferation and ability to metastasize. Endothelin-1 (ET-1) the most potent vasoconstrictor plays a crucial role in migration and metastasis of human cancer cells. We found that treatment of human chondrosarcoma (JJ012 cells) with ET-1 increased migration and expression of matrix metalloproteinase (MMP)-13. ET-1-mediated cell migration and MMP-13 expression were reduced by pretreatment with inhibitors of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), as well as the NF-κB inhibitor and the IκB protease inhibitor. In addition, ET-1 treatment induced phosphorylation of FAK, PI3K, AKT, and mTOR, and resulted in increased NF-κB-luciferase activity that was inhibited by a specific inhibitor of PI3K, Akt, mTOR, and NF-κB cascades. Taken together, these results suggest that ET-1 activated FAK/PI3K/AKT/mTOR, which in turn activated IKKα/β and NF-κB, resulting in increased MMP-13 expression and migration in human chondrosarcoma cells. © 2011 Wiley Periodicals, Inc.
Wu M.H.,China Medical University at Taichung |
Chen L.-M.,Central Taiwan University of Science and Technology |
Chen L.-M.,Armed Forces Taichung General Hospital |
Hsu H.-H.,Mackay Memorial Hospital |
And 8 more authors.
Biochimica et Biophysica Acta - General Subjects | Year: 2013
Background Chondrosarcoma is a type of highly malignant tumor with a potent capacity of local invasion and distant metastasis. The effect of endothelin-1 (ET-1) on migration activity in human chondrosarcoma cells is not clearly understood. Here, we found that ET-1 increased the migration and expression of cyclooxygenase (COX)-2 in human chondrosarcoma cells. Methods ET-1-mediated COX-2 expression was assessed by qPCR and Western blot analysis. The mechanisms of action of ET-1 in different signaling pathways were studied using Western blotting. Knockdown of proteins was achieved by transfection with siRNA. Chromatin immunoprecipitation assays were used to study in vivo binding of c-Jun to the COX-2 promoter. Results Human chondrosarcoma tissues had significant expression levels of ET-1 and COX-2, which were higher than that in normal cartilage. Exogenous ET-1 increased cell migration and the expression of COX-2. In addition, COX-2 protein levels and cell migration ability were abolished by ET receptor antagonists. Activation of the mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1) pathways after ET-1 treatment was demonstrated, and ET-1-induced COX-2 expression and cell migration activity were inhibited by the specific inhibitor and mutant of MAPK and AP-1 cascades. ET-1 increased the binding of c-Jun to the AP-1 element on the COX-2 promoter. Furthermore, knockdown of ET-1 decreased cell metastasis in vitro and in vivo. Conclusions Our results indicated that ET-1 enhances the cell migration of chondrosarcoma by increasing COX-2 expression through the ET receptors, MAPK, and AP-1 signal transduction pathway. General significance We link high ET-1 and COX-2 expression to chondrosarcoma. © 2013 Elsevier B.V.
Lin H.W.,Armed Forces Taichung General Hospital |
Lin H.W.,Central Taiwan University of Science and Technology |
Lin H.W.,Asia University, Taiwan |
Yu T.C.,Asia University, Taiwan |
And 2 more authors.
European Journal of Gynaecological Oncology | Year: 2011
The term "human papillomavirus" has been used as the keyword during searching titles, abstracts, and keywords based on the online version of Science Citation Index (SCI), Web of Science from 1993 to 2008. Twelve document types were found among the 14,943 papers published in 1,072 journals that were listed in 99 SCI subject categories. All the articles referring to human papillomavirus were assessed by using the following aspects: characteristics of publication output, distribution of output in journals, publication output of source country, source institute, and analysis of word clusters in title, author keywords, and keywords plus. The results have shown that the USA ranked first using five publication indicators including total, single country, international, first author, and corresponding author publications. China has had the sharpest rise of publications since 2004. The top four European countries in 2008 were France, Germany, the UK, and Italy, respectively. Trend studies with word cluster analysis were performed with regards to the areas of immunology, screening methodology, behavioral sciences, economics, and meta-analysis. All those areas have shown a sharp upward rise since 2004. In addition, hypermethylation-induced inactivation of the p16 gene in the early stages of oncogenesis has been getting more interest in recent years.
Hung L.-F.,National Health Research Institute |
Huang K.-Y.,Graduate Institute of Microbiology and Immunology |
Yang D.-H.,Armed Forces Taichung General Hospital |
Chang D.-M.,Tri Service General Hospital |
And 3 more authors.
Mechanisms of Ageing and Development | Year: 2010
Accumulation of advanced glycation end products (AGEs) is a hallmark in aged people. T cells play important roles in maintaining homeostasis of immune function. This study investigated the effects of AGEs-bovine serum albumin (AGEs) in human T cells. Incubation of Jurkat and several immortalized T cell lines with AGEs resulted in cell death dose-dependently. AGEs-induced cell death was partially but significantly blocked by neutralizing antibodies recognizing receptor of AGEs. In addition to detecting DNA nick, simultaneous stainings of annexin V with 7-amino-actinomycin D further confirmed the apoptotic nature of cell death. AGEs also caused apoptosis in purified T cells. Although AGEs-induced apoptosis could be blocked by the pan-caspase inhibitor, Ala-Asp-fluomethyl ketone (Z-VAD-fmk), there was no activation of caspase-3, -5, -8 and -9. AGEs caused mitochondrial outer membrane permeabilization and this process was prevented by an antioxidant or Z-VAD-fmk. Furthermore, AGEs treatment led to translocation of apoptosis inducing factor (AIF) from the mitochondria into the nucleus. Altogether, this report demonstrated that AGEs induced T cell apoptosis in an oxidative stress-associated and caspase-dependent manner with involvement of the mitochondrial pathway. It is likely that AGEs-induced T cell apoptosis may play a role in T cell homeostasis in ageing. © 2010 Elsevier Ireland Ltd.
