Yung-Luen Yu

China Medical University (ROC), 臺中市, Taiwan, Taiwan

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Publications (45)203.69 Total impact

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    ABSTRACT: Posttranslational modifications of histones play fundamental roles in many biological functions. Specifically, histone H4-K20 methylation is critical for DNA synthesis and repair. However, little is known about how these functions are regulated by the upstream stimuli. Here, we identify a tyrosine phosphorylation site at Y72 of histone H4, which facilitates recruitment of histone methyltransferases (HMTases), SET8 and SUV4-20H, to enhance its K20 methylation, thereby promoting DNA synthesis and repair. Phosphorylation-defective histone H4 mutant is deficient in K20 methylation, leading to reduced DNA synthesis, delayed cell cycle progression, and decreased DNA repair ability. Disrupting the interaction between epidermal growth factor receptor (EGFR) and histone H4 by Y72 peptide significantly reduced tumor growth. Furthermore, EGFR expression clinically correlates with histone H4-Y72 phosphorylation, H4-K20 monomethylation, and the Ki-67 proliferation marker. These findings uncover a mechanism by which EGFR transduces signal to chromatin to regulate DNA synthesis and repair.
    07/2014; 30(2):224–237.
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    ABSTRACT: Cytolethal distending toxin (CDT) produced by Campylobacter jejuni is a genotoxin that induces cell-cycle arrest and apoptosis in mammalian cells. Recent studies have demonstrated that prostate cancer (PCa) cells can acquire radio-resistance when DOC-2/DAB2 interactive protein (DAB2IP) is downregulated. In this study, we showed that CDT could induce cell death in DAB2IP-deficient PCa cells. A combination of CDT and radiotherapy significantly elicited cell death in DAB2IP-deficient PCa cells by inhibiting the repair of ionizing radiation (IR)-induced DNA double-strand break (DSB) during G2/M arrest, which is triggered by ataxia telangiectasia mutated (ATM)-dependent DNA damage checkpoint responses. We also found that CDT administration significantly increased the efficacy of radiotherapy in a xenograft mouse model. These results indicate that CDT can be a potent therapeutic agent for radio-resistant PCa.
    Oncotarget 06/2014; · 6.64 Impact Factor
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    ABSTRACT: Methotrexate (MTX) has been widely used for rheumatoid arthritis therapy for a long time. MTX is also used as an anticancer drug for various tumors. However, many studies have shown that high-dose MTX treatment for cancer therapy may cause liver and renal damage. Alhough the mechanisms involved in MTX-induced liver and renal damage require further research, many studies have indicated that MTX-induced cytotoxicity is associated with increases in oxidative stress and caspase activation. In order to reduce MTX-induced side-effects and increase anticancer efficiency, currently, combination treatments of low-dose MTX and other anticancer drugs are considered and applied for various tumor treatments. The present study showed that MTX induces increases in H2O2 levels and caspase-9/-3 activation leading to cell death in hepatocellular carcinoma Hep3B cells. Importantly, this study is the first to demonstrate that vitamin C can efficiently aid low-dose MTX in inducing cell death in Hep3B cells. Therefore, the present study provides a possible powerful therapeutic method for tumors using a combined treatment of vitamin C and low-dose MTX.
    Oncology reports. 06/2014;
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    ABSTRACT: The survival rate of malignant tumors, and especially hepatocellular carcinoma (HCC), has not improved primarily because of uncontrolled metastasis. In our previous studies, we have reported that Terminalia catappa leaf extract (TCE) exerts antimetastasis effects on HCC cells. However, the molecular mechanisms of urokinase-type plasminogen activator (u-PA) in HCC metastasis have not been thoroughly investigated, and remain poorly understood.
