• Journal of Life Science
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• v.28 no.4
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• pp.488-495
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• 2018

The p53 gene plays a critical role in the transcriptional regulation of cellular response to stress, DNA damage, hypoxia, and tumor development. Keeping in mind the recently discovered manifold physiological functions of p53, its involvement in the regulation of cancer is not surprising. In about 50% of all human cancers, inactivation of p53's protein function occurs either through mutations in the gene itself or defects in the mechanisms that activate it. This disorder plays a crucial role in tumor evolution by allowing the evasion of a p53-dependent response. Many recent studies have focused on directly targeting p53 mutants by identifying selective, small molecular compounds to deplete them or to restore their tumor-suppressive function. These small molecules should effectively regulate various interactions while maintaining good drug-like properties. Among them, the discovery of the key p53-negative regulator, MDM2, has led to the design of new small molecule inhibitors that block the interaction between p53 and MDM2. Some of these small molecule compounds have now moved from proof-of-concept studies into clinical trials, with prospects for further, more personalized anti-carcinogenic medicines. Here, we review the structural and functional consequences of wild type and mutant p53 as well as the development of therapeutic agents that directly target this gene, and compounds that inhibit the interaction between it and MDM2.

• Tuberculosis and Respiratory Diseases
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• v.61 no.2
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• pp.143-149
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• 2006

Background: Irinotecan (topoisomerase I inhibitor) is effective as a monotherapy against small-cell lung cancer(SCLC). Cisplatin is also an important drug against SCLC. A phase II study of irinotecan combined with cisplatin was carried out to evaluate the efficacy and toxicity of this combined regimen as a first line treatment in patients with extensive SCLC. Methods: Thirty-nine patients with previously untreated extensive SCLC were enrolled in this study. Irinotecan $60mg/m^2$ was administered intravenously on days 1, 8 and 15, and in combination with cisplatin $60mg/m^2$ on day 1 and every 28 days thereafter. Four cycles of chemotherapy were given to the patients. Results: The overall response rate was 77% with a complete response (CR) rate of 8%. The median survival time, 1- and 2-year survival rate were 14.8 months, 60.9% and 27.6%, respectively. The median progression free survival time, 6-and 12-month progression free survival rate were 8.4 months, 75% and 18.8%, respectively. The WHO grade 3 or more toxicity encountered were leukopenia (23%), diarrhea (26%). Two patients changed their chemotherapeutic regimen and one patient died from severe diarrhea. Conclusion: The combination of irinotecan and cisplatin is effective as a first line therapy in extensive SCLC is effective, but has severe or fatal diarrhea as toxicity.

• Progress in Medical Physics
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• v.16 no.2
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• pp.53-61
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• 2005

The quality factors for cylindrical ionization chambers for kV X-rays were determined by Monte Carlo calculation and measurement. In this study, the X-rays of 60-300 kV beam (lSO-4037) installed in KFDA and specified in energy spectra and beam qualities, and the chambers of PTW N23333 and N30001 were investigated. In calculations, the $R_{\mu}\;and\;R_{Q,Q_{0}}$ in IAEA dosimetry protocols were determined from the air kerma and the cavity dose obtained by theoretical and Monte Carlo calculations. It is shown that the N30001 chamber has a flat response of $\pm1.7\%$ in $110\~300kV$ region, while the response range of two chambers were shown to $\pm3\~4\%$ in $80\~250kV$ region. From this work we have discussed dosimetry protocol for the kV X-rays and we have found that the estimation of energy dependency is more important to apply dosimetry protocol for kV X-rays.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.909-914
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• 2012

