Browsing by Author "Ho, Shu-Yi"

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cIAP-2 Expression Increases in Elderly Patients with Squamous Cell Carcinoma of the Head and Neck
(2017-03-01)
Chen, Chi-Long
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Chiang, Chun-Yi
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Liao, Kuang-Wen
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Ho, Shu-Yi
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Chang, Yi-Fang
Background: Evidence indicates apoptosis deregulation is associated with aging. We correlated expression of cIAP-2, a member of the inhibitor of apoptosis protein family, with survival and age in patients with resected squamous cell carcinoma of head and neck (SCCHN). Methods: Immunohistochemical (IHC) staining for cIAP-2 and other markers were performed using tissue microarrays from 103 resected SCCHN patients. Expression was grouped according to IHC scores (0 -3) and statistical association with clinicalepathological factors was determined. Results: High expression of cIAP-2 was found to be increased in patients aged 60 or greater. High expression of cIAP-2 and an age >= 60 were significantly associated with worse survival in univariate analysis, but only an age >= 60, and not cIAP-2 expression, was prognostic in multivariate analysis. Conclusion: High expression of cIAP-2 was found more frequently in elderly SCCHN patients but was not independently associated with survival after adjusting other clinicalepathologic factors. Copyright (C) 2017, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier Taiwan LLC.
Development of a computational promoter with highly efficient expression in tumors
(2018-04-27)
Ho, Shu-Yi
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Chang, Bo-Hau
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Chung, Chen-Han
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Lin, Yu-Ling
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Chuang, Cheng-Hsun
Background: Gene therapy is a potent method to increase the therapeutic efficacy against cancer. However, a gene that is specifically expressed in the tumor area has not been identified. In addition, nonspecific expression of therapeutic genes in normal tissues may cause side effects that can harm the patients' health. Certain promoters have been reported to drive therapeutic gene expression specifically in cancer cells; however, low expression levels of the target gene are a problem for providing good therapeutic efficacy. Therefore, a specific and highly expressive promoter is needed for cancer gene therapy. Methods: Bioinformatics approaches were utilized to analyze transcription factors (TFs) from high-throughput data. Reverse transcription polymerase chain reaction, western blotting and cell transfection were applied for the measurement of mRNA, protein expression and activity. C57BL/6JNarl mice were injected with pD5-hrGFP to evaluate the expression of TFs. Results: We analyzed bioinformatics data and identified three TFs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B), cyclic AMP response element binding protein (CREB), and hypoxia-inducible factor-1 alpha (HIF-1 alpha), that are highly active in tumor cells. Here, we constructed a novel mini-promoter, D5, that is composed of the binding sites of the three TFs. The results show that the D5 promoter specifically drives therapeutic gene expression in tumor tissues and that the strength of the D5 promoter is directly proportional to tumor size. Conclusions: Our results show that bioinformatics may be a good tool for the selection of appropriate TFs and for the design of specific mini-promoters to improve cancer gene therapy.
Dimmable sunlight-like organic light emitting diodes with ultra-high color rendering index
(2016-05)
Wu, Jin-Han
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Chi, Chien-An
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Chiang, Chang-Lin
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Chen, Guan-Yu
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Lin, Yi-Ping
We propose novel dimmable sunlight-like white organic light-emitting diodes that were fabricated using three luminophores to form an emitting spectrum similar to black body radiation at 2250 K with ultra-high color rendering index (CRI) value of 91, which nearly remained the constant at various luminance values ranging from 100 to more than 2500 cd/m(2) at Commission Internationale de l\'Eclairage chromaticity coordinates of (0.51, 0.41). Introducing charge modification layers suppressed the energy transfer between the emitting material layers and increased the probability of carrier recombination. Moreover, we reveal that covering long-wavelength ranges played a vital role in achieving high CRI values; the CRI values of a spectrum artificially shifted toward a long-wavelength direction (from 610 to 620 nm) remained constant, whereas those of a spectrum shifted toward a short-wavelength direction (from 610 to 600 nm) dropped to 79. (C) 2016 Elsevier B.V. All rights reserved.
