• Journal of Microbiology
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• v.45 no.6
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• pp.572-577
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• 2007

To enhance therapeutic potential of murine monoclonal antibody, humanization by CDR grafting is usually used to reduce immunogenic mouse residues. Most humanized antibodies still have mouse residues critical for antigen binding, but the mouse residues may evoke immune responses in humans. Previously, we constructed a new humanized version (AKA) of mouse CC49 antibody specific for tumor-associated glycoprotein, TAG-72. In this study, to select a completely human antibody light chain against TAG-72, guided selection strategy using phage display was used. The heavy chain variable region (VH) of AKA was used to guide the selection of a human TAG-72-specific light chain variable region (VL) from a human VL repertoire constructed from human PBL. Most of the selected VLs were identified to be originated from the members of the human germline VK1 family, whereas the VL of AKA is more homologous to the VK4 family. Competition binding assay of the selected Fabs with mouse CC49 suggested that the epitopes of the Fabs overlap with that of CC49. In addition, they showed better antigen-binding affinity compared to parental AKA. The selected human VLs may be used to guide the selection of human VHs to get completely human anti-TAG72 antibody.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6991-6996
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• 2015

In the past decade, the incidence and mortality rates of cholangiocarcinoma (CCA) have been increasing worldwide. The relatively low responsiveness of CCA to conventional chemotherapy leads to poor overall survival. Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) has emerged as the most promising anti-cancer therapeutic agent since it is able to selectively induce apoptosis of tumor cells but not normal cells. In this study, we aimed to investigate the therapeutic effect of TRAIL in CCA cell lines (M213, M214 and KKU100) compared with the immortal biliary cell line, MMNK1, either alone or in combination with a subtoxic dose of 5-fluorouracil (5-FU). We found that recombinant human TRAIL (rhTRAIL) was a potential agent which significantly inhibited cell proliferation and mediated caspase activities (caspases 8, 9 and 3/7) and apoptosis of CCA cells. The combined treatment of rhTRAIL and 5-FU effectively enhanced inhibition of CCA cell growth with a smaller effect on MMNK1. Our finding suggests TRAIL to be a novel anti-cancer therapeutic agent and advantage of its combination with a conventional chemotherapeutic drug for effective treatment of CCA.

• BMB Reports
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• v.49 no.11
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• pp.585-586
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• 2016

Extracellular vesicles (EVs) are natural carriers of biomolecules that play central roles in cell-to-cell communications. Based on this, there have been various attempts to use EVs as therapeutic drug carriers. From chemical reagents to nucleic acids, various macromolecules were successfully loaded into EVs; however, loading of proteins with high molecular weight has been huddled with several problems. Purification of recombinant proteins is expensive and time consuming, and easily results in modification of proteins due to physical or chemical forces. Also, the loading efficiency of conventional methods is too low for most proteins. We have recently proposed a new method, the so-called exosomes for protein loading via optically reversible protein-protein interaction (EXPLORs), to overcome the limitations. Since EXPLORs are produced by actively loading of intracellular proteins into EVs using blue light without protein purification steps, we demonstrated that the EXPLOR technique significantly improves the loading and delivery efficiency of therapeutic proteins. In further in vitro and in vivo experiments, we demonstrate the potential of EXPLOR technology as a novel platform for biopharmaceuticals, by successful delivery of several functional proteins such as Cre recombinase, into the target cells.

• BMB Reports
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• v.51 no.11
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• pp.563-571
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• 2018

Colorectal cancer (CRC), the third most common cancer in the world, has no specific biomarkers that facilitate its diagnosis and subsequent treatment. The miRNAs, small single-stranded RNAs that repress the mRNA translation and trigger the mRNA degradation, show aberrant levels in the CRC, by which these molecules have been related with the initiation, progression, and drug-resistance of this cancer type. Numerous studies show the microRNAs influence the cellular mechanisms related to the cell cycle, differentiation, apoptosis, and migration of the cancer cells through the post-transcriptionally regulated gene expression. Specific patterns of the upregulated and down-regulated miRNA have been associated with the CRC diagnosis, prognosis, and therapeutic response. Concretely, the downregulated miRNAs represent attractive candidates, not only for the CRC diagnosis, but for the targeted therapies via the tumor-suppressing microRNA replacement. This review shows a general overview of the potential uses of the miRNAs in the CRC diagnosis, prognosis, and treatment with a special focus on the downregulated ones.

• Biomolecules & Therapeutics
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• v.9 no.3
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• pp.156-161
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• 2001

Inflammation is a frequent radiation-induced following therapeutic irradiation. Treatment of human umbilical endothelial cells (HUVEC) with ${\gamma}$-irradiation (${\gamma}$IR) induces the expression of adhesion proteins such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Since the upregulation of these proteins on endothelial cell surface has been known to be associated with inflammation, interfering with the expression of adhesion molecules is an important therapeutic target. In the present study, we demonstrate that bioflavonoid rutin inhibits ${\gamma}$IR induced expression of ICAM-1, VCAM-1, and E-selectin on HUVEC in a dose- and time dependent manner. Rutin also inhibited ${\gamma}$IR induced production of NO. These data suggest that rutin has therapeutic potential for the treatment of various inflammatory disorder associated with an increase of endothelial leukocyte adhesion molecules.