Background: Gefitinib, a tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), is used both as a single drug and concurrently with whole brain radiotherapy (WBRT) the standard treatment for brain metastases (BM), and is reported to be effective in a few small studies of patients with BM from non-small-cell lung cancer (NSCLC). However, no study has compared the two treatment modalities. This retrospective analysis was conducted to compare the efficacy of gefitinib alone with gefitinib plus concomitant WBRT in treatment of BM from NSCLC. Methods: We retrospectively reviewed 90 patients with BM from NSCLC who received gefitinib alone (250mg/day, gefitinib group) or with concomitant WBRT (40Gy/20f/4w, gefitinib-WBRT group) between September 2005 and September 2009 at Sun Yat-Sen University Cancer Center. Forty-five patients were in each group. Results: The objective response rate of BM was significantly higher in gefitinib-WBRT group (64.4%) compared with gefitinib group (26.7%, P<0.001). The disease control rate of BM was 71.1% in gefitinib-WBRT group and 42.2% in gefitinib group (P=0.006). The median time to progression of BM was 10.6 months in gefitinib-WBRT group and 6.57 months in gefitinib group (P<0.001). The median overall survival(OS) of gefitinib-WBRT and gefitinib alone group was 23.40 months and 14.83 months, respectively (HR, 0.432, P=0.002). Conclusion: Gefitinib plus concomitant WBRT had higher response rate of BM and significant improvement in OS compared with gefitinib alone in treatment of BM from NSCLC.

• Journal of Korean Academy of Nursing
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• v.30 no.3
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• pp.549-559
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• 2000

The purpose of this study was to investigate the correlation between the knowledge and educational needs related to recurrent in coronary artery bypass graft patients as a basis to provide an individual nursing education for the population. The subjects consisted of 110 patients who had coronary artery bypass graft(CABG) at Asan Medical Center in Seoul and Sechong hospital in Buchon. Data was obtained from a knowledge questionnaire and a learning needs questionnaire between November 1998 and February 1999. Data were analyzed using SAS program for Wilcoxon rank sum test and Spearman correlation coefficient. The results were as follows : 1. With regard to the 18 items to measure knowledge, the mean (median) of items 'don't know' was 4.9(4) items. The mean (median) of items answered wrong was 3.2(3) items. The number of items answered 'don't know' tend to show higher in those who had less education, blue color jobs and myocardiac infarction history than in their counter parts. There were higher frequency of items answered 'don't know' in those who had no hypertension 2. With regard to the level of knowledge by questionnaire about CABG, The most "I dont know" (59.1%) highly response was 'He has to be treated with anticoagulant drug to prevent revasculized vessel from obstructing.' The seond highest response (56.4%) was 'If you were hypotensive, the coronary attack would collapse. 'During the hospitalized day, the patient has complete bedrest.' The highest error probability was cholesterol has not to intake.', 'After surgery, the sexual life is need controlled for 1 year. 3. The mean of educational needs was 3.38. With regard to the level of learning needs by sentence about CABG, 'Food that benefit heart disease', 'Recurrence possibility of heart disease', 'Management method of operation site', 'Risk symptom that visit hospital or report immediately' were higher than other sentenses. With regard to the level of learning needs by factor 'food(5 items)', 'disease(9 items)' and 'exercise(3 items)' showed the highest than other factors. The educational needs by patients characteristics tend to show higher in males, under the age of 49, middle or high school degree, previous experience of admission with coronary artery disease, history of myocardial infarction, expierience of PTCA, history of cerebro-vascular accident, previous expierience of smoking than in their counter parts. 4. The number of items answered 'don't know', wrong and correct weren't correlated with the level educational needs. As the results, the number of items answered 'don't know' tend to show higher in those who had less educated, blue color jobs and myocardiac infarction history than in their counter parts. There were higher frequency of items answered 'don't know' in those who had no hypertension .There were higher frequency of items answered 'don't know' on anti-thrombolitic theraphy, hypotension and pain relief. Also there were higher frequency of items answered wrong on bed rest period, cholesterol intake, and sexual life. Educational needs were higher in young age group, had previous experience of procesure and history of other disease. And when we educate CABG patients, education for diet, recurrence possibility of disease, management methods of operation site and risk symptom should be emphasized.

