• Korean Journal of Clinical Laboratory Science
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• v.54 no.2
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• pp.119-124
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• 2022

Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are typical opportunistic pathogens. Moreover, these bacteria are known to possess multidrug-resistant (MDR) properties. This study investigates the antimicrobial activity of six fermented products, which have varying efficacies against P. aeruginosa, E. coli, and S. aureus. To identify novel candidate genes, differential expression analysis was performed using an annealing control primer. In the disk diffusion method, Fig vinegar (FV) and Diospyros kaki Thunb vinegar (DTV) showed the greatest increase in inhibition compared to other fermented products, whereas fermented Korean traditional nature herb (FKTNH) had no antibacterial effect. This study identified down-regulation of Escherichia coli O157:H7 ompW gene for outer membrane protein W, whereas gene for synthetic construct Lao1 gene for L-amino acid oxidase were up-regulated in E. coli treated with 5% FV. Consuming fermented vinegar helps prevent bacterial infections. Especially, FV and DTV are potentially useful alternative natural products for multidrug resistance. Furthermore, both are expected to be used as effective natural antimicrobial agents, such as disinfectants.

• Tuberculosis and Respiratory Diseases
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• v.85 no.3
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• pp.256-263
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• 2022

Background: Mycobacterium tuberculosis (Mtb) is resistant to the β-lactam antibiotics due to a non-classical transpeptidase in the cell wall with β-lactamase activity. A recent study showed that meropenem combined with clavulanate, a β-lactamase inhibitor, was effective in multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). However, in Korea, clavulanate can only be used as drugs containing amoxicillin. In this study, we investigated the susceptibility and genetic mutations of drug-resistant Mtb isolates to amoxicillin-clavulanate and meropenem-clavulanate to improve the diagnosis and treatment of drug-resistant TB patients. Methods: The minimum inhibitory concentration (MIC) of amoxicillin-clavulanate and meropenem-clavulanate was examined by resazurin microtiter assay. We used 82 MDR and 40 XDR strains isolated in Korea and two reference laboratory strains. Mutations of drug targets blaC, blaI, ldtA, ldtB, dacB2, and crfA were analyzed by polymerase chain reaction and DNA sequencing. Results: The MIC₉₀ values of amoxicillin/clavulanate and meropenem/clavulanate in drug-resistant Mtb isolates were 64/2.5 and 16/2.5 mg/L, respectively. Gene mutations related to amoxicillin/clavulanate and meropenem/clavulanate resistance could not be identified, but T448G mutation was found in the blaC gene related to β-lactam antibiotics' high susceptibility. Conclusion: Our results provide clinical consideration of β-lactams in treating drug-resistant TB and potential molecular markers of amoxicillin-clavulanate and meropenem-clavulanate susceptibility.

• Journal of Pharmaceutical Investigation
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• v.37 no.5
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• pp.287-290
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• 2007

Intrinsic or acquired resistance to chemotherapeutic drugs is one of the major obstacles to effective cancer treatment. Hypoxia is widespread in solid tumors as a consequence of decreased blood flow in the tumor-derived neovasculature. The recent finding of a link between hypoxia and chemoresistance prompted us to investigate whether hypoxia induces doxorubicin resistance in human MCF-7 breast cancer cells. Low oxygen concentration decreased the doxorubicin sensitivity in MCF-7 cells. The expression of p-glycoprotein, a major MDR-related transporter, and those of apoptosis-related proteins (anti-apoptotic Bcl-2, Bcl-XL and pro-apoptotic Bax) were not altered by hypoxia in MCF-7 cells. Intracellular uptake of doxorubicin was significantly decreased under hypoxic conditions. Decreased cellular uptake of doxorubicin under hypoxia may contribute to causing doxorubicin resistance in these cells. The use of agents that can modulate the doxorubicin uptake for adjuvant therapy may contribute to improving the therapeutic efficacy of doxorubicin in breast cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3021-3027
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• 2014

Background: The multidrug resistance 1 gene (MDR1) C3435T polymorphism has been demonstrated to influence the P-glycoprotein (P-gp) activity level which is related to inflammation and carcinogenesis. This meta-analysis was performed to estimate the association between the MDR1 C3435T polymorphism and the risk of gastric cancer (GC) and peptic ulcer (PU). Materials and Methods: A literature search was conducted with PubMed, Embase and the Cochrane library up to November 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Data were analyzed using Review Manager (Version 5.2), and Stata package (version 12.0) for estimation of publication bias. Results: Six case-control studies were included, of which five were for GC and two for PU. Overall, no evidence was found for any association between the MDR1 C3435T polymorphism and the susceptibility to GC and PU. In the stratified analysis by H. pylori infection status, stage and histology classification of GC, and PU type, there was still no significant association between them. Conclusions: This meta-analysis suggested that the MDR1 C3435T polymorphism is not associated with susceptibility to GC and PU. Large and well-designed studies are warranted to validate our findings.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3213-3217
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• 2013

Background: P-glycoprotein (Pgp), encoded by the multidrug resistance 1 (MDR1) gene, is an efflux transporter which plays an important role in pharmacokinetics. The current preliminary study was designed to determine associations between a germ-line polymorphism in the MDR1 gene with differentiated thyroid carcinoma (DTC). Materials and Methods: In the current case-control study, 60 differentiated thyroid cancers (DTC)- 45 papillary TC (PTC), 9 follicular TC(FTC) and 6 well-differentiated tumors of uncertain malignant potential (WDT-UMP) were examined. Results were compared to a healthy control group (n=58) from the same population. Genomic DNA was extracted from peripheral blood with EDTA and the target gene was genotyped by real-time PCR. Results: Carriers of the variant allele of MDR1 exon 26 polymorphism were at 2.8-fold higher risk of DTC than the control group (odds ratio [OR]: 0.3805, 95% confidence interval [Cl]: 0.1597-0.9065 (p> 0.046). Conclusions: Presented results suggest that the MDR1 3435TT genotype might influence risk of development of DTC and that the CC genotype might be linked to a poor prognosis. Large-scale studies are now needed to validate this association.

