• Title/Summary/Keyword: drug sensitivity

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Guidance for the Evaluation Method of Drugs of Abused in vitro Diagnostic Devices

  • Kang, Shin-Jung;Choi, Hyun-Ceol;Kim, Ho-Jeong;Park, Sang-Aeh;Chug, Hee-Sun
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.291.1-291.1
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    • 2003
  • The purpose of this study is to provide KFDA's guidance for premarket notification submission and labeling for prescription use drugs of abuse in vitro diagnostic devices. To evaluate in vitro diagnostic devices the following performance characteristics should be described in detail within the submission: analytical sensitivity or minimum detection limit, cutoff concentration, specificity and cross reactivity, interference, precision, method comparison and stability. (omitted)

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miR-335 Targets SIAH2 and Confers Sensitivity to Anti-Cancer Drugs by Increasing the Expression of HDAC3

  • Kim, Youngmi;Kim, Hyuna;Park, Deokbum;Jeoung, Dooil
    • Molecules and Cells
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    • v.38 no.6
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    • pp.562-572
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    • 2015
  • We previously reported the role of histone deacetylase 3 (HDAC3) in response to anti-cancer drugs. The decreased expression of HDAC3 in anti-cancer drug-resistant cancer cell line is responsible for the resistance to anti-cancer drugs. In this study, we investigated molecular mechanisms associated with regulation of HDAC3 expression. MG132, an inhibitor of proteasomal degradation, induced the expression of HDAC3 in various anti-cancer drug-resistant cancer cell lines. Ubiquitination of HDAC3 was observed in various anti-cancer drug-resistant cancer cell lines. HDAC3 showed an interaction with SIAH2, an ubiquitin E3 ligase, that has increased expression in various anti-cancer drug-resistant cancer cell lines. miRNA array analysis showed the decreased expression of miR-335 in these cells. Targetscan analysis predicted the binding of miR-335 to the 3'-UTR of SIAH2. miR-335-mediated increased sensitivity to anti-cancer drugs was associated with its effect on HDAC3 and SIAH2 expression. miR-335 exerted apoptotic effects and inhibited ubiquitination of HDAC3 in anti-cancer drug-resistant cancer cell lines. miR-335 negatively regulated the invasion, migration, and growth rate of cancer cells. The mouse xenograft model showed that miR-335 negatively regulated the tumorigenic potential of cancer cells. The down-regulation of SIAH2 conferred sensitivity to anti-cancer drugs. The results of the study indicated that the miR-335/SIAH2/HDAC3 axis regulates the response to anti-cancer drugs.

Evaluation and Improvement of Bioassay for Residual Antibiotics in Foods (식품 내의 잔류 항생제에 대한 미생물학적 간이검사법의 평가 및 개선)

  • Park, Min-Hee;Kim, Tae-Woon;Jo, Nam-Uk;Jeong, Ji-Yoon;Lee, Soon-Ho;Lee, Jong-Ok;Kim, Hae-Yeong
    • Microbiology and Biotechnology Letters
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    • v.36 no.4
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    • pp.360-365
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    • 2008
  • For the screening of residual antibiotics in foods, bioassays and microbiological inhibitor tests are commonly applied. These methods are tested by the various susceptibility of bacteria against different kinds of antibiotics. However, the sensitivity of bioassay is generally insufficient to detect some residual antibiotics at level of interest. This study was performed to investigate the detection limit of variable antibiotics of the bioassay and to improve the sensitivity to some antibiotics. The sensitivity of bioassay using Bacillus megaterium ATCC 9885, B. subtilis ATCC 6633, B. cereus ATCC 11778 and Geobacillus stearothermophilus ATCC 10149 was low in the detection of macrolides, quinolones, chloramphenicol, and monensin. On the contrary, Micrococcus luteus ATCC 9341 showed high sensitivity to macrolides and Escherichia coli ATCC 11303 was highly sensitive to quinolones and aminoglycosides. Consequently, both strains would be useful to improve sensitivity of bioassay with a wide detection range.

