• Korean Journal of Veterinary Research
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• v.28 no.1
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• pp.83-87
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• 1988

The in vitro drug susceptibility of 83 strains of Bordetella bronchiseptica recovered from Korean pigs with atrophic rhinitis was investigated by the use of disk diffusion method. The majority of the organisms were highly resistant in order of prevalence to penicillin(98.7%), ampicillin(91.5%), streptomycin(90.3%), triple sulfa(83.1%), and trimethoprim/sulfamethoxazole(70.7%) while none of them were resistant to gentamicin, only 3.6% to colistin, chloramphenicol and kanamycin and 6.0% to tetracycline. The percentage of the organism resistant to bicozamycin, cephalothin and neomycin were 34.9%, 34.1% and 18.4%, respectively. A high prevalence of multiple drug resistance was observed and the 3 most common resistant patterns among 35 patterns noted were Am Pc Sm Sss Sxt(26.5%), Am Cf Pc Sm Sss Sxt(12.%) and Am Bm Pc Sm Sss Sxt(9.6%) patterns.

• Journal of Life Science
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• v.26 no.7
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• pp.835-846
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• 2016

Chemo-resistance is the biggest issue of effective cancer therapy. ABCG2 is highly correlated with multi-drug resistance, and represent a typical phenotype of multiple cancer stem-like cells. Accumulating evidence recently reported that oncolytic viruses represent a new strategy for multiple aggressive cancers and drug resistant cancers including cancer stem cell-like cells and ABCG2 expressing cells. In this study, we generated an evolutionally engineered vaccinia virus, SLJ-496, for drug-resistant cancer therapy. We first showed that SLJ-496 treatment enhanced tumor affinity using cytopathic effect assay, plaque assay, as well as cell viability assay. Next, we clearly demonstrated that in vitro SLJ-496 treatment represents significant cytotoxic effect in multiple cancers including colorectal cancer cells (HT-29, HCT-116, HCT-8), gastric cancer cells (AGS, NCI-N87, MKN-28), Hepatocellular carcinoma cells (SNU-449, SNU-423, SNU-475, HepG2), as well as mesothelioma cell (NCI-H226, NCI-H28, MSTO-221h). Highly ABCG2 expressing HT-29 cells represent cancer stem like phenotype including stem cell marker expression, and self-renewal bioactivities. Interestingly, we demonstrated that in vitro treatment of SLJ-496 showed significant cytotoxicity effect, as well as viral replication capacity in ABCG2 overexpressing cell. In addition, we also demonstrated the cytotoxic effect of SLJ-496 in Adriamycin-resistant cell lines, SNU-620 and ADR-300. Taken together, these findings provide us a pivotal clue that cancer therapy using SLJ-496 vaccinia virus might be new therapeutic strategy to overcome ABCG2 expressing cancer stem-like cell and multiple chemo-resistance cancer cells.

• BMB Reports
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• v.47 no.5
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• pp.274-279
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• 2014

Bortezomib has been known as the most promising anti-cancer drug for multiple myeloma (MM). However, recent studies reported that not all MM patients respond to bortezomib. To overcome such a stumbling-block, studies are needed to clarify the mechanisms of bortezomib resistance. In this study, we established a bortezomib-resistant cell line (U266/velR), and explored its biological characteristics. The U266/velR showed reduced sensitivity to bortezomib, and also showed cross-resistance to the chemically unrelated drug thalidomide. U266/velR cells had a higher proportion of CD138 negative subpopulation, known as stem-like feature, compared to parental U266 cells. U266/velR showed relatively less inhibitory effect of prosurvival NF-${\kappa}B$ signaling by bortezomib. Further analysis of RNA microarray identified genes related to ubiquitination that were differentially regulated in U266/velR. Moreover, the expression level of CD52 in U266 cells was associated with bortezomib response. Our findings provide the basis for developing therapeutic strategies in bortezomib-resistant relapsed and refractory MM patients.

