• Title/Summary/Keyword: Drug sensitivity

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Validation Process of HPLC Assay Methods of Drugs in Biological Samples (생체시료내 약물의 HPLC 분석법에 대한 유효성 검토방법)

  • Chi, Sang-Cheol;Jun, H.-Won
    • Journal of Pharmaceutical Investigation
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    • v.21 no.3
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    • pp.179-188
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    • 1991
  • An HPLC assay method of a drug to be applied to the pharmacokinetic studies of the drug should be completely validated. The validation process for an HPLC assay method in a biological sample was discussed using the data obtained from the development of HPLC method for the simultaneous quantitation of verapamil and norverapamil in human serum. The validation criteria included were specificity, linearity, accuracy, precision, sensitivity, recovery, drug stability, and ruggedness of an assay method.

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DOWN-REGULATION OF RAF-1 KINASE IS ASSOCIATED WITH PACLITAXEL RESISTANCE IN HUMAN BREAST CANCER MCF-7/ADR CELLS

  • Lee, Michael;Jung Kwon;Wayne B. Anderson;Chung, Moon-Koo
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.11b
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    • pp.136-136
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    • 2002
  • Experiments were carried out to determine the role of Raf-1 kinase in the development of drug resistance and apoptosis induced by paclitaxel. In the present study, paclitaxel sensitivity, Raf-1 activity and MAPKs activation were compared in 2 cell lines: parental human breast cancer cells and its drug resistant variant (MCF-7/Adr) cells.(omitted)

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Drug Sensitivity and Relapsed Period of Relapsed Pulmonary Tuberculous Patients registered in Some Public Health Offices, in Seoul (폐결핵 재발 환자의 약제 감수성과 재발 간격에 관한 단면 연구 - 서울시 일부 보건소 등록 환자를 중심으로)

  • Park, Hye-Sook;Ha, Eun-Hee;Wie, Cha-Hyung;Kang, Ji-Yong
    • Journal of Preventive Medicine and Public Health
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    • v.29 no.1 s.52
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    • pp.67-78
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    • 1996
  • The purpose of this study was examine the general characteristics of relapsed pulmonary tuberculous patients (i.e. age, sex, weight, occupation, previous forms of treatment, drug sensitivity, and the frequency of relapse) in order to improve future treatments of tuberculosis as well as to perpetuate health education. The data was obtained from the medical records of 186 relapsed pulmonary tuberculosis patients who were registered for treatment at various public health offices in Seoul during the year of 1994. The major findings obtained from the study were as follows; 1) The male to female ratio of relapsed pulmonary tuberculous patients was about 7:3, more specifically 23.7% of the men and 30.9% of the women were between 20 and 29 years of age. 2) Comparing initial less aggravated states to relapsed states, patients with minimal X-ray findings later proved moderately advanced X-ray findings. Furthermore, patients with negative sputum AFB findings later proved positive sputum AFB findings. 3) Of the 186 patients studied, 91.9% suffered, relapse and 8.1% suffered 2 or more relapses. Of the patients who suffered at least 1 relapse, 54.8% received short-term treatment, 26.9% received long-term treatment, and 18.3% received treatment of an unknown during their initial tuberculosis treatment periods. 4) fifty five point four percent of the patients had no reaction to the drug treatment(not available), 25.9% of the patients had sensitive reaction to the drug treatment, 18.7% of the patients had resistant reaction to the- drug treatment. Drug resistance was higher in patients that exhibited positive X-ray findings as well as in patients that exhibited positive sputum AFB findings. furthermore, patients receiving treatment of an unknown nature(35.5%) exhibited higher drug resistance than those receiving short-term treatment(13.6%) and long-term treatment(17.0%). 5) Of the 160 patients who suffered relapses, 8.8% suffered a relapse within 1 year after treatment and 91.2% suffered a relapse at least 1 year after treatment. Furthermore, our study showed that women, under 30, who received short-term treatment and encounterd complications during their primary treatment suffered relapses faster than any other groups studied. In addition, minimal X-ray findings and sputum AFB findings were not correlated to the time relapse occured. Therefore, the seater efforts are needed to prevent relapsed pulmonary tuberculosis.