Fabrication of a Parallel Polymer Cantilever to Measure the Contractile Force of Drug-treated Cardiac Cells (약물처리된 심장세포의 세포 수축력 측정을 위한 병렬 폴리머 캔틸레버 제작)

  • Kim, Dong-Su;Lee, Dong-Weon
    • Journal of Sensor Science and Technology
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    • v.29 no.2
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    • pp.100-104
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    • 2020
  • Thus far, several in vivo biosensing platforms have been proposed to measure the mechanical contractility of cultured cardiomyocytes. However, the low sensitivity and screening rate of the developed sensors severely limit their practical applications. In addition, intensive research and development in cardiovascular disease demand a high-throughput drug-screening platform based on biomimetic engineering. To overcome the drawbacks of the current state-of-the-art methods, we propose a high-throughput drug-screening platform based on 16 functional high-sensitivity well plates. The proposed system simulates the physiological accuracy of the heart function in an in vitro environment. We fabricated 64 cantilevers using highly flexible and optically transparent silicone rubber and placed in 16 independent wells. Nanogrooves were imprinted on the surface of the cantilever to promote cell alignment and maturation. The adverse effects of the cardiovascular drugs on the cultured cardiomyocytes were systematically investigated. The 64 cantilevers demonstrated a highly reliable and reproducible mechanical contractility of the drug-treated cardiomyocytes. Real-time high-throughput screening and simultaneous evaluation of the cardiomyocyte mechanical contractility under multiple drugs verified that the proposed system could be used as an efficient drugtoxicity test platform.

Drug-Induced Haploinsufficiency of Fission Yeast Provides a Powerful Tool for Identification of Drug Targets

  • PARK, JO-YOUNG;YOUNG-JOO JANG;SEOG-JONG YOU;YOUNG-SOOK KIL;EUN-JUNG KANG;JEE-HEE AHN;YOUNG-KWON RYOO;MIN-YOUN LEE;MISUN WON
    • Journal of Microbiology and Biotechnology
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    • v.13 no.2
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    • pp.317-320
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    • 2003
  • Genome-wide systematic deletion mutants were generated using a PCR-based targeted mutagenesis of Schizosacchaaromyces pombe. In a drug-sensitivity assay using thiabendazole(TBZ), an inhibitor of microtubule assembly, a heterozygous nda2 mutant ($nda2^+/nda2^-$), deleting one copy of nda2 encoding the microtubule subunit alpha1 demonstrated a distinct sensitivity to TBZ, indicating TBZ-induced haploinsufficiency. This result suggests that profiling drug-induced haploinsufficiency can be exploited to identify target genes for drugs and discover new drugs.

A Drug Sensitivity Test for Shortening of Detection Time (항균성물질(抗菌性物質) 감수성시험(感受性試驗)의 시간단축(時間短縮)과 임상적응용(臨床的應用))

  • Kim, Kyo-Joon;Hu, Min-Do;Lee, Myung-Hwan
    • Korean Journal of Veterinary Research
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    • v.23 no.1
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    • pp.123-128
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    • 1983
  • This study was conducted to evaluate the modified drug sensitivity test for the shortening of detection time and clinical application. The results obtained were summarized as follows. 1. Inhibitory zone in 6 strains of Staphylococcus and Escherichia coli tested to sensitivity teat were reached at 100% between 2 and 6 hours. 2. The sensitivity test of Staphylococcus A, B and E. coli No. 2, No. 3 to antibacterial ointment drugs were strong positive(+++), but Staphylococcus A. A. and E. coli No. 1 were mild resistant(+). 3. The sensitivity test of Staphylococcus A. B and E. coli No. 2, No. 3 to antibacterial injection drugs in 6 hours after treatment were strong positive(+++), and Staphylococcus A. A. and E. coli No. 1 were moderate positive(++). 4. This modified method was detected 86% degree of sensitive between 7 to 12 hours after treatment. 5. We think this modified method was more practical compare to other methods.

