• Journal of Life Science
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• v.18 no.1
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• pp.75-83
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• 2008

This studies were designed to elucidate whether inhibitors of topoisomerase regulate function and activity of topoisomerase, and gene expression in HL-60 human leukemia cells. HL-60 cells were treated with 10-hydroxycamptothecin or doxorubicin, total RNA was isolated, and expressed genes were investigated with human oligonucleotide microarray containing 10K gene, respectively. Expression profiles of the human leukemia HL-60 cells treated with 10-hydroxycamptothecin (10-CIT) or doxorubicin associated with signal transduction,. cell adhesion, cell cycle, cell growth, cell proliferation, cell differentiation, transcription and immune response, especially genes related with transcription and cell growth. In HL-60 cells treated with 10-CPT, the expression of topoisomerase III${\alpha}$, III${\beta}$ and I gene from oligo chip microarray analysis were increased over, but the expression of topoisomerase II${\alpha}$ and II${\beta}$ gene were decreased over. In contrast, the expression of topoisomerase II${\alpha}$ and II${\beta}$ gene were increased over in HL-60 cells treated with doxorubicin, whereas the expression of topoisomerase III${\alpha}$ and III${\beta}$ mRNA remained no significant change. These results suggest that these data may be useful for novel therapeutic markers.

• Journal of Life Science
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• v.23 no.10
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• pp.1280-1287
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• 2013

The current study investigated the effects of [6]-gingerol, a ginger phytochemical, on the expression of autophagy-related genes and the activation of antioxidative enzymes in the pancreas of mice with cerulein-induced acute pancreatitis. The following were studied: pancreatic edema, ${\alpha}$-amylase activity in serum, expression of autophagy genes, activities of antioxidative defense enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the production of lipid peroxidation (LPO). The results revealed that cerulein-induced edema in the pancreas and ${\alpha}$-amylase activity in the cerulein group significantly increased compared with that of the control. However, that of the [6]-gingerol pretreated group was significantly decreased compared with that of the cerulein-alone injected group (positive control). There was no significant difference compared with that of control. The expression of autophagy-related proteins, including Beclin-1 and cleaved microtubule-associated protein 1 light chain 3, were significantly increased in the positive control but significantly decreased in the [6]-gingerol-pretreated group. Furthermore, the activities of SOD and GSH-Px in the positive control were decreased compared with those of the control. However, those of the [6]-gingerol pretreated group were significantly increased compared with those of the cerulein-alone group. The mRNA levels and antioxidant enzyme activities were similar. The production of LPO in the cerulein with and without [6]-gingerol groups was increased by 133.1% and 26.3%, respectively, compared with that of the control, whereas that of the [6]-gingerol-pretreated group was significantly decreased by 48.5% compared with that of the positive control. Therefore, [6]-gingerol may be a strong candidate in reducing autophagy and LPO production and in enhancing antioxidative enzyme activities to help prevent acute and chronic pancreatitis.

• Journal of Life Science
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• v.28 no.10
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• pp.1140-1146
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• 2018

Dual-specificity phosphatases (DUSPs) play a role in cell growth and differentiation by modulating mitogen-activated protein kinases. DUSPs are considered targets for drugs against cancers, diabetes, immune diseases, and neuronal diseases. Part of the DUSP family, DUSP19 modulates c-Jun N-terminal kinase activity and is involved in osteoarthritis pathogenesis. Here, we report screening of cavity-creating mutants and the crystal structure of a cavity-creating L75A mutant of DUSP19 which has significantly enhanced enzyme activity in comparison to the wild-type protein. The crystal structure reveals a well-formed cavity due to the absent Leu75 side chain and a rotation of the active site-bound sulfate ion. Despite the cavity creation, residues surrounding the cavity did not rearrange significantly. Instead, a tightened hydrophobic interaction by a remote tryptophan residue was observed, indicating that the protein folding of the L75A mutant is stabilized by global folding energy minimization, not by local rearrangements in the cavity region. Conformation of the rotated active site sulfate ion resembles that of the phosphor-tyrosine substrate, indicating that cavity creation induces an optimal active site conformation. The activity enhancement by an internal cavity and its structural information provide insight on allosteric modulation of DUSP19 activity and development of therapeutics.

