Browsing by Author "Lai, Yiu-Kay"

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7,7 ''-Dimethoxyagastisflavone-induced Apoptotic or Autophagic Cell Death in Different Cancer Cells
(2012-04-01)
Hwang, Chia-Hsiang
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Lin, Yu-Ling
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Liu, Yen-Ku
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Chen, Chia-Hung
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Wu, Hsin-Yi
7,7''-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from the needles of Taxus X media cv. Hicksii, was evaluated for its antiproliferative and antineoplastic effects in three human cancer cell lines. Interestingly, DMGF caused cell death via different pathways in different cancer cells. DMGF induced apoptosis, activated caspase-3 activity and changed the mitochondrial membrane potential in HT-29 human colon cancer cells. However, the apoptotic pathway is not the major pathway involved in DMGF-induced cell death in A549 human lung cancer cells and HepG2 human hepatoma cells. Treatment with 3-MA, an inhibitor of autophagy, significantly decreased DMGF-induced cell death in HepG2 and A549 cells, but did not affect DMGF-induced cell death in HT-29 cells. Following DMGF treatment, the HepG2 cells increased expression of LC3B-II, a marker used to monitor autophagy in cells. Thus, DMGF induced apoptotic cell death in HT-29 cells, triggered both apoptotic and autophagic death in A549 cells and induced autophagic cell death in HepG2 cells. Copyright (C) 2011 John Wiley & Sons, Ltd.
A fusion protein with the receptor binding domain of vascular endothelial growth factor-A (VEGF-A) is an antagonist of angiogenesis in cancer treatment
(2010-11-01)
Tseng, Feng-Jen
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Chen, Yu-Cheng
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Lin, Yu-Ling
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Tsai, Nu-Man
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Lee, Ru-Ping
Vascular endothelial growth factor (VEGF) is an angiogenic factor that signals through VEGFR-1 and VEGFR-2, which are expressed preferentially in proliferating endothelial cells. Thus, simultaneous blockage of both VEGF receptors may provide a more efficient therapeutic response in cancer treatment. We created a recombinant fusion protein (RBDV-IgG1 Fc), which is composed of the receptor binding domain of human VEGF-A (residues 8-109) and the Fc region of human IgG1 immunoglobulin. The recombinant protein can bind to both mouse VEGFR-1 and VEGFR-2 to decrease VEGF-induced proliferation and tube formation of endothelial cells in vitro. In this study, the RBDV-IgG1 Fc fusion protein reduced the effects of proliferation, migration and tube formation induced by VEGF in murine endothelial cells in vitro. In vivo tumor therapy with RBDV-IgG1 Fc resulted in tumor inhibition by reducing angiogenesis. Pathological evidence also shows that RBDV-IgG1 Fc can seriously damage vessels, causing the death of tumor cells. These findings suggest that this chimeric protein has potential as an angiogenesis antagonist in tumor therapy.
Clinical evaluation of the eBsensor hand-held blood glucose monitoring system
(2007-02-01)
Chen, Chien-Chih
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Tai, Der-Yan
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Ho, Ping
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Lai, Yiu-Kay
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Lin, Jui-Jane
Background: Home glucose monitoring system is increasingly recognized as an important tool for glycemic control. We evaluated the clinical performance of the eBsensor glucose monitoring system. Methods: Fingertip capillary blood glucose concentrations from 282 subjects were measured using eBsensor glucose monitoring system and compared against predicate devices and the Yellow Springs Instruments (YSI) 2300 blood glucose analyzer. Accuracy and precision of the eBsensor glucose monitoring system were assessed using several methods. The comparative study between the eBsensor and 2 currently marketed monitoring systems was performed. Results: The 282 eBsensor readings covered a wide range from 2.6 to 24.4 mmol/l. Deming regression and Pearson correlation analyses showed a linear relationship between the eBsensor readings and the YSI reference method (eBsensor=0.9496 YSI+0.4127 mmol/l; r=0.98). Error Grid analysis demonstrated that 100% of the eBsensor readings in clinically acceptable zones A and B. The CVs for the 6 lots of strips were within the satisfactory interval (< 6%). The comparative study showed that the eBsensor readings correlated well with the OneTouch Ultra values (r=0.97) and the Glucocard II values (r=0.97). Conclusions: eBsensor is a reliable glucose monitoring system which provides high accurate and precise glucose readings over a wide range of glucose concentrations. (c) 2006 Elsevier B.V. All rights reserved.
