• Title/Summary/Keyword: Drug-resistance

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Cellular Resistance to Antifolates (항엽산제에 대한 세포의 저항성 기작)

  • 김정상
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.22 no.6
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    • pp.839-845
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    • 1993
  • One of the major problems of cancer chemotheraphy is the development of drug resistance in tumors, resulting in reduced responsiveness to subsequent treatments. The folate antagonists are being used to treat such diverse illnesses as cancer, leukemia, psoriasis, rheumatoid arthritis, etc. Previous studies have established that resistance to antifolates may occur in mammalian tumor cells by one or more of five mechanisms ; (a) an increase in the levels of the target enzyme, generally as a consequence of gene amplification ; (b) an alteration in the target enzyme, leading to an enzyme with a decreased binding affinity for the drug ; (c) a decrease in the uptake of the drug into the cells ; (d) increased extrusion of drugs out of cells ; (e) impaired ability to polyglutamylate the parent drug which is capable of being intracellularly metabolized to longer chain length.

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Prevalence and Characteristics of Antimicrobial-Resistant Staphylococcus aureus and Methicillin-Resistant Staphylococcus aureus from Retail Meat in Korea

  • Kim, Yong Hoon;Kim, Han Sol;Kim, Seokhwan;Kim, Migyeong;Kwak, Hyo Sun
    • Food Science of Animal Resources
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    • v.40 no.5
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    • pp.758-771
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    • 2020
  • This study was to investigate the prevalence and characteristics of antimicrobial-resistant Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) from 4,264 retail meat samples including beef, pork, and chicken in Korea between 2013 and 2018. A broth microdilution antimicrobial susceptibility testing was performed for S. aureus. Molecular typing by multilocus sequence typing (MLST), spa typing, and pulsed-field gel electrophoresis (PFGE), was performed on mecA-positive S. aureus strain. S. aureus was isolated at a rate of 18.2% (777/4,264), of which MRSA comprised 0.7% (29 strains). MLST analysis showed that 11 out of the 29 MRSA isolates were predominantly sequence type (ST) 398 (37.9%). In addition, ST72, ST692, ST188, ST9, and ST630 were identified in the MRSA isolates. The spa typing results were classified into 11 types and showed a high correlation with MLST. The antimicrobial resistance assays revealed that MRSA showed 100% resistance to cefoxitin and penicillin. In addition, resistance to tetracycline (62.1%), clindamycin (55.2%), and erythromycin (55.2%) was relatively high; 27 of the 29 MRSA isolates exhibited multidrug resistance. PFGE analysis of the 18 strains excluding the 11 ST398 strains exhibited a maximum of 100% homology and a minimum of 64.0% homology. Among these, three pairs of isolates showed 100% homology in PFGE; these results were consistent with the MLST and spa typing results. Identification of MRSA at the final consumption stage has potential risks, suggesting that continuous monitoring of retail meat products is required.

Effect of MUC1 siRNA on Drug Resistance of Gastric Cancer Cells to Trastuzumab

  • Deng, Min;Jing, Da-Dao;Meng, Xiang-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.127-131
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    • 2013
  • Trastuzumab is the first molecular targeting drug to increase the overall survival rate in advanced gastric cancer. However, it has also been found that a high intrinsic or primary trastuzumab resistance exists in some proportion of gastric cancer patients. In order to explore the mechanism of resistance to trastuzumab, firstly we investigated the expression of MUC1 (membrane-type mucin 1) in gastric cancer cells and its relationship with drug-resistance. Then using gene-silencing, we transfected a siRNA of MUC1 into drug-resistant cells. The results showed the MKN45 gastric cell line to be resistant to trastuzumab, mRNA and protein expression of MUC1 being significantly upregulated. After transfection of MUC1 siRNA, protein expression of MUC1 in MKN45cells was significantly reduced. Compared with the junk transfection and blank control groups, the sensitivity to trastuzumab under MUC1 siRNA conditions was significantly increased. These results imply that HER2-positive gastric cancer cell MKN45 is resistant to trastuzumab and this resistance can be cancelled by silencing expression of the MUC1 gene.