• Journal of Life Science
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• v.30 no.11
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• pp.939-946
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• 2020

Stroke is one of the leading causes of neurological disability worldwide and stroke patients exhibit a range of motor, cognitive, and psychiatric impairments. GPR88 is an orphan G protein-coupled receptor (GPCR) that is highly expressed in striatal medium spiny neurons; its deletion results in poor motor coordination and motor learning. There are currently no studies on the involvement of GPR88 in stroke or in post-stroke brain function recovery. In this study, we found a decrease in GPR88 protein and mRNA expression levels in an ischemic mouse model using Western blot and real-time PCR, respectively. In addition, we observed that, among the three types of cells derived from the brain (brain microvascular endothelial cells, BV2 microglial cells, and HT22 hippocampal neuronal cells), the expression of GPR88 was highest in HT22 neuronal cells, and that GPR88 expression was downregulated in HT22 cells under oxygen-glucose deprivation (OGD) conditions. Moreover, pretreatment with RTI- 13951-33 (10 mg/kg), a brain-penetrant GPR88 agonist, ameliorated brain injury following ischemia, as evidenced by improvements in infarct volume, vestibular-motor function, and neurological score. Collectively, our results suggest that GPR88 could be a potential drug target for the treatment of central nervous system (CNS) diseases, including ischemic stroke.

• Journal of Music and Human Behavior
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• v.11 no.1
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• pp.21-37
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• 2014

The significant role of joint attention in the development of children with autism spectrum disorder (ASD) has highlighted the importance of early intervention. With the emphasis on the effective cueing and reinforcer for orienting to social stimuli in improving responding to joint attention (RJA) of children with ASD, the use of musical cue was hypothesized. This study aimed to examine the occurrence of RJA behaviors depending on the attentional cue, which differed in the level of information and type of auditory modality. Nine children with ASD participated in this study. The use of eight different joint attention cues were analyzed in terms of the frequency and accuracy of RJA behaviors elicited. The results of the study showed that RJA behaviors occurred more frequently with musical cues than with verbal cues and the mean accuracy rate of RJA was higher with musical cues (p = .047). Musically delivered eliciting and directing cues accompanied with pointing elicited the highest attentional shift and RJA accuracy. The significant increases in RJA with the use of musical cues indicated that incorporating musical elements into an attentional cue may provide more accurate cue information, enough to improve RJA behaviors of children with autism.

• Journal of the Korean Magnetics Society
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• v.27 no.1
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• pp.18-22
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• 2017

The purpose of this study was to present an improved method of dose modulation over the increase of build-up for existing 6 MV photon beam. Two neodymium permanent magnets with a strength of 0.5 T (Tesla) were applied with a magnetic field perpendicular to the photon beam. The effects of dose on build-up region with or without the magnetic field were measured according to the magnet-to-magnet distance (MMS) and the magnet-to-surface distance (MSD). For MMS = 6 cm and MSD = 2.5 cm, $D_{0mm}$, $D_{2mm}$, $D_{5mm}$, and $D_{10mm}$ showed improved doses of 6.8 %, 14.6 %, 6.9 %, and 2.1 %, respectively, as compared with 6 MV open beam. In this study, the device with low strength magnetic field can be applied directly to the outside of the human body when the target volume located close to the skin is delivered with radiation. It is expected that the method of build-up modulation using a low strength magnetic field will be feasible in the clinical applications.

• Journal of Life Science
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• v.17 no.6 s.86
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• pp.748-755
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• 2007

The in vitro activity of ST1571, an inhibitor of the Abl group of protein-tyrosine kinases, alone or in combination with camptothecin (CPT), a specific topoisomerase I inhibitor, was evaluated against human cancer cells with different metastatic capacity and drug resistance potency. These cell lines showed different sensitivity to ST157 on growth inhibition, and the expression of DNA-dependent protein kinase (DNA-PK), which interacts constitutively with c-Abl, was significantly decreased in drug sensitive CEM and MCF-7 cells and poorly metastatic PC3 and KMl2 cells as compared with that of multidrug resistant CEM/MDR and MCF-7/MDR cells and highly metastatic PC3-MM2 and KM/L4a cells, respectively. These results suggest differential modulation of DNA-PK by ST1571 treatment in drug resistance and metastatic degree dependent manner. We showed that CPT as well as ST1571 significantly inhibits the expression of DNA-PK. The combined treatment with ST15fl and CPT revealed synergistic effect, and the effect was accompanied by inhibition of cell proliferation due to significant reduced expression of DNA-PK components, which resulted in CPT sensitizes human cancer cells resistant to ST1571. Therefore, the results of our study suggested that the suppression of DNA-PK using combination of ST1571 and CPT could be a novel molecular target for against drugresistant and metastatic cancer cells.