    BMC Complementary and Alternative Medicine 04/2014; 14(1):141. · 2.08 Impact Factor
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    ABSTRACT: Acetaminophen (APAP), is a safe analgesic and antipyretic drug at therapeutic dose, and is widely used in the clinic. However, high doses of APAP can induce hepatotoxicity and nephrotoxicity. Most studies have focused on high‑dose APAP‑induced acute liver and kidney injury. So far, few studies have investigated the effects of the therapeutic dose (1/10 of the high dose) or of the low dose (1/100 of the high dose) of APAP on the cells. The aim of this study was to investigate the cellular effects of therapeutic- or low‑dose APAP treatment on hepatoma cells and kidney fibroblasts. As expected, high‑dose APAP treatment inhibited while therapeutic and low‑dose treatment did not inhibit cell survival of kidney tubular epithelial cells. In addition, therapeutic-dose treatment induced an increase in the H2O2 level, activated the caspase‑9/‑3 cascade, and induced cell apoptosis of hepatoma cells. Notably, APAP promoted fibroblast proliferation, even at low doses. This study demonstrates that different cellular effects are exerted upon treatment with different APAP concentrations. Our results indicate that treatment with the therapeutic dose of APAP may exert an antitumor activity on hepatoma, while low‑dose treatment may be harmful for patients with fibrosis, since it may cause proliferation of fibroblasts.
    Molecular Medicine Reports 03/2014; · 1.17 Impact Factor
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    ABSTRACT: Frog ribonucleases have been demonstrated to have anticancer activities. However, whether RC-6 ribonuclease exerts anticancer activity on human embryonal carcinoma cells remains unclear. In the present study, RC-6 induced cytotoxicity in NT2 cells (a human embryonal carcinoma cell line) and our studies showed that RC-6 can exert anticancer effects and induce caspase-9 and -3 activities. Moreover, to date, there is no evidence that frog ribonuclease-induced cytotoxicity effects are related to cellular senescence. Therefore, our studies showed that RC-6 can increase p16 and p21 protein levels and induce cellular senescence in NT2 cells. Notably, similar to retinoic acid-differentiated NT2 cells, neuron-like morphology was found on some remaining live cells after RC-6 treatment. In conclusion, our study is the first to demonstrate that RC-6 can induce cytotoxic effects, caspase-9/-3 activities, cellular senescence and neuron-like morphology in NT2 cells.
    Oncology Reports 02/2014; · 2.30 Impact Factor
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    ABSTRACT: The aim of this study was to examine the plasma level changes of soluble Axl (sAxl) prior to and following treatment with antibiotics in hospitalized adult patients with community-acquired pneumonia (CAP), and to investigate the correlating clinical and laboratory manifestations of CAP with plasma sAxl levels. Blood samples were obtained from 61 adult CAP patients (prior to and following treatment with antibiotics) and 60 healthy controls in order to measure the plasma concentrations of sAxl using the enzyme-linked immunosorbent assay. The plasma-soluble Axl concentration level was markedly elevated in patients with CAP prior to treatment, compared with the controls, and decreased markedly following treatment. The levels of white blood cells, neutrophils, and C-reactive protein decreased markedly following treatment with antibiotics and did not correlate with the concentration level of sAxl. However, the plasma concentration of sAxl correlated with the severity of CAP with the pneumonia severity index score (r=0.350, P=0.006, n=61), the CURB-65 score (r=0.281, P=0.028, n=61) and the acute physiology and chronic health evaluation II score (r=0.313, P=0.014, n=61). In conclusion, plasma sAxl may be involved in the clinical assessment of the severity of CAP, which may guide the development of treatment strategies and predict the clinical outcome.
