• The Korean Journal of Physiology and Pharmacology
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• v.12 no.4
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• pp.143-148
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• 2008

Caveolin-1 (CAV1) is an integral membrane protein that may function as a scaffold for plasma membrane proteins and acts as a tumor suppressor protein. One causative factor of chemotherapy-resistant cancers is P-plycoprotein (P-gp), the product of the multidrug resistance-1 gene (MDR1), which is localized in the caveolar structure. Currently, the interactive roles of CAV1 and MDR1 expression in the death of cancer cells remain controversial. In this study, we investigated the effects of indomethacin on the cell viability and the expression levels of MDR1 mRNA and protein in a CAV1-siRNA-mediated gene knockdown hepatoma cell line (SK-Hep1). Cell viability was significantly decreased in CAV1-siRNA-transfected cells compared with that of control-siRNA-transfected cells. Furthermore, the viability of cells pretreated with CAV1 siRNA was markedly decreased by treatment with indomethacin (400${\mu}$M for 24 h). However, the protein and mRNA levels of MDR1 were unchanged in CAV1-siRNA-transfected cells. These results suggest that CAV1 plays an important role as a major survival enzyme in cancer cells, and indomethacin can sensitively induce cell death under conditions of reduced CAV1 expression, independent of MDR1 expression.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.4
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• pp.670-677
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• 2020

Objective: Interleukin-6 (IL-6) is a T cell-derived B cell stimulating factor which plays an important role in inflammatory diseases. In this study, the pharmacokinetic properties of LMT-28 including physicochemical property, in vitro liver microsomal stability and an in vivo pharmacokinetic study using BALB/c mice were characterized. Methods: LMT-28 has been synthesized and is being developed as a novel therapeutic IL-6 inhibitor. The physicochemical properties and in vitro pharmacokinetic profiles such as liver microsomal stability and Madin-Darby canine kidney (MDCK) cell permeability assay were examined. For in vivo pharmacokinetic studies, pharmacokinetic parameters using BALB/c mice were calculated. Results: The logarithm of the partition coefficient value (LogP; 3.65) and the apparent permeability coefficient values (P_app; 9.7×10^-6 cm/s) showed that LMT-28 possesses a moderate-high cell permeability property across MDCK cell monolayers. The plasma protein binding rate of LMT-28 was 92.4% and mostly bound to serum albumin. The metabolic half-life (t_1/2) values of LMT-28 were 15.3 min for rat and 21.9 min for human at the concentration 1 μM. The area under the plasma drug concentration-time curve and C_max after oral administration (5 mg/kg) of LMT-28 were 302±209 h·ng/mL and 137±100 ng/mL, respectively. Conclusion: These data suggest that LMT-28 may have good physicochemical and pharmacokinetic properties and may be a novel oral drug candidate as the first synthetic IL-6 inhibitor to ameliorate mammalian inflammation.

• Restorative Dentistry and Endodontics
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• v.26 no.4
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• pp.316-325
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• 2001

The purpose of this study was to evaluate the effect of adhesive curing timing on the direction of polymerization shrinkage of light-curing composite resin. In this study, the curing times of adhesive and composite resin were measured by differential scanning calorimeter(DSC). 28 extracted human molars were embedded in clear resin and box-type cavities were prepared. Based on DSC data, the experimental teeth were divided into 4 groups. Group 1: no bond; Group 2: late curing; Group 3: Intermediate curing; Group 4: Early curing. After treating with adhesive, the buccal cavities were filled with Z-100 hybrid composite resin and the lingual ones were filled with AEliteflo flowable composite resin. The depressions at the surface were measured by surface profilometer, then the specimens were embedded in clear resin and sectioned. Impressions were obtained and used to get epoxy resin replicas. The epoxy replicas were gold-coated and observed under SEM. Average Maximum Gap(AMG), Gap Proportion(GP), Average Marginal Index(AMI) were used to compare the shrinkage gap of each group. The results were statistically analyzed using the Kruskal-Wallis One Way ANOVA, Student-Newman-Keuls method. The results of this study were as follows. 1. Average Maximum Gap, Gap Proportion, Average Marginal Index and depression at the surface or Z-100 hybride composite resin were smaller than those of AEliteflo flowable composite resin(P<0.05). 2. When the bonding between composite resin and tooth structure was strong, the shrinkage gap was small, and depression at the surface was deep(P<0.05). 3. In the well-bonded group, light-curing composite resin shrank toward bonded cavity wall, not toward light source. The result suggested that the direction of polymerization shrinkage was affected by the quality of bonding in the dentin-resin interface. The strong was the bonding between composite resin and tooth structure, the smaller was the gap and the deeper was the depression at the surface. Then the flow to compensate the polymerization shrinkage proceeded from surface to bonded cavity wall.