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Tubulin Beta3 Serves as a Target of HDAC3 and Mediates Resistance to Microtubule-Targeting Drugs

  • Kim, Youngmi;Kim, Hyuna;Jeoung, Dooil
    • Molecules and Cells
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    • v.38 no.8
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    • pp.705-714
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    • 2015
  • We investigated the role of HDAC3 in anti-cancer drug-resistance. The expression of HDAC3 was decreased in cancer cell lines resistant to anti-cancer drugs such as celastrol and taxol. HDAC3 conferred sensitivity to these anti-cancer drugs. HDAC3 activity was necessary for conferring sensitivity to these anti-cancer drugs. The down-regulation of HDAC3 increased the expression of MDR1 and conferred resistance to anti-cancer drugs. The expression of tubulin ${\beta}3$ was increased in drug-resistant cancer cell lines. ChIP assays showed the binding of HDAC3 to the promoter sequences of tubulin ${\beta}3$ and HDAC6. HDAC6 showed an interaction with tubulin ${\beta}3$. HDAC3 had a negative regulatory role in the expression of tubulin ${\beta}3$ and HDAC6. The down-regulation of HDAC6 decreased the expression of MDR1 and tubulin ${\beta}3$, but did not affect HDAC3 expression. The down-regulation of HDAC6 conferred sensitivity to taxol. The down-regulation of tubulin ${\beta}3$ did not affect the expression of HDAC6 or MDR1. The down-regulation of tubulin ${\beta}3$ conferred sensitivity to anti-cancer drugs. Our results showed that tubulin ${\beta}3$ serves as a downstream target of HDAC3 and mediates resistance to microtubule-targeting drugs. Thus, the HDAC3-HDAC6-Tubulin ${\beta}$ axis can be employed for the development of anti-cancer drugs.

Application of Bovine Viral Diarrhoea Virus as an Internal Control in Nucleic Acid Amplification Tests for Hepatitis C Virus RNA in Plasma-Derived Products

  • Yoo Si Hyung;Hong Seung Hee;Jung Sa Rah;Park Su Jin;Lee Nam Kyung;Kim Soon Nam;Kang Sang Mo;Min Hong Ki;Park Sue Nie;Hong Seung Hwa
    • Journal of Microbiology
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    • v.44 no.1
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    • pp.72-76
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    • 2006
  • Plasma-derived products are produced from plasma via fractionation and chromatography techniques, but can also be produced by other methods. In the performance of nucleic acid amplification tests (NAT) with plasma-derived products, it is necessary to include an internal control for the monitoring of all procedures. In order to avoid false negative results, we confirmed the usefulness of the bovine viral diarrhoea virus (BVDV) for use as an internal control in the detection of hepatitis C virus (HCV) RNA in plasma-derived products. These products, which were spiked with BVDV, were extracted and then NAT was performed. Specificity and sensitivity were determined via the adjustment of primer concentrations and annealing temperatures. BVDV detection allows for validation in the extraction, reverse transcription, and amplification techniques used for HCV detection in plasma-derived products.

A Physiologically Based Pharmacokinetic Model for Absorption and Distribution of Imatinib in Human Body

  • Chowdhury, Mohammad Mahfuz;Kim, Do-Hyun;Ahn, Jeong-Keun
    • Bulletin of the Korean Chemical Society
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    • v.32 no.11
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    • pp.3967-3972
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    • 2011
  • A whole body physiologically based pharmacokinetic (PBPK) model was applied to investigate absorption, distribution, and physiologic variations on pharmacokinetics of imatinib in human body. Previously published pharmacokinetic data of the drug after intravenous (i.v.) infusion and oral administration were simulated by the PBPK model. Oral dose absorption kinetics were analyzed by adopting a compartmental absorption and transit model in gut section. Tissue/plasma partition coefficients of drug after i.v. infusion were also used for oral administration. Sensitivity analysis of the PBPK model was carried out by taking parameters that were commonly subject to variation in human. Drug concentration in adipose tissue was found to be higher than those in other tissues, suggesting that adipose tissue plays a role as a storage tissue for the drug. Variations of metabolism in liver, body weight, and blood/plasma partition coefficient were found to be important factors affecting the plasma concentration profile of drug in human body.