Multiple Drug Resistance and Transferable R-plasmid of Streptococci Isolated from Diseased Olive Flounder (연쇄상구균의 약제내성과 전이성 R-plasmid의 특성)

  • Kim, Jong-Hun;Im, Dae-Hwan;Lee, Chang-Hun;Lee, Su-Jeong;Lee, Wol-Ra;Hwang, Mi-Hye;Kim, Eun-Hui
    • Journal of fish pathology
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    • v.16 no.1
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    • pp.61-68
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    • 2003
  • MICs of 8 chemotherapeutic agents against forty streptococcal isolates were determined. These strains were isolated from diseased olive flounder, Paralichthys olivaceus, and showed 2-5 multiple drug resistance against different antibacterial agents including ampicillin, doxycycline (DOXY), erythromycin, florfenicol, flumequine, norfloxacin, oxolinic acid, and oxytetracycline (OTC). In conjugation experiment, we found transferable R plasmids carrying OTC and DOXY resistance determinant in 3 drug resistance strains analyzed. Six out of 40 isolates showed positive signal in colony hybridization with the R plasmid DNA (pST9) as a probe. It suggests that other types R plasmid different from pST9 is also involving in multiple drug resistance of streptococci isolated from olive flounder.

Monitoring antimalarial drug-resistance markers in Somalia

  • Abdifatah Abdullahi Jalei;Kesara Na-Bangchang;Phunuch Muhamad;Wanna Chaijaroenkul
    • Parasites, Hosts and Diseases
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    • v.61 no.1
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    • pp.78-83
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    • 2023
  • The use of an effective antimalarial drug is the cornerstone of malaria control. However, the development and spread of resistant Plasmodium falciparum strains have placed the global eradication of malaria in serious jeopardy. Molecular marker analysis constitutes the hallmark of the monitoring of Plasmodium drug-resistance. This study included 96 P. falciparum PCR-positive samples from southern Somalia. The P. falciparum chloroquine resistance transporter gene had high frequencies of K76T, A220S, Q271E, N326S, and R371I point mutations. The N86Y and Y184F mutant alleles of the P. falciparum multidrug resistance 1 gene were present in 84.7 and 62.4% of the isolates, respectively. No mutation was found in the P. falciparum Kelch-13 gene. This study revealed that chloroquine resistance markers are present at high frequencies, while the parasite remains sensitive to artemisinin (ART). The continuous monitoring of ART-resistant markers and in vitro susceptibility testing are strongly recommended to track resistant strains in real time.

Effects of Vinorelbine on Cisplatin Resistance Reversal in Human Lung Cancer A549/DDP Cells

  • Zhou, Yu-Ting;Li, Kun;Tian, Hui
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4635-4639
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    • 2013
  • Multi-drug resistance (MDR) is an essential aspect of human lung cancer chemotherapy failure. Recent studies have shown that vinorelbine is involved in underlying processes in human tumors, reversing the MDR inseveral types of cancer cells. However, the roles and potential mechanism are not fully clear. In this study, we explored effects of vinorelbine in multi-drug resistance reversal of human lung cancer A549/DDP cells. We found that vinorelbine increased drug sensitivity to cisplatin and intracellular accumulation of rhodamine-123, while decreasing expression of P-glycoprotein (P-gp), multi-drug resistance-associated protein (MRP1) and glutathione-S-transferase ${\pi}$ (GST-${\pi}$) in A549/DDP cells. At the same time, we also established downregulation of p-Akt and decreased transcriptional activation of NF-${\kappa}B$ and twist after vinorelbine treatment. The results indicated that vinorelbine might be used as a potential therapeutic strategy in human lung cancer.

Azole Resistance Caused by Increased Drug Efflux in Candida glabrata Isolated from the Urinary Tract of a Dog with Diabetes Mellitus

  • Kim, Minchul;Lee, Hyekyung;Hwang, Sun-Young;Lee, Inhyung;Jung, Won Hee
    • Mycobiology
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    • v.45 no.4
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    • pp.426-429
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    • 2017
  • A yeast-like organism was isolated from a urine sample of a 6-year-old neutered male miniature poodle dog with urinary tract infection, diabetes ketoacidosis, and acute pancreatitis. We identified the yeast-like organism to be Candida glabrata and found that this fungus was highly resistant to azole antifungal drugs. To understand the mechanism of azole resistance in this isolate, the sequences and expression levels of the genes involved in drug resistance were analyzed. The results of our analysis showed that increased drug efflux, mediated by overexpression of ATP transporter genes CDR1 and PDH1, is the main cause of azole resistance of the C. glabrata isolated here.

