• Molecules and Cells
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• v.37 no.8
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• pp.605-612
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• 2014

The p73 gene contains an extrinsic P1 promoter and an intrinsic P2 promoter, controlling the transcription of the pro-apoptotic TAp73 isoform and the anti-apoptotic ${\Delta}Np73$ isoform, respectively. The DNA methylation status of both promoters act equally in the epigenetic transcriptional regulation of their relevant isoforms. The aim of this study was to analyze the different effects of these p73 isoforms in 5-aza-2'-deoxycytidine (5-aza-dC)-induced apoptosis in breast cancer cells. We investigated the effects of the DNA demethylation agent, 5-aza-dC, on the T-47D breast cancer cell line, and evaluated the methylation status of the p73 promoters and expression of TAp73 and ${\Delta}Np73$. Furthermore, we assessed the expression of p53 and p73 isoforms in 5-aza-dC-treated T-47D cells and p53 knockout cells. 5-aza-dC induced significant anti-tumor effects in T-47D cells, including inhibition of cell viability, G1 phase arrest and apoptosis. This was associated with p73 promoter demethylation and a concomitant increase in TAp73 mRNA and protein expression. In contrast, the methylation status of promoter P2 was not associated with ${\Delta}Np73$ mRNA or protein levels. Furthermore, demethylation of P2 failed to inhibit the expression of ${\Delta}Np73$ with 5-aza-dC in the p53 knockdown cell model. Our study suggests that demethylation of the P1 and P2 promoters has opposite effects on the expression of p73 isoforms, namely up-regulation of TAp73 and down-regulation of ${\Delta}Np73$. We also demonstrate that p53 likely contributes to 5-aza-dC-induced ${\Delta}Np73$ transcriptional inactivation in breast cancer cells.

• Radiation Oncology Journal
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• v.22 no.3
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• pp.217-224
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• 2004

Purpose: It is well known that the radiosensitivity of tumor cells can be significantly reduced under hypoxic conditions. Hypoxia-inducible factor-1 $\alpha$ (HIF-1 $\alpha$) plays a pivotal role in the essential adaptive responses to hypoxia. Therefore this study investigated the relationship between HIF-1 $\alpha$ expression and radiosensitivity. M Mouse hepatoma cell line hepafcic7 and HIF-1 $\beta$-deficient mutant cell line hepa1C4 were used to analyze the role of HIF-1 a. on radiosensitivity. These cells were exposed for 6 h to desferrioxamine (DFX) before radiation. HIF-1$\alpha$. expression was examined by Western blot. Apoptosis was assessed by DNA fragmentation, propidium iodide staining, and apoptotic cell death detection ELISA kit. Radiation sensitivity was determined using MTT assay. The radiobioiogical parameters, surviving fractions at 2 Gy and 8 Gy, and mean inactivation dose (MID) from the linear-quadratic model were used to assess radiation sensitivity in the statistical analyses. Results: The expression of HIF-1 $\alpha$. was Increased, whereas apoptosis was decreased, by radiation In the presence of DFX In hepal cl c7, but not In hepal C4. The radlosensitivity of hepal C4 cells was not significantly affected by DFX treatment. The radiosensitivlty of hepal cl c7 cells was significantly decreased in the presence of DFX Conclusion: The expression of HIF-1 w by hypoxia-mimic agent DFX reduced apoptosls and radiosensitlvity in mouse hepatoma cell line hepafclc7. These results suggested that HIF-1 u could be Induced by irradiation in hypoxic ceils of tumor masses, and that this mlght Increase radioresistance in hypoxic cells.

