• International Journal of Oral Biology
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• v.46 no.4
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• pp.176-183
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• 2021

Oral squamous cell carcinoma (OSCC) metastasis is characterized by distant metastasis and local recurrence. Combined chemotherapy with cisplatin and 5-fluorouracil is routinely used to treat patients with OSCC, and the combined use of gefitinib with cytotoxic drugs has been reported to enhance the sensitivity of cancer cells in vitro. However, the development of drug resistance because of prolonged chemotherapy is inevitable, leading to a poor prognosis. Therefore, understanding alterations in signaling pathways and gene expression is crucial for overcoming the development of drug resistance. However, the altered characterization of Ca²⁺ signaling in drug-resistant OSCC cells remains unclear. In this study, we investigated alterations in intracellular Ca²⁺ ([Ca²⁺]_i) mobilization upon the development of gefitinib resistance in human tongue squamous carcinoma cell line (HSC)-3 and HSC-4 using ratiometric analysis. This study demonstrated the presence of altered epidermal growth factor- and purinergic agonist-mediated [Ca²⁺]_i mobilization in gefitinib-resistant OSCC cells. Moreover, Ca²⁺ content in the endoplasmic reticulum, store-operated calcium entry, and lysosomal Ca²⁺ release through the transient receptor potential mucolipin 1, were confirmed to be significantly reduced upon the development of apoptosis resistance. Consistent with [Ca²⁺]_i mobilization, we identified modified expression levels of Ca²⁺ signaling-related genes in gefitinib-resistant cells. Taken together, we propose that the regulation of [Ca²⁺]_i mobilization and related gene expression can be a new strategy to overcome drug resistance in patients with cancer.

• Korean Journal of Health Education and Promotion
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• v.22 no.2
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• pp.125-139
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• 2005

Objectives: More than half of youth smokers start to use cigarettes in their middle-school ages. Thus, middle school students should be the primary target population for smoking prevention education although the technical smoking rate is higher in high school students than in middle school students. Based on this significance, this study examined personal and social factors reinforcing non-smoking middle school students to acquire positive attitudes on smoking cigarettes. Methods: A total of 1,081 students of the 3 middle schools in Seoul participated in the self-administered survey. The designated schools were conveniently selected and all the 2nd-grade students of the schools participated in the survey. The questionnaire asked reinforcing social factors of smoking such as, family and parental history of drug use, close-people's smoking and drug use, personal experience of drug use, perceived smoking and drug use knowledge and attitudes, perceived smoking intention in future, and other delinquent behaviors. Results: Personal experience of drug and delinquent behaviors, perceived smoking intention in future, perceived knowledge of smoking, educational experience, and close-people's smoking and drug use were significantly related to students' attitudes on smoking. The significant factors affecting the positive attitudes of smoking were living with broken family and few education experience of smoking in school as social factors and strong smoking intention in future, high score of delinquent behavior, and low score of drug use knowledge as personal factors. Conclusions: Adolescents' strong smoking intention and little smoking education experience would primary personal and social factors reinforcing positive attitudes on smoking. Thus, school-based educational programs preventing smoking intention need to be developed and to be delivered to middle school students to minimize the future smoking population in a long-term perspective.

• Biomolecules & Therapeutics
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• v.18 no.4
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• pp.448-453
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• 2010

Drug-induced long QT syndrome is known to be associated with the onset of torsades de pointes (TdP), resulting in a fatal ventricular arrhythmia. QT interval prolongation can result from blocking the human ether-a-go-go-related gene (hERG) channel, which is important for the repolarization of cardiac action potential. Nicardipine, a Ca-channel blocker and antihypertensive agent, has been reported to increase the risk of occasional serious ventricular arrhythmias. We studied the effects of nicardipine on hERG $K^+$ channels expressed in HEK293 cells and Xenopus oocytes. The cardiac electrophysiological effect of nicardipine was also investigated in this study. Our results revealed that nicardipine dose-dependently decreased the tail current of the hERG channel expressed in HEK293 cells with an $IC_{50}$ of 0.43 ${\mu}M$. On the other hand, nicardipine did not affect hERG channel trafficking. Taken together, nicardipine inhibits the hERG channel by the mechanism of short-term channel blocking. Two S6 domain mutations, Y652A and F656A, partially attenuated (Y652A) or abolished (F656A) the hERG current blockade, suggesting that nicardipine blocks the hERG channel at the pore of the channel.