    Molecular Medicine Reports 02/2014; · 1.17 Impact Factor
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    ABSTRACT: The gene EZH2, the polycomb group protein enhancer of zeste 2, encodes a transcriptional repressor that also serves as a histone methyltransferase that is associated with progression to more advanced disease in a variety of malignancies. EZH2 expression level in urothelial cell carcinoma (UCC) is highly correlated with tumor aggressiveness, but it has not been determined if specific EZH2 genetic variants are associated with UCC risk. This study investigated the potential associations of EZH2 single-nucleotide polymorphisms with UCC susceptibility and its clinicopathologic characteristics. A total of 233 UCC patients and 552 cancer-free controls, all of whom were from Taiwan, were analyzed for four EZH2 single-nucleotide polymorphisms (rs6950683, rs2302427, rs3757441, and rs41277434) using real-time PCR genotyping. After adjusting for other co-variants, we found that individuals carrying at least one C allele at EZH2 rs6950683 had a lower risk of developing UCC than did major allele carriers. The CCCA or TGTA haplotype among the four EZH2 sites was also associated with a reduced risk of UCC. Furthermore, UCC patients who carried at least one G allele at rs2302427 had a lower invasive tumor stage than did patients carrying the major allele. The rs6950683 SNPs of EZH2 might contribute to the prediction of UCC susceptibility. This is the first study to provide insight into risk factors associated with EZH2 variants in carcinogenesis of UCC in Taiwan.
    PLoS ONE 01/2014; 9(4):e93635. · 3.53 Impact Factor
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    ABSTRACT: The α-fetoprotein fraction L3 (AFP-L3), which is synthesized by malignant cells and incorporates a fucosylated oligosaccharide, has been investigated as a diagnostic and prognostic marker for hepatocellular carcinoma (HCC). Quantification of AFP-L3 by conventional enzyme-linked immunosorbent assay (ELISA) has not always produced reliable results for serum samples with low AFP, and thus we evaluated the clinical utility of quantifying AFP-L3 using a new and highly sensitive glycan microarray assay. Sera from 9 patients with chronic hepatitis B and 32 patients with hepatitis B virus (HBV)-related HCC were tested for AFP-L3 level using the glycan microarray. Additionally, we compared receiver operator characteristic curves for the ELISA and glycan microarray methods for determination of the AFP-L3: AFP-L1 ratio in patient samples. This ratio was calculated for 8 HCC patients who underwent transarterial embolization therapy pre- or post-treatment with AFP-L3. Glycan microarrays showed that the AFP-L3 ratio of HBV-related HCC patients was significantly higher than that measured for chronic hepatitis B patients. Overall parameters for estimating AFP-L3% in HCC samples were as follows: sensitivity, 53.13%; specificity, 88.89%; and area under the curve, 0.75. The elevated AFP-L3% in the 8 patients with HBV-related HCC was strongly associated with HCC progression. Following one month of transarterial embolization therapy, the relative mean AFP-L3% decreased significantly. In addition, we compared Fut8 gene expression between paired tumor and non-tumor tissues from 24 patients with HBV-related HCC. The Fut8 mRNA expression was significantly increased in tumorous tissues in these patients than that in non-tumor tissue controls. Higher expression of Fut8 mRNA in tumorous tissues in these patients was associated with poor differentiation than well and moderate differentiation. Our results describe a new glycan microarray for the sensitive and rapid quantification of fucosylated AFP; this method is potentially applicable to screening changes in AFP-L3 level for assessment of HCC progression.
    PLoS ONE 01/2014; 9(6):e99959. · 3.53 Impact Factor
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    ABSTRACT: Olfactory ensheathing cells (OECs) are unique glia cells restricted to the primary olfactory system including the olfactory mucosa, olfactory nerve, and the outer nerve layer of the olfactory bulb. OECs guide growing olfactory axons from the neurons of the nasal cavity olfactory mucosa to the olfactory bulb to connect both the peripheral nervous system (PNS) and central nervous system (CNS). Based on these specialized abilities of OECs, transplantation of OECs to injury sites has been widely investigated for their potential therapeutic applications in neural repair in different injuries. In this article, we reviewed the properties of OECs and their roles in olfactory regeneration and in treatment of different injuries including spinal cord injury, PNS injury, and stroke and neurodegenerative diseases.