• Korean Journal of Head & Neck Oncology
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• v.25 no.1
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• pp.3-7
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• 2009

Background and Objectives : Panax ginseng C.A. Meyer is a medical plant that has been widely utilized as a tonic and nutritional agent since ancient times in Korea. Ginseng has anti-metastatic property of cancer and immunomodulating activity. The novel acidic polysaccharide compound(MB40) was isolated from the leaves of Panax ginseng C.A. Meyer. To determine immunomodulating activities of MB40, we evaluate anti-cancer and anti-metastatic effects of MB40 in tumor bearing immune competent mice. Material and Methods : C3H mice were divided into three equal groups(Cisplatin treatment group, MB40 treat-ment group, Cisplatin and MB40 treatment group) and were transplanted SCC(Squamous Cell Carcinoma) cells(2${\times}$106) to the lateral side of abdomen. From day 4 after transplantation, MB40 was administrated at dose of 10mg/kg, respectively, every other day by intratumoral injection. Cisplatin was systemically administrated at doses of 1mg/kg, respectively, every week by intraperitoneal injection. Results : 5 days after administration, tumors can be palpated in every mice group. After 13 days of administration, the mice group to which MB40 were administrated exhibited reduction in tumor size respectively, compared to cisplatin group. Overall status of mice such as body weight and activity were superior in MB40 group than cisplatin group. Conclusion : The result of this study indicates MB40 may have significant therapeutic effect and decreases complications induced by systemic chemotheraphy. MB40 may be developed as a novel and potent immunotropics to improve the cell immune system and anti-cancer drug for the treatment of cancer patients in head and neck squamous cell carcinoma.

• Journal of KIISE:Information Networking
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• v.32 no.3
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• pp.370-381
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• 2005

Mobile IP provides an efficient and scalable mechanism for host mobility within the Internet. Using Mobile If, mobile nodes may change their point of attachment to the Internet without changing their If address. However, it would result in a high signaling cost. To reduce the signaling cost, we factor in the fact that mobile users will not be actively communicating much of the time. In fact, there Is no necessity to send a binding update message to the home agent when an mobile node does not communicates with others while moving. From this point of view, we propose a lazy update strategy for minimizing signaling cost using the forwarding pointer in hierarchical Mobile IPv6. In our proposal, binding updates are sent only when a mobile node is in a busy mode. If an mobile node is in a dormant mode, binding update messages are delayed until busy mode using the forwarding pointer. As a result, our proposal can reduce the total signaling cost by eliminating unnecessary binding update messages when a mobile node Is in a dormant mode. In addition to, our proposal reduces unnecessary location update cost resulting from ping-pong effect under mobile node's dormant mode. Analysis results using the discrete analytic model presented in this paper shows that our proposal can has superior performance than hierarchical Mobile nv6 when the call-to-mobility ratio is low and the length of the forwarding pointer chain K is low.

• Korean Journal of Environmental Agriculture
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• v.18 no.3
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• pp.292-297
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• 1999

This study was performed to estimate the possibility of use of plant materials as catalytic agents fur the decontamination of waste waters contaminated with organic pollutants by using 2,4-dichlorophenol(2,4-DCP) as a model pollutant. Plant materials containing high peroxidase activity were selected as catalysts for the removal of 2,4-DCP. Peroxidase activity, which plant materials were containing, was measured, and the greatest peroxidase activity was observed in shepherd's purse, followed by turnip, sweet potato, Chinese cabbage and white radish. The peroxidase activity in shepherd's purse was four times higher than that of horseradish purchased in U.S.A. Using shepherd' s purse and turnip, it was investigated the effect of various factors on the decontamination of 2,4-DCP through oxidative coupling. The removal of 2,4-DCP was extremely fast, and a maximal removal could be achieved within 3 min for shepherd' s purse and 15min for turnip. The pH range was from 3.0 to 8.0 and the amount of $H_2O_2$ added was 9mM when maximal removal was achieved(over 90%). No increasing removal of 2,4-DCP was observed due to increasing the amount of $H_2O_2$ added (over 9mM). The initial concentration affected the transformation of 2,4-DCP incubated with plant materials. When turnip was used as catalytic agent, it was observed decreasing transformation of 2,4-DCP due to increasing initial concentration.

