Armed Forces Taichung General Hospital
Armed Forces Taichung General Hospital
Tseng H.-C.,Chung Shan Medical University |
Liu W.-S.,Chung Shan Medical University |
Tyan Y.-S.,Chung Shan Medical University |
Chiang H.-C.,Chung Shan Medical University |
And 5 more authors.
Chemico-Biological Interactions | Year: 2011
Many recent efforts have focused on targeting cell death pathways for discovering new cancer therapies. The relative resistance of liver cancer cells to ionizing radiation (IR) and chemotherapeutic agents due to autophagic response limits the available treatment options for this type of cancer. In this study, 3-methyladenine (3-MA), an autophagy inhibitor, was investigated for its potential to enhance radio-sensitivity under radio-resistant conditions both in vitro and in vivo. Hep3B and HepG2 cells were used to examine the radio-resistance of liver cancer cells. The results show that Hep3B cells respond to irradiation with increased apoptotic cell death and that HepG2 is radio-resistant due to the IR-induced autophagy, as verified by DNA fragmentation, electron microscopy, acidic vesicular organelle formation, and Western blot analysis. Application of IR with 3-MA to inhibit autophagy simultaneously suppressed the expression of LC3 and enhanced cell death. The tumor xenograft model in nude mice verified the synergistic cytotoxic effect of 3-MA and IR, which resulted in significant repression of tumor growth. The results demonstrate that IR-induced autophagy provides a self-protective mechanism against radiotherapy in HepG2 cells. In addition, 3-MA enhances the cytotoxicity of IR in cell models and suppresses tumor growth in animal models. Based on the results, application of 3-MA, or other autophagy inhibitors, could be used as an adjuvant for radiotherapy when radio-resistance develops as a result of autophagy response. © 2011 Elsevier Ireland Ltd. All rights reserved.
Chiu Y.-W.,Tungs Taichung MetroHarbor Hospital |
Chiu Y.-W.,Chung Shan Medical University |
Lin T.-H.,Taichung Veterans General Hospital |
Huang W.-S.,Chang Gung Memorial Hospital Chiayi |
And 15 more authors.
Toxicology and Applied Pharmacology | Year: 2011
Flavonoids have been demonstrated to exert health benefits in humans. We investigated whether the flavonoid baicalein would inhibit the adhesion, migration, invasion, and growth of human hepatoma cell lines, and we also investigated its mechanism of action. The separate effects of baicalein and baicalin on the viability of HA22T/VGH and SK-Hep1 cells were investigated for 24 h. To evaluate their invasive properties, cells were incubated on matrigel-coated transwell membranes in the presence or absence of baicalein. We examined the effect of baicalein on the adhesion of cells, on the activation of matrix metalloproteinases (MMPs), protein kinase C (PKC), and p38 mitogen-activated protein kinase (MAPK), and on tumor growth in vivo. We observed that baicalein suppresses hepatoma cell growth by 55%, baicalein-treated cells showed lower levels of migration than untreated cells, and cell invasion was significantly reduced to 28%. Incubation of hepatoma cells with baicalein also significantly inhibited cell adhesion to matrigel, collagen I, and gelatin-coated substrate. Baicalein also decreased the gelatinolytic activities of the matrix metalloproteinases MMP-2, MMP-9, and uPA, decreased p50 and p65 nuclear translocation, and decreased phosphorylated I-kappa-B (IKB)-κ. In addition, baicalein reduced the phosphorylation levels of PKC? and p38 proteins, which regulate invasion in poorly differentiated hepatoma cells. Finally, when SK-Hep1 cells were grown as xenografts in nude mice, intraperitoneal (i.p.) injection of baicalein induced a significant dose-dependent decrease in tumor growth. These results demonstrate the anticancer properties of baicalein, which include the inhibition of adhesion, invasion, migration, and proliferation of human hepatoma cells in vivo. © 2011 Elsevier Inc.
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.
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.