• Archives of Pharmacal Research
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• v.24 no.5
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• pp.466-471
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• 2001

Inflammation is a frequent radiation-induced reaction following therapeutic irradiation. Treatment of human umbilical endothelial cells (HUVEC) with $\gamma$-irradiation ($\gamma$IR) induces the expression of adhesion proteins such as intercellular adhesion molecule-1 (VCAM-1 ), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Since the upregulation of these proteins on endothelial cell surface has been known to be associated with inflammation, interioring with the expression of adhesion molecules is an important therapeutic target. In the present study, we demonstrate that high mannronic acid-containing alginate (HMA) inhibits $\gamma$IR induced expression of ICAM-1, VCAM-1, and E-selectin on HUVEC in a dose dependent manner. HMA also inhibited $\gamma$IR induced production of Nitric oxide (NO). These data suggest that HMA has therapeutic potential for the treatment of various inflammatory disorder associated with an increase of endothelial leukocyte adhesion molecules.

• BMB Reports
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• v.50 no.3
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• pp.117-125
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• 2017

Most of the cancers are still incurable human diseases. According to recent findings, especially targeting cancer stem cells (CSCs) is the most promising therapeutic strategy. CSCs take charge of a cancer hierarchy, harboring stem cell-like properties involving self-renewal and aberrant differentiation potential. Most of all, the presence of CSCs is closely associated with tumorigenesis and therapeutic resistance. Despite the numerous efforts to target CSCs, current anti-cancer therapies are still impeded by CSC-derived cancer malignancies; increased metastases, tumor recurrence, and even acquired resistance against the anti-CSC therapies developed in experimental models. One of the most forceful underlying reasons is a "cancer heterogeneity" due to "CSC plasticity". A comprehensive understanding of CSC-derived heterogeneity will provide novel insights into the establishment of efficient targeting strategies to eliminate CSCs. Here, we introduce findings on mechanisms of CSC reprogramming and CSC plasticity, which give rise to phenotypically varied CSCs. Also, we suggest concepts to improve CSC-targeted therapy in order to overcome therapeutic resistance caused by CSC plasticity and heterogeneity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10557-10563
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• 2015

It is well known that conventional chemotherapy and radiation therapy can result in toxicity to both normal cells and tumor cells, which causes limitations in the application of these therapeutic strategies for cancer control. Novel and effective therapeutic strategies for cancers with no or low toxicity for normal cells are a high priority. Therefore, natural products with anticancer activity have gained more and more attention due to their favorable safety and efficacy profiles. Pre-clinical and clinical studies have demonstrated that several representative natural compounds such as resveratrol, epigallocatechin-3-gallate, curcumin, allicin and ginsenosides have obvious anticancer potential. In this article, we summarize autophagy-associated targeting pathways of such natural products for inducing the death of cancer cells, and discuss the core autophagic pathways involved in cancer treatments. Recent advances in the discovery, evaluation and exploitation of natural compounds as therapeutic agents for cancers will provide references and support in pre-clinical and clinical application of novel natural drugs for the treatment of primary and metastatic tumors in the future.

• Journal of Pharmaceutical Investigation
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• v.40 no.6
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• pp.333-337
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• 2010

Combining cell- and gene-based therapy is a promising therapeutic strategy in regenerative medicine. The aim of this study was to develop genetically modified mesenchymal stem cell (MSC) aggregates using a poly(ethylene glycol) (PEG) hydrogel micro-well array technique. Stable PEG hydrogel micro-well arrays with diameters of 200 to $500\;{\mu}m$ were fabricated and used to generate genetically engineered MSC aggregates. Rat bone marrow-derived MSCs were transfected with a green fluorescent protein (GFP) plasmid as a reporter gene, and aggregated by culturing in the PEG hydrogel micro-well arrays. The resultant cell aggregates had a mean diameter of less than $200\;{\mu}m$, and maintained the mesenchymal phenotype even after genetic modification and cell aggregation. Transplantation of MSC aggregates that are genetically modified to express therapeutic or cell-survival genes may be a potential therapeutic approach for regenerative medicine.

• IMMUNE NETWORK
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• v.2 no.1
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• pp.6-11
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• 2002

Background: Inflammation is a frequent reaction following therapeutic irradiation. Since the upregulation of adhesion molecules on endothelial cell surface is known to be associated with inflammation, the expression of adhesion molecules is an important therapeutic target. Methods: Treatment of human umbilical endothelial cells (HUVECs) with ${\gamma}$-irradiation (${\gamma}IR$) induces the expression of adhesion proteins such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Changes in the expression of these proteins on ${\gamma}$-irradiated HUVECs which had been treated previously with allicin were measured by ELISA. Results: In the present study, we demonstrate that allicin inhibits the ${\gamma}IR$ induced expression of ICAM-1, VCAM-1, and E-selectin on HUVEC in a dose-dependent manner. Allicin was also found to inhibit the ${\gamma}IR$ induced production of nitric oxide (NO). Conclusion: These data suggest that allicin has a therapeutic potential for the treatment of various inflammatory disorders associated with increase numbers of endothelial leukocyte adhesion molecules.