• Journal of Life Science
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• v.22 no.12
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• pp.1600-1607
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• 2012

The matrix metalloproteinase (MMP) family plays essential roles in physiological processes such as embryonic development, angiogenesis, wound healing, and tissue homeostasis as a consequence of MMPr capacity for breaking down many types of extracellular matrix proteins. Imbalanced regulation of MMP expression can also lead to pathological conditions such as tumor progression. We recently reported that the Drosophila Mmp1 gene is highly expressed in the digestive tract and is required for the maintenance of intestinal homeostasis such as by restriction of uncontrolled intestinal stem cell proliferation. However, the regulatory mechanisms of MMP gene expression in the intestine remain unclear. In this study, we determined that the expression of Mmp1 is regulated by the homeodomain transcription factor Caudal. Experiments using the targeted expression of Caudal under the regulation of Gal4-UAS system indicated that endogenous Caudal is required for the Mmp1 gene expression in the adult Drosophila intestine and that exogenous Caudal induces Mmp1 expression. Transient transfection experiments indicated that Caudal can activate the promoter activity of Mmp1 and that several putative Caudal binding sites in the 5'-flanking region of the Mmp1 gene may be critical to the upregulation by Caudal. Our data suggest that Mmp1 is one of the target genes of Caudal in physiological normal condition and in tumorigenesis.

• Polymer(Korea)
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• v.26 no.5
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• pp.691-700
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• 2002

Interstitial therapy using biodegradable polymeric device loaded with anticancer agent can deliver the drug to the tumor site at high concentration, resulting in an increase of therapeutic efficacy. 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine) is most commonly used as chemotherapeutic agent for brain tumors. The design of implantable device is regarded as an important factor lot the efficient delivery of antitumor agent to targeting site. In order to control the release profile of drug, the release pattern of BCNU with the changes of various dimension and additives was investigated. The PLGA wafers containing 3.85, 10, 20 and 30% of BCNU were prepared in various shape (diameter of 3, 5 and 10 mm, thickness of 0.5, 1 and 2 mm) by direct compression method. In vitro drug release profile of BCNU-loaded PLGA wafers could be controlled by changing the dimension of wafers such as initial drug content, weight, diameter, thickness, volume and surface area of wafers, as well as PLGA molecular weight and additives. Drug release from BCNU-loaded PLGA wafers was facilitated with an increase of BCNU-loading amount or presence of poly(N-vinylpyrrolidone)(PVP) or sodium chloride (NaCl). The effects of various geometric factors and additives on the BCNU release pattern were confirmed by the investigation of mass loss and morphology of BCNU-loaded PLGA wafers.

• Journal of the Korean Society of Radiology
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• v.13 no.1
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• pp.133-140
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• 2019

Triglycerides (TG) are one of the triggers of chronic inflammatory lesions in the blood vessels. In the key factors in the development of inflammatory diseases, Pro-inflammatory cytokines such as tumor necrosis factor-alpha $(TNF-){\alpha}$ and interleukin-1 beta ($IL-1{\beta}$) contribute to the development of inflammatory lesions by recruiting other immune cells in the inflamed area or causing cell necrotic death. In this study, I investigated the effect of Jurkat T lymphocytes and U937 monocytes involved in vascular inflammation development on the expression of $TNF-{\alpha}$ and $IL-1{\beta}$ on exposure to TGs. In Jurkat cells, mRNA expression of $TNF-{\alpha}$ is increased by exposure to TGs. However, the expression levels of $TNF-{\alpha}$ and $IL-1{\beta}$ were increased by TGs in U937 cells. To investigate whether inducible nitric oxide synthase (iNOS) is involved in the increase of expression of $TNF-{\alpha}$ and $IL-1{\beta}$ by TGs, treatment of W1400 (an iNOS inhibitor) resulted in recovery of expression level both $TNF-{\alpha}$ and $IL-1{\beta}$. Based on the present study, it was confirmed that the expression of $TNF-{\alpha}$ and $IL-1{\beta}$ in monocytes and T lymphocytes. This increased cytokines contribute to development of vascular inflammatory lesions. In addition, iNOS is involved in the increase of $TNF-{\alpha}$ and $IL-1{\beta}$ expression by TGs.