    Cell Transplantation 01/2014; 23(4):567-71. · 4.42 Impact Factor
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    ABSTRACT: Epigenetic regulation plays a critical role in glioblastoma (GBM) tumorigenesis. However, how microRNAs (miRNAs) and cytokines cooperate to regulate GBM tumor progression is still unclear. Here, we show that interleukin-6 (IL-6) inhibits miR142-3p expression and promotes GBM propagation by inducing DNA methyltransferase 1-mediated hypermethylation of the miR142-3p promoter. Interestingly, miR142-3p also suppresses IL-6 secretion by targeting the 3' UTR of IL-6. In addition, miR142-3p also targets the 3' UTR and suppresses the expression of high-mobility group AT-hook 2 (HMGA2), leading to inhibition of Sox2-related stemness. We further show that HMGA2 enhances Sox2 expression by directly binding to the Sox2 promoter. Clinically, GBM patients whose tumors present upregulated IL-6, HMGA2, and Sox2 protein expressions and hypermethylated miR142-3p promoter also demonstrate poor survival outcome. Orthotopic delivery of miR142-3p blocks IL-6/HMGA2/Sox2 expression and suppresses stem-like properties in GBM-xenotransplanted mice. Collectively, we discovered an IL-6/miR142-3p feedback-loop-dependent regulation of GBM malignancy that could be a potential therapeutic target.
    Molecular cell 12/2013; 52(5):693-706. · 14.61 Impact Factor
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    ABSTRACT: Triple-negative breast cancer (TNBC), a subtype of breast cancer with negative expressions of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), is frequently diagnosed in younger women and has poor prognosis for disease-free and overall survival. Due to the lack of known oncogenic drivers for TNBC proliferation, clinical benefit from currently available targeted therapies is limited, and new therapeutic strategies are urgently needed. Triple-negative breast cancer cell lines were treated with proteasome inhibitors in combination with lapatinib (a dual epidermal growth factor receptor (EGFR)/HER2 tyrosine kinase inhibitor). Their in vitro and in vivo viability was examined by MTT assay, clonogenic analysis, and orthotopic xenograft mice model. Luciferase reporter gene, immunoblot, and RT-qPCR, immunoprecipitation assays were used to investigate the molecular mechanisms of action. Our data showed that nuclear factor (NF)-kappaB activation was elicited by lapatinib, independent of EGFR/HER2 inhibition, in TNBCs. Lapatinib-induced constitutive activation of NF-kappaB involved Src family kinase (SFK)-dependent p65 and IkappaBalpha phosphorylations, and rendered these cells more vulnerable to NF-kappaB inhibition by p65 small hairpin RNA. Lapatinib but not other EGFR inhibitors synergized the anti-tumor activity of proteasome inhibitors both in vitro and in vivo. Our results suggest that treatment of TNBCs with lapatinib may enhance their oncogene addiction to NF-kappaB, and thus augment the anti-tumor activity of proteasome inhibitors. These findings suggest that combination therapy of a proteasome inhibitor with lapatinib may benefit TNBC patients.
