• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6813-6823
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• 2015

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive of human brain tumors and has a stunning progression with a mean survival of one year from the date of diagnosis. High cell proliferation, angiogenesis and/or necrosis are histopathological features of this cancer, which has no efficient curative therapy. This aggressiveness is associated with particular heterogeneity of the tumor featuring multiple genetic and epigenetic alterations, but also with implications of aberrant signaling driven by growth factors. The transforming growth factor ${\beta}$ ($TGF{\beta}$) superfamily is a large group of structurally related proteins including $TGF{\beta}$ subfamily members Nodal, Activin, Lefty, bone morphogenetic proteins (BMPs) and growth and differentiation factor (GDF). It is involved in important biological functions including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing and inflammation. This superfamily is also considered to impact on cancer biology including that of GBM, with various effects depending on the member. The $TGF{\beta}$ subfamily, in particular, is overexpressed in some GBM types which exhibit aggressive phenotypes. This subfamily impairs anti-cancer immune responses in several ways, including immune cells inhibition and major histocompatibility (MHC) class I and II abolishment. It promotes GBM angiogenesis by inducing angiogenic factors such as vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI-I) and insulinlike growth factor-binding protein 7 (IGFBP7), contributes to GBM progression by inducing metalloproteinases (MMPs), "pro-neoplastic" integrins (${\alpha}v{\beta}3$, ${\alpha}5{\beta}1$) and GBM initiating cells (GICs) as well as inducing a GBM mesenchymal phenotype. Equally, Nodal promotes GICs, induces cancer metabolic switch and supports GBM cell proliferation, but is negatively regulated by Lefty. Activin promotes GBM cell proliferation while GDF yields immune-escape function. On the other hand, BMPs target GICS and induce differentiation and sensitivity to chemotherapy. This multifaceted involvement of this superfamily in GBM necessitates different strategies in anti-cancer therapy. While suppressing the $TGF{\beta}$ subfamily yields advantageous results, enhancing BMPs production is also beneficial.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.2
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• pp.109-114
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• 2016

Carbamoyl phosphate synthetase 1 (CPS1) deficiency is an autosomal recessive urea cycle disorder which causes hyperammonemia. CPS1 is the first enzyme step in the urea cycle and almost patients present their symptoms during neonatal period. We report a case of CPS1 deficiency in a boy who developed symptoms including lethargy and seizure at 3 days of age. The ammonia level was up to $2,325{\mu}mol/L$, sodium benzoate (250 mg/kg/d) and high calories of both dextrose and lipid was promptly administered. Central access by experienced pediatric surgeon and emergent continuous hemodialysis by pediatric nephrologist was performed within 3 hours and ammonia was less than $100{\mu}mol/L$ at 5 days of age. Currently, he has showed excellent response to treatments including scavenging drugs and a low-protein diet. Despite of diffuse increasing signal intensity on cerebral white matters and basal ganglia on brain MRI, his development and weight gain were good at the last follow-up at 11 months of age. Molecular assay of the CPS1 gene demonstrated that patient had compound heterozygous for c.1529del ($p.Gly510Alafs^*5$) in exon 14 and c.3142-1G>C (IVS25(-1)G>C) in intron 25 and exon 26 boundary. The splicing mutation was novel mutation and inherited from patient's mother. Here, we report a neonatal lethal type CPS1 deficiency patient having novel mutation.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.103-114
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• 1995

Platinum coordination complexes are currently one of the most compounds used in the treatment of solid tumors. However, its use is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (Ⅱ) complex analogue containing 1,2-diaminocyclohexane (dach) as carrier ligand and 1,2-bis(diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of [Pt(trans-ddach)(DPPE).$2NO_3(PC)$ was synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $^{13}carbon$ nuclear magnetic resonance (NMR)]. PC demonstrated acceptable antitumor activity aganist P388, L-1210 lymphocytic leukemia cells and SK=OV3 human ovarian adenocarcinoma cells, and significant. activity as compared with that. cisplatin. The toxicity of PC was found quite less than thar of cisplatin using MTT, $[^3H]$ thymidine uptake and glucose consumption tests in rabbit proximal tubule cells, human kidney cortical cells and human renal cortical tissues. Based on these results, this novel platinum compound represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low toxicity.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7045-7056
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• 2013

Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.