• Biomolecules & Therapeutics
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• v.17 no.3
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• pp.299-304
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• 2009

Rosiglitazone maleate (RGM) is widely used for improving insulin resistance. RGM is a moderate inhibitor of cytochrome P450 2C8 (CYP2C8) and is also mainly metabolized by CYP2C8. The aim of this study was to determine whether the effect of RGM on CYP2C8 is altered by co-treatment with other drugs, and whether amlodipine camsylate (AC) changes the pharmacokinetics (PK) of RGM. Of the 11 drugs that are likely to be co-administered with RGM in diabetic patients, seven drugs lowered the $IC_{50}$ value of RGM on CYP2C8 by more than 80%. In vitro CYP2C8 inhibitory assays of RGM in combination with drugs of interest showed that the $IC_{50}$ of RGM was decreased by 98.9% by AC. In a pharmacokinetic study, Sprague-Dawley (SD) rats were orally administered 1 mg/kg of RGM following by single or 10-consecutive daily administrations of 1.5 mg/kg/day of AC. No significant changes in the pharmacokinetic parameters of RGM were observed after a single administration of AC, but the AUC and $C_{max}$ values of RGM were significantly reduced by 36% and 31%, respectively, by multiple administrations of AC. In conclusion, RGM was found to be affected by AC by in vitro CYP2C8 inhibition testing, and multiple dosing of AC appreciably changed the pharmacokinetics of RGM. These findings suggest that a drug interaction exists between AC and RGM.

• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.29-41
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• 2001

Background : The appearance of multiple-drug-resistant Mycobacterium tuberculosis strains has been seriously compromising successful control of tuberculosis. Rifampin-resistance, caused by mutations in the rpoB gene, can be indicative of multiple-drug-resistance, and its detection is of great importance. The present study aimed to develop an oligonucleotide chip for accurate and convenient screening of drug-resistance. Methods : In order to detect point mutations in the rpoB gene, an oligonucleotide chip was prepared by immobilizing specific probe DNA to a microscopic slide glass by a chemical reaction. The probe DNA that was selected from the 81 bp core region of the rpoB gene was designed to have mutation sites at the center. A total of 17 mutant probes related to rifampin-resistance including 8 rifabutin-sensitive mutant probes were used in this study. For accurate determination, wild type probes were prepared for each mutation position with an equal length, which enabled a direct comparison of the hybridization intensities between the mutant and wild type. Results : Mycobacterial genomic DNA from clinical samples was tested with the oligonucleotide chip and the results were compared with those of the drug-susceptibility test in addition to sequencing and INNO-LiPA Rif. TB kit test in some cases. Out of 15 samples, the oligonucleotide chip results of 13 samples showed good agreement with the rifabutin-sensitivity results. The two samples with conflicting result also showed a discrepancy between the other tests, suggesting such possibilities as existence of mixed strains and difference in drug-sensitivity. Further verification of these samples in addition to more case studies are required before the final evaluation of the oligonucleotide chip can be made. Conlcusion : An oligonucleotide chip was developed for the detection of rpoB gene mutations related to drugsusceptibility. The results to date show the potential for using the oligonucleotide chip for accurate and convenient screening of drug-resistance to provide useful information in antituberculosis drug therapy.

• Journal of fish pathology
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• v.9 no.2
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• pp.195-201
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• 1996

Ninety-six isolates of Edwardsiella tarda recovered from outbreaks of Edwardsiellosis in cultured eels(Anguilla japonica) in Kunsan, were examined for drug susceptibility, distribution and transferabilities of R plasmid. All of the E. tarda isolates examined were sensitive to gentamicin(GM), streptomycin(SM), norfloxacin(NF), and amikacin(AK). But most isolates were resistant to sulfadimethoxine(SD, 86 strains), ampicillin(AM, 84 strains), penicillin G(PM, 80 strains), nalidixic acid (NA, 67 strains), oxytetracycline(OT, 44 strains), and oxolinic acid(OA, 37 strains). Twenty different combinations of drug resistance patterns were observed : the frequently encountered pattern was SD-AM-PM-NA-OA(16 strains), SD-AM-PM-NA(14 strains), SD-AM-PM-NA-OT-OA(12 strains), SD-AM-PM-OT(10 strains), and SD-AM-PM-NA-OT(8 strains). Transferable R plasmids were found out to be carried in 78 out of 94 resistant strains, indicating that these isolates carry conjugally transferable R plasmids associated with single or multiple drugs. The frequently observed transferarble R plasmids were AM(8 strains), AM-PM-NA(8 strains), Am-SD(6 strains), PM(6 strains), and SD(6 strains) These results suggest that high dose of various antibacterials might have already been introduced to eel culture system leading to the acquirement of multi-drug resistance to wide range of antibacterials.