• Journal of the Korean Association of Geographic Information Studies
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• v.2 no.3
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• pp.91-100
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• 1999

To extract value-added products from satellite images for the benefit of science and human life, the Satellite Technology Research Center at Korea Advanced Institute of Science and Technology has developed an integrated software 'Valadd-Pro'. In this paper, the 'Valadd-Pro' software is briefly introduced and its main components such as geometric correction, ortho correction and digital elevation model extraction are described. The performances of the 'Valadd-Pro' was assessed on $60km{\times}60km$ SPOT panchromatic images using ground control points from GPS measurements. Also, the height accuracy was measured by comparing our results with the $DTEDs^3$ produced by USGS and the DEM generated from the digitized countours of maps produced by the National Geographic Institute. In geometric correction, the 'Valadd-Pro' software needed fewer ground control points than a commercial software 'P' for the satisfactory results. In ortho correction, the 'Valadd-Pro' software show the similar performance to a commercial software 'P'. In digital elevation model extraction, the 'Valadd-Pro' software is two times more accurate and four times faster than a commercial software 'P'.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3773-3778
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• 2014

Background: The study was aimed to evaluate the prevalence and genotype distribution of HPV infection in vulvar squamous cell carcinoma (SCC) in northern Thailand and the clinicopathological difference with regard to HPV infection status. Materials and Methods: Formalin-fixed paraffin-embedded tissue samples of vulvar SCC diagnosed between January 2006 and December 2012 were collected. HPV infection was detected by nested polymerase chain reaction (PCR) with primers MY09/11 and GP5+/6+. HPV genotyping was performed using the Linear Array Genotyping Test, followed by type-specific PCR targeting the E6/E7 region of HPV16/18/52 if the Linear Array test was negative. The histologic slides of vulvar lesions and the medical records were reviewed. Results: There were 47 cases of vulvar SCC included in the study (mean patient age $57.9{\pm}13.2$ years). HPV infection was detected in 29 cases (62%), all of which had single HPV infections. HPV16 accounted for 23 (49%). The patients with HPV-positive SCC had a significantly younger mean age than those with HPV-negative tumors (52.7 years vs 66.2 years, p<0.001). There was no significant difference in tumor stage distribution with regard to the status of HPV infection. The presence of vulvar intraepithelial neoplasia (VIN) of usual type (basaloid or warty) was significantly more frequent in HPV-positive cases compared with HPV-negative cases (62% vs 6%, p<0.001), whereas differentiated-type VIN was more common in HPV-negative cases (24% vs 0%, p=0.019). Conclusions: HPV infection was detected in 62% of vulvar SCC in northern Thailand. HPV16 was the predominant genotype similar to the data reported from other regions. HPV-positive SCC occurred in younger patients compared with HPV-negative SCC, and was associated with usual-type VIN. Vaccination against HPV16/18 may potentially prevent almost one half of vulvar SCC in northern Thailand.

• Restorative Dentistry and Endodontics
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• v.26 no.4
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• pp.263-272
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• 2001