    Breast cancer research: BCR 11/2013; 15(6):R108. · 5.87 Impact Factor
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    ABSTRACT: Globo H, a cancer-associated carbohydrate antigen, is highly expressed in various types of cancers. However, the role of Globo H in hepatocellular carcinoma (HCC) remains elusive. In the current study, we performed glycan microarray analysis of 134 human serum samples to explore anti-Globo H antibody changes and found that Globo H is up-regulated in hepatitis B virus (HBV)-positive HCC. Likewise, immunohistochemistry showed that Globo H expression was higher in tumors compared with normal tissues. In addition, fucosyltransferase 2 (FUT2), the main synthetic enzyme of Globo H, was also increased in HCC cells overexpressing HBV X protein (HBX). HBX plays an important role in promoting cell proliferation and may be related to increased levels of FUT2 and Globo H. Furthermore, using microRNA profiling, we observed that microRNA-15b (miR-15b) was down-regulated in patients with HCC and confirmed association of FUT2 expression with expression of its product, Globo H. Therefore, our results suggest that HBX suppressed the expression of miR-15b, which directly targeted FUT2 and then increased levels of Globo H to enhance HCC cell proliferation. Additionally, proliferation of HBX-overexpressing HCC cells was significantly inhibited by treatment with Globo H antibody in vitro. In xenograft animal experiments, we found that overexpression of miR-15b effectively suppressed tumor growth. The newly identified HBX/miR-15b/FUT2/Globo H axis suggests one possible molecular mechanism of HCC cell proliferation and represents a new potential therapeutic target for HCC treatment. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 10/2013; · 6.20 Impact Factor
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    ABSTRACT: Stress-inducible protein-1 (STI-1) is the proposed ligand for the cellular prion protein (PrP(C) ), which is thought to facilitate recovery following stroke. Whether STI-1 expression is affected by stroke and how its signalling facilitates recovery remain elusive. Brain slices from patients that died of ischemic stroke were collected for STI-1 immunohistochemistry. These findings were compared to results from cell cultures, mice with or without the PrP(C) knockout, and rats. Based on these findings, molecular and pharmacological interventions were administered to investigate the underlying mechanisms and to test the possibility for therapy in experimental stroke models. STI-1 was upregulated in the ischemic brains from humans and rodents. The increase in STI-1 expression in vivo was not cell-type specific, as it was found in neurons, glia and endothelial cells. Likewise, this increase in STI-1 expression can be mimicked by sublethal hypoxia in primary cortical cultures (PCCs) in vitro, and appear to have resulted from the direct binding of the hypoxia inducible factor-1α (HIF-1α) to the STI-1 promoter. Importantly, this STI-1 signalling promoted bone marrow derived cells (BMDCs) proliferation and migration in vitro and recruitment to the ischemic brain in vivo, and augmenting its signalling facilitated neurological recovery in part by recruiting BMDCs to the ischemic brain. Our results thus identified a novel mechanism by which ischemic insults can trigger a self-protective mechanism to facilitate recovery.
    EMBO Molecular Medicine 07/2013; · 7.80 Impact Factor
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    ABSTRACT: Here, we have examined the plasma levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), the MMP-9/TIMP-1 molar ratio, the TIMP-1 single nucleotide polymorphisms (SNPs) 372C/T and the susceptibility to community-acquired pneumonia (CAP). An enzyme-linked immunosorbent assay (ELISA) was used to measure plasma MMP-9 and TIMP-1 concentrations in 60 patients with CAP and 60 healthy individuals. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to detect the TIMP-1 SNPs 372C/T. The plasma MMP-9, TIMP-1 levels and the MMP-9/TIMP-1 molar ratio were significantly increased in patients with CAP compared to normal controls. The MMP-9/TIMP-1 molar ratio decreased significantly in patients with CAP after treatment. Furthermore, the plasma TIMP-1 concentration was positively correlated with the pneumonia severity index (PSI), the CURB score, the results of the acute physiology and chronic health evaluation II (APACHE II) and the length of the hospital stay. No significant difference was found in the genotype distribution of TIMP-1 372C/T between patients with CAP and normal controls. We hypothesize that MMP-9 levels and the MMP-9/TIMP-1 molar ratio plays a role in the development of CAP and is related to the severity of CAP. Based on our data, we suggest that incorporating plasma MMP-9 levels and the MMP-9/TIMP-1 molar ratio into a clinical evaluation will aid in CAP diagnosis.
