228 results on '"Han-Chung Wu"'
Search Results
202. Development of a Humanized Antibody with High Therapeutic Potential against Dengue Virus Type 2
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I-Ju Liu, Chien-Yu Chiu, Gwong-Jen J. Chang, Mei-Ying Liao, Pi-Chun Li, Ping-Chang Cheng, Jian-Jong Liang, Han-Chung Wu, and Yi-Ling Lin
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lcsh:Arctic medicine. Tropical medicine ,Phage display ,lcsh:RC955-962 ,medicine.drug_class ,viruses ,Viral Plaque Assay ,Biology ,Dengue virus ,Antibodies, Monoclonal, Humanized ,Antibodies, Viral ,Humanized antibody ,medicine.disease_cause ,Monoclonal antibody ,Antiviral Agents ,Epitope ,Neutralization ,Dengue ,Mice ,Plaque reduction neutralization test ,Neutralization Tests ,medicine ,Animals ,Humans ,Mice, Inbred BALB C ,lcsh:Public aspects of medicine ,Public Health, Environmental and Occupational Health ,Antibodies, Monoclonal ,virus diseases ,lcsh:RA1-1270 ,Dengue Virus ,biochemical phenomena, metabolism, and nutrition ,Antibodies, Neutralizing ,Survival Analysis ,Virology ,Disease Models, Animal ,Infectious Diseases ,Epitope mapping ,Medicine ,Female ,Immunotherapy ,Epitope Mapping ,Research Article - Abstract
Background Dengue virus (DENV) is a significant public health threat in tropical and subtropical regions of the world. A therapeutic antibody against the viral envelope (E) protein represents a promising immunotherapy for disease control. Methodology/Principal Findings We generated seventeen novel mouse monoclonal antibodies (mAbs) with high reactivity against E protein of dengue virus type 2 (DENV-2). The mAbs were further dissected using recombinant E protein domain I-II (E-DI-II) and III (E-DIII) of DENV-2. Using plaque reduction neutralization test (PRNT) and mouse protection assay with lethal doses of DENV-2, we identified four serotype-specific mAbs that had high neutralizing activity against DENV-2 infection. Of the four, E-DIII targeting mAb DB32-6 was the strongest neutralizing mAb against diverse DENV-2 strains. Using phage display and virus-like particles (VLPs) we found that residue K310 in the E-DIII A-strand was key to mAb DB32-6 binding E-DIII. We successfully converted DB32-6 to a humanized version that retained potency for the neutralization of DENV-2 and did not enhance the viral infection. The DB32-6 showed therapeutic efficacy against mortality induced by different strains of DENV-2 in two mouse models even in post-exposure trials. Conclusions/Significance We used novel epitope mapping strategies, by combining phage display with VLPs, to identify the important A-strand epitopes with strong neutralizing activity. This study introduced potential therapeutic antibodies that might be capable of providing broad protection against diverse DENV-2 infections without enhancing activity in humans., Author Summary Dengue virus (DENV) infection remains a serious health threat despite the availability of supportive care in modern medicine. Monoclonal antibodies (mAbs) of DENV would be powerful research tools for antiviral development, diagnosis and pathological investigations. Here we described generation and characterization of seventeen mAbs with high reactivity for E protein of DENV. Four of these mAbs showed high neutralizing activity against DENV-2 infection in mice. The monoclonal antibody mAb DB32-6 showed the strongest neutralizing activity against diverse DENV-2 and protected DENV-2-infected mice against mortality in therapeutic models. We identified neutralizing epitopes of DENV located at residues K310 and E311 of viral envelope protein domain III (E-DIII) through the combination of biological and molecular strategies. Comparing the strong neutralizing activity of mAbs targeting A-strand with mAbs targeting lateral ridge, we found that epitopes located in A-strand induced stronger neutralizing activity than those located on the lateral ridge. DB32-6 humanized version was successfully developed. Humanized DB32-6 variant retained neutralizing activity and prevented DENV infection. Understanding the epitope-based antibody-mediated neutralization is crucial to controlling dengue infection. Additionally, this study also introduces a novel humanized mAb as a candidate for therapy of dengue patients.
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- 2012
203. Abstract 2520: CHC promotes tumor growth and angiogenesis through regulation of HIF-1α and VEGF signaling
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Kuo-Hua Tung and Han-Chung Wu
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Cancer Research ,Angiogenesis ,Cancer ,Biology ,medicine.disease ,Small hairpin RNA ,Oncology ,RNA interference ,Pancreatic cancer ,Cancer cell ,Immunology ,Cancer research ,medicine ,Adenocarcinoma ,Transcription factor - Abstract
Pancreatic adenocarcinoma is an aggressive disease with a high mortality rate. Currently, treatment options are limited. In an effort to improve the efficacy of treatments for pancreatic adenocarcinoma, we have newly generated a monoclonal antibody (mAb), Pa65-2, which specifically binds to various cancer cells and tumor blood vessels but not to normal cells. According to immunoaffinity chromatography, LC-MS/MS analysis, co-immunoprecipitation and RNA interference studies, the target protein of Pa65-2 is human clathrin heavy chain (CHC). Knocking down CHC with shRNA reduced tumor cell growth, colony formation and invasion in vitro, and inhibited tumor angiogenesis and growth. One of the key functions of CHC was to bind with the transcription factor subunit HIF-1α, increasing the stability of this protein and facilitating its nuclear translocation, thereby regulating the expression of VEGF. In animal studies using NOD/SCID mice bearing pancreatic cancer xenografts, Pa65-2 and CHC shRNA could each inhibit tumor growth and angiogenesis by regulating HIF-1α and VEGF. Furthermore, the expression of CHC, HIF-1α and VEGF was significantly correlated with tumor stage, suggesting that CHC might be a useful prognostic indicator for cancer. Considered together, our results indicate that CHC interacts with and stabilizes HIF-1α, and plays a role in HIF-1α nuclear localization and HRE promoter binding, leading to an increased production of VEGF. These results suggest that the CHC mAb, Pa65-2, can potentially be used to inhibit tumor angiogenesis and growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2520. doi:1538-7445.AM2012-2520