Determination of Ceftiofur Residues by Simple Solid Phase Extraction Coupled with Liquid Chromatography-Tandem Mass Spectrometry in Eel, Flatfish, and Shrimp

  • Kim, Joohye;Shin, Dasom;Kang, Hui-Seung;Lee, Eunhye;Choi, Soo Yeon;Lee, Hee-Seok;Cho, Byung-Hoon;Lee, Kang-Bong;Jeong, Jiyoon
    • Mass Spectrometry Letters
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    • v.10 no.2
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    • pp.43-49
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    • 2019
  • The aim of this study was conducted to develop an analytical method to determine the concentration of ceftiofur residue in eel, flatfish, and shrimp. For derivatization and extraction, the sample was hydrolyzed with dithioerythritol to produce desfuroylceftiofur, which was then derivatized by iodoacetamide to obtain desfuroylceftiofur acetamide. For purification, the process of solid phase extraction (Oasis HLB) was used. The target analytes were confirmed and quantified in $C_{18}$ column using liquid chromatography-tandem mass spectrometry with 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B) as the mobile phase. The linearity of the standard calibration curve was confirmed by a correlation coefficient, $r^2>0.99$. The limit of quantification for ceftiofur was 0.002 mg/kg; the accuracy (expressed as the average recoveries) was 80.6-105%; the precision (expressed as the coefficient of variation) was below 6.3% at 0.015, 0.03, and 0.06 mg/kg. The validated method demonstrated high accuracy and acceptable sensitivity to meet the Codex guideline requirements. The developed method was tested using market samples. As a results, ceftiofur was detected in one sample. Therefore, it can be applied to the analysis of ceftiofur residues in fishery products.

Role of Integrin-Linked Kinase in Multi-drug Resistance of Human Gastric Carcinoma SGC7901/DDP Cells

  • Song, Wei;Jiang, Rui;Zhao, Chun-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5619-5625
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    • 2012
  • Gastric carcinoma is a leading cause of cancer death in the world and multi-drug resistance (MDR) is an essential aspect of gastric carcinoma chemotherapy failure. Recent studies have shown that integrin-linked kinase (ILK) is involved in metastasis of human tumors, expression silencing of ILK inhibiting the metastasis of several types of cultured human cancer cells. However, the role and potential mechanism of ILK to reverse the multi-drug resistance in human gastric carcinoma is not fully clear. In this report, we focused on roles of expression silencing of ILK in multi-drug resistance reversal of human gastric carcinoma SGC7901/DDP cells, including increased drug sensitivity to cisplatin, cell apoptosis rates, and intracellular accumulation of Rhodamine-123, and decreased mRNA and protein expression of multi-drug resistance gene (MDR1), multi-drug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase -${\pi}$ (GST-${\pi}$) and RhoE, and transcriptional activation of AP-1 and NF-${\kappa}B$ in ILK silenced SGC7901/DDP cells. We also found that there was a decreased level of p-Akt and p-ERK. The results indicated that ILK might be used as a potential therapeutic strategy to combat multi-drug resistance through blocking PI3K-Akt and MAPK-ERK pathways in human gastric carcinoma.

pH 및 온도에 동시에 민감한 생분해성 하이드로젤의 합성 및 특성

  • Sin, Mun-Sik;Gang, Hyeong-Seok;Park, Tae-Gwan;Yang, Ji-Won
    • 한국생물공학회:학술대회논문집
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    • 2000.04a
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    • pp.562-565
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    • 2000
  • pH- and thermo-sensitive hydrogels containing maleilated chitosan(MC) and N-isopropylacrylamide(NIPAAm) were prepared and characterized for their swelling behavior, biodegradability and drug release profiles. The hydrogels exhibited a typical pH-sensitivity due to the carboxylic acid groups of maleilated chitosan. The change of ratio of NIPAAm to MC in weight did not affect on either lower critical solution temperature(LCST) or EWC significantly. The pH sensitivity of the hydrogel, however, depended on the amounts of carboxylic acid groups of MC. MC was degradable up to 80% weight reduction in 2 hours. The in vitro drug relase profiles were established both in buffer solution pH 1.4 and pH 7.4. Only a negligible amount of indomethacin was released at pH 1.4 in 6 hours, while at pH 7.4 more than 90% of the total drug in the hydrogel was gradually released over ca. 5 hours.

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