Helicobacter pylori-derived heat shock protein 60 increases the induction of regulatory T-cells associated with persistent infection
(2018-06-01)
Hsu, Wei-Tung
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Ho, Shu-Yi
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Jian, Ting-Yan
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Huang, Han-Ning
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Lin, Yu-Ling
Local Treg responses are involved in Helicobacter pylori-related inflammation and clinical outcomes after infection, and H. pylori-derived HSP60 (HpHSP60) is an important virulence factor associated with gastric carcinogenesis. This study to investigate the role of HpHSP60 in immunosuppression, particularly with regard to whether it could induce the production of Treg cells. For this purpose, human peripheral blood mononuclear cells (PBMCs) were treated with or without HpHSP60 in the presence of an anti-CD3 mAb to determine the effect of HpHSP60 on cell proliferation. In this report, HpHSP60 decreased the expression of CDK4 to significantly arrest the proliferation of mitogen-stimulated T-cells, which correlated with the induction of Treg cells. Moreover, monocytic cells were essential for the induction of HpHSP60-induced Treg cells via the secretion of IL-10 and TGF-beta after treatment with HpHSP60. Blockage of HpHSP60 with specific monoclonal antibodies significantly reduced the colonization of H. pylori and the expression of Treg cells in vivo. Overall, our results suggest that HpHSP60 could act on macrophages to trigger the expression of IL-10 and TGF-beta, thereby leading to an increase in Treg cells and inhibition of T-cell proliferation.
In vivo amelioration of endogenous antitumor autoantibodies via low-dose P4N through the LTA4H/activin A/BAFF pathway
(2016-11-29)
Lin, Yu-Ling
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Tsai, Nu-Man
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Hsieh, Cheng-Hao
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Ho, Shu-Yi
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Chang, Jung
Cancer progression is associated with the development of antitumor autoantibodies in patients\' sera. Although passive treatment with antitumor antibodies has exhibited remarkable therapeutic efficacy, inhibitory effects on tumor progression by endogenous antitumor autoantibodies (EAAs) have been limited. In this study, we show that P4N, a derivative of the plant lignan nordihydroguaiaretic acid (NDGA), enhanced the production of EAAs and inhibited tumor growth at low noncytotoxic concentrations via its immunoregulatory activity. Intratumoral injection of P4N improved the quantity and quality of EAAs, and passive transfer of P4N-induced EAAs dramatically suppressed lung metastasis formation and prolonged the survival of mice inoculated with metastatic CT26 tumor cells. P4N-induced EAAs specifically recognized two surface antigens, 78-kDa glucose-regulated protein (GRP78) and F1F0 ATP synthase, on the plasma membrane of cancer cells. Additionally, P4N treatment led to B-cell proliferation, differentiation to plasma cells, and high titers of autoantibody production. By serial induction of autocrine and paracrine signals in monocytes, P4N increased B-cell proliferation and antibody production via the leukotriene A4 hydrolase (LTA4H)/activin A/B-cell activating factor (BAFF) pathway. This mechanism provides a useful platform for studying and seeking a novel immunomodulator that can be applied in targeting therapy by improving the quantity and quality of the EAAs.
Inhibitory Effects of Chloroform Extracts Derived from Corbicula fluminea on the Release of Pro-inflammatory Cytokines
(2012-04-25)
Lin, Ching-Min
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Lin, Yu-Ling
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Tsai, Nu-Man
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Wu, Hsin-Yi
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Ho, Shu-Yi
Corbicula fluminea, the primary freshwater bivalve cultivated in Taiwan, was formerly used as a remedy for hepatitis. Recent reports indicate that C. fluminea has many bioactivities, but it remains unknown whether C. fluminea affects inflammation. This study explored the anti-inflammatory activity of C.fluminea. C. fluminea was first treated with chloroform to obtain clam chloroform extracts (CCEs). On the basis of the assay for the release of pro-inflammatory cytokines in vitro and in vivo, the results show that the CCEs significantly lowered the release of lipopolysaccharide (LPS)-induced pro-inflammatory cytokines. Additionally, the CCEs reduced LPS-induced organ damage. Real-time polymerase chain reaction analysis suggested that CCEs inhibit the LPS-induced mRNA expression of interleukin-1 beta and tumor necrosis factor-alpha. Western blot analysis indicated that the CCEs increased expression of I kappa B and attenuated the phosphorylation of I kappa B. Gas chromatography mass spectrometry suggests that phytosterols and fatty adds are responsible for the anti-inflammatory properties of CCEs. Taken together, CCEs have the potential to be developed as an anti-inflammatory functional food.