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- 2012
204. Abstract 194: MicroRNA-1 induces apoptosis by targeting prothymosin alpha in nasopharyngeal carcinoma cells
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Chin-Tarng Lin, Cheng-Der Wu, Han-Chung Wu, and Yuan-Sung Kuo
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Cancer Research ,Transfection ,Biology ,Prothymosin Alpha ,biology.organism_classification ,Molecular biology ,HeLa ,Oncology ,Apoptosis ,Annexin ,Cell culture ,microRNA ,medicine ,Camptothecin ,medicine.drug - Abstract
MiR-1 (microRNA-1) can be used as a positive control and for optimizing transfection conditions in microRNA experiments (e.g., Ambion Pre-miR miRNA Starter Kit, QIAGEN Syn-hsa-miR-1 miScript miRNA mimic positive control). We noticed that transfection of nasopharyngeal carcinoma cells with miR-1 reveals a typical apoptotic process when observed by time-lapse microscopy. Annexin V and TUNEL staining and caspase assay confirm that miR-1 induces nasopharyngeal carcinoma cell apoptosis. MiR-1 transfection of HeLa, Cal-27, KYSE30 and NPC-TW06 cell lines which express low levels of endogenous miR-1 also induces apoptosis. However, miR-1 transfection of cell lines such as SW620, HepG2, HEK-293T, SAS and PC-13 which express high levels of endogenous miR-1 does not induce apoptosis. To determine miR-1 target genes that are involved in apoptosis, we analyzed microRNA and pathway databases, and cDNA expression microarrays from miR-1 transfected cells. Using qRT-PCR analysis and luciferase reporter vector assays, we found that miR-1 directly targets PTMA (prothymosin alpha). We used PTMA siRNA to down regulate PTMA mRNA levels and observed whether PTMA siRNA could induce apoptosis. Knocking down PTMA expression alone did not induce apoptosis but could accelerate apoptotic progression in cells treated with apoptosis inducers. We also found that transfection of miR-1 could up regulated some pro-apoptotic proteins (HTRA, SMAC, p53, TNF-R1, TNF-R2, TRAILR-1, TNF-alpha, TNF-beta). They are not miR-1 directly target genes but involve in miR-1 inducing apoptosis. We conclude that miR-1 can induced apoptosis in low levels of endogenous miR-1 cell lines. This is a novel model of microRNA-induced cell apoptosis. The apoptotic inducers including actinomycin D, camptothecin and etoposide are also the chemotherapeutic drugs in clinical cancer therapy and PTMA siRNA can accelerate apoptotic progression in cells treated with those apoptosis inducers. Therefore PTMA siRNA may have potential applications as an adjuvant in cancer chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 194. doi:1538-7445.AM2012-194
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- 2012
205. MicroRNA-1 induces apoptosis by targeting prothymosin alpha in nasopharyngeal carcinoma cells
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Chin-Tarng Lin, Han-Chung Wu, Yuan-Sung Kuo, and Cheng-Der Wu
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microRNA-1 (miR-1) ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,PTMA (prothymosin alpha ,Nasopharyngeal neoplasm ,lcsh:Medicine ,Biology ,Prothymosin Alpha ,Transfection ,Cell Line, Tumor ,microRNA ,medicine ,Carcinoma ,Humans ,Pharmacology (medical) ,Protein Precursors ,Molecular Biology ,Biochemistry, medical ,nasopharyngeal carcinoma (NPC) ,Nasopharyngeal Carcinoma ,Research ,lcsh:R ,Biochemistry (medical) ,apoptosis ,Nasopharyngeal Neoplasms ,Cell Biology ,General Medicine ,medicine.disease ,Molecular biology ,Thymosin ,MicroRNAs ,Nasopharyngeal carcinoma ,Cell culture ,Apoptosis ,ProTalpha) - Abstract
Background MiR-1 (microRNA-1) has been used as a positive control in some microRNA experiments. We found that miR-1 transfection of nasopharyngeal carcinoma cells reveals a typical apoptotic process as shown by time-lapse microscopy so we investigated the mechanisms of miR-1 inducing apoptosis. Methods To confirm that miR-1 induces apoptosis, we used Annexin V and TUNEL staining and caspase assay. To determine that miR-1 directly targets genes that involve in apoptosis, we analyzed microRNA and pathway databases, and cDNA expression microarrays from miR-1 transfected cells. To demonstrate candidate miR-1 targeted genes, we used qRT-PCR analysis and luciferase reporter vector assays. To assess the miR-1 target gene PTMA (prothymosin alpha, ProTalpha) involves in apoptosis, we used PTMA siRNA to knock down PTMA. Results Annexin V and TUNEL staining and caspase assay confirm that miR-1 induces nasopharyngeal carcinoma cell apoptosis. MiR-1 transfection of HeLa, Cal-27, KYSE30 and NPC-TW06 cell lines which express low levels of endogenous miR-1 also induces apoptosis. However, miR-1 transfection of cell lines such as SW620, HepG2, HEK-293T, SAS and PC-13 which express high levels of endogenous miR-1 does not result in apoptosis. MiR-1 directly targets PTMA gene. PTMA siRNA and miR-1 accelerate the apoptotic process in cells treated with apoptosis inducers. Conclusions The exogenous expression of miR-1 induces apoptosis in a number of cell lines. This is a model of microRNA-induced cell apoptosis. The PTMA is one of miR-1 target genes which involve in miR-1 inducing apoptosis. The apoptotic inducers including actinomycin D, camptothecin and etoposide are also the chemotherapeutic drugs in clinical cancer therapy and PTMA siRNA can accelerate apoptotic progression in cells treated with those apoptosis inducers. Therefore PTMA siRNA may have potential applications as an adjuvant in cancer chemotherapy.