• The Korean Journal of Applied Statistics
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• v.31 no.2
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• pp.303-313
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• 2018

This study considers time series models to forecast drug expenditures in national health insurance. We adopt autoregressive error model (ARE) and transfer function model (TFM) with segmented level and trends (before and after 2012) in order to reflect drug price reduction in 2012. The ARE has only a segmented deterministic term to increase the forecasting performance, while the TFM explains a causality mechanism of drug expenditure with closely related exogenous variables. The mechanism is developed by cross-correlations of drug expenditures and exogenous variables. In both models, the level change appears significant and the number of drug users and ratio of elderly patients variables are significant in the TFM. The ARE tends to produce relatively low forecasts that have been influenced by a drug price reduction; however, the TFM does relatively high forecasts that have appropriately reflected the effects of exogenous variables. The ARIMA model without the exogenous variables produce the highest forecasts.

• Biomolecules & Therapeutics
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• v.20 no.2
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• pp.234-238
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• 2012

Propofol is an anesthetic commonly used to provide sedation or to induce and maintain an anesthetic stated. However, there are reports which indicate propofol may cause psychological dependence or be abused. In the present study, we used various behavioral tests including climbing test, jumping test, conditioned place preference, and self-administration test to assess the dependence potential and abuse liability of propofol compared to a positive control (methamphetamine) or a negative control (saline or intralipid). Among the tests, the conditioned place preference test was conducted with a biased method, and the selfadministration test was performed under a fixed ratio (FR) 1 schedule, 1 h per session. No difference was found in the climbing test and jumping test, but propofol (30 mg/kg, i.p.) increased the rewarding effect in the conditioned place preference test, and it showed a positive reinforcing effect compared to the vehicle. These results indicate that propofol tends to show psychological dependence rather than physical dependence, and it seems not to be related with dopaminergic system.

• Korean Journal of Clinical Pharmacy
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• v.21 no.4
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• pp.311-318
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• 2011

Misinformation and inappropriate use of medication has become one of the most pressing concerns in drug safety. The purpose of this study was to survey public perception on drug safety as well as the channels most relied upon providing such information. The survey was performed for patients or their families visiting pharmacies in a local city in Korea. Analysis was performed from 367 respondents to the survey. The contents of this survey revealed that consumers were aware of the fact that medications should not be taken at any higher dosage or more often than directed by their prescriptions. The survey revealed a general awareness that symptoms might not be relieved immediately by their medications. However, the perception that there could be adverse drug reaction (ADR) at therapeutic dose was low except among the young or highly educated members. Respondents recognized that skin rashes were the most whereas drowsiness was the least common ADR symptom. There was a high awareness of drug-food or drug-drug interactions except in the case of certain nutraceuticals. Doctors and pharmacists were ranked as the most reliable resources to the consumer for providing drug related information. However, public relations or education programs were in need since there were still not negligible numbers of consumers depending on personal experience rather than health professionals.

• Journal of Korean Academy of Nursing
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• v.23 no.3
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• pp.487-503
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• 1993

This study was designed to investigate the situation of adolescent drug use in Seoul, and to com-pare this with the 1991 survey in order to better understand the present situation. The subject for this study were 1000 students in High School and Middle School. The data were collected during the period from september 1, 1992 to December 30, 1992. The guestionnaire developed by Kim So Ya Ja (1991) to survey adolescent drug use was used. The data was analyzed using descriptive statistics, 1-test and ANOVA with the SPSS program. The results of this study can be summarized as follows 1. Prevalence of Substance use : Antihistamines were used by 0.3% of adolescent, Sedatives 0.6%, Stimulants 8.1%, Hallucinogens 0.9%, Inhalants 3.2%, Narcotics 1.7%, and Analgetics 154.3%. 2. Trend in substance use compared to the 1991 surbey : Alcohol use increased from 52.8% to 63.7% and narcotics from 0.6% to 1.7%, while Smeking, Analgetics, Antihistamines, Sedatives, and Inhalants showed a decrease. 3. Smoking and Alcohol use : Twenty five percent of school adolescent had experienced cigarette smoking and 63.7% of school adolescent had experienced alcohol use. 4. Motives for drug use : The highest was avoidence of sleep at 49.4% and the next highest was adventure seeking at 27.7%. As to feeling after drug use, 34.3％ felt apathy, 22.8% had feelings of sleepiness and unconsciousness. 5. Places were dreg were purchased : The most frequent was the drug store (78.3%) and 84.4% of the respondents answered that drug purchase was easy and 86.7% that drug use was mainly at home. 6. Related Variables : There was a statistically significent high score for drug and alcohol use by adolescents whose fathers used drugs. (PC.05) In conclusion, adolescents in Seoul showed in decrease in the tendency to use drugs compared to the 1991 survey, however drugs which are habit-forming and lead to dependency are still being abused. Therefore, counter-plans and preventive stratiges are important.