• The Korea Journal of Herbology
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• v.35 no.6
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• pp.11-19
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• 2020

Objective : The genus Glycyrrhiza has been used in food and traditional herbal medicine. Glycyrrhiza new varieties Wongam and Sinwongam have been developed by Korea Rural Development Administration and investigated to register on Korean Pharmacopoeia of the Ministry of Food and Drug Safety. The aim of this study is to investigate the immunomodulatory effect of Wongam and Sinwongam comparing with listed Glycyrrhiza species (Glycyrrhiza uralensis Fischer and G. glabra Linne) for evaluations about pharmacological effect of Glycyrrhiza new varieties. Methods : We studied the immunomodulatory effect of Wongam and Sinwongam compared with G. uralensis and G. glabra using THP-1 cell in vitro model. The cells were treated with phorbol 12-myristate 13-acetate (PMA) for differentiation and stimulated with lipopolysaccharides (LPS) to induce immune activation. We analyzed and compared the effects Glycyrrhiza new varieties and listed Glycyrrhiza species using nitric oxide (NO) assay, western blot, and reverse transcription-quantitative polymerase chain reaction analysis. 1) Results : Wongam and Sinwongam showed no cytotoxicity in THP-1 cells. Wongam and Sinwongam, and listed Glycyrrhiza species increased NO production, and cyclooxygenase (COX)-2 expression with or without LPS in differentiated THP-1 macrophages. Furthermore, Wongam and Sinwongam and listed Glycyrrhiza species upregulated the mRNA expressions of T helper type 1 (Th 1)-associated cytokines in LPS-stimulated THP-1 macrophages. Conclusion : These results indicated that Wongam and Sinwongam would have effect of enhancing immune response through the increase of NO and COX-2 expression, and activate Th1-associated cytokines. The findings of this study suggest the wide applicability of Glycyrrhiza new varieties.

• KSBB Journal
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• v.27 no.5
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• pp.308-312
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• 2012

Argon-plasma jet (Ar-PJ) is generated by ionizing Ar gas, and the resulting Ar-PJ consists of a mixture of neutral particles, positive ions, negative electrons, and various reactive species. Although Ar-PJ has been used in various biomedical applications, little is known about the biological effects on cells located near the plasma-exposed region. Here, we investigated the effects of the Ar-PJ on actin cytoskeleton of mouse embryonic fibroblasts (MEFs) in response to indirect as well as direct exposure to Ar-PJ. This Ar-PJ was generated at 500 mL/min of flow rate and 100 V electric power by our device mainly consisting of electrodes, dielectrics, and a high-voltage power supply. Because actin cytoskeleton is the key cellular machinery involved in cellular movement and is implicated in regulation of cancer metastasis and thus resulting in a highly desirable cancer therapeutic target, we examined the actin filament architectures in Ar-PJ-treated MEFs by staining with an actin-specific phalloidin labeled with fluorescent dye. Interestingly, the Ar-PJ treatment causes destabilization of actin filament architectures in the regions indirectly exposed to Ar-PJ, but no differences in MEFs treated with Ar gas alone and in untreated cell control, indicating that this phenomenon is a specific cellular response against Ar-PJ in the live cells, which are indirectly exposed to Ar-PJ. Collectively, our study raises the possibility that Ar-PJ may have potential as anti-cancer drug effect through direct destabilization of the actin cytoskeleton.

• Journal of Periodontal and Implant Science
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• v.35 no.1
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• pp.99-109
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• 2005

It has been focused on the importance of the host inflammatory response in periodontal pathogenesis and progression, treatment has been introduced to control the host response and the method, which diminishes production and activity of MMP by doxycycline, has been used in periodontal field. MMP is a proteolytic enzyme which plays a major role in tissue destruction and MMP-1 is secreted in the periodontally healthy tissue, while MMP-8, 9, 13, etc in the inflammatory state. Among these, MMP-13 has been discovered lately and reported to degrade primarily type II collagen. Periodontal ligament (PDL) cell plays a role in destruction of periodontal tissue. This study was to evaluate the effect of doxycycline and mefenamic acid, non-steroidal antiinflammatory drug on MMP-13 mRNA expression in the rat PDL cell. Doxycycline concentration of $1{\sim}100\;{\mu}g/ml$ was added rat PDL cell and cell activity was measured by MIT assay at day 1 and 3. MMP-13 gene expression was evaluated by RT-PCR after PDL cells were pre-treated for 1hour with doxycycline (50 ${\mu}g/ml$) alone or with mefenamic acid ($10^{-6}M$), then added $IL-1{\beta}$(1.0 ng/ml) and incubated for 16-18 hours. The results are as follows: 1. Cell activity decreased Significantly at 24 and 72 hours in 100 ${\mu}g/ml$ (p<0.05). 2. Level of MMP-13 mRNA was in 20.2% increase by $IL-1{\beta}$ and in pre-treating doxycycline group, expression of $IL-1{\beta}$ induced MMP-13 mRNA was inhibited by 31% than $IL-1{\beta}$ treated only. 3. Mefenamic acid did not inhibit on the expression of $IL-1{\beta}$ induced MMP-13 mRNA, while mefenamic acid in combination with doxycycline inhibited the expression by 41% compared to only $IL-1{\beta}$ stimulation. These results suggest that doxycycline synergistically inhibit the expression of $IL-1{\beta}$ induced MMP-13 mRNA in combination with mefenamic acid.