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- 2011
206. Abstract 1366: Computer-modeled novel cancer targeting peptides for therapy and imaging
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I-Ju Chen, Nai-Chuan Chang, John Yu, Alice L. Yu, Han-Chung Wu, and Sheng-Hung Wang
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chemistry.chemical_classification ,Cancer Research ,education.field_of_study ,business.industry ,medicine.medical_treatment ,Population ,Peptide ,Bioinformatics ,Targeted therapy ,Oncology ,chemistry ,Cancer cell ,medicine ,Cancer research ,Target protein ,Pharmacophore ,Peptide library ,education ,business ,Peptide sequence - Abstract
We have recently developed practical software programs for optimization of cancer targeting peptides, including combinatorial construction of 3D peptide library (Buildpep), binding pocket analyzer (PscanMS) and high accuracy protein-ligand scoring program (HotLig). Based on these programs, a strategy of structure-based optimization of cancer targeting peptides in silico is developed to target human GRP78 which consists of 654 amino acids. The homology modeling of human GRP78 was constructed through aligning amino acid sequence and 3D structure with its homologs. This protein contains two major structural domains, the peptide-binding domain and the ATPase. Based on the results from the molecular modeling, new peptide analogs were designed and examined for optimized binding to the targeted GRP78 through in silico analysis. We had thus delineated the pharmacophore description of binding motif targeting peptide-binding domain of GRP78 as Pro-X1-Leu-X2. Peptides possessing this motif can be applied in cancer-targeted drug delivery system. We have thus designed several new tumor-targeted peptides [P-12, P-13, and P-6]. Their ability to bind target protein was confirmed in subsequent in vitro binding through Biacore analysis. We next examined their capacity to target cancer cells in the in vitro binding with various cancer cells, and in vivo tumor imaging and targeted chemotherapeutic studies. The results indicate that these peptides exhibit promising therapeutic potential by their selective binding to cancer cells, but not normal cells. Notably, these peptide analogs can bind to breast cancer stem cell (CSC) population in xenografts of primary breast cancer suggesting that they can target breast CSC enriched subpopulation. The microSPECT/CT molecular imaging of a primary human breast tumors, BC0244, xenograft with 188Re-liposome-PEG-P12 or P13 peptide showed significantly more uptake of radioactivity as compared to 188Re- liposome-PEG-L-peptide in the BC0244 breast tumors in NOD/SCID mice at 6, 24 and 48 h after intravenous injection, and even greater difference was found as compared to that of 188Re-liposome alone. To further compare P12 labeled liposome with L-peptide labeled liposome for therapeutic efficacy, mice bearing BC0244 xenografts were distributed into 4 groups for treatment with P12-Lipo-Dox, L-peptide-Lipo-Dox, Lipo-Dox, and PBS. The tumor growth of P12-lipo-Dox group was 1.57-fold slower than that of the L-peptide group; both of them showed significant increase in the therapeutic efficiency than Lipo-Dox control. These optimized cancer targeting peptides may be useful for imaging and targeted therapy of cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1366. doi:10.1158/1538-7445.AM2011-1366
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- 2011
207. Abstract 2182: IGFBP-6 in nasopharyngeal carcinoma is a candidate tumor suppressor gene by regulating the expression of EGR-1
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Yuan-Sung Kuo, Han-Chung Wu, and Chin-Tarng Lin
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Cancer Research ,Gene knockdown ,Microarray analysis techniques ,Cancer ,Biology ,medicine.disease ,medicine.disease_cause ,Candidate Tumor Suppressor Gene ,stomatognathic diseases ,Oncology ,Nasopharyngeal carcinoma ,Cell culture ,Immunology ,otorhinolaryngologic diseases ,medicine ,Cancer research ,Carcinogenesis ,Chromatin immunoprecipitation ,hormones, hormone substitutes, and hormone antagonists - Abstract
Nasopharyngeal carcinoma (NPC) is one of the common cancers in South-Eastern Asia, particularly southern China, Singapore and Taiwan. It has been proposed to be closely associated with Epstein-Barr virus (EBV), but other researches also show that EBV can enhance the NPC proliferation but not related with initiation or promotion of NPC carcinogenesis. The aim of this study was to identify the pivotal genes that may be altered during NPC progression. Using cDNA microarray analysis, we compared the expression of 18 genes between NPC and normal nasomucosal cells. Q-RT-PCR analysis found the expression of IBFBP-6 in NPC cell lines and immunolocalization of IGFBP-6 in NPC cells and biopsy specimens to be very weak. To explore the effects of IGFBP-6 on NPC tumor growth, we constructed inducible plasmids containing full-length IGFBP-6 cDNA (pBIG2i-IGFBP-6) and established pBIG2i-IGFBP-6-transfected NPC stable cell lines (NPC-TW01-pBIG2i-IGFBP-6). We then performed in vitro and in vivo functional analysis of the IGFBP-6 in these cell lines. Over-expression of IGFBP-6 significantly suppressed the proliferation, invasion and metastatic activity of NPC cells and increased their apoptosis. We found the EGR-1, caspase-1 and TSP-1 genes to be markedly up-regulated when NPC-TW01-pBIG2i-IGFBP-6 was treated with doxycycline. Knocking down EGR-1 with EGR-1 siRNA resulted in a decrease in expression of caspase-1, TSP-1 and EGR-1 but not the expression of IGFBP-6. However, in knockdown cells the unchanged expression of IGFBP-6 did not inhibit the migration of NPC cells. Chromatin immunoprecipitation and luciferase reporter assay experiments showed that IGFBP-6 bound the EGR-1 promoter regions and activated EGR-1 promoter. We conclude that IGFBP-6 can regulate the progression of NPC by regulating the expression of EGR-1. These results suggest that IGFBP-6 could be used as a new target for NPC therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2182. doi:10.1158/1538-7445.AM2011-2182
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- 2011
208. α-Enolase–binding peptide enhances drug delivery efficiency and therapeutic efficacy against colorectal cancer.