• Applied Chemistry for Engineering
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• v.16 no.4
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• pp.533-541
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• 2005

Non-aqueous cleaning agents were formulated with 2,2,2-trifluoroethanol (TFEA) and hydrofluoroether (HFE), and their physical properties and cleaning abilities were examined. TFEA-based aqueous cleaning agents were also formulated with nonionic surfactants, hydrotropes and builders, and their cleaning abilities were compared. Possibilities of these cleaning agents as substitutes for CFC-113 and 1,1,1-TCE were finally evaluated. In this work, fluxes, cutting oils, greases, and fluoric oils were selected as model contaminants for cleaning experiments. These contaminants have different properties of water-solubility or hydrophilicity, and fat-solubility or lypophilicity. Cleaning abilities of TFEA-based cleaning agents were analyzed and compared through the measurement of contaminant weight changes as a function of cleaning time, and their possibilities as alternative cleaning agents were evaluated. As a result, it was shown that TFEA and HFE-based non-aqueous cleaning agents have quite a good cleaning power for fluxes and fluorine soils but low one for greases. And TFEA-based agueous cleaning agents which consisted of nonionic surfactants, hydrotrope, and builders were very effective for cleaning fluxes and greases under certain formulation conditions. Thus, it was revealed that the TFEA-based cleaning agents were very effective for cleaning specific contaminants and can be used as substitutes for CFC-113 and 1,1,1-TCE in some industrial applications.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.41 no.3
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• pp.243-252
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• 2015

Melanosome, the pigment granule in melanocyte, determines the color of skin when it moves into the keratinocyte. Inhibition of melanosome transfer from melanocyte to keratinocyte results in skin depigmentation. Protease activated receptor-2 (PAR-2) is involved in signal transduction systems via cell membrane and increases the melasome transfer when it is activated by cleavage of their extracellular amino acid sequence by trypsin or by a peptide such as SLIGKV. Here, we showed that lobaric acid inhibited PAR-2 activation and affected the mobilization of $Ca2^+$. The uptake of fluorescent microspheres and isolated melanosomes from melan-a melanocytes to keratinocytes induced by SLIGKV were inhibited by lobaric acid. Also, confocal microscopy studies illustrated a decreased melanosome transfer to keratinocytes in melanocyte-keratinocyte co-culture system by lobaric acid. In addition, lobaric acid induced visible skin lightening effect in human skin tissue culture model, melanoderm$^{(R)}$. Our data suggest that lobaric acid could be an effective skin lightening agent that works via regulation of phagocytic activity of keratinocytes.

• Archives of Pharmacal Research
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• v.28 no.5
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• pp.604-611
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• 2005

Polyethylene glycol (PEG) 6000-based solid dispersions (SDs), by incorporating various pharmaceutical excipients or microemulsion systems, were prepared using a fusion method, t o compare the dissolution rates and bioavailabilities in rats. The amorphous structure of the drug in SDs was also characterized by powder X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). The ketoconazole (KT), as an antifungal agent, was selected as a model drug. The dissolution rate of KT increased when solubilizing excipients were incorporated into the PEG-based SDs. When hydrophilic and lipophilic excipients were combined and incorporated into PEG-based SDs, a remarkable enhancement of the dissolution rate was observed. The PEG-based SDs, incorporating a self microemulsifying drug delivery system (SMEDDS) or microemulsion (ME), were also useful at improving the dissolution rate by forming a microemulsion or dispersible particles within the aqueous medium. However, due to the limited solubilization capacity, these PEG-based SDs showed dissolution rates, below 50% in this study, under sink conditions. The PEG-based SD, with no pharmaceutical excipients incorporated, increased the maximum plasma concentration (C$_{max}$) and area under the plasma concentration curve (AUC$_{0-6h}$) two-fold compared to the drug only. The bioavailability was more pronounced in the cases of solubilizing and microemulsifying PEG-based SDs. The thermograms of the PEG-based SDs showed the characteristic peak of the carrier matrix around 60$^{\circ}C$, without a drug peak, indicating that the drug had changed into an amorphous structure. The diffraction pattern of the pure drug showed the drug to be highly crystalline in nature, as indicated by numerous distinctive peaks. The lack of the numerous distinctive peaks of the drug in the PEG-based SDs demonstrated that a high concentration of the drug molecules was dissolved in the solid-state carrier matrix of the amorphous structure. The utilization of oils, fatty acid and surfactant, or their mixtures, in PEG-based SD could be a useful tool to enhance the dissolution and bioavailability of poorly water-soluble drugs by forming solubilizing and microemulsifying systems when exposed to gastrointestinal fluid.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.655-663
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• 2002