• Journal of Microbiology and Biotechnology
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• v.28 no.11
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• pp.1928-1936
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• 2018

Recently, human infections caused by severe fever with thrombocytopenia syndrome virus (SFTSV), which can lead to fatality, have dramatically increased in East Asia. With the unavailability of vaccines or antiviral drugs to prevent and/or treat SFTSV infection, early rapid diagnosis is critical for prevention and control of the disease. Here, we report the development of a simple, rapid and sensitive portable detection method for SFTSV infection applying reverse transcription-loop mediated isothermal amplification (RT-LAMP) combined with one-pot colorimetric visualization and electro-free reaction platform. This method utilizes a pocket warmer to facilitate diagnosis in a resource-limited setting. Specific primers were designed to target the highly-conserved region of L gene of SFTSV. The detection limit of the RT-LAMP assay was approximately $10^0$ viral genome copies from three different SFTSV strains. This assay exhibited comparable sensitivity to qRT-PCR and 10-fold more sensitivity than conventional RT-PCR, with a rapid detection time of 30 to 60 minutes. The RT-LAMP assay using SFTSV clinical specimens has demonstrated a similar detection rate to qRT-PCR and a higher detection rate compared to conventional RT-PCR. Moreover, there was no observed cross-reactive amplification of other human infectious viruses including Japanese Encephalitis Virus (JEV), Dengue, Enterovirus, Zika, Influenza and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This highly sensitive, electro- and equipment-free rapid colorimetric visualization method is feasible for resource-limited SFTSV field diagnosis.

• Polymer(Korea)
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• v.31 no.6
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• pp.505-511
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• 2007

Poly(lactide-co-glycolide)(PLGA) and hyaluronic acid (HA) has been widely used as biocompatible scaffold materials to regenerate tissue. In this present study, we fabricated microporous PLGA and HA loaded PLGA scaffolds by a emusion freeze-drying method. In order to confirm that the release profile of cytokine or water-soluble drugs, we manufactured the granulocyte macrophage colony stimulating factor(GM-CSF) loaded PLGA and HA-PLGA scaffold. All scaffolds were characterized using scanning electron microscope(SEM), mercury porosimeter and wettability measurement. Cell proliferation and viability were assessed by a 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium-bromide (MTT) test. The porosity of HA-PLGA scaffold was greater than 95% with the total pore area of $261\;m^2/g$. The HA-FLGA scaffold exhibited well interconnected pores to allow greater cell adhesion and prolixferation. It was proven by higher cell viability in the HA-PLGA scaffold than PLGA alone. This may be due to the enhanced natural properties and higher water retention capacity of HA.

• Journal of Oral Medicine and Pain
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• v.37 no.1
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• pp.9-17
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• 2012

Lichen planus is a chronic inflammatory mucocutaneous disease that affects multiple sites of the body. Often it involves the oral mucosa, but also involve other sites such as skin, genitals, scalp and nails. There is no clear cause of oral lichen planus (OLP), current data suggest that OLP is a T-cell mediated autoimmune disorder which may have an altered self-peptide triggering apoptosis of oral epithelial cells. Usually OLP appears in middle-aged women which tends to be chronic with periods of exacerbation and remission. There are many theories those causes the OLP such as psychological and environmental factors, genetic tendency, drugs and more. 60-70% of lichen planus is accompanied by oral lesions, and more than half of its cases are not able to defined by their skin. In this study, among all the possibility(possible) theories, we tried to evaluate the influence of emotional stress in exacerbating OLP. There were thirty patients with a clinical or histological diagnosis of OLP and other thirty subjects who did not show any signs of systemic disorders include OLP. They were evaluated by using modified Holmes and Rahe's Social Readjustment Rating Scale (SRRS). As a result, a significantly higher level of stress was found in the OLP patients than the control group. Therefore it could be concluded that psychological stressors play an important role in the exacerbating OLP.