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Chien-Hsun Wu, Yi-Huei Kuo, Ruey-Long Hong, and Han-Chung Wu
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ENOLASE ,PEPTIDES ,DRUG delivery systems ,DOXORUBICIN ,TUMOR treatment ,TARGETED drug delivery ,THERAPEUTICS - Abstract
The article focuses findings of a study on an alpha-Enolase–binding peptide that enhances drug delivery and therapeutic efficacy against colorectal cancer. It states that targeting peptide pHCT74 showed potential for drug delivery in both in vitro and in vivo studies, and mentions that combined pHCT74-conjugated liposomal doxorubicin therapy exhibited an enhanced anti-tumor effect. It infers that alpha-enolase– targeted lipid nanoparticles have can be used on targeted drug delivery.
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- 2015
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209. Generation of an anti-EpCAM antibody and epigenetic regulation of EpCAM in colorectal cancer.
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MEI-YING LIAO, MARK YEN-PING KUO, TUNG-YING LU, YI-PING WANG, and HAN-CHUNG WU
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- 2015
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210. Podocalyxin-like 1 is associated with tumor aggressiveness and metastatic gene expression in human oral squamous cell carcinoma.
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CHENG-WEI LIN, MIN-SIOU SUN, and HAN-CHUNG WU
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- 2014
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211. Astrocyte elevated gene-1 is associated with metastasis in head and neck squamous cell carcinoma through p65 phosphorylation and upregulation of MMP1.
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Yi-Ping Wang, I-Ju Liu, Chiung-Pin Chiang, and Han-Chung Wu
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Background: The survival rate of head and neck squamous cell carcinoma (HNSCC) at advanced stage is poor, despite contemporary advances in treatment modalities. Recent studies have indicated that astrocyte elevated gene-1 (AEG-1), a single transmembrane protein without any known functional domains, is overexpressed in various malignancies and is implicated in both distant metastasis and poor survival. Results: High expression of AEG-1 in HNSCC was positively correlated with regional lymph node metastasis and a poor 5-year survival rate. Knockdown of AEG-1 in HNSCC cell lines reduced their capacity for colony formation, migration and invasion. Furthermore, decreased tumor volume and metastatic foci were observed after knockdown of AEG-1 in subcutaneous xenografts and pulmonary metastasis assays in vivo, respectively. We also demonstrated that AEG-1 increased phosphorylation of the p65 subunit of NF-κB, and regulated the expression of MMP1 in HNSCC cells. Moreover, compromised phosphorylation of the p65 (RelA) subunit of NF-κB at serine 536 was observed upon silencing of AEG-1 in both HNSCC cell lines and clinical specimens. Conclusion: High expression of AEG-1 is associated with lymph node metastasis and its potentially associated mechanism is investigated. [ABSTRACT FROM AUTHOR]
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- 2013
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212. Króppel-like factor 4 is involved in cell scattering induced by hepatocyte growth factor.
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Jun-Kai Lai, Han-Chung Wu, Yuh-Chiang Shen, Hsin-Ying Hsieh, Shu-Yi Yang, and Chia-Che Chang
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KRUPPEL-like factors , *CELLS , *HEPATOCYTE growth factor , *CADHERINS , *CHROMATIN - Abstract
Hepatocyte growth factor/scatter factor (HGF) is unique by inducing epithelial cell scattering, a cellular event pivotal to HGF-mediated invasive-growth response essential for embryonic development and metastasis. Krüppel-like factor 4 (KLF4) is a multifunctional zincfinger transcription factor involved in cell proliferation, differentiation and self-renewal. We herein present the first evidence for the functional connection between KLF4 and HGF-induced cell scattering. In particular, we found that KLF4 was upregulated by HGF in two independent epithelial cell types, HepG2 and MDCK, whereas KLF4 knockdown inhibited HGF-induced E-cadherin suppression and cell scattering. Moreover, enforced nuclear KLF4 expression alone was sufficient to upregulate KLF4, downregulate E-cadherin and trigger scattering. Chromatin immunoprecipitation (ChIP) analysis further revealed that KLF4 induced suppression of E-cadherin transcription by directly binding to the E-cadherin promoter. Additionally, we proved that HGF-induced upregulation of KLF4 transcription and cell scattering require activation of the MEK/ERK signaling pathway and the induction of early growth response 1 (EGR-1). At the mechanistic level, ChIP analysis validated a direct binding of EGR-1 to the KLF4 promoter to induce KLF4 transcription; in turn, EGR-1-induced KLF4 binds to its own promoter, thus creating a positive feedback mechanism to sustain KLF4 expression and the resultant cell scattering. We conclude that KLF4 upregulation by HGF represents a novel mechanism mediating HGF-induced cell scattering and perhaps other associated events such as cell migration and invasion. [ABSTRACT FROM AUTHOR]
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- 2012
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213. Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy.
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Han-Chung Wu and De-Kuan Chang
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TUMORS , *CANCER treatment , *ANTINEOPLASTIC agents , *LIPOSOMES , *CELL receptors , *DRUG delivery systems - Abstract
Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy. [ABSTRACT FROM AUTHOR]
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- 2010
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214. Effect of Epstein–Barr virus infection on global gene expression in nasopharyngeal carcinoma.
