• Radiation Oncology Journal
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• v.22 no.2
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• pp.77-90
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• 2004

Purpose: The purpose of this review Is to provide an update on novel radiation treatments for head and neck cancer Recent Findings: Despite the remarkable advances In chemotherapy and radiotherapy techniques, the management of advanced head and neck cancer remains challenging. Epidermal growth factor receptor (EGFR) Is an appealing target for novel therapies In head and neck cancer because not only EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Furthermore, EGFR overexpression Is known to be portended for a worse outcome in patients with advanced head and neck cancer. Two categories of compounds designed to abrogate EGFR signaling, such as monoclonal antibodies (Cetuxlmab) and tyrosine kinase inhibitors (ZD1839 and 051-774) have been assessed and have been most extensively studied In preclinical models and clinical trials. Additional TKIs In clinical trials include a reversible agent, Cl-1033, which blocks activation of all erbB receptors. Encouraging preclinical data for head and neck cancers resulted In rapid translation Into the clinic. Results from Initial clinical trials show rather surprisingly that only minority of patients benefited from EGFR inhibition as monotherapy or In combination with chemotherapy. In this review, we begin with a brief summary of erbB- mediated signal transduction. Subsequently, we present data on prognostic-predictive value of erbB receptor expression in HNC followed by preclinlcal and clinical data on the role of EGFR antagonists alone or in combination with radiation In the treatment of HNC. Finally, we discuss the emerging thoughts on resistance to EGFR biockade and efforts In the development of multiple-targeted therapy for combination with chemotherapy or radiation. Current challenges for investigators are to determine (1 ) who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2) how to sequence these agents with radiation and/or cytotoxlc compounds, (3) reliable markers for patient selection and verification of effective blockade of signaling in vivo, and (4) mechanisms behind intrinsic or acquired resistance to targeted agents to facilitate rational development of multi-targeted therapy, Other molecuiar-targeted approaches In head and neck cancer were briefly described, Including angloenesis Inhibitors, farnesyl transferase inhibitors, cell cycle regulators, and gene therapy Summary: Novel targeted theraples are highly appealing in advanced head and neck cancer, and the most premising strategy to use them Is a matter of intense Investigation.

• Journal of Life Science
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• v.30 no.11
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• pp.999-1006
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• 2020

The suppression of neuroinflammatory responses in microglial cells, well known as the main immune cells in the central nervous system (CNS), are considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Teleogryllus emma is widely consumed around the world for its broad-spectrum therapeutic effect. In a previous work, we performed transcriptome analysis on T. emma in order to obtain the diversity and activity of its antimicrobial peptides (AMPs). AMPs are found in a variety of species, from microorganisms to mammals. They have received much attention as candidates oftherapeutic drugs for the treatment of inflammation-associated diseases. In this study, we investigated the anti-neuroinflammatory effect of Teleogryllusine (VKWKRLNNNKVLQKIYFVKI-NH₂) derived from T. emma on lipopolysaccharide (LPS) induced BV-2 microglia cells. Teleogryllusine significantly inhibited nitric oxide (NO) production without cytotoxicity, and reducing pro-inflammatory enzymes expression such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, Telegryllusine also inhibited the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) through down-regulation of the mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathway. These results suggest that T. emma-derived Teleogryllusine could be a good source of functional substances that prevent neuroinflammation and neurodegenerative diseases.

• Microbiology and Biotechnology Letters
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• v.26 no.2
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• pp.122-129
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• 1998

It were reported that antifungal mechanism of Enterobacter cloacae is a volatile ammonia that produced by the strain in soil, and the production of ammonia is related to the bacterial urease activity. A powerful bacterium SH14 against soil-borne pathogen Fusarium solani, which cause root rot of many important crops, was selected from a ginseng pathogen suppressive soil. The strain SH14 was identified as Bacillus subtilis by cultural, biochemical, morphological method, and $API^{circledR}$ test. From several in vitro tests, the antifungal substance that is produced from B. subtilis SH14 was revealed as heat-stable and low-molecular weight antibiotic substance. In order to construct the multifunctional biocontrol agent, the urease gene of Bacillus pasteurii which can produce pathogenes-suppressive ammonia transferred into antifungal bacterium. First, a partial BamH I digestion fragment of plasmid pBU11 containing the alkalophilic B. pasteurii l1859 urease gene was inserted into the BamH I site of pEB203 and expressed in Escherichia coli JM109. The recombinant plasmid was designated as pGU366. The plasmid pGU366 containing urease gene was introduced into the B. subtilis SH14 with PEG-induced protoplast transformation (PIP) method. The urease gene was very stably expressed in the transformant of B. subtilis SH14. Also, the optimal conditions for transformation were established and the highest transformation frequency was obtained by treatment of lysozyme for 90 min, and then addition of 1.5 ${mu}g$/ml DNA and 40% PEG4000. From the in vitro antifungal test against F. solani, antifungal activity of B. subtilis SH14(pGu366) containing urease gene was much higher than that of the host strain. Genetical development of B. subtilis SH14 by transfer of urease gene can be responsible for enhanced biocontrol efficacy with its antibiotic action.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.37 no.3
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• pp.257-264
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• 2011