• The Journal of Korean Medicine
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• v.30 no.4
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• pp.129-141
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• 2009

Objective: This study was to investigate the anti-tumor effect, safety, safety, mechanism and metabolizing enzyme of Agrimonia pilosa LEDEB (APL) in female C57B/L mouse tumor (in vivo). Method: First, to evaluate the antitumor activity of APL, we divided the mice into four groups: normal, control, APL50 (50mg/kg), and APL100 (100mg/kg). LLC-obtained American Type Culture Collection was used. LLC had been inoculated to induce tumors. To measure the anti-tumor effect of APL, we calibrated tumor size and weight. To analyze the mechanism of anti-tumor in APL, we used western blotting and to observe metabolizing enzyme in APL we used to real-time PCR. Result: APL50 and APL100 significantly inhibited tumor growth from 12 days after medicine injected. APL did not induce caspase-dependent apoptosis in LLC-bearing mouse tumor. In APL100, it decreased 41% and 71% in CYP2D22 and CYP3A11, respectively. Conclusion: These results suggest that APL has some anti-tumor effects in female C57B/L mouse tumor. APL should be used carefully with other drugs related with CYP2D22 and CYP3A11.

• Journal of Veterinary Clinics
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• v.29 no.1
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• pp.12-17
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• 2012

Many drugs are administered intramuscularly to immobilize and anesthetize dogs. There are many established intramuscular (IM) anesthetic combinations for dogs; however, little information is available on the effects of a xylazinediazepam-ketamine (XDK) combination. The purpose of this study was to investigate the anesthetic effects of the XDK combination in dogs. Twelve adult mixed bred dogs were used. All dogs were anesthetized with an IM injection of diazepam (0.5 mg/kg) and xylazine (1.1 mg/kg) with low-dose ketamine (5 mg/kg; group 1) or high-dose ketamine (10 mg/kg; group 2) in one syringe. After administration of the test dose, the animals were positioned in a right lateral recumbency, and analgesia and cardiopulmonary data were collected and recorded. The duration of anesthesia in group 2 was significantly longer than that of group 1 (mean [sd] 68.0 [7.6] v 51.3 [2.7] minutes). Blood pressure increased significantly after XDK administration in both groups, and $S_aO_2$ levels decreased significantly from baseline at 10, 20, and 30 minutes in both groups. XDK administration produced satisfactory sedation and analgesia in all dogs. In conclusion, intramuscular administration of xylazine-diazepam-ketamine combination at a doses of 1.1 mg/kg xylazine, 0.5 mg/kg diazepam, and 5 or 10 mg/kg ketamine appeared to be effective short duration anesthetic protocols in dogs.

• The Journal of the Korean Society for Microbiology
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• v.14 no.1
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• pp.49-61
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• 1979

Two hundred and ninety-five strains of Peudomonas aeruginosa isolated from clinical sources were tested for drug resistance and demonstration of R plasmids by intraspecies conjugation system. Sixty strains were found highly resistant to two or more of drugs. The rate of resistant strains were 38.9% to kanamycin(km), 33.2% to streptomydn(sm), 22.7% to sulfisomidine(Sa), 14.2% to chloramphenicol(Cp), 13.8% to tetracycline(Tc), 3.0% to carbenicillin(Cb), and to gentamicin(Gm), respectively. But no strains was resistant to nalidixic acid and colistine. They were resistant to per milliliter to more than $400{\mu}g$ per ml. of Tc, $800{\mu}g$ per ml of Cp and of Sm, $6,400{\mu}g$ per ml. of Sa, $200{\mu}g$ per ml. of Cb, $100{\mu}g$ per ml. of Gm, and $25{\mu}g$ per ml. of colistine. Forty-three strains of Pseudomonas aeruginosa could be transferred their resistance to Pseudomonas aeruginosa 2-70, 1005 rifampin resistant FP-auxotrophic mutant. Of sixty multiple resistant strains, forty-three(71.6%) demonstrated R plasmids; nineteen carried resistance to(Tc Cp Sm Sa), six to(Tc Cp Sm), three to(Tc Cp Sa), and Cp, five to(Tc Sm Sa), two to(Tc Sa), (Cp Sm) and Tc, and one to(Cp Sm Sa). Degree of resistance of recipients recieving R plasmids from donors were almost the same level of resistance as the donor in regardless of mating temperature at $25^{\circ}C$ and $37^{\circ}C$. Resistance to Tc, Sm, and Sa were transferred to a very few of recipient cells at five minutes after mating with donor and recipient cells but resistance to Cp were transferred to the majority of recipient cells. The transfer frequency of Tc, Cp, Sm, and Sa resistance from donors to recipients were from $1.0^{-1.4}\;to\;1.0^{-3.5}$ at $25^{\circ}C$ for 18 hours of incubation and were from $1.0^{-1.5}\;to\;1.0^{-3.5}$ at $37^{\circ}C$ for 18 hours of incubation.