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Yuan-Chii Gladys Lee, Yu-Chyi Hwang, Kuang-Chi Chen, Yong-Shiang Lin, Dah-Yeou Huang, Tao-Wei Huang, Cheng-Yan Kao, Han-Chung Wu, Chin-Tarng Lin, and Chi-Ying F. Huang
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EPSTEIN-Barr virus ,GENES ,EPITHELIAL cells ,GENE expression ,GENOMES - Abstract
It was proposed that Epstein–Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC); however, the molecular mechanisms involved in the effect of EBV on NPC host genes have not yet been well defined. For this study, two sets of microarray experiments, NPC (EBV-free) vs normal epithelial cells and EBV
+ vs EBV− NPC arrays, were analyzed and the datasets were cross-compared to identify any correlation between gene clusters involved in EBV targeting and the NPC host gene expression profiles. Statistical analysis revealed that EBV seems to have a preference for targeting more genes from the differentially expressed group in NPC cells than those from the ubiquitously expressed group. Furthermore, this trend is also reflected in log ratios where the EBV target genes of the differentially expressed group origin showed greater log ratios than genes with an origin from the ubiquitously expressed NPC group. Taken together, the genome-wide comparative scanning of EBV and NPC transcriptomes has successfully demonstrated that EBV infection has an intensifying effect on the signals involved in NPC gene expression both in breadth (the majority of the genes) and in depth (greater log ratios). [ABSTRACT FROM AUTHOR]- Published
- 2007
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215. Disease-Specific B Cell Epitopes for Serum Antibodies from Patients with Severe Acute Respiratory Syndrome (SARS) and Serologic Detection of SARS Antibodies by Epitope-Based Peptide Antigens.
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I-Ju Liu, Po-Ren Hsueh, Chin-Tarng Lin, Chien-Yu Chiu, Chuan-Liang Kao, Mei-Ying Liao, and Han-Chung Wu
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SARS disease ,CORONAVIRUS diseases ,BLOOD plasma ,LYMPHOCYTES ,IMMUNOGLOBULIN G ,AMINO acid sequence ,PROTEIN analysis ,IMMUNE response - Abstract
Severe acute respiratory syndrome (SARS) has emerged as a highly contagious, sometimes fatal disease. To find disease-specific B cell epitopes, phage-displayed random peptide libraries were panned on serum immunoglobulin (Ig) G antibodies from patients with SARS. Forty-nine immunopositive phage clones that bound specifically to serum from patients with SARS were selected. These phageborne pep tides had 4 consensus motifs, of which 2 corresponded to amino acid sequences reported for SARS-associated coronavirus (SARS- CoV). Synthetic peptide binding and competitive-inhibition assays further confirmed that patients with SARS generated antibodies against SARS-CoV. Immunopositive phage clones and epitope-based peptide antigens demonstrated clinical diagnostic potential by reacting with serum from patients with SARS. Antibody-response kinetics were evaluated in 4 patients with SARS, and production of IgM, IgG, and IgA were documented as part of the immune response. In conclusion, B cell epitopes of SARS corresponded to novel coronavirus. Our epitope-based serologic test may be useful in laboratory detection of the virus and in further study of the pathogenesis of SARS. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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216. The Association of Heterotrimeric GTP-Binding Protein (Go) with Microtubules.
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Han-Chung Wu, Chien-Yu Chiu, John V., Pei-Hsin Huang, John V., and Chin-Tarng Lin, John V.
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ADENOSINE diphosphate , *PRECIPITATION (Chemistry) , *PROTEINS , *MICROTUBULES , *TUBULINS - Abstract
The heterotrimeric GTP-binding regulatory proteins (G proteins) play an important role in the regulation of membrane signal transduction. Recently, we identified the association of Go protein with mitotic spindles. Here we have investigated the relationship between Go protein and microtubules. We used temperature-dependent reversible assembly and taxol methods to purify microtubules from bovine brains. Goα and Gβ proteins were identified in the microtubular fraction by both methods. The Goα subunit in the microtubular fraction could be ADP ribosylated by pertussis toxin. Co-immunoprecipitation data also revealed that Go protein can interact with microtubules. Exogenous Go protein could be incorporated into the assembled microtubular fraction, and 5 μg/ml (60 nM) of Go protein inhibited 40% of microtubule assembly. Western blot analysis of Goα-1 and Goα-2 in microtubular fractions showed that only Goα-1 is associated with microtubules. We conclude that the Goα-1βγ proteins are associated with microtubules and may play some role in regulating the assembly and disassembly of microtubules.Copyright © 2001 National Science Council, ROC and S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2001
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217. Characterization of Neutralizing Antibodies and Identification of Neutralizing Epitope Mimics on...
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Han-Chung Wu, Chia-Tsui Yeh, Yue-Ling Huang, Lih-Jeng Tarn, and Chien-Cheng Lung
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MONOCLONAL antibodies , *MICE , *TOXINS , *IMMUNOLOGY - Abstract
Examines the monoclonal antibodies BT57-1 and BT150-3 that protect mice against lethal doses of BTx-A protein toxins. Measure of neutralizing abilities; Analysis of phage-displayed peptide libraries with neutralizing antibody; Identification of neutralizing epitopes; Binding assay of synthetic peptide mimic.
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- 2001
218. MDM2 expression in EBV-infected nasopharyngeal carcinoma cells.
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Han-Chung Wu, Tung-Ying Lu, Jeng-Jie Lee, Jen-Kuo Hwang, Yu-Ju Lin, Chung-Kwe Wang, and Chin-Tarng Lin
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- 2004
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219. Functional Analysis of EBV in Nasopharyngeal Carcinoma Cells.