    Clinica chimica acta; international journal of clinical chemistry 06/2013; · 2.54 Impact Factor
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    ABSTRACT: Exchange protein activated by cAMP-1 (Epac1) plays an important role in cell proliferation, cell survival and neuronal signaling, and activation of Epac1 in endothelial progenitor cells increases their homing to ischemic muscles and promotes neovascularization in a model of hind limb ischemia. Moreover, upregulation of Epac1 occurs during organ development and in diseases such as myocardial hypertrophy, diabetes, and Alzheimer's disease. We report here that hypoxia upregulated Epac1 through HIF-1α induction in the CD34-immunosorted human umbilical cord blood hematopoietic stem cells (hUCB(34)). Importantly, implantation of hUCB(34) subjected to hypoxia-preconditioning (HP-hUCB(34)) improved stroke outcome, more than did implantation of untreated hUCB(34), in rodents subjected to cerebral ischemia, and this required Epac1-to-matrix metalloproteases (MMPs) signaling. This improved therapeutic efficacy correlated with better engraftment and differentiation of these cells in the ischemic host brain. In addition, more than did implantation of untreated HP-hUCB(34), implantation of HP-hUCB(34) improved cerebral blood flow into the ischemic brain via induction of angiogenesis, facilitated proliferation/recruitment of endogenous neural progenitor cells in the ischemic brain, and promoted neurite outgrowth following cerebral ischemia. Consistent with our proposed role of Epac1-to-MMPs signaling in hypoxia-preconditioning, the above mentioned effects of implanting HP-hUCB(34) could be abolished by pharmacological inhibition and genetic disruption/deletion of Epac1 or MMPs. We have discovered a HIF-1α-to-Epac1-to-MMPs signaling pathway that is required for the improved therapeutic efficacy resulting from hypoxia preconditioning of hUCB(34) in vitro prior to their implantation into the host brain in vivo.
    Neurobiology of Disease 05/2013; · 5.62 Impact Factor
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    ABSTRACT: EZH2 plays an important role in stem cell renewal and maintenance by inducing gene silencing via its histone methyltransferase activity. Previously, we showed that EZH2 downregulation enhances neuron differentiation of human mesenchymal stem cells (hMSCs); however, the underlying mechanisms of EZH2-regulated neuron differentiation are still unclear. Here, we identify Smurf2 as the E3 ubiquitin ligase responsible for the polyubiquitination and proteasome-mediated degradation of EZH2, which is required for neuron differentiation. A ChIP-on-chip screen combined with gene microarray analysis revealed that PPARγ was the only gene involved in neuron differentiation with significant changes in both its modification and expression status during differentiation. Moreover, knocking down PPARγ prevented cells from undergoing efficient neuron differentiation. In animal model, rats implanted with intracerebral EZH2-knocked-down hMSCs or hMSCs plus treatment with PPARγ agonist (rosiglitazone) showed better improvement than those without EZH2 knockdown or rosiglitazone treatment after a stroke. Together, our results support Smurf2 as a regulator of EZH2 turnover to facilitate PPARγ expression, which is specifically required for neuron differentiation, providing a molecular mechanism for clinical applications in the neurodegenerative diseases.
    EMBO Molecular Medicine 03/2013; · 7.80 Impact Factor
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    ABSTRACT: Lapatinib, a dual EGFR/HER2 kinase inhibitor, showed clinical benefits in advanced HER2-positive breast cancer patients. Because some triple-negative breast cancers (TNBCs) frequently overexpress EGFR, the anti-tumor activity of lapatinib in such diseases was also tested. However, the results showed a worse event-free survival rate. It remains unknown whether and how lapatinib elicits the aggressiveness of such cancer cells. In this study, our results demonstrated that lapatinib facilitated axillary and lung metastases of triple-negative MDA-MB-231 breast cancer cells without affecting their viability, leading to worse survival in orthotopic xenograft mice. The lapatinib-increased motility was attributed by the elevation of EGFR through the downregulation of microRNA-7 and by the subsequent overexpression of cyclooxygenase-2 (COX-2). Strikingly, independent of its kinase activity, the elevated EGFR at least partly stabilized COX-2 expression by enhancing the binding of HuR to COX-2 mRNA. Our results suggest that lapatinib may increase the migration and invasion of MDA-MB-231 cells by upregulating EGFR and COX-2 through the downregulation of microRNA-7, providing a potential explanation for the worse clinical outcome of TNBC patients who receive lapatinib-based treatment. These findings also shed new light on the molecular mechanism of COX-2 mRNA stabilization by EGFR in a kinase-independent manner.