In this study, to evaluate the antioxidative activities and anti-inflammatory effects of kaempferol and its rhamnosides, we performed the free radical scavenging assay, ROS inhibition assay and TARC (thymus and activation-regulated chemokine) assay. Also, we studied physiological activity of kaempferol and its rhamnosides (${\alpha}$-rhamnoisorobin, afzelin, kaempferitn) by structure-activity relations. The free radical (1,1-diphenyl-2-picrylhydrazyl, DPPH) scavenging activities were determined with kaempferol (62.5 ${\mu}M$) and ${\alpha}$-rhamnoisorobin (50.0 ${\mu}M$) but afzelin and kaempferitrin did not show free radical scavenging activities. Kaempferol showed a 97.5, 57.8, 47.8 % inhibition of ROS (reactive oxygen species) generated at concentrations of 10, 50 and 100 ${\mu}M$, compared to control (100 %). ${\alpha}$-rhamnoisorobin showed a 93.1, 59.1 and 41.4 % inhibition of ROS at the same concentration. We investigated the inhibitory effects of kaempferol and its rhamnosides on TARC expression. Kaempferol showed a 48.8, 5.5 and 4.4 % inhibition of TARC generated at 10, 50 and 100 ${\mu}M$, compared to control. ${\alpha}$-Rhamnoisorobin showed a 88.1, 19.0 and 1.0 % inhibition of TARC generated at the same concentration. In conclusion, these results indicate that kaempferol and ${\alpha}$-rhamnoisorobin have good antioxidative activities and anti-inflammatory effects that could be applicable to new functional cosmetics for anti-aging and anti-inflammation.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.546-557
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• 2000

Background : Oligonucleotide chip technology has proven to be a very useful tool in the rapid diagnosis of infectious disease. Rifampin resistance is considered as a useful marker of multidrug-resistance in tuberculosis. Mutations in the rpoB gene coding $\beta$ subunit of RNA polymerase represent the main mechanism of rifampin resistance. The purpose of this study was to develop a diagnosis kit using oligonucleotide chip for the rapid and accurate detection of rifampin-resistance in Mycobacterium tuberculosis. Method : The sequence specific probes for mutations in the rpoB gene were designed and spotted onto the glass slide, oligonucleotide chip. 38 clinical isolates of Mycobacterium were tested. A part of rpoB was amplified, labelled, and hybridized on the oligonucleotide chip with probes. Results were analyzed with a laser scanner. Direct sequencing was done to verify the results. Result : The low-density oligonucleotide chip design어 to determine the specific mutations in the rpoB gene of M. tuberculosis accurately detected rifampin resistance associated with mutations in 28 clinical isolates. Mutations at codons 531, 526, and 513 were confirmed by direct sequencing analysis. Conclusion : Mutant detection using oligonucleotide chip technology is a reliable and useful diagnostic tool for the detection of multidrug-resistance in M. tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.90-98
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• 1998

Background : The CD4+ T-helper cells comprise functionally distinct subsets of Th1 and Th2 cells that are distinguished on the basis of differential cytokines production Th1 cells secrete interferon-$\gamma$, lymphotoxin, interleukin-2. Th2 cells produce interleukin-4, interleukin-5, interleukin-10. A previous study shown that Th2 cells and their cytokines increased in patients with atopic asthma. We compared cytokines(IL-4, IFN-$\gamma$) activity and subpopulation of T-lymphocytes in peripheral blood from atopic asthmatics versus non-asthmatics. Method: Fifteen patients with atopic asthma(nine men, six women), twelve patients with chronic bronchitis(six men, six women), five healthy persons(three men, two women) were studied. Activity of IL-4, IFN-$\gamma$ and T-cell subpopulation in peripheral blood were estimated. Results: Patients had a median age of 55yr. The mean activity of IL-4 of asthmatics was significantly increased(control $0.75{\pm}1.1pmol/L$, atopic asthmatics $3.50{\pm}0.75pmol/L$, chronic bronchitis $2.01{\pm}1.2pmol/L$), but IFN-$\gamma$ was not significantly increased. In the T lymphocyte sunsets the percent of CD62L+ T-lymphoeytes of asthmatics was not significantly increased (control $16.7{\pm}16.4%$, atopic asthmatics $24.8{\pm}23.6%$, chronic bronchitis $17.0{\pm}16.9%$). Conclusion: In this study elevated production of IL-4 was observed in atopic asthmatics. CD62L+T-lymphoeytes was not increased in atopic asthma.

