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1.  A Novel Synthetic Compound 3-Amino-3-(4-Fluoro-Phenyl)-1H-Quinoline-2,4-Dione (KR22332) Exerts a Radioprotective Effect via the Inhibition of Mitochondrial Dysfunction and Generation of Reactive Oxygen Species 
Yonsei Medical Journal  2014;55(4):886-894.
Acute side effects of radiation such as oral mucositis are observed in most patients. Although several potential radioprotective agents have been proposed, no effective agent has yet been identified. In this study, we investigated the effectiveness of synthetic compound 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR22332) as a radioprotective agent.
Materials and Methods
Cell viability, apoptosis, the generation of reactive oxygen species (ROS), mitochondrial membrane potential changes, and changes in apoptosis-related signaling were examined in human keratinocyte (HaCaT).
KR22332 inhibited irradiation-induced apoptosis and intracellular ROS generation, and it markedly attenuated the changes in mitochondrial membrane potential in primary human keratinocytes. Moreover, KR22332 significantly reduced the protein expression levels of ataxia telangiectasia mutated protein, p53, and tumor necrosis factor (TNF)-╬▒ compared to significant increases observed after radiation treatment.
KR22332 significantly inhibited radiation-induced apoptosis in human keratinocytes in vitro, indicating that it might be a safe and effective treatment for the prevention of radiation-induced mucositis.
PMCID: PMC4075391  PMID: 24954315
Radiation induced oral mucositis; 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR22332); apoptosis; radioprotection
2.  Proteomic analysis of domestic pig pancreas during development using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry 
Laboratory Animal Research  2014;30(2):45-53.
Pig pancreas may be a therapeutic resource for human diabetic patients. However, this potential is hindered by a lack of knowledge of the molecular events of pig pancreas development. In this study, the embryonic day 60, neonate and 6-month protein profiles of pig pancreas were ascertained at using two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization-time of flight mass spectrometry. Twenty four proteins were differentially expressed during pig pancreas development. Among them, 12 spots increased and 7 spots decreased according to development. The expression of 5 protein were highest at birth. Expression of digestive enzymes including trypsin, pancreatic triacylglycerol lipase and pancreatic alpha-amylase was elevated in adults, whereas chymotrypsins were highly expressed in neonates. Proteins that were abundantly expressed during gestation were alpha-1-antitrypsin, alpha-fetoprotein and transferrins. Taken together, we found out that several proteins were significantly up- or down- regulated from pig pancreas based on developmental stage. This study will provide basis for understanding development of pig pancreas.
PMCID: PMC4079831  PMID: 24999358
Domestic pig; pancreas; development; 2-DE proteomics; MALDI-TOF
3.  Protective effects of Korean red ginseng against radiation-induced apoptosis in human HaCaT keratinocytes 
Journal of Radiation Research  2013;55(2):245-256.
Radiation-induced oral mucositis is a dose-limiting toxic side effect for patients with head and neck cancer. Numerous attempts at improving radiation-induced oral mucositis have not produced a qualified treatment. Ginseng polysaccharide has multiple immunoprotective effects. Our aim was to investigate the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in the human keratinocyte cell line HaCaT and in an in vivo zebrafish model. Radiation inhibited HaCaT cell proliferation and migration in a cell viability assay and wound healing assay, respectively. KRG protected against these effects. KRG attenuated the radiation-induced embryotoxicity in the zebrafish model. Irradiation of HaCaT cells caused apoptosis and changes in mitochondrial membrane potential (MMP). KRG inhibited the radiation-induced apoptosis and intracellular generation of reactive oxygen species (ROS), and stabilized the radiation-induced loss of MMP. Western blots revealed KRG-mediated reduced expression of ataxia telangiectasia mutated protein (ATM), p53, c-Jun N-terminal kinase (JNK), p38 and cleaved caspase-3, compared with their significant increase after radiation treatment. The collective results suggest that KRG protects HaCaT cells by blocking ROS generation, inhibiting changes in MMP, and inhibiting the caspase, ATM, p38 and JNK pathways.
PMCID: PMC3951072  PMID: 24078877
Korean red ginseng (KRG); head and neck cancer; radiation-induced mucositis; apoptosis; radioprotection
4.  Tolfenamic Acid Induces Apoptosis and Growth Inhibition in Head and Neck Cancer: Involvement of NAG-1 Expression 
PLoS ONE  2012;7(4):e34988.
Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) is induced by nonsteroidal anti-inflammatory drugs and possesses proapoptotic and antitumorigenic activities. Although tolfenamic acid (TA) induces apoptosis in head and neck cancer cells, the relationship between NAG-1 and TA has not been determined. This study investigated the induction of apoptosis in head and neck cancer cells treated by TA and the role of NAG-1 expression in this induction. TA reduced head and neck cancer cell viability in a dose-dependent manner and induced apoptosis. The induced apoptosis was coincident with the expression of NAG-1. Overexpression of NAG-1 enhanced the apoptotic effect of TA, whereas suppression of NAG-1 expression by small interfering RNA attenuated TA-induced apoptosis. TA significantly inhibited tumor formation as assessed by xenograft models, and this result accompanied the induction of apoptotic cells and NAG-1 expression in tumor tissue samples. Taken together, these results demonstrate that TA induces apoptosis via NAG-1 expression in head and neck squamous cell carcinoma, providing an additional mechanistic explanation for the apoptotic activity of TA.
PMCID: PMC3334943  PMID: 22536345
5.  Efficacy of Itraconazole Prophylaxis for Autologous Stem Cell Transplantation in Children with High-Risk Solid Tumors: A Prospective Double-Blind Randomized Study 
Yonsei Medical Journal  2011;52(2):293-300.
The risk of invasive fungal infection is greater for allogeneic hematopoietic stem cell transplantation (HSCT) than for autologous transplantation. Therefore, many transplantation centers use antifungal prophylaxis for allogeneic HSCT, however, there exists no standard guidelines or consensus regarding autologous HSCT.
Materials and Methods
A prospective double-blind randomized study was conducted in autologous HSCT recipients who were divided into prophylaxis and empirical treatment groups, and we investigated the efficacy of itraconazole prophylaxis in pediatric autologous HSCT.
Total 87 autologous HSCT episodes in 55 children with high-risk solid tumors were studied. No invasive fungal infections occurred in either group. However, patients in the prophylaxis group had a significantly shorter duration of fever (p < 0.05) and received antibacterial treatment of shorter duration (p < 0.05) with fewer numbers of antibiotics (p < 0.05 for the use of second line antibiotics) than those in the empirical group. No significant additional adverse events were found with itraconazole prophylaxis.
Although beneficial effects such as a shorter duration of fever and reduced need for antibiotic use were observed in the prophylaxis group, the results were not sufficient to draw a definite recommendation about the routine use of antifungal prophylaxis in pediatric autologous HSCT recipients with high-risk solid tumors (Trial registration: NCT00336531).
PMCID: PMC3051209  PMID: 21319349
Itraconazole; autologous transplantation; antifungal prophylaxis; solid tumor
6.  Growth Inhibition and Apoptosis with H31 Metabolites from Marine Bacillus SW31 in Head and Neck Cancer Cells 
To determine whether a novel marine micro-organism with anticancer properties, H31, the metabolic product of Bacillus SW31, has anti-tumor effects on head and neck cancer, and potential for apoptotic-enhancing anti-cancer treatment of affected patients.
The cell viability and apoptosis assays were performed. Changes in the signal pathway related to apoptosis were investigated. Then, the therapeutic effects of H31 were explored in mouse xenograft model and drug toxicity of H31 was examined in zebrafish model.
We identified the anticancer activity of H31, a novel metabolic product of Bacillus SW31. Bacillus SW31, a new marine micro-organism, has 70% homology with Bacillus firmus and contains potent cytotoxic bioactivity in head and neck cancer cells using MTT assay. Combined with c-JUN, p53, cytochrome C, and caspase-3, H31 induced apoptosis of KB cells, a head and neck cancer cell line. In a separate in vivo model, tumor growth in C3H/HeJ syngeneic mice was suppressed by H31. In addition, in a zebrafish model used for toxicity testing, a considerable dose of H31 did not result in embryo or neurotoxicity.
Growth inhibition and apoptosis were achieved both in vitro and in vivo in head and neck cancer cells after exposure to H31, a metabolite from the marine Bacillus species, without any significant toxicity effects even at considerable H31 dose concentrations.
PMCID: PMC3010542  PMID: 21217964
Apoptosis; Bacillus; Marine toxins; Head and neck cancer; Cytotoxicity

Results 1-6 (6)