Helicobacter pylori-derived Heat shock protein 60 enhances angiogenesis via a CXCR2-mediated signaling pathway
(2010-06-25)
Lin, Chen-Si
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He, Pei-Juin
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Hsu, Wei-Tung
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Wu, Ming-Shiang
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Wu, Chang-Jer
Helicobacter pylori is a potent carcinogen associated with gastric cancer malignancy. Recently. H. pylori Heat shock protein 60 (HpHSP60) has been reported to promote cancer development by inducing chronic inflammation and promoting tumor cell migration. This study demonstrates a role for HpHSP60 in angiogenesis, a necessary precursor to tumor growth. We showed that HpHSP60 enhanced cell migration and tube formation, but not cell proliferation, in human umbilical vein endothelial cells (HUVECs). HpHSP60 also indirectly promoted HUVEC proliferation when HUVECs were co-cultured with supernatants collected from HpHSP60-treated AGS or THP-1 cells. The angiogenic array showed that HpHSP60 dramatically induced THP-1 cells and HUVECs to produce the chemotactic factors IL-8 and GRO. Inhibition of CXCR2, the receptor for IL-8 and GRO, or downstream PLC beta 2/Ca2+-mediated signaling, significantly abolished HpHSP60-induced tube formation. In contrast, suppression of MAP K or PI3 K signaling did not affect HpHSP60-mediated tubulogenesis. These data suggest that HpHSP60 enhances angiogenesis via CXCR2/PLC beta 2/Ca2+ signal transduction in endothelial cells. (C) 2010 Elsevier Inc. All rights reserved.
Probing the binding kinetics of proinflammatory cytokine-antibody interactions using dual color fluorescence cross correlation spectroscopy
(2011)
Wu, Chia-Yan
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Huang, Chuan-Keng
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Chung, Chao-Yu
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Huang, I-Ping
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Hwu, Yeukuang
Dual color fluorescence cross correlation spectroscopy (FCCS) was used to investigate quantitatively the binding kinetics of tumor necrosis factor (TNF alpha) with TNF alpha antibody (anti-TNF alpha) following fluorescent labeling. Through the analysis of the auto correlation curves of fluorescence correlation spectroscopy (FCS), diffusion coefficients of 100.06 +/- 4.9 mu m(2) s(-1) and 48.96 +/- 2.52 mu m(2) s(-1) for Alexa488-TNF alpha and Atto647N-anti-TNF alpha were obtained. In addition, the calculated hydrodynamic diameters of the Alexa488-TNF alpha and Atto647N-anti-TNF alpha were approximately 4.89 +/- 0.24 nm and 9.99 +/- 0.52 nm, respectively, which agrees with the values of 5.20 +/- 1.23 nm and 9.28 +/- 0.86 nm for the native TNF alpha and the anti-TNF alpha as determined from dynamic light scattering measurements. For the binding kinetics, association (k(on)) and dissociation (k(off)) rate constants were (1.13 +/- 0.08) x 10(4) M(-1) s(-1) and (1.53 +/- 0.19) x 10(-3) s(-1) while the corresponding dissociation constant (K(d)) at 25 degrees C was (1.36 +/- 0.10) x 10(-7) M. We believe this is the first report on the binding kinetics for TNF alpha-antibody recognition in the homogeneous phase. Using this technology, we have shown that controlled experiments can be performed to gain insight into molecular mechanisms involved in the immune response.