The aim of this study was to investigate the influence of four different light curing modes on the marginal leakage of Class V composite resin restoration. Eighty extracted human premolars were used. Wedge-shaped class Y cavities were prepared on the buccal surface of the tooth with high-speed diamond bur without bevel. The cavities were positioned half of the cavity above and half beyond the cemento-enamel junction. The depth, height, and width of the cavity were 2 mm, 3 mm and 2 mm respectively. The specimens were divided into 4 groups of 20 teeth each. All the specimen cavities were treated with Prime & Bond$^{R}$ NT dental adhesive system (Dentsply DeTrey GmbH, Germany) according to the manufacturer's instructions and cured for 10 seconds except group VI which were cured for 3 seconds. All the cavities were restored with resin composite Spectrum$^{TM}$ TPH A2 (Dentsply DeTrey GmbH, Germany) in a bulk. Resin composites were light-cured under 4 different modes. A regular intensity group (600 mW/${cm}^2$, group I) was irradiated for 30 s, a low intensity group (300 mW/${cm}^2$, group II) for 60 s and a ultra-high intensity group (1930 mW/${cm}^2$, group IV) for 3 s. A pulse-delay group (group III) was irradiated with 400 mW/${cm}^2$ for 2 s followed by 800 mW/${cm}^2$ for 10 s after 5 minutes delay. The Spectrum$^{TM}$ 800 (Dentsply DeTrey GmbH, Germany) light-curing units were used for groups I, II and III and Apollo 95E (DMD, U.S.A.) was used for group IV. The composite resin specimens were finished and polished immediately after light curing except group III which were finished and polished during delaying time. Specimens were stored in a physiologic saline solution at 37$^{\circ}C$ for 24 hours. After thermocycling (500$\times$, 5-55$^{\circ}C$), all teeth were covered with nail varnish up to 0.5 mm from the margins of the restorations, immersed in 37$^{\circ}C$, 2% methylene blue solution for 24 hours, and rinsed with tap water for 24 hours. After embedding in clear resin, the specimens were sectioned with a water-cooled diamond saw (Isomet$^{TM}$, Buehler Co., Lake Bluff, IL, U.S.A.) along the longitudinal axis of the tooth so as to pass the center of the restorations. The cut surfaces were examined under a stereomicroscope (SZ-PT Olympus, Japan) at ${\times}$25 magnification, and the images were captured with a CCD camera (GP-KR222, Panasonic, Japan) and stored in a computer with Studio Grabber program. Dye penetration depth at the restoration/dentin and the restoration/enamel interfaces was measured as a rate of the entire depth of the restoration using a software (Scion image, Scion Corp., U.S.A.) The data were analysed statistically using One-way ANOVA and Tukey's method. The results were as follows : 1. Pulse-Delay group did not show any significant difference in dye penetration rate from other groups at enamel and dentin margins (p>0.05) 2. At dentin margin, ultra-high intensity group showed significantly higher dye penetration rate than both regular intensity group and low intensity group (p<0.05). 3. At enamel margin, there were no statistically significant difference among four groups (p>0.05). 4. Dentin margin showed significantly higher dye penetration rate than enamel margin in all groups (p<0.05).

• Archives of Pharmacal Research
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• v.28 no.3
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• pp.249-268
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• 2005

Drug metabolizing enzymes (DMEs) play central roles in the metabolism, elimination and detoxification of xenobiotics and drugs introduced into the human body. Most of the tissues and organs in our body are well equipped with diverse and various DMEs including phase I, phase II metabolizing enzymes and phase III transporters, which are present in abundance either at the basal unstimulated level, and/or are inducible at elevated level after exposure to xenobiotics. Recently, many important advances have been made in the mechanisms that regulate the expression of these drug metabolism genes. Various nuclear receptors including the aryl hydrocarbon receptor (AhR), orphan nuclear receptors, and nuclear factor-erythoroid 2 p45-related factor 2 (Nrf2) have been shown to be the key mediators of drug-induced changes in phase I, phase II metabolizing enzymes as well as phase III transporters involved in efflux mechanisms. For instance, the expression of CYP1 genes can be induced by AhR, which dimerizes with the AhR nuclear translocator (Arnt) , in response to many polycyclic aromatic hydrocarbon (PAHs). Similarly, the steroid family of orphan nuclear receptors, the constitutive androstane receptor (CAR) and pregnane X receptor (PXR), both heterodimerize with the ret-inoid X receptor (RXR), are shown to transcriptionally activate the promoters of CYP2B and CYP3A gene expression by xenobiotics such as phenobarbital-like compounds (CAR) and dexamethasone and rifampin-type of agents (PXR). The peroxisome proliferator activated receptor (PPAR), which is one of the first characterized members of the nuclear hormone receptor, also dimerizes with RXR and has been shown to be activated by lipid lowering agent fib rate-type of compounds leading to transcriptional activation of the promoters on CYP4A gene. CYP7A was recognized as the first target gene of the liver X receptor (LXR), in which the elimination of cholesterol depends on CYP7A. Farnesoid X receptor (FXR) was identified as a bile acid receptor, and its activation results in the inhibition of hepatic acid biosynthesis and increased transport of bile acids from intestinal lumen to the liver, and CYP7A is one of its target genes. The transcriptional activation by these receptors upon binding to the promoters located at the 5-flanking region of these GYP genes generally leads to the induction of their mRNA gene expression. The physiological and the pharmacological implications of common partner of RXR for CAR, PXR, PPAR, LXR and FXR receptors largely remain unknown and are under intense investigations. For the phase II DMEs, phase II gene inducers such as the phenolic compounds butylated hydroxyanisol (BHA), tert-butylhydroquinone (tBHQ), green tea polyphenol (GTP), (-)-epigallocatechin-3-gallate (EGCG) and the isothiocyanates (PEITC, sul­foraphane) generally appear to be electrophiles. They generally possess electrophilic-medi­ated stress response, resulting in the activation of bZIP transcription factors Nrf2 which dimerizes with Mafs and binds to the antioxidant/electrophile response element (ARE/EpRE) promoter, which is located in many phase II DMEs as well as many cellular defensive enzymes such as heme oxygenase-1 (HO-1), with the subsequent induction of the expression of these genes. Phase III transporters, for example, P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs), and organic anion transporting polypeptide 2 (OATP2) are expressed in many tissues such as the liver, intestine, kidney, and brain, and play crucial roles in drug absorption, distribution, and excretion. The orphan nuclear receptors PXR and GAR have been shown to be involved in the regulation of these transporters. Along with phase I and phase II enzyme induction, pretreatment with several kinds of inducers has been shown to alter the expression of phase III transporters, and alter the excretion of xenobiotics, which implies that phase III transporters may also be similarly regulated in a coordinated fashion, and provides an important mean to protect the body from xenobiotics insults. It appears that in general, exposure to phase I, phase II and phase III gene inducers may trigger cellular 'stress' response leading to the increase in their gene expression, which ultimately enhance the elimination and clearance of these xenobiotics and/or other 'cellular stresses' including harmful reactive intermediates such as reactive oxygen species (ROS), so that the body will remove the 'stress' expeditiously. Consequently, this homeostatic response of the body plays a central role in the protection of the body against 'environmental' insults such as those elicited by exposure to xenobiotics.

