Browsing by Author "Chen, Huang-Jen"

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Fabrication of Novel Three-Step Drift-Doped Low-Temperature Polycrystalline Silicon Lateral Double-Diffusion Metal-Oxide-Semiconductor Using Excimer Laser Crystallization
(2009-03-01)
Lin, Jyh-Ling
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Chen, Huang-Jen
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Chang, Fang-Long
;
Cheng, Huang-Chung
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電子工程學系及電子研究所
Low-temperature polycrystalline silicon (poly-Si) thin-film transistor lateral double-diffusion metal-oxide-semiconductor field-effect transistors (LTPS TFT LDMOSFETs) and lateral insulated-gate bipolar transistors (LIGBTs) were fabricated by combining a thin-film transistor with a power structure, three-step drift doping, and excimer laser annealing. The maximum breakdown voltage of the three-step drift-doped LTPS-LDMOS after excimer laser annealing is 286 V with a 35 mu m drift region length (L(drift)). The specific on-resistance is low (approximately 9 Omega cm(2)) and the ON/OFF current ratio is about 1.28 x 10(6) with L(drift) = 15 mu m. The subthreshold swing (SS) is about 1 V/decade. Comparing the three-step drift-doped LDMOS with the three-step drift-doped LIGBT under the same processing conditions clearly indicates that the breakdown voltage and current capacity of LIGBT exceeds those of LDMOS. (C) 2009 The Japan Society of Applied Physics
Inhibition of p38 MAPK-dependent MutS homologue-2 (MSH2) expression by metformin enhances gefitinib-induced cytotoxicity in human squamous lung cancer cells
(2013-12-01)
Ko, Jen-Chung
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Chiu, Hsien-Chun
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Wo, Ting-Yu
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Huang, Yi-Jhen
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Tseng, Sheng-Chieh
Objectives: Gefitinib, a quinazoline-derived tyrosine kinase inhibitor, has anti-tumor activity in vivo and in vitro. Human MutS homologue-2 (MSH2) plays a central role in promoting genetic stability by correcting DNA replication errors. The present study investigated the effects of p38 mitogen-activated protein kinase (MAPK) signal on gefitinib-induced MSH2 expression in two human non-small cell lung squamous cancer cell lines. Materials and methods: After the gefitinib treatment, the expressions of MSH2 mRNA were determined by real-time PCR and RT-PCR analysis. Protein levels of MSH2, phospho-MKK3/6, phospho-p38 MAPK were determined by Western blot analysis. We used specific MSH2, and p38 MAPK small interfering RNA to examine the role of p38 MAPK-MSH2 signal in regulating the chemosensitivity of gefitinib. Cell viability was assessed by MTS assay, trypan blue exclusion, and colony-forming ability assay. Results: Exposure of gefitinib increased MSH2 protein and mRNA levels, which was accompanied by MKK3/6-p38 MAPK activation in H520 and H1703 cells. Moreover, blocking p38 MAPK activation by SB202190 significantly decreased gefitinib-induced MSH2 expression by increasing mRNA and protein instability. In contrast, enhancing p38 activation using constitutively active MKK6 (MKK6E) increased MSH2 protein and mRNA levels. Specific inhibition of MSH2 expression by siRNA enhanced gefitinib-induced cytotoxicity. Metformin, an anti-diabetic drug, might reduce cancer risk. In human lung squamous cancer cells, metformin decreased gefitinib-induced MSH2 expression and augmented the cytotoxic effect and growth inhibition by gefitinib. Transient expression of MKK6E or HA-p38 MAPK vector could abrogate metformin and gefitinib-induced synergistic cytotoxic effect in H520 and H1703 cells. Conclusion: Together, down-regulation of MSH2 expression can be a possible strategy to enhance the sensitivity of gefitinib to human lung squamous cancer cells. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
Pemetrexed downregulates ERCC1 expression and enhances cytotoxicity effected by resveratrol in human nonsmall cell lung cancer cells
(2013-12-01)
Chen, Ruey-Shyang
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Ko, Jen-Chung
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Chiu, Hsien-Chun
;
Wo, Ting-Yu
;
Huang, Yi-Jhen
The multitargeted antifolate pemetrexed has demonstrated certain clinical activities against nonsmall cell lung cancer (NSCLC). Resveratrol (3,5,4-trihydroxy-trans-stilbene) is a polyphenol found in grapes and other plants and has great potential as a preventative and therapeutic agent due to its anticarcinogenic activity. The efficacy of adding resveratrol to pemetrexed to prolong the survival of patients with NSCLC still remains unclear. The excision repair cross-complementation 1 (ERCC1) is a DNA repair gene coding 5' endonuclease in nucleotide excision repair and is overexpressed in chemo- or radioresistant carcinomas. In this study, resveratrol (10-50 mu M) inhibited cell survival in two NSCLC cells, H520 and H1975. Treatment with resveratrol increased ERCC1 messenger RNA and protein levels in a MKK3/6-p38 MAPK signal activation-dependent manner. Furthermore, blocking p38 MAPK activation by SB202190 or knocking down ERCC1 expression by transfection with small interfering RNA of ERCC1 enhanced the cytotoxicity of resveratrol. Combining resveratrol with pemetrexed resulted in a synergistic cytotoxic effect, accompanied with the reduction of phospho-p38 MAPK and ERCC1 protein levels, and a DNA repair capacity. Expression of constitutively active MKK6 (MKK6E) or HA-p38 MAPK vectors significantly rescued the decreased p38 MAPK activity, and restored ERCC1 protein levels and cell survival in resveratrol and pemetrexed cotreated NSCLC cells. In this study, for the first time, we have demonstrated the synergistic effect of combined treatment with resveratrol and pemetrexed in human NSCLC cells through downregulation of the MKK3/6-p38 MAPK-ERCC1 signal, suggesting a potential benefit of combining resveratrol and pemetrexed to treat lung cancer in the future.