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Han-Chung Wu, Yu-Ju Lin, Jeng-Jie Lee, Yung-Jung Liu, Sung-Tzu Liang, Yet Peng, Yung-Wen Chiu, Chen-Wen Wu, and Chin-Tarng Lin
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- 2003
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220. Identification of the carboxyl-terminal amino acids important for the ADP-ribosylation activity of Pseudomonas exotoxin A
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Mei-Shya Chen, Han-Chung Wu, J. T. Chow, and Jenn-Kang Hwang
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chemistry.chemical_classification ,Gel electrophoresis ,Cell Biology ,Biology ,medicine.disease_cause ,biology.organism_classification ,Biochemistry ,Enterobacteriaceae ,Amino acid ,chemistry ,ADP-ribosylation ,medicine ,Pseudomonas exotoxin ,Cytotoxicity ,Molecular Biology ,Escherichia coli ,Exotoxin - Abstract
The ADP-ribosylation domain of Pseudomonas exotoxin A (PE) has been identified to reside in structural domain III (residues 405-613) and a portion of domain Ib (residues 385-404) of the molecule (Hwang, J., FitzGerald, D. J., Adhya, S., and Pastan, I. (1987) Cell 48, 129-136). To further determine the carboxyl end region essential for ADP-ribosylation activity, we constructed sequential deletions at the carboxyl-terminal of PE. Our results show that a clone with a deletion of the carboxyl-terminal amino acid residues from Arg-609 to Lys-613 and replaced with Arg-Asn retained wild-type PE ADP-ribosylation activity. Deletion of the terminal amino acid residues from Ala-596 to Lys-613 and replaced with Val-Ile-Asn reduced ADP-ribosylation activity by 75%, while deletions of 36 or more amino acids from the carboxyl terminus completely lose their ADP-ribosylation activity. These modified PEs were also examined for their ability to block PE cytotoxicity. Our results shown that modified PEs which lost their ADP-ribosylation activity correspondingly lost their cytotoxicity. Furthermore, extracts containing PE fragments without ADP-ribosylation activity were able to block the cytotoxic activity of intact PE. Our results thus indicate that carboxyl-terminal amino acids in the Ser-595 region are crucial for ADP-ribosylation activity and, consequently, cytotoxicity of PE. The modified PEs which have lost their ADP-ribosylation activity may also be a route to new PE vaccines.
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- 1989
221. Improving dengue viral antigens detection in dengue patient serum specimens using a low pH glycine buffer treatment
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Gwong-Jen J. Chang, Day-Yu Chao, Han-Chung Wu, Wen-Fan Shen, Chwan-Chuen King, and Jedhan Ucat Galula
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0301 basic medicine ,Serotype ,Microbiology (medical) ,viruses ,030231 tropical medicine ,Glycine ,lcsh:QR1-502 ,Enzyme-Linked Immunosorbent Assay ,NS1 antigen ,Antigen-Antibody Complex ,Viral Nonstructural Proteins ,Dengue virus ,Antibodies, Viral ,medicine.disease_cause ,lcsh:Microbiology ,Dengue fever ,Dengue ,03 medical and health sciences ,Tissue culture ,0302 clinical medicine ,Antigen ,Aedes ,Immunology and Microbiology(all) ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Immunology and Allergy ,Antigens, Viral ,Vero Cells ,Infectious virus ,Viral antigens ,General Immunology and Microbiology ,business.industry ,Virion ,virus diseases ,General Medicine ,Dengue Virus ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Virology ,030104 developmental biology ,Infectious Diseases ,Immunoglobulin M ,Immunoglobulin G ,Antigen-capture ELISA ,business ,Viral load ,Viral particle - Abstract
Background/Purposes Early diagnosis of dengue virus (DENV) infection to monitor the potential progression to hemorrhagic fever can influence the timely management of dengue-associated severe illness. Nonstructural protein 1 (NS1) antigen detection in acute serum specimens has been widely accepted as an early diagnostic assay for dengue infection; however, lower sensitivity of the NS1 antigen-capture enzyme-linked immunosorbent assay (Ag-ELISA) in secondary dengue viral infection has been reported. Methods In this study, we developed two forms of Ag-ELISA capable of detecting E-Ag containing virion and virus-like particles, and secreted NS1 (sNS1) antigens, respectively. The temporal kinetics of viral RNA, sNS1, and E-Ag were evaluated based on the in vitro infection experiment. Meanwhile, a panel of 62 DENV-2 infected patients' sera was tested. Results The sensitivity was 3.042 ng/mL and 3.840 ng/mL for sNS1 and E, respectively. The temporal kinetics of the appearance of viral RNA, E, NS1, and infectious virus in virus-infected tissue culture media suggested that viral RNAs and NS1 antigens could be detected earlier than E-Ag and infectious virus. Furthermore, a panel of 62 sera from patients infected by DENV Serotype 2 was tested. Treating clinical specimens with the dissociation buffer increased the detectable level of E from 13% to 92% and NS1 antigens from 40% to 85%. Conclusion Inclusion of a low-pH glycine buffer treatment step in the commercially available Ag-ELISA is crucial for clinical diagnosis and E-containing viral particles could be a valuable target for acute DENV diagnosis, similar to NS1 detection.
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222. Astrocyte elevated gene-1 is associated with metastasis in head and neck squamous cell carcinoma through p65 phosphorylation and upregulation of MMP1
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I-Ju Liu, Yi Ping Wang, Chiung-Pin Chiang, and Han-Chung Wu
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Male ,Pathology ,Cancer Research ,MMP1 ,Gene Expression ,Kaplan-Meier Estimate ,Mice, SCID ,Metastasis ,Mice ,Mice, Inbred NOD ,Phosphorylation ,Aged, 80 and over ,Gene knockdown ,p65 ,Head and neck squamous cell carcinoma (HNSCC) ,RNA-Binding Proteins ,Middle Aged ,Tumor Burden ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Oncology ,Enzyme Induction ,Lymphatic Metastasis ,Carcinoma, Squamous Cell ,Molecular Medicine ,Female ,Mouth Neoplasms ,Matrix Metalloproteinase 1 ,Adult ,medicine.medical_specialty ,Biology ,Astrocyte elevated gene-1 (AEG-1) ,Downregulation and upregulation ,Cell Line, Tumor ,Carcinoma ,medicine ,Matrix metalloproteinase 1 (MMP1) ,Gene silencing ,Animals ,Humans ,Survival rate ,Aged ,Research ,Transcription Factor RelA ,Membrane Proteins ,medicine.disease ,Head and neck squamous-cell carcinoma ,Cancer research ,Cell Adhesion Molecules ,Protein Processing, Post-Translational ,Neoplasm Transplantation - Abstract
BackgroundThe survival rate of head and neck squamous cell carcinoma (HNSCC) at advanced stage is poor, despite contemporary advances in treatment modalities. Recent studies have indicated that astrocyte elevated gene-1 (AEG-1), a single transmembrane protein without any known functional domains, is overexpressed in various malignancies and is implicated in both distant metastasis and poor survival.ResultsHigh expression of AEG-1 in HNSCC was positively correlated with regional lymph node metastasis and a poor 5-year survival rate. Knockdown of AEG-1 in HNSCC cell lines reduced their capacity for colony formation, migration and invasion. Furthermore, decreased tumor volume and metastatic foci were observed after knockdown of AEG-1 in subcutaneous xenografts and pulmonary metastasis assaysin vivo, respectively. We also demonstrated that AEG-1 increased phosphorylation of the p65 subunit of NF-κB, and regulated the expression of MMP1 in HNSCC cells. Moreover, compromised phosphorylation of the p65 (RelA) subunit of NF-κB at serine 536 was observed upon silencing of AEG-1 in both HNSCC cell lines and clinical specimens.ConclusionHigh expression of AEG-1 is associated with lymph node metastasis and its potentially associated mechanism is investigated.