Lipoplex-based targeted gene therapy for the suppression of tumours with VEGFR expression by producing anti-angiogenic molecules
(2020-04-09)
Ho, Shu-Yi
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Chen, Pin-Rong
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Chen, Chia-Hung
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Tsai, Nu-Man
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Lin, Yu-Hsin
Background The anti-angiogenic fusion protein RBDV-IgG1 Fc (RBDV), which comprises the receptor-binding domain of vascular endothelial growth factor-A (VEGF-A), has shown antitumour effects by reducing angiogenesis in vivo. This study used the cationic lipoplex lipo-PEG-PEI-complex (LPPC) to simultaneously encapsulate both the RBDV targeting protein and the RBDV plasmid (pRBDV) without covalent bonds to assess VEGFR targeting gene therapy in mice with melanoma in vivo. Results LPPC protected the therapeutic transgene from degradation by DNase, and the LPPC/RBDV complexes could specifically target VEGFR-positive B16-F10 cells both in vitro and in vivo. With or without RBDV protein-targeting direction, the pRBDV-expressing RBDV proteins were expressed and reached a maximal concentration on the 7th day in the sera after transfection in vivo and significantly elicited growth suppression against B16-F10 melanoma but not IgG1 control proteins. In particular, LPPC/pRBDV/RBDV treatment with the targeting molecules dramatically inhibited B16-F10 tumour growth in vivo to provide better therapeutic efficacy than the treatments with gene therapy with IgG1 protein targeting or administration of a protein drug with RBDV. Conclusions The simultaneous combination of the LPPC complex with pRBDV gene therapy and RBDV protein targeting might be a potential tool to conveniently administer targeted gene therapy for cancer therapy.
miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database
(2016-01-04)
Chou, Chih-Hung
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Chang, Nai-Wen
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Shrestha, Sirjana
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Hsu, Sheng-Da
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Lin, Yu-Ling
MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides, which negatively regulate the gene expression at the post-transcriptional level. This study describes an update of the miRTarBase (http://miRTarBase.mbc.nctu.edu.tw/) that provides information about experimentally validated miRNA-target interactions (MTIs). The latest update of the miRTarBase expanded it to identify systematically Argonaute-miRNA-RNA interactions from 138 crosslinking and immunoprecipitation sequencing (CLIP-seq) data sets that were generated by 21 independent studies. The database contains 4966 articles, 7439 strongly validated MTIs (using reporter assays or western blots) and 348 007 MTIs from CLIP-seq. The number of MTIs in the miRTarBase has increased around 7-fold since the 2014 miRTarBase update. The miRNA and gene expression profiles from The Cancer Genome Atlas (TCGA) are integrated to provide an effective overview of this exponential growth in the miRNA experimental data. These improvements make the miRTarBase one of the more comprehensively annotated, experimentally validated miRNA-target interactions databases and motivate additional miRNA research efforts.
miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions
(2014-01-01)
Hsu, Sheng-Da
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Tseng, Yu-Ting
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Shrestha, Sirjana
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Lin, Yu-Ling
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Khaleel, Anas
MicroRNAs (miRNAs) are small non-coding RNA molecules capable of negatively regulating gene expression to control many cellular mechanisms. The miRTarBase database (http://mirtarbase.mbc.nctu.edu.tw/) provides the most current and comprehensive information of experimentally validated miRNA-target interactions. The database was launched in 2010 with data sources for >100 published studies in the identification of miRNA targets, molecular networks of miRNA targets and systems biology, and the current release (2013, version 4) includes significant expansions and enhancements over the initial release (2010, version 1). This article reports the current status of and recent improvements to the database, including (i) a 14-fold increase to miRNA-target interaction entries, (ii) a miRNA-target network, (iii) expression profile of miRNA and its target gene, (iv) miRNA target-associated diseases and (v) additional utilities including an upgrade reminder and an error reporting/user feedback system.
miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions
(2018-01-04)
Chou, Chih-Hung
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Shrestha, Sirjana
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Yang, Chi-Dung
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Chang, Nai-Wen
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Lin, Yu-Ling
MicroRNAs (miRNAs) are small non-coding RNAs of similar to 22 nucleotides that are involved in negative regulation of mRNA at the post-transcriptional level. Previously, we developed miRTarBase which provides information about experimentally validated miRNA-target interactions (MTIs). Here, we describe an updated database containing 422 517 curated MTIs from 4076 miRNAs and 23 054 target genes collected from over 8500 articles. The number of MTIs curated by strong evidence has increased similar to 1.4-fold since the last update in 2016. In this updated version, target sites validated by reporter assay that are available in the literature can be downloaded. The target site sequence can extract new features for analysis via a machine learning approach which can help to evaluate the performance of miRNA-target prediction tools. Furthermore, different ways of browsing enhance user browsing specific MTIs. With these improvements, miRTarBase serves as more comprehensively annotated, experimentally validated miRNA-target interactions databases in the field of miRNA related research. miRTarBase is available at http://miRTarBase.mbc.nctu.edu.tw/.
Significant color space blue-shift of green OLED emitter with sustaining lifetime and substantial efficiency enhancement
(2017-08-28)
Li, Jung-Yu
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Chen, Shih-Pu
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Siao, Huei-Jhen
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Wu, Jin-Han
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Chen, Guan-Yu
In this study, we demonstrate that by embedding a plasmonic coupling metal layer beneath the active layer of an organic light-emitting diode, the resultant device is capable of inducing significant blue shifts in CIE color space coordinates of emitting light from the green emitting material without compromising the lifetime of the parent material. The implemented device consists of multilayers of organic emitting materials sandwiched by two thin metal layers to form a metal-dielectric-metal (MDM) cavity-like structure. The original green emission with CIE coordinates of (0.22, 0.56) was significantly color space blue-shifted to CIE coordinates of (0.10, 0.53). The MDM device exhibits an efficiency of 62 cd/A at a luminance of 1000 cd/m(2), which represents a two-fold enhancement of current efficiency. Moreover, the spectral peak intensity is 4.3 times higher than that in a conventional device, which is much higher than that expected for an optical microcavity model, suggesting that the Purcell effect resulting from the coupling of surface plasmon waves may contribute to the extra enhancement of emission intensity. Published by AIP Publishing.
Significant color space blue-shift of green OLED emitter with sustaining lifetime and substantial efficiency enhancement (vol 111, 093301, 2017)
(2017-09-11)
Li, Jung-Yu
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Chen, Shih-Pu
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Siao, Huei-Jhen
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Wu, Jin-Han
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Chen, Guan-Yu
The inhibitory effect of 7, 7 ''-dimethoxyagastisflavone on the metastasis of melanoma cells via the suppression of F-actin polymerization
(2017-09-01)
Lin, Ching-Min
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Lin, Yu-Ling
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Ho, Shu-Yi
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Chen, Pin-Rong
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Tsai, Yi-Hsuan
7,7"-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from Taxus x media cv. Hicksii, induces apoptotic and autophagic cell death. However, whether DMGF suppresses tumor metastasis is unclear. The aim of this study was to investigate the anti-metastatic activities of DMGF on the metastatic processes of melanoma cells in vivo and in vitro. A transwell assay showed that DMGF could effectively attenuate the motility of B16F10 cells, and the results of real-time PCR revealed that DMGF also suppressed the expressions of matrix metalloproteinase-2 (MMP-2). Moreover, DMGF did not influence tube formation but inhibited the migration of endothelial cells. Furthermore, animal models were used to monitor the effects of DMGF on tumor metastasis, and all models showed that DMGF significantly suppressed the metastatic behaviors of B16F10 cells, including intravasation, colonization, and invasion of the lymphatic duct. In addition, DMGF could also reduce the densities of the blood vessels in the tumor area in vivo. Further investigation of the molecular mechanisms of anti-metastatic activity revealed that DMGF can down-regulate the levels of key modulators of the Cdc42/Rac1 pathway to interfere in F-actin polymerization and suppress the formation of lamellipodia by reducing the phosphorylation of CREB. These data suggested that DMGF presents anti-metastatic activities in B16F10 melanoma cells. Here, we demonstrated that DMGF can inhibit the metastasis of highly invasive melanoma cancer cells through the down-regulation of F-actin polymerization. Considering these findings, DMGF may be further developed to serve as a chemoprevention drug for patients with metastatic melanoma.