• KSBB Journal
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• v.24 no.4
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• pp.403-409
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• 2009

H2AX, a crucial component of chromatin, is implicated in DNA repair, cell cycle check point and tumor suppression. The aim of this study was to identify direct binding partners of H2AX to regulate cellular responses to above mechanisms. Literature reviews and bioinformatical tools were attempted intensively to find binding partners of H2AX, which resulted in identifying two potential proteins, breast cancer-1 (BRCA1) and BRCA1-associated RING domain 1 (BARD1). Although it has been reported in vivo that BRCA1 co-localizes with H2AX at the site of DNA damage, their biochemical mechanism for H2AX were however only known that the complex monoubiquitinates histone monomers, including unphosphorylated H2AX in vitro. Therefore, it is important to know whether the complex directly interacts with H2AX, and also which regions of these are specifically mediated for the interaction. Using in vitro GST pull-down assay, we present here that BRCA1 and BARD1 directly bind to H2AX. Moreover, through combinational approaches of domain analysis, fragment clonings and in vitro binding assay, we revealed molecular details of the BRCA1-H2AX and BARD1-H2AX complex. These data provide the potential evidence that each of the BRCA1 nuclear localization signal (NLS) and BARD1 BRCA1 C-terminal (BRCT) repeat domain is the novel mediator of H2AX recognition.

• Journal of Life Science
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• v.16 no.4
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• pp.612-617
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• 2006

Phosphoinositide-specific phospholipase $C-{\gamma}\;1\; (PLC-{\gamma}\;1)$ has pivotal roles in cellular signaling by producing second messengers, inositol 1,4,5-trisphosphate $(IP_3)$ and diacylglycerol (DG). Tubulin is a main component of microtubules and mitotic spindle fibers, which are composed of ${\alpha}-$ and ${\beta}-tubulin$ heterodimers in all eukaryotic cells. In humans, six ${\beta}-tubulin$ isotypes have been identified which display a distinct pattern of tissue expression. Previously we found that $PLC-{\gamma}\;1$ and one of four ${\beta}-tubulin$ isotypes including ${\beta}1$, ${\beta}2$, ${\beta}3$ and ${\beta}6$, colocalized in COS-7 cells and cotranslocated to the plasma membrane to activate $PLC-{\gamma}\;1$ upon agonist stimulation. In the present study, we demonstrate that the remaining two, tubulin ${\beta}4$ and ${\beta}5$, also showed a potential to activate $PLC-{\gamma}\;1$. The phosphatidylinositol 4,5-bisphosphate $(PIP_2)$ hydrolyzing activity of $PLC-{\gamma}\;1$ was substantially increased in the presence of purified ${\beta}4$ and ${\beta}5$ tubulin in vitro, whereas the activity was not promoted by bovine serum albumin, suggesting that tubulin ${\beta}4$ and ${\beta}5$ also activate $PLC-{\gamma}\;1$. Taken together, our results suggest that all the ${\beta}-tubulin$ isotype activates $PLC-{\gamma}\;1$ activity to regulate cellular signaling.

• Journal of Life Science
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• v.25 no.4
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• pp.463-472
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• 2015

Adrenomedullin (AM) is a peptide expressed in all body tissues, and its related receptors are increased in liver fibrosis. In this study, we evaluated the effect of AM deficiency on liver fibrogenesis induced by $CCl_4$ using AM heterozygous (HT) mice. The animals received a single injection of $CCl_4$ or olive oil for the acute experiment, and received $CCl_4$ or olive oil three times a week for 6 weeks for the chronic experiment. Fibrosis was accessed using histopathological analysis and the western blot. The AM HT mice showed mild pericentrilobular degeneration when compared to the AM wild type (WT) mice. In the acute experiment, there was no significant difference between the AM WT and AM HT mice. However, in the chronic experiment, the $CCl_4$-treated AM HT mice showed more severe liver fibrosis than that of the CCl₄-treated AM WT mice. The AST and ALT levels of the AM HT $CCl_4$ group were higher than those of the AM WT CCl₄ group. Additionally, the collagen deposition, $\alpha$- SMA protein and TGF-$\beta$ protein were increased in the AM HT $CCl_4$ group when compared to the AM WT $CCl_4$ group. The AM HT mice also exhibited severe lipid peroxidation through the GSH decrement. Taken together, our data suggest that AM deficiency increases the susceptibility to liver fibrosis induced by $CCl_4$, indicating a novel therapeutic target for patients with liver fibrosis.

• Journal of Life Science
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• v.22 no.9
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• pp.1243-1253
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• 2012

The production and secretion of growth hormone (GH) in the anterior pituitary gland can be induced by several natural products to control cell proliferation, differentiation, and migration. To investigate whether Chungkookjang (CKJ) produced by the fermentation process affects GH-related metabolism, the secretion and the response of GH were observed in pituitary cells and GH target cells. Among six CKJs manufactured by different strains of glycine max, only three CKJs, including Daewon (DW), Daepung (DP), and Taegwang (TG), induced GH secretion from GH3 cells at 5.0 mg/ml concentration. There were no significant changes detected in the viability of any of the cells treated with these CKJs. In addition, the increase in GH secretion from the GH3 cells was dependent on the concentration of the three types of CKJs. The proliferation of cell lines, including MG63 and HepG2 cells, that originated from those derived from the GH target organs was significantly activated by treatment with the GH-containing conditional medium (GCM) harvested from the three CKJ-treated GH3 cells, although their induction rate was different from each other. In these cells, p-STAT5 was maximally translocated into the nucleus of MG63 cells 30 min after DW treatment, while it was translocated in HepG2 cells at 60 min. These results suggest that these three types of CKJ could enhance the secretion of GH, as well as the GCM-derived response, in the two target organs.