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223. The extracellular domain of epithelial cell adhesion molecule (EpCAM) enhances multipotency of mesenchymal stem cells through EGFR-LIN28-LET7 signaling.
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Kuan, I.-I., Chi-Chiu Lee, Chien-Hsu Chen, Jean Lu, Yuan-Sung Kuo, and Han-Chung Wu
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CELL adhesion molecules , *MESENCHYMAL stem cells , *EPITHELIAL cells , *RUNX proteins , *EPIDERMAL growth factor receptors , *OSTEOBLASTS - Abstract
Mesenchymal stem cells (MSCs) are widely considered to be an attractive cell source for regenerative therapies, but maintaining multipotency and self-renewal in cultured MSCs is especially challenging. Hence, the development and mechanistic description of strategies that help promote multipotency in MSCs will be vital to future clinical use. Here, using an array of techniques and approaches, including cell biology, RT-quantitative PCR, immunoblotting, immunofluorescence, flow cytometry, and ChIP assays, we show that the extracellular domain of epithelial cell adhesion molecule (EpCAM) (EpEX) significantly increases the levels of pluripotency factors through a signaling cascade that includes epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), and Lin-28 homolog A (LIN28) and enhances the proliferation of human bone marrow MSCs. Moreover, we found that EpEXinduced LIN28 expression reduces the expression of the microRNA LET7 and up-regulates that of the transcription factor high-mobility group AT-hook 2 (HMGA2), which activates the transcription of pluripotency factors. Surprisingly, we found that EpEX treatment also enhances osteogenesis of MSCs under differentiation conditions, as evidenced by increases in osteogenic markers, including Runt-related transcription factor 2 (RUNX2). Taken together, our results indicate that EpEX stimulates EGFR signaling and thereby context-dependently controls MSC states and activities, promoting cell proliferation and multipotency under maintenance conditions and osteogenesis under differentiation conditions. [ABSTRACT FROM AUTHOR]
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- 2019
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224. sj-pdf-1-lup-10.1177_09612033221099766 – Supplemental Material for α-2,6-sialic acid/IgG anti-dsDNA ratios correlate with human lupus disease activity and possible mechanisms: A pilot study
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Liou, Lieh-bang, Wang, Ting-yi, Liu, I-Ju, Wu, Han-Chung, Ke, Po-Yuan, Fang, Yao-Fan, and Chen, Yen-Fu
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immune system diseases ,111702 Aged Health Care ,FOS: Health sciences ,skin and connective tissue diseases - Abstract
Supplemental Material, sj-pdf-1-lup-10.1177_09612033221099766 for α-2,6-sialic acid/IgG anti-dsDNA ratios correlate with human lupus disease activity and possible mechanisms: A pilot study by Lieh-bang Liou, Ting-yi Wang, I-Ju Liu, Han-Chung Wu, Po-Yuan Ke, Yao-Fan Fang and Yen-Fu Chen in Lupus
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- 2022
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225. Molecular Mimicry of Human Endothelial Cell Antigen by Autoantibodies to Nonstructural Protein 1 of Dengue Virus.
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I.-Ju Liu, Chien-Yu Chiu, Yun-Ching Chen, and Han-Chung Wu
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MOLECULAR mimicry , *DENGUE hemorrhagic fever , *DENGUE viruses , *AUTOANTIBODIES , *VASCULAR endothelium , *B cells , *UMBILICAL veins , *CHROMATOGRAPHIC analysis - Abstract
The pathogenesis of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), both serious complications of dengue virus (DV) infection, remains unclear. In this study, we found that anti-DV NS1 (nonstructural protein 1) polyclonal antibodies cross-reacted with human umbilical vein endothelial cells (HUVECs). We further identified a complex-specific mAb, DB16-1, which could recognize DV NS1 and cross-react with HUVECs and human blood vessels. The target protein of DB16-1 was further purified by immunoaffinity chromatography. LC-MS/MS analysis and co-immunoprecipitation revealed that the target protein of DB16-1 was human LYRIC (lysine-rich CEACAM1 co-isolated). Our newly generated anti-LYRIC mAbs bound to HUVECs in a pattern similar to that of DB16-1. The B-cell epitope of DB16-1 displayed a consensus motif, Lys-X-Trp-Gly (KXWG), which corresponded to amino acid residues 116-119 of DV NS1 and mimicked amino acid residues 334-337 in LYRIC. Moreover, the binding activity of DB16-1 in NS1 of DV-2 and in LYRIC disappeared after the KXWG epitope was deleted in each. In conclusion, DB16-1 targeted the same epitope in DV NS1 and LYRIC protein on human endothelial cells, suggesting that it might play a role in the pathogenesis of DHF/DSS. Future studies on the role of the anti-NS1 antibody in causing vascular permeability will undoubtedly be performed on sera collected from individuals before, during, and after the endothelial cell malfunction phase of a dengue illness. [ABSTRACT FROM AUTHOR]
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- 2011
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226. Epithelial Cell Adhesion Molecule Regulation Is Associated with the Maintenance of the Undifferentiated Phenotype of Human Embryonic Stem Cells.