Drug Resistance Patterns of the Bacterial Strains Isolated from Rural Areas and an Urban General Hospital (무의촌균주(無醫村菌株) 및 병원균주(病院菌株)의 항균제(抗菌劑) 내성(耐性) 양상(樣相)에 관(關)한 연구(硏究))

  • Rhee, Kwang-Ho;Kim, Ik-Sang;Shin, Hee-Sup;Cha, Chang-Yong;Lee, Seung-Hoon;Chang, Woo-Hyun;Lim, Jung-Kyoo
    • The Journal of the Korean Society for Microbiology
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    • v.15 no.1
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    • pp.19-32
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    • 1980
  • Besides the benefits of antimicrobial agents in the control of various infectious diseases, widespread and prolonged use of particular antimicrobial agents has brought about the increase of drug-resistant strains in a community and the profound changes in the pattern of infectious diseases. In Korea, there are some remote villages where no clinics and drug stores are available and the residents in those areas are assumed to have fewer chances to contact with antimicrobial agents. In the present study, the differences in susceptibilities to 14 antimicrobial agents between the isolates from rural areas(R) and Seoul National University Hospital(SNUH, H) were studied. The isolates and their numbers were Staphylococcus aureus, R;55, H;68), Enterococci(R;28, H;30), Escherichia coli(R;40, H;40), Enterobacter aerogenes(R;25, H;21) and Klebsiella pneunoniae(R;58, H;67). Minimal inhibitory concentrations(MIC's) of penicillin, ampicillin, carbenicillin, cephalexin, tetracycline, oxytetracyline, doxycycline, minocycline, gentamicin, kanamycin, streptomycin, erythromycin, troleandomycin and co-trimoxazole were determined by agar dilution method. I. Comparison of MIC's and resistant strain proportions between isolates from SNUH and rural areas. MIC's and/or resistant strain proportions of the isolates from SNUH were significantly higher than those of the isolates from rural areas in the cases of 1. S. aureus to doxycycline, streptomycin and kanamycin. 2. E. coli to penicillin, ampicillin, carbenicillin, tetracycline, oxytetracycline, doxycycline, minocycline, streptomycin, kanamycin, erythromycin and co-trimoxazole. 3. E. aerogences to carbenicillin, tetracycline, oxytetracycline, doxycycline, minocycline, streptomycin, kanamycin, genaamicin and co-trimoxazole. 4. K pneunoniae to penicillin, ampicillin, tetracycline, oxytetracycline, doxycycline, monocycline, streptomycin, kanamycine, gentamicin and co-trimoxazole. However, the mean MIC and resistant strain proportion of S. aureus to tetracycline were higher in isolates from rural areas than in those from SNUH and Enterococci showed no differences in susceptibilities to the antimicrobial agents between isolates from rural areas and from SNUH. Therefore, in general, differenes in susceptibility to these antimicrobial agents between the isolates from rural areas and SNUH were remarkably greater and broader in gram negative enteric bacteria. II. Multiple drug resistance pattern. Patterns and incidences of multiple drug resistance were studied with penicillin, ampicillin, tetracycline, cephalexin, gentamicin, streptomcin, kanamycin and co-trimoxazole in Enterococci, E. coli, E. aeroges and K. pneumoniae. There appeared significant differences in the incidence of multiply drug-resistant strains and multiple drug resistance patterns between the isolates from SNUH and rural areas in Enterococci, E. coli, E. aerogenes and K. pneumoniae. However, there was no difference in the incidence of multiply drug-resistant strains between isolates of S. aureus from SNUH and rural areas but the pattern of multiple resistance of the SNUH strains of S. aureus was diverse, while that of the rural strains was predominantly confined to penicillin-tetracycline combination. The incidence of multigly drug-resistant strains and diversity of their patterns were the highest in E. coli strains isolated from SNUH and there were no multiply drug resistant strrains in Enterococci and K. pneumoniae strains isolated from rural areas. The number of drug-resistance determinants was also different between the isolates from rural areas and SNUH. Most of the multiply drug-resistant strains of E. coli, E. aerogenes and K. pneumoniae isolated from SNUH were resistant to more than 3 kinds of antimicrobial agents, most frequently to ampicillin, tetracycline and streptomycin, while multiply drug-resistant strains from rural areas were resistant to 2 kinds of antimicrobial agents among ampicillin, tetracycline and streptomycin. With drug-resistant E. coli strains, resistance to tetracycline which was used most widely since 1951 was most frequently involved as a part of mutliple drug-resistance, followed by resistance to ampicillin and streptomycin. This strongly suggests that emergence of drug-restant strains in a community is directly dependent on the selective pressure exerted by the antimicrobial agent used. III. Cross resistance. Cross resistance of bacteria was studied among tetracycline penicillin, aminoglycoside and macrolide derivatives by analyzing correlation coefficients of sucseptibilities using the least square method. In this study, there were high correlations among the susceptibilities to related derivatives. It appears that the relatively low correlations in susceptibilities present in some cases are due to intrinsic resistance of E. aerogenes to penicillin, Enterococci to aminoglycoside and E. coli E. aerogenes and K. pneumoniae to macrolide derivatives.