• Advances in Traditional Medicine
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• v.4 no.3
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• pp.179-185
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• 2004

The ethanol extract of Indigofera cordifolia was studied for in vivo gastroprotective activity, cytotoxic activity against oral tumor and normal cells, multidrug resistance (MDR) reversal activity, anti-human immunodeficiency virus (HIV) activity and radical scavenging activity. The extract of I. cordifolia showed potent gastric mucosal protective activity against stomach injury induced by HCl/EtOH solution. However, the gastroprotective activity could not be related to the radical mechanism, because the extract weakly scavenged both OH radical and $O_2*^-$. The extract also showed promising levels of MDR-reversing activity. This study demonstrates the tumor-specific cytotoxic action of the plant extract. However, the extract had no anti-HIV activity. From above results, the study suggests the medicinal importance of I. cordiforia extract.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.27-29
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• 2004

Drug transporters play an essential role in the absorption, distribution and elimination of clinical drugs, nutrients and toxicants. The importance of the transporters is exampled by therapeutic failure in cancer chemotherapy that is mainly caused by the overexpression of multidrug resistance (MDR)-related transporters. In addition, the transporters may involve in drug-drug interactions that lead to serious adverse drug responses and some transporters also contribute to inter-individual variation in drug responses. As an effort to understand the mechanism underlying the inter-individual variation of transporters activity, genetic and environmental factors influencing the expression or function of the transporters have extensively explored through last decade. Among them, genetic polymorphism of drug transporter encoding genes has generated much interest since the discovery of functional single nucleotide polymorphisms (SNP) of MDR1 gene. Besides drug transporters, xenobiotic receptors also modulate drug disposition by regulating the transcription of drug metabolizing enzymes and drug transporters. Among many xenobiotic receptors, pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are two most well characterized since these receptors show wide substrate specificities and regulate the expression of various enzymes involved in drug disposition. Recently, several functional genetic polymorphisms were reported in PXR coding gene. In the present study, genetic polymorphisms of two drug transporters, MDR1 and BCRP, and two xenobiotic receptors, PXR and CAR, were investigated in Korean population.

• Journal of Preventive Medicine and Public Health
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• v.52 no.1
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• pp.66-70
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• 2019

Objectives: In the Republic of Korea (ROK), the notified incidence of tuberculosis in foreign-born individuals (NITFBI) has increased recently, as has the rate of multidrug-resistant (MDR) and rifampicin-resistant (RR) tuberculosis in foreigners staying in the ROK. As Jeju Province in ROK has a no-visa entry policy, control programs for NITFBI should be consolidated. The aim was to evaluate the status of NITFBI, with a focus on the distribution of MDR/RR tuberculosis by nationality. Methods: Data on tuberculosis incidence in individuals born in Jeju Province and in foreign-born individuals were extracted from the Korean Statistical Information Service of Statistics Korea, and the Infectious Disease Surveillance Web Statistics of the Korea Centers for Disease Control and Prevention, respectively. Results: Among all notified incident cases of tuberculosis, the proportion of NITFBI increased from 1.46% in 2011 to 6.84% in 2017. China- and Vietnam-born individuals accounted for the greatest proportion of the 95 cases of NITFBI. Seven cases of MDR/RR tuberculosis were found, all involving patients born in China. Conclusions: In Jeju Province, ROK, NITFBI might become more common in the near future. Countermeasures for controlling active tuberculosis in immigrants born in high-risk nations for tuberculosis should be prepared in Jeju Province, since it is a popular tourist destination.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.77 no.4
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• pp.161-166
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• 2014

Since tuberculosis (TB) remains a major global health concern and the incidence of multi-drug resistant (MDR)-TB is increasing globally, new modalities for the detection of TB and drug resistant TB are needed to improve TB control. The Xpert MTB/RIF test can be a valuable new tool for early detection of TB and rifampicin resistance, with a high sensitivity and specificity. Late-generation fluoroquinolones, levofloxacin, and moxifloxacin, which are the principal drugs for the treatment of MDR-TB, show equally high efficacy and safety. Systemic steroids may reduce the overall TB mortality attributable to all forms of TB across all organ systems, although inhaled corticosteroids can increase the risk of TB development. Although fixed dose combinations were expected to reduce the risk of drug resistance and increase drug compliance, a recent meta-analysis found that they might actually increase the risk of relapse and treatment failure. Regarding treatment duration, patients with cavitation and culture positivity at 2 months of TB treatment may require more than 6 months of standard treatment. New anti-TB drugs, such as linezolid, bedaquiline, and delamanid, could improve the outcomes in drug-resistant TB. Nontuberculous mycobacterial lung disease has typical clinical and immunological phenotypes. Mycobacterial genotyping may predict disease progression, and whole genome sequencing may reveal the transmission of Mycobacterium abscessus. In refractory Mycobacterium avium complex lung disease, a moxifloxacin-containing regimen was expected to improve the treatment outcome.