• Korean Journal of Environmental Agriculture
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• v.34 no.3
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• pp.230-237
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• 2015

BACKGROUND: To identify the sources of inaccuracy in LC/MS/MS methods used in the routine quantitation of small molecules are described and discussed. METHODS AND RESULTS: Various UPLC coupled to triple quadrupole mass spectrometer and time of flight (TOF) were used to identify the potential sources of inaccuracy and inducing the pitfalls of qualification and quntitation during the veterinary drug residue analysis. Some of stable isotope labelled veterinary drugs, which were used as internal standards, presented "cross-talk", regardless of manufactures of mass spectrometer and types of spectrometer. Group of sulfonamides also presented inaccuracy qualification and quantitation due to the multi-residue analytical method with the same fragment ions at the close retention times. CONCLUSION: The phenomena of "cross-talk" occurring between subsequently monitored transition from stable isotope labelled and isotope non-labelled authentic chemical were identified. To prevent errors and achieve more accurate data during the analysis of small molecules by LC/MS/MS SRM method, Followings should be taken care of and kept checking; purity and concentration of stable isotope as an internal standard, prevention of carry-over during the separation in column, minimizing the ion suppression by matrix effect, identification of retention time, precursor ion and product ion, and full knowledge of data processing including smoothing and peak integration.

• Genomics & Informatics
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• v.19 no.4
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• pp.39.1-39.8
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• 2021

Tamoxifen (TAM) is an anticancer drug used to treat estrogen receptor (ER)-positive breast cancer. However, its ER-independent cytotoxic and antifungal activities have prompted debates on its mechanism of action. To achieve a better understanding of the ER-independent antifungal action mechanisms of TAM, we systematically identified TAM-sensitive genes through microarray screening of the heterozygous gene deletion library in fission yeast (Schizosaccharomyces pombe). Secondary confirmation was followed by a spotting assay, finally yielding 13 TAM-sensitive genes under the drug-induced haploinsufficient condition. For these 13 TAM-sensitive genes, we conducted a comparative analysis of their Gene Ontology (GO) 'biological process' terms identified from other genome-wide screenings of the budding yeast deletion library and the MCF7 breast cancer cell line. Several TAM-sensitive genes overlapped between the yeast strains and MCF7 in GO terms including 'cell cycle' (cdc2, rik1, pas1, and leo1), 'signaling' (sck2, oga1, and cki3), and 'vesicle-mediated transport' (SPCC126.08c, vps54, sec72, and tvp15), suggesting their roles in the ER-independent cytotoxic effects of TAM. We recently reported that the cki3 gene with the 'signaling' GO term was related to the ER-independent antifungal action mechanisms of TAM in yeast. In this study, we report that haploinsufficiency of the essential vps54 gene, which encodes the GARP complex subunit, significantly aggravated TAM sensitivity and led to an enlarged vesicle structure in comparison with the SP286 control strain. These results strongly suggest that the vesicle-mediated transport process might be another action mechanism of the ER-independent antifungal or cytotoxic effects of TAM.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.11-16
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• 2012

Cancer stem cells (CSCs) are often characterized by the elevated expression of drug-resistance related stem-cell surface markers, such as CD133 and ABCG2. Recently, we reported that CSCs have a high level of expression of the IL-6 receptor (IL-6R). The purpose of this study was to investigate the effect of anticancer drugs on the expression of the drug resistance-related cancer stem cell markers, ABCG2, IL-6R, and CD133 in non-small cell lung cancer (NSCLC) cell lines. A549, H460, and H23 NSCLC cell lines were treated with the anticancer drugs 5-fluorouracil (5-FU; $25{\mu}g/ml$) and methotrexate (MTX; $50{\mu}g/ml$), and the expression of putative CSC markers was analyzed by fluorescent activated cell sorter (FACS) and the gene expression level of abcg2, il-6r and cd133 by reverse transcriptase-polymerase chain reaction (RT-PCR). We found that the fraction of ABCG2-positive(+) cells was significantly increased by treatment with both 5-FU and MTX in NSCLC cells, and the elevation of abcg2, il-6r and cd133 expressions in response to these drugs was also confirmed using RT-PCR. Also, the number of IL-6R(+) cells was increased by MTX in the 3 cell lines mentioned and increased by 5-FU in the H460 cell line. The number of CD133(+) cells was also significantly increased by both 5-FU and MTX treatment in all of the cell lines tested. These results indicate that 5-FU and MTX considerably enhance the expression of drug-resistance related CSC markers in NSCLC cell lines. Thus, we suggest that antimetabolite cancer drugs, such as 5-FU and MTX, can lead to the propagation of CSCs through altering the expression of CSC markers.