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Drug resistance of bladder cancer cells through activation of ABCG2 by FOXM1

  • Roh, Yun-Gil;Mun, Mi-Hye;Jeong, Mi-So;Kim, Won-Tae;Lee, Se-Ra;Chung, Jin-Woong;Kim, Seung Il;Kim, Tae Nam;Nam, Jong Kil;Leem, Sun-Hee
    • BMB Reports
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    • v.51 no.2
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    • pp.98-103
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    • 2018
  • Recurrence is a serious problem in patients with bladder cancer. The hypothesis for recurrence was that the proliferation of drug-resistant cells was reported, and this study focused on drug resistance due to drug efflux. Previous studies have identified FOXM1 as the key gene for recurrence. We found that FOXM1 inhibition decreased drug efflux activity and increased sensitivity to Doxorubicin. Therefore, we examined whether the expression of ABC transporter gene related to drug efflux is regulated by FOXM1. As a result, ABCG2, one of the genes involved in drug efflux, has been identified as a new target for FOXM1. We also demonstrated direct transcriptional regulation of ABCG2 by FOXM1 using ChIP assay. Consequently, in the presence of the drug, FOXM1 is proposed to directly activate ABCG2 to increase the drug efflux activation and drug resistance, thereby involving chemoresistance of bladder cancer cells. Therefore, we suggest that FOXM1 and ABCG2 may be useful targets and important parameters in the treatment of bladder cancer.

Drug Resistance and R-Plasmid Profile of Shigella Isolated in 1986-1988 (이질균의 약제 내성과 R-Plasmid)

  • Chung, Kyu-Sun;Byun, Hye-Kyung
    • YAKHAK HOEJI
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    • v.34 no.1
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    • pp.54-63
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    • 1990
  • These studies were made to assess the present stage of resistance of Shigella species to antibiotics and to find characteristics of R-plasmid of these bacteria. From 1986 to 1988, 125 strains of Shigella species were isolated from patients specimens collected in Chung Cheong-do Hospital, Kyunghee Medical Center, city an provincial health & environmental institutes. These specimens were tested for resistance to 12 kinds of antimicrobial agents by agar dilution method. Using Muller-Hinton agar for the assay of drug resistance and Trypticane Soy Broth as propagating medium for conjugation. All the strains (100%) were resistant to one or more antibiotics. Drug resistance patterns of isolated strains were found as the highest resistance to ampicillin (98%) in 1986, to tetracycline (98%) in 1987, to tetracycline (100%) in 1988, all strains were sensitive to gentamicin, amikacin, tobramycin. Chronologically, resistance decreased gradually as it was shown in relation to kanamycin, rifampicin in 1986, 1987 and 1988, (4%, 2%) (4%, 2%) (0%, 0%) respectively. But, resistance was increased year by year as it was shown in relation to tetracycline, nalidixic acid, streptomycin in 1986, 1987, 1988 (89%, 19%, 45%) (98%, 46%, 71%) and (100%, 58%, 88%). The resistance in correlation to more than 5 drugs, which was 13 strains among 47 strains in 1986, 38 strains among 87 strains in 1987, 23 strains among 26 strains in 1988, was increased gradually. In the transfer test of drug resistance by conjugation methods, the rate which was 3 strains (50%) in 1986, 8 strains (62%) in 1987, 3 strains (100%) in 1988, was increased gradually. When the donor strains were conjugated with the recipient strains, the conjugation rate was high in the multiple resistant strains. The relationships of transferring patterns of drug resistance and molecular weight of R-plasmid were variable. However, only a plasmid which has more than 35 Mgd was transferred.

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