• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8467-8471
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• 2016

Background: One of the major mechanisms for drug resistance is associated with altered anticancer drug transport, mediated by the human-adenosine triphosphate binding cassette (ABC) transporter superfamily proteins. The overexpression of adenosine triphosphate binding cassette, sub-family B, member 1 (ABCB1) by multidrug-resistant cancer cells is a serious impediment to chemotherapy. In our study we have studied the possibility that structural single-nucleotide polymorphisms (SNP) are the mechanism of ABCB1 overexpression. Materials and Methods: A total of 101 gastric cancer multidrug resistant cases and 100 controls were genotyped with sequence-specific primed PCR (SSP-PCR). Gene expression was evaluated for 70 multidrug resistant cases and 54 controls by real time PCR. The correlation between the two groups was based on secondary structures of RNA predicted by bioinformatics tool. Results: The results of genotyping showed that among 3 studied SNPs, rs28381943 and rs2032586 had significant differences between patient and control groups but there were no differences in the two groups for C3435T. The results of real time PCR showed over-expression of ABCB1 when we compared our data with each of the genotypes in average mode. Prediction of secondary structures in the existence of 2 related SNPs (rs28381943 and rs2032586) showed that the amount of ${\Delta}G$ for original mRNA is higher than the amount of ${\Delta}G$ for the two mentioned SNPs. Conclusions: We have observed that 2 of our studied SNPs (rs283821943 and rs2032586) may elevate the expression of ABCB1 gene, through increase in mRNA stability, while this was not the case for C3435T.

• Biomolecules & Therapeutics
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• v.20 no.4
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• pp.393-398
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• 2012

Recently, we reported that defective autophagy may contribute to the inhibition of the growth in response to PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), a selective SFK inhibitor, in multidrug-resistant v-Ha-ras-transformed NIH 3T3 cells (Ras-NIH 3T3/Mdr). In this study, we demonstrated that PP2 induces LC3 conversion via a mechanism that is uncoupled from autophagy and increases apoptosis in Ras-NIH 3T3/Mdr cells. PP2 preferentially induced autophagy in Ras-NIH 3T3 cells rather than in Ras-NIH 3T3/Mdr cells as determined by LC3-I to LC3-II conversion and GFP-LC3 fluorescence microscopy. Beclin 1 knockdown experiments showed that, regardless of drug resistance, PP2 induces autophagy via a Beclin 1-dependent mechanism. PP2 induced a conformational change in Beclin 1, resulting in the enhancement of the pro-autophagic activity of Beclin 1, in Ras-NIH 3T3 cells. Further, PI3K inhibition induced by wortmannin caused a significant increase in apoptosis in Ras-NIH 3T3 cells, as demonstrated by flow cytometric analysis of Annexin V staining, implying that autophagy inhibition through PI3K increases apoptosis in response to PP2 in Ras-NIH 3T3 cells. However, despite the fact that wortmannin abrogates PP2-induced GFP-LC3 punctae formation, some LC3 conversion remains in Ras-NIH 3T3/Mdr cells, suggesting that LC3 conversion may occur in an autophagy-independent manner. Taken together, these results suggest that PP2 induces LC3 conversion independent of PI3K, concomitant with the uncoupling of LC3 conversion from autophagy, in multidrug-resistant cells.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.2
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• pp.107-122
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• 2001

A function of the kidney is elimination of a variety of xenobiotics ingested and wasted endogenous compounds from the body. Organic anion and cation transport systems play important roles to protect the body from harmful substances. The renal proximal tubule is the primary site of carrier-mediated transport from blood into urine. During the last decade, molecular cloning has identified several families of multispecific organic anion and cation transporters, such as organic anion transporter (OAT), organic cation transporter (OCT), and organic anion-transporting polypeptide (oatp). Additional findings also suggested ATP-dependent organic ion transporters such as MDR1/P-glycoprotein and the multidrug resistance-associated protein (MRP) as efflux pump. The substrate specificity of these transporters is multispecific. These transporters also play an important role as drug transporters. Studies on their functional properties and localization provide information in renal handling of drugs. This review summarizes the latest knowledge on molecular properties and pharmacological significance of renal organic ion transporters.

• Tuberculosis and Respiratory Diseases
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• v.78 no.3
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• pp.168-174
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• 2015

Drug-resistant tuberculosis (TB) is still a major threat worldwide. However, recent scientific advances in diagnostic and therapeutic tools have improved the management of drug-resistant TB. The development of rapid molecular testing methods allows for the early detection of drug resistance and prompt initiation of an appropriate treatment. In addition, there has been growing supportive evidence for shorter treatment regimens in multidrug-resistant TB; and for the first time in over 50 years, new anti-TB drugs have been developed. The World Health Organization has recently revised their guidelines, primarily based on evidence from a meta-analysis of individual patient data (n=9,153) derived from 32 observational studies, and outlined the recommended combination and correct use of available anti-TB drugs. This review summarizes the updated guidelines with a focus on the medical management of drug-resistant TB.