• Reproductive and Developmental Biology
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• v.31 no.3
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• pp.161-167
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• 2007

In this study, we constructed and tested retrovirus vectors designed to express the human thrombopoietin gene under the control of the tetracycline-inducible promoters. To increase the hTPO gene expression at him-on state, WPRE sequence was also introduced into retrovirus vector at downstream region of either the hTPO gene or the sequence encoding reverse tetracycline-controlled transactivator (rtTA). Primary culture cells (PFF, porcine fetal fibroblast; CEF, chicken embryonic fibroblast) infected with the recombinant retrovirus were cultured in the medium supplemented with or without doxycycline for 48hr, and induction efficiency was measured by comparing the hTPO gene expression level using RT-PCR, western blot and ELISA. Higher hPTO expression and tighter expression control were observed from the vector in which the WPRE sequence was placed at downstream of the hTPO (in CEF) or rtTA(in PFF) gene. This resulting tetracycline inducible vector system may be helpful in solving serious physiological disturbance problems which have been a major obstacle in successful production of transgenic animals.

• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.382-392
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• 2003

Purpose: Uptakes of Tc-99m MIBI (MIBI) and Tc-99m tetrofosmin (tetrofosmin) in human non-small cell lung cancer A549, multidrug-resistance associated protein (MRP) expressing cell, were investigated in vitro and in vivo. Materials and Methods: Western blot analysis and immunohistochemistry were used for detection of MRP in A549 cells with anti-MRPr1 antibody. Cellular uptakes of two tracers were evaluated at $100{\mu}M$ of verapamil (Vrp), $50{\mu}M$ of cyclosporin A (CsA) and $25{\mu}M$ of butoxysulfoximide (BSO) after incubation with MIBI and tetrofosmin for 30 and 50 min at $37^{\circ}C$, using single cell suspensions at $1{\times}10^6cells/ml$. Radioactivities in supernatants and pellets were measured with gamma well counter. A549 cells were inoculated in each flanks of 24 nude mice. Group 1 (Gr1) and Gr3 mice were treated with only MIBI or tetrofosmin, and Gr2 and Gr4 mice were treated with 70mg/kg of CsA i.p. for 1 hour before injection of 370KBq of MIBI or tetrofosmin. Mice were sacrificed at 10, 60 and 240 min. Radioactivities of organs and tumors were expressed as percentage injected dose per gram of tissue (%ID/gm). Results: Western blot analysis of the A549 cells detected expression of MRPr1 (190 kDa) and immunohistochemical staining of tumor tissue for MRPr1 revealed brownish staining in cell membrane but not P-gp. Upon incubating A549 cells for 60 min with MIBI and tetrofosmin, cellular uptake of MIBI was higher than that of tetrofosmin. Coincubation with modulators resulted in an increase in cellular uptakes of MIBI and tetrofosmin. Percentage increase of MIBI was higher than that of tetrofosmin with Vrp by 623% and 427%, CsA by 753% and 629% and BSO by 219% and 140%, respectively. There was no significant difference in tumoral uptakes of MIBI and tetrofosmin between Gr1 and Gr3. Percentage increases in MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively higher by the time up to 240 min with CsA. Conclusion: These results indicate that MIBI and tetrofosmin are suitable tracers for imaging MRP-mediated drug resistance in A549 tumors. MIBI may be a better tracer than tetrofosmin for evaluating MRP reversal effect of modulators.