Liver fibrosis is a prepathological state wherein damaged liver tissues in chronic liver diseases, such as hepatitis, are not repaired to normal tissues, but converted to fibrous tissue. 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz), a cancer chemopreventive agent, is effective against a wide variety of chemical carcinogens. Recently, we reported that oltipraz inhibits liver fibrogenesis (Kang et al., 2002). In the present study, the effects of oltipraz in combination with dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDb) on dimethylnitrosamine (DMN)-induced liver fibrogenesis were assessed in rats. Oltipraz (30 mg/kg body weight, po, 3 times per week for 4 weeks) was found to inhibit the increases in plasma ALT, AST and bilirubin by DMN, whereas DDB (30 mg/kg body weight, po, 3 times per week for 4 weeks) attenuated the increases in the plasma ALT and bilirubin. The lowered plasma protein and albumin contents in DMN-treated rats were completely restored by oltipraz, but not by DDB. DDB decreases liver cell injury and inflammation through inhibition of nuclear factor-kB. DMN increased the accumulation of liver collagen, as indicated by the increase in the 4-hydroxyproline content in liver homogenates, which was reduced by treatment with oltipraz, but not by DDB. Given the differential effect between oltipraz and DDB, the potential enhancement of antifibrotic efficacy by the drugs was assessed in the animal model. Despite the minimal effect of DDB on DMN-induced fibrogenesis, DDB (5-25 mg/kg), administered together with oltipraz (25-5 mg/kg), showed an additive protective effect against hepatotoxicity and fibrosis induced by DMN, which was shown by the blood chemistry parameters and histopathological analysis. The adequate composition ratio of oltipraz to DDB was 5:1. These results provide information on the pharmaceutical composition, comprising of oltipraz and DDB as the active components, for the treatment and/or prevention of liver fibrosis and cirrhosis.

• Journal of dental hygiene science
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• v.15 no.6
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• pp.800-806
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• 2015

The aim of this study was to investigate whether intracisternal administrations of triptolide and N-nitro-L-arginine Methyl Ester (L-NAME) are involved in the regulation of temporomandibular joint (TMJ) pain. The TMJ pain was induced by the injection of 5% formalin ($30{\mu}l$) into TMJ capsule of rats. The pain behavioral responses was recorded the number of grooming or scratching on the left TMJ area for 9 successive 5 minutes intervals. Triptolide and L-NAME were administrated intracisternally 10 minutes before formalin injection. The intra-articular injection of formalin produced a biphasic pattern of pain response (first phase: 0~10 minutes and second phase: 11~45 minutes). The intracisternal administration of triptolide ($1{\mu}g/10{\mu}l$) and L-NAME ($0.1{\mu}g/10{\mu}l$) suppressed the TMJ pain behavior in each experiment. Co-administration of two drugs was shown the enhanced effect than the analgesic effect by single-administration of triptolide ($1{\mu}g/10{\mu}l$). The triptolide could be a useful analgesic agent for the treatment of TMJ pain, and it is expected to reduce the substantial amount of it via co-administration of synthetic chemical compound and natural products.