• Journal of Microbiology and Biotechnology
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• v.15 no.6
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• pp.1214-1220
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• 2005

Decreased porin-mediated outer membrane penetration of hydrophilic antibiotics is a common mechanism of antibiotic resistance in Gram-negative bacteria. This study was undertaken to determine whether a null mutation in Pseudomonas putida would suppress porin synthesis, and therefore reduce the susceptibility of the organism to streptomycin, norfloxacin, and tetracycline. Inverse PCR amplification and double-stranded DNA sequencing were used to identify chromosomal genes carrying TnphoA'-1 inserts. Genome database available was used to identify putative homologue genes, one of which encodes protein with homology to domains of the MutS of P. putida, suggesting a crucial role in the multidrug resistance. Increased resistance to streptomycin, norfloxacin, and tetracycline might be due to accumulation of compensatory mutations. Either no growth or slow growth was observed in P. putida KH1027 when grown in minimal medium containing gluconate, glucose, or citrate; however, it is not clear whether the growth patterns contributed to the multidrug resistance.

• BMB Reports
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• v.49 no.4
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• pp.238-243
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• 2016

The efficacy of anticancer drugs depends on a variety of signaling pathways, which can be positively or negatively regulated. In this study, we show that SETDB1 HMTase is down-regulated at the transcriptional level by several anticancer drugs, due to its inherent instability. Using RNA sequence analysis, we identified FosB as being regulated by SETDB1 during anticancer drug therapy. FosB expression was increased by treatment with doxorubicin, taxol and siSETDB1. Moreover, FosB was associated with an increased rate of proliferation. Combinatory transfection of siFosB and siSETDB1 was slightly increased compared to transfection of siFosB. Furthermore, FosB was regulated by multiple kinase pathways. ChIP analysis showed that SETDB1 and H3K9me3 interact with a specific region of the FosB promoter. These results suggest that SETDB1-mediated FosB expression is a common molecular phenomenon, and might be a novel pathway responsible for the increase in cell proliferation that frequently occurs during anticancer drug therapy.

• BMB Reports
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• v.55 no.11
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• pp.547-552
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• 2022

Sorafenib, originally identified as an inhibitor of multiple oncogenic kinases, induces ferroptosis in hepatocellular carcinoma (HCC) cells. Several pathways that mitigate sorafenib-induced ferroptosis confer drug resistance; thus strategies that enhance ferroptosis increase sorafenib efficacy. Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is upregulated in human HCC tissues and plays a role in cancer cell proliferation. The aim of this study was to determine whether inhibition of ERRγ with DN200434, an orally available inverse agonist, can overcome resistance to sorafenib through induction of ferroptosis. Sorafenib-resistant HCC cells were less sensitive to sorafenibinduced ferroptosis and showed significantly higher ERRγ levels than sorafenib-sensitive HCC cells. DN200434 induced lipid peroxidation and ferroptosis in sorafenib-resistant HCC cells. Mechanistically, DN200434 increased mitochondrial ROS generation by reducing glutathione/glutathione disulfide levels, which subsequently reduced mTOR activity and GPX4 levels. DN200434 induced amplification of the antitumor effects of sorafenib was confirmed in a tumor xenograft model. The present results indicate that DN200434 may be a novel therapeutic strategy to re-sensitize HCC cells to sorafenib.

• Tuberculosis and Respiratory Diseases
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• v.79 no.4
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• pp.282-288
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• 2016

Background: Tuberculosis (TB) is a major health problem, and accurate and rapid diagnosis of multidrug-resistant (MDR) and extended drug-resistant (XDR) TB is important for appropriate treatment. In this study, performances of solid and liquid culture methods were compared with respect to MDR- and XDR-TB isolate recovery and drug susceptibility testing. Methods: Sputum specimens from 304 patients were stained with Ziehl-Neelsen method. Mycobacterium tuberculosis (Mtb) isolates were tested for recovery on $L{\ddot{o}wenstein$-Jensen (LJ) medium and the BacT Alert 3D system. For drug susceptibility testing of Mtb, isolates were evaluated on M-KIT plates and the BacT Alert 3D system. Results: The recovery rates were 94.9% (206/217) and 98.2% (213/217) for LJ medium and the BacT Alert 3D system, respectively (kappa coefficient, 0.884). The rate of drug resistance was 13.4% for at least one or more drugs, 6.0% for MDR-TB and 2.3% for XDR-TB. M-KIT plate and BacT 3D Alert 3D system were comparable in drug susceptibility testing for isoniazid (97.7%; kappa coefficient, 0.905) and rifampin (98.6%; kappa coefficient, 0.907). Antibiotic resistance was observed using M-KIT plates for 24 of the total 29 Mtb isolates (82.8%). Conclusion: The liquid culture system showed greater reduction in the culture period, as compared with LJ medium; however, drug susceptibility testing using M-KIT plates was advantageous for simultaneous testing against multiple drug targets.