    Molecular pharmacology 01/2013; · 4.53 Impact Factor
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    ABSTRACT: Japanese encephalitis virus (JEV), a mosquito‑borne flavivirus, causes acute encephalitis and nervous damage. Previous studies have demonstrated that JEV induces apoptosis in infected cells. However, to date the mechanisms of JEV‑induced apoptosis are unclear. In order to identify the viral proteins associated with JEV‑induced apoptosis, pEGFP‑non‑structural protein 3 (NS3) 1‑619 (expressing the JEV NS3 intact protein, including the protease and helicase domains), pEGFP‑NS3 1‑180 (expressing the protease domain) and pEGFP‑NS3 163‑619 (expressing the helicase domain) were transfected into target cells to study cell death. Results demonstrate that the JEV NS3 intact protein and protease and helicase domains induce cell death. In addition, cell death was identified to be significantly higher in cells transfected with the NS3 protease domain compared with the intact protein and helicase domain. Caspase activation was also analyzed in the current study. NS3 intact protein and NS3 protease and helicase domains activated caspase‑9/‑3‑dependent and ‑independent pathways. However, caspase‑8 activity was not found to be significantly different in NS3‑transfected cells compared with control. In summary, the present study demonstrates that the NS3 helicase and protease domains of JEV activate caspase‑9/‑3‑dependent and ‑independent cascades and trigger cell death.
    Molecular Medicine Reports 01/2013; · 1.17 Impact Factor
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    ABSTRACT: Glioblastoma is the most aggressive primary brain tumor and its prognosis remains poor despite different treatment modalities including surgery, radiotherapy and chemotherapy. Therefore, more useful treatments for glioblastoma patients are required. Human interleukin 15 (hIL15) is an immunomodulator that has antitumor activities. hIL15 combined with gene therapy method is also currently under cosideration as a treatment option. Since recombinant adeno-associated virus serotype 2 (rAAV2) with low immunogenicity and long-term gene expression in human clinical trials has been demonstrated, rAAV2 encoding hIL15 (rAAV2-hIL15) were used to inhibit human glioblastoma growth in the present study. rAAV2-hIL15, which is able to express IL15 protein with bioactivity, was successfully produced and purified. Data of this study demonstrated that the long-term expression of rAAV2-hIL15 enhances immunoglobulin (Ig) production and the cytotoxic activity of lymphokine-activated killer (LAK) cells. In addition, results of the present study showed that rAAV2-hIL15 delays tumor growth on a xenografted human glioblastoma mice model. Taken together, these results indicated that rAAV2-hIL15 constitutes a powerful and potent gene immunotherapy method for human glioblastoma treatment.
    Molecular and clinical oncology. 01/2013; 1(2):321-325.

Publication Stats

396 Citations
203.69 Total Impact Points

Institutions

  • 2010–2014
    • China Medical University (ROC)
      臺中市, Taiwan, Taiwan
  • 2009–2014
    • Asia University
      • Department of Biotechnology
      臺中市, Taiwan, Taiwan
  • 2008–2014
    • China Medical University Hospital
      • Department of Radiology
      臺中市, Taiwan, Taiwan
  • 2013
    • I-Shou University
      Kao-hsiung-shih, Kaohsiung, Taiwan
  • 2008–2013
    • Tzu Chi University
      • Institute of Medical Sciences
      Hua-lien, Taiwan, Taiwan
  • 2007–2010
    • University of Texas MD Anderson Cancer Center
      • Department of Molecular and Cellular Oncology
      Houston, TX, United States