• Journal of Veterinary Clinics
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• v.21 no.4
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• pp.402-405
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• 2004

A 5-year-old Rottweiler neutered female dog was presented with signs of mandibular and popliteal lymphadenopathy, erosion in mucocutaneous junction of muzzle and lips, multiple papules and nodules in right rear limb and neck, and alopecia in right thorax. There was no further clinical sign except anorexia, sporadic fever and ocular hyperemia. She hadn't shown any response to carprofen prescribed by local veterinarian. Hematological abnormalities included mild anemia and severe lymphocytosis. On serum biochemical profile, only elevated AST level was noticed. On cytological examination, there was an evidence of mild bacterial infection which seemed to occur secondarily. Three sites were biopsied that included muzzle, upper lip and right thoracic region. Histopathologically, multifocal confluent pyogranulomatous dermatitis, scattered granulomatous inflammation in subcutis and severe septal panniculitis were observed. Special stainings(Gram, Acid-fast, PAS, Giemsa) were performed to reveal that a dog was negative for any organism. Finally, sterile pyogranuloma/granuloma syndrome (SPGS) was diagnosed. The treatment was initiated with predinsolone and enrofloxacin. The condition was successfully resolved after 4 weeks of treatment. This good response suggests that SPGS may be immune-mediated disease of its pathogenesis and this drug combination may be a viable therapeutic option for dogs suffering from SPGS. Also, this article reports a case of SPGS in Rottweiller for the first time.

• The Korean Journal of Pharmacology
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• v.16 no.1 s.26
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• pp.41-50
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• 1980

Chenodeoxycholic acid(CDCA) has been used as a gallstone dissolving agent since 1972. Recently, ursodeoxycholic acid(UDCA) has been reported to be effective in dissolving gallstones. Both bile acids increased bile flow. The increase in bile flow associated with an increase in cholesterol level in bile after CDCA or UDCA infusion was reported. In this study, using the smooth muscle strips of guinea pig and fowl, responses of the cholates were observed. In addition, the influence of adrenergic blocking agents on the response of the strips to cholates was investigated. Also the effects of cholates on cardiac function were examined by using isolated atria of rabbit and heart of anesthetized frog. The results are as follows: 1) All cholates, such as UDCA, CDCA, and CA produced a marked inhibitory effect on the motility in isolated duodenal strip of guinea pig and fowl, however, only UDCA showed the contraction in the isolated esophagus of fowl. These effects of cholates were blocked by propranolol. 2) In isolated guinea pig stomach strip and gall bladder, cholates exhibited a marked inhibitory effect on the motility and the effects due to UDCA and CA were blocked by phenoxybenzamine while CDCA was not affected. 3) The spontaneous and ouabain induced arrhythmia was partially abolished by cholates. However, concomitant administration of cholates with ouabain or epinephrine caused a marked prolongation in occurrence of atrial arrhythmia in comparison with ouabain or epinephrine alone in isolated rabbit atria. 4) In the heart of anesthetized frog, the epinephrine-induced arrhythmia was partially abolished by cholates. The combined treatment with cholates and ouabain or epinephrine produced a marked prolongation in occurrence of the arrhythmia in comparison with, ouabain or epinephrine alone. From the above results, it can be suggested that the effects of cholates on the smooth muscle of duodenum and esophagus are produced in response to adrenergic ${\beta}$-receptor and the effect or gall bladder and stomach is more likely due to the direct effect on the muscle. In addition, cholates exhibit a slight antiarrhythmic effect on heart, therefore, cholates can be classified as a nonselective antiarrhythmic drug, such as propranolol.