PubMed | Taichung Veterans General Hospital, Armed Forces Taichung General Hospital, Kuang Tien General Hospital, National Chung Hsing University and 2 more.
Type: Journal Article | Journal: Journal of pineal research | Year: 2016
Peritoneal dissemination of tumor has high mortality and is associated with the loss of epithelial features, acquisition of motile mesenchymal morphology characteristics, and invasive properties by tumor cells. Melatonin is an endogenously produced molecule in all plant species that is known to exert antitumor activity, but to date, its underlying mechanisms and antiperitoneal metastasis efficacy is not well defined. This study determined the antiperitoneal dissemination potential of melatonin in vivo and assessed its association with the inhibition of epithelial-to-mesenchymal transition (EMT) signaling mechanism by endoplasmic reticulum (ER) stress, which may be a major molecular mechanism of melatonin against cancer. The results demonstrate that melatonin inhibited peritoneal metastasis in vivo and activated ER stress in Cignal ERSE Reporter Assay, organelle structure in transmission electron microscopy images, calpain activity, and protein biomarkers like p-elf2. Moreover, the overexpression of transcription factor C/EBP in gastric cancer interacted with NFB and further regulates COX-2 expression. These were dissociated and downregulated by melatonin, as proven by immunofluorescence imaging, immunoprecipitation, EMSA, and ChIP assay. Melatonin or gene silencing of C/EBP decreased the EMT protein markers (E-cadherin, Snail, and Slug) and Wnt/beta-catenin activity by Topflash activity, and increased ER stress markers. In an animal study, the results of melatonin therapy were consistent with those of in vitro findings and attenuated systemic proangiogenesis factor production. In conclusion, C/EBP and NFB inhibition by melatonin may impede both gastric tumor growth and peritoneal dissemination by inducing ER stress and inhibiting EMT.
Chang T.-S.,National Chung Hsing University |
Chang T.-S.,Armed Forces Taichung General Hospital |
Chang J.-H.,National Taiwan Normal University |
Wang C.-S.,National Chung Hsing University |
And 2 more authors.
Journal of Orthopaedic Surgery and Research | Year: 2010
Background: To investigate how unilateral cage-instrumented posterior lumbar interbody fusion (PLIF) affects the three-dimensional flexibility in degenerative disc disease by comparing the biomechanical characteristics of unilateral and bilateral cage-instrumented PLIF.Methods: Twelve motion segments in sheep lumbar spine specimens were tested for flexion, extension, axial rotation, and lateral bending by nondestructive flexibility test method using a nonconstrained testing apparatus. The specimens were divided into two equal groups. Group 1 received unilateral procedures while group 2 received bilateral procedures. Laminectomy, facectomy, discectomy, cage insertion and transpedicle screw insertion were performed sequentially after testing the intact status. Changes in range of motion (ROM) and neutral zone (NZ) were compared between unilateral and bilateral cage-instrumented PLIF.Results: Both ROM and NZ, unilateral cage-instrumented PLIF and bilateral cage-instrumented PLIF, transpedicle screw insertion procedure did not revealed a significant difference between flexion-extension, lateral bending and axial rotation direction except the ROM in the axial rotation. The bilateral group's ROM (-1.7 ± 0. 8) of axial rotation was decreased significantly after transpedicle screw insertion procedure in comparison with the unilateral group (-0.2 ± 0.1). In the unilateral cage-instrumented PLIF group, the transpedicle screw insertion procedure did not demonstrate a significant difference between right and left side in the lateral bending and axial rotation direction.Conclusions: Based on the results of this study, unilateral cage-instrumented PLIF and bilateral cage-instrumented PLIF have similar stability after transpedicle screw fixation in the sheep spine model. The unilateral approach can substantially reduce exposure requirements. It also offers the biomechanics advantage of construction using anterior column support combined with pedicle screws just as the bilateral cage-instrumented group. The unpleasant effect of couple motion resulting from inherent asymmetry was absent in the unilateral group. © 2010 Chang et al; licensee BioMed Central Ltd.
Huang S.-J.,China Medical University at Taichung |
Fu R.-H.,China Medical University at Taichung |
Shyu W.-C.,China Medical University at Taichung |
Liu S.-P.,China Medical University at Taichung |
And 8 more authors.
Cell Transplantation | Year: 2013
In mammals, the two main types of adipose tissues, white and brown adipose tissues, exert different physiological functions. White adipose tissue (WAT) is for storing energy, while brown adipose tissue (BAT) is for energy consumption. Adipose-derived stem cells (ADSCs) are abundant in WAT and BAT, have multipotent characteristics, and are easily extracted. ADSCs can be differentiated into several cell lineages, including adipocytes, osteoblasts, chondrocytes (cartilage cells), myocytes, and neuronal cells. Therefore, ADSC could be considered as a strategy for future regenerative medicine and tissue engineering. © 2013 Cognizant Comm. Corp.