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KNOCKDOWN OF IGF-1R BY ANTISENSE OLIGODEOXYNUCLEOTIDE AUGUMENTS THE SENSITIVITY OF BLADDER CANCER CELLS TO MMC

  • Wu, Shu-Fang;Sun, Hong-Zhi;Tu, Zeng-Hong
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.203-204
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    • 2001
  • Background and Aim: Transitional cell carcinoma (TCC) of the bladder represents the fifth most prevalent malignancy in Western population, with peak incidence found in males of the 50- to 70-year-old age group. A major problem in the management of bladder cancer is the low sensitivity of a large proportion (approximately 40%) among bladder tumors to chemotherapy and the high risk for recurrence of bladder tumors after transurethral resection.(omitted)

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Prediction of pharmacokinetics and drug-drug interaction potential using physiologically based pharmacokinetic (PBPK) modeling approach: A case study of caffeine and ciprofloxacin

  • Park, Min-Ho;Shin, Seok-Ho;Byeon, Jin-Ju;Lee, Gwan-Ho;Yu, Byung-Yong;Shin, Young G.
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.1
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    • pp.107-115
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    • 2017
  • Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction (DDI) liability at the drug discovery or development stage. Herein, we describe a case study to illustrate the use of PBPK approach in predicting human PK as well as DDI using in silico, in vivo and in vitro derived parameters. This case was composed of five steps such as: simulation, verification, understanding of parameter sensitivity, optimization of the parameter and final evaluation. Caffeine and ciprofloxacin were used as tool compounds to demonstrate the "fit for purpose" application of PBPK modeling and simulation for this study. Compared to caffeine, the PBPK modeling for ciprofloxacin was challenging due to several factors including solubility, permeability, clearance and tissue distribution etc. Therefore, intensive parameter sensitivity analysis (PSA) was conducted to optimize the PBPK model for ciprofloxacin. Overall, the increase in $C_{max}$ of caffeine by ciprofloxacin was not significant. However, the increase in AUC was observed and was proportional to the administered dose of ciprofloxacin. The predicted DDI and PK results were comparable to observed clinical data published in the literatures. This approach would be helpful in identifying potential key factors that could lead to significant impact on PBPK modeling and simulation for challenging compounds.

Drug Resistance and in Vitro Susceptibility of Plasmodium falciparum in Thailand during 1988-2003

  • Suwandittakul, Nantana;Chaijaroenkul, Wanna;Harnyuttanakorn, Pongchai;Mungthin, Mathirut;Bangchang, Kesara Na
    • Parasites, Hosts and Diseases
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    • v.47 no.2
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    • pp.139-144
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    • 2009
  • The aim of the present study was to investigate antimalarial drug pressure resulting from the clinical use of different antimalarials in Thailand. The phenotypic diversity of the susceptibility profiles of antimalarials, i.e., chloroquine (CQ), quinine (QN), mefloquine (MQ), and artesunate (ARS) in Plasmodium falciparum isolates collected during the period from 1988 to 2003 were studied. P. falciparum isolates from infected patients were collected from the Thai-Cambodian border area at different time periods (1988-1989, 1991-1992, and 2003), during which 3 different patterns of drug use had been implemented: MQ+sulphadoxine (S)+pyrimethamine (P), MQ alone and MQ+ARS, respectively. The in vitro drug susceptibilities were investigated using a method based on the incorporation of $[^3H]$ hypoxanthine. A total of 50 isolates were tested for susceptibilities to CQ, QN, MQ, and ARS. Of these isolates, 19, 16, and 15 were adapted during the periods 1988-1989, 1991-1993, and 2003, respectively. P. falciparum isolates collected during the 3 periods were resistant to CQ. Sensitivities to MQ declined from 1988 to 2003. In contrast, the parasite was sensitive to QN, and similar sensitivity profile patterns were observed during the 3 time periods. There was a significantly positive but weak correlation between the $IC_{50}$ values of CQ and QN, as well as between the $IC_{50}$, values of QN and MQ. Drug pressure has impact on sensitivity of P. falciparum to MQ. A combination therapy of MQ and ARS is being applied to reduce the parasite resistance, and also increasing the efficacy of the drug.