• YAKHAK HOEJI
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• v.37 no.6
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• pp.621-624
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• 1993

The clirical isolate Staphylococcus aureus SA2 had four kinds of plasmids and was resistant to ampicillin, chloroamphenicol, clindamycin. erythromycin, gentamicin, kanamycin, methicillin, streptomycin, tetracycline and tobramycin. Transformation experiment demonstrated that 4.14kb plasmid(pKH7) encoded resistance to chloramphenicol. The cleavage map of pKH7 was determined by restriction enzyme mapping techniques. The cleavage map is given for BstEll, Hindlll, Hpall, and Xbal. The above restriction endonucleases have a single site, but nucleases BamHl, Bgll, BglII, EcoRl, EcoRV, HaeIII, Hpal, Kpnl, Pstl, PvnII, Sall, Smal, and XhoI have no site on this plasmid.

• YAKHAK HOEJI
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• v.46 no.2
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• pp.108-112
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• 2002

Drug resistance is one of the most significant impediments to successful chemotherapy of cancer. Multidrug-resistance (MDR) is characterized by decreased cellular sensitivity to anticancer agents due to the overexpression of P-glycoprotein. By employing a resistant subline of HCT15 to adriamycin (CL02), we undertook the screening for agents which were effective to multidrug-resistant cancer cells. As a result, a myxobacterial strain JW150 was selected for study since an activity against CL02 cells was discovered in the strain. Cytotoxicity-guided fractionation of the culture broth led to the isolation of cystothiazole A and melithiazole F. The producing organism was identified as Myxococcus stipitatus by taxonomic comparison with type strains of Myxococcus sp. as well as its morphological and physiological characteristics. Cystothiazole A and melithiazole F demonstrated potent cytotoxicity against certain human cancer cells with $IC_{50}$ values ranging from 0.03~ $0.72{\mu}{\textrm{g}}$/ml. Both compounds were interestingly as active against drug-resistant sublines CL02 and CP70 as against the corresponding parental cells.

• Tuberculosis and Respiratory Diseases
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• v.66 no.3
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• pp.198-204
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• 2009

Background: First-line drugs, if sensitive, are the most potent drugs in the treatment of multidrug-resistant tuberculosis (MDR-TB). This study examined the frequency and risk factors associated with acquired drug resistance to first-line drugs during a standardized treatment using first-line drugs in patients with MDR-TB. Methods: This study included patients who were diagnosed with MDR-TB at the National Masan Tuberculosis Hospital between January 2004 and May 2008, treated with standardized first-line drugs, and for whom the preand post-treatment results of the drug susceptibility test were available. Their medical records were reviewed retrospectively. Results: Of 41 MDR-TB patients, 14 (34.1%) acquired additional resistance to ethambutol (EMB) or pyrazinamide (PZA). Of 11 patients initially resistant to isoniazid (INH) and rifampicin (RFP), 3 (27.3%) acquired additional resistance to both EMB and PZA, and 3 (27.3%) to PZA. Of 18 patients initially resistant to INH, RFP and EMB, 6 (33.3%) acquired additional resistance to PZA. Of 6 patients initially resistant to INH, RFP and PZA, 2 (33.3%) acquired additional resistance to EMB. Ten of the 41 MDR-TB patients (24.4%) changed from resistant to susceptible. No statistically significant risk factors associated with acquired resistance could be found. Conclusion: First-line drugs should be used cautiously in the treatment of MDR-TB in Korea considering the potential acquisition of drug resistance.

• Korean Journal of Microbiology
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• v.54 no.4
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• pp.442-444
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• 2018

Recently, we isolated a multidrug-resistant Escherichia coli strain KBN10P04869 from a patient with acute myeloid leukemia. We report the complete genome of this strain which consists of 5,104,264 bp with 4,457 protein-coding genes, 88 tRNAs, and 22 rRNAs, and the co-occurrence of multidrug- resistant genes including $^{bla}CMY-2$, $^{bla}TEM-1$, $^{bla}CTX-M-15$, $^{bla}NDM-5$, and $^{bla}OXA-18$.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.44-51
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• 1998

• Proceedings of the Zoological Society Korea Conference
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• 2003.08a
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• pp.26-26
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• 2003

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