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Tung-Ying Lu, Ruei-Min Lu, Mei-Ying Liao, John Yu, Chu-Hung Chung, Cheng-Fu Kao, and Han-Chung Wu
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GLYCOPROTEINS , *EMBRYONIC stem cells , *IMMUNOFLUORESCENCE , *WESTERN immunoblotting , *GENE expression , *CELL differentiation , *CANCER - Abstract
Human embryonic stem cells (hESCs) are unique pluripotent cells capable of self-renewal and differentiation into all three germ layers. To date, more cell surface markers capable of reliably identifying hESCs are needed. The epithelial cell adhesion molecule (EpCAM) is a type I transmembrane glycoprotein expressed in several progenitor cell populations and cancers. It has been used to enrich cells with tumor-initiating activity in xenograft transplantation studies. Here, we comprehensively profile the expression of EpCAM by immunofluorescence microscopy, Western blotting, and flow cytometry using an anti-EpCAM monoclonal antibody (mAb) 0C98-1. We found EpCAM to be highly and selectively expressed by undifferentiated rather than differentiated hESCs. The protein and transcript level of EpCAM rapidly diminished as soon as hESC had differentiated. This silencing was closely and exclusively associated with the radical transformation of histone modification at the EpCAM promoter. Moreover, we demonstrated that the dynamic pattern of lysine 27 trimethylation of histone 3 was conferred by the interplay of SUZ12 and JMJD3, both of which were involved in maintaining hESC pluripotency. In addition, we used chromatin immunoprecipitation analysis to elucidate the direct regulation by EpCAM of several reprogramming genes, including c-MYC, OCT-4, NANOG, SOX2, and KLF4, to help maintain the undifferentiation of hESCs. Collectively, our results suggest that EpCAM might be used as a surface marker for hESC. The expression of EpCAM may be regulated by epigenetic mechanisms, and it is strongly associated with the maintenance of the undifferentiated state of hESCs. [ABSTRACT FROM AUTHOR]
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- 2010
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227. Antiangiogenic Targeting Liposomes Increase Therapeutic Efficacy for Solid Tumors.
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De-Kuan Chang, Chien-Yu Chiu, Szu-Yao Kuo, Wei-Chuan Lin, Lo, Albert, Yi-Ping Wang, Pi-Chun Li, and Han-Chung Wu
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LIPOSOMES , *BLOOD vessels , *VASCULAR endothelial growth factors , *PEPTIDES , *TUMOR growth , *DOXORUBICIN - Abstract
It is known that solid tumors recruit new blood vessels to support tumor growth, but the molecular diversity of receptors in tumor angiogenic vessels might also be used clinically to develop better targeted therapy. In vivo phage display was used to identify peptides that specifically target tumor blood vessels. Several novel peptides were identified as being able to recognize tumor vasculature but not normal blood vessels in severe combined immunodeficiency (S9D) mice bearing human tumors. These tumor-homing peptides also bound to blood vessels in surgical specimens of various human cancers. The peptide-linked liposomes containing fluorescent substance were capable of translocating across the plasma membrane through endocytosis. With the conjugation of peptides and liposomal doxorubicin, the targeted drug delivery systems enhanced the therapeutic efficacy of the chemotherapeutic agent against human cancer xenografts by decreasing tumor angiogenesis and increasing cancer cell apoptosis. Furthermore, the peptide-mediated targeting liposomes improved the pharmacokinetics and pharmacodynamics of the drug they delivered compared with nontargeting liposomes or free drugs. Our results indicate that the tumor-homing peptides can be used specifically target tumor vasculature and have the potential to improve the systemic treatment of patients with solid tumors. [ABSTRACT FROM AUTHOR]
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- 2009
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228. Antibodies to Envelope Glycoprotein of Dengue Virus during the Natural Course of Infection Are Predominantly Cross-Reactive and Recognize Epitopes Containing Highly Conserved Residues at the Fusion Loop of Domain II.
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Chih-Yun Lai, Wen-Yang Tsai, Su-Ru Lin, Chuan-Liang Kao, Hsien-Ping Hu, Chwan-Chuen King, Han-Chung Wu, Gwong-Jen Chang, and Wei-Kung Wang
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IMMUNOGLOBULINS , *GLYCOPROTEINS , *DENGUE viruses , *EPITOPES , *SERUM , *BLOOD plasma , *VACCINATION , *PREVENTIVE medicine - Abstract
The antibody response to the envelope (E) glycoprotein of dengue virus (DENV) is known to play a critical role in both protection from and enhancement of disease, especially after primary infection. However, the relative amounts of homologous and heterologous anti-E antibodies and their epitopes remain unclear. In this study, we examined the antibody responses to E protein as well as to precursor membrane (PrM), capsid, and nonstructural protein 1 (NS1) of four serotypes of DENV by Western blot analysis of DENV serotype 2-infected patients with different disease severity and immune status during an outbreak in southern Taiwan in 2002. Based on the early-convalescent-phase sera tested, the rates of antibody responses to PrM and NS1 proteins were significantly higher in patients with secondary infection than in those with primary infection. A blocking experiment and neutralization assay showed that more than 90% of anti-E antibodies after primary infection were cross-reactive and nonneutralizing against heterologous serotypes and that only a minor proportion were type specific, which may account for the type-specific neutralization activity. Moreover, the E-binding activity in sera of 10 patients with primary infection was greatly reduced by amino acid replacements of three fusion loop residues, tryptophan at position 101, leucine at position 107, and phenylalanine at position 108, but not by replacements of those outside the fusion loop of domain II, suggesting that the predominantly cross-reactive anti-E antibodies recognized epitopes involving the highly conserved residues at the fusion loop of domain II. These findings have implications for our understanding of the pathogenesis of dengue and for the future design of subunit vaccine against DENV as well. [ABSTRACT FROM AUTHOR]
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- 2008
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