• Title/Summary/Keyword: multidrug

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Characterization and Resistance Mechanisms of A 5-fluorouracil-resistant Hepatocellular Carcinoma Cell Line

  • Gu, Wei;Fang, Fan-Fu;Li, Bai;Cheng, Bin-Bin;Ling, Chang-Quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4807-4814
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    • 2012
  • Purpose: The chemoresistance of human hepatocellular carcinoma (HCC) to cytotoxic drugs, especially intrinsic or acquired multidrug resistance (MDR), still remains a major challenge in the management of HCC. In the present study, possible mechanisms involved in MDR of HCC were identified using a 5-fluorouracil (5-FU)-resistant human HCC cell line. Methods: BEL-7402/5-FU cells were established through continuous culturing parental BEL-7402 cells, imitating the pattern of chemotherapy clinically. Growth curves and chemosensitivity to cytotoxic drugs were determined by MTT assay. Doubling times, colony formation and adherence rates were calculated after cell counting. Morphological alteration, karyotype morphology, and untrastructure were assessed under optical and electron microscopes. The distribution in the cell cycle and drug efflux pump activity were measured by flow cytometry. Furthermore, expression of potential genes involved in MDR of BEL-7402/5-FU cells were detected by immunocytochemistry. Results: Compared to its parental cells, BEL-7402/5-FU cells had a prolonged doubling time, a lower mitotic index, colony efficiency and adhesive ability, and a decreased drug efflux pump activity. The resistant cells tended to grow in clusters and apparent changes of ultrastructures occurred. BEL-7402/5-FU cells presented with an increased proportion in S and G2/M phases with a concomitant decrease in G0/G1 phase. The MDR phenotype of BEL-7402/5-FU might be partly attributed to increased drug efflux pump activity via multidrug resistance protein 1 (MRP1), overexpression of thymidylate synthase (TS), resistance to apoptosis by augmentation of the Bcl-xl/Bax ratio, and intracellular adhesion medicated by E-cadherin (E-cad). P-glycoprotein (P-gp) might play a limited role in the MDR of BEL-7402/5-FU. Conclusion: Increased activity or expression of MRP1, Bcl-xl, TS, and E-cad appear to be involved in the MDR mechanism of BEL-7402/5-FU.

Multidrug-Resistant Tuberculosis Presenting as Miliary Tuberculosis without Immune Suppression: A Case Diagnosed Rapidly with the Genotypic Line Probe Assay Method

  • Ko, Yousang;Lee, Ho Young;Lee, Young Seok;Song, Junwhi;Kim, Mi-Yeong;Lee, Hyun-Kyung;Shin, Jeong Hwan;Choi, Seok Jin;Lee, Young-Min
    • Tuberculosis and Respiratory Diseases
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    • v.76 no.5
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    • pp.245-248
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    • 2014
  • Miliary tuberculosis (TB) is a rare extrapulmonary form of TB, and there have been only two reports of miliary TB associated with infection with multidrug-resistant (MDR)-TB pathogen in an immunocompetent host. A 32-year-old woman was referred to our hospital because of abnormal findings on chest X-ray. The patient was diagnosed with MDR-TB by a line probe assay and was administered proper antituberculous drugs. After eight weeks, a solid-media drug sensitivity test revealed that the pathogen was resistant to ethambutol and streptomycin in addition to isoniazid and rifampicin. The patient was then treated with effective antituberculous drugs without delay after diagnosis of MDR-TB. To the best of our knowledge, this is the first case of miliary TB caused by MDR-TB pathogen in Korea.

Four Children with Multidrug-resistant Acinetobactor baumanii Infections in the Intensive Care Units of a University Hospital (단일 3차 의료기관 집중치료실에서 발생한 다약제내성 Acinetobacter baumannii의 4례)

  • Lee, Kyung Suk;Lee, Gyu Min;Yoon, Hoi Soo;Chung, Sa Jun;Cha, Sung-Ho;Chun, Hee-Kyung
    • Pediatric Infection and Vaccine
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    • v.18 no.1
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    • pp.97-102
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    • 2011
  • The Multidrug-resistant Acinetobactor baumanii (MDRAB) is an opportunistic pathogen. Patients with long periods of hospital stay and/or under intensive care unit (ICU) receiving invasive management are more susceptible to this pathogen. In this report, four children with MDRAB infection are reviewed and described their clinical characteristics. There had been concurrent outbreaks of MDRAB infection in adult patients in the ICU at this period of time. The first child had received a craniotomy and epidural hematoma evacuation. The second child was admitted for status epilepticus with hydrocephalus. The third child had pneumonia with status epilepticus with hydrocephalus. The fourth child had poor activity due to hypoxic ischemic encephalopathy and convulsive disorder. Except the fourth child, all had not been exposed to carbapenem prior to infection of MDRAB. That imply the cause of MDRAB infections may be associated with invasive management and prolonged hospitalization together with the previous exposure to carbapenem in our cases. We would like to emphasize the importance and minimizing the spread of hospital infection in patients under prolonged intensive care management regardless of the use of carbapenem.

Characterization of Drug-Resistant Salmonella enterica Serotype Typhimurium by Antibiograms, Plasmids, Integrons, Resistance Genes, and PFGE

  • Benacer, Douadi;Thong, Kwai Lin;Watanabe, Haruo;Puthucheary, Savithri Devi
    • Journal of Microbiology and Biotechnology
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    • v.20 no.6
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    • pp.1042-1052
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    • 2010
  • Forty-seven Salmonella Typhimurium (33 zoonotic, 14 clinical) strains were tested for antimicrobial resistance using the standard disk diffusion method. The presence of relevant resistance genes and class 1 integrons were investigated by using PCR. Pulsed-field gel electrophoresis (PFGE) and plasmid profiling were carried out to determine the genomic diversity of Salmonella Typhimurium. Approximately 57.4% of the S. Typhimurium strains were multidrug resistant (MDR) and showed high resistance rates to tetracycline (70.2%), sulfonamides (57.4%), streptomycin (53.1%), ampicillin (29.7%), nalidixic acid (27.6%), kanamycin (23.4%), chloramphenicol (21.2%), and trimethoprim (19.1%). Resistance towards cephalosporins was noted for cephalothin (27.6%), cephradine (21.2%), amoxicillin clavulanic acid (17.0%), and cephalexin (17.0%). Resistance genes, $bla_{TEM}$, strA, aadA, sul1, sul2, tetA, tetB, and tetC, were detected among the drug-resistant strains. Thirtythree strains (70.2%) carried class 1 integrons, which were grouped in 9 different profiles. DNA sequencing identified sat, aadA, pse-1, and dfrA genes in variable regions on class 1 integrons. Thirty-five strains (74.4%) were subtyped to 22 different plasmid profiles, each with 1-6 plasmids (2.0 to 95 kb). PFGE subtyped the 47 strains into 39 profiles. In conclusion, high rates of multidrug resistance were found among the Malaysian Salmonella Typhimurium strains. The emergence of multidrug-resistant Salmonella Typhimurium to cephalosporin antibiotics was also observed. The strains were very diverse and no persistent clone was observed. The emergence of MDR Salmonella Typhimurium is a worldwide problem, and this report provides information for the better understanding of the prevalence and epidemiology of MDR S. Typhimurium in Malaysia.

Biocidal Activity of Metal Nanoparticles Synthesized by Fusarium solani against Multidrug-Resistant Bacteria and Mycotoxigenic Fungi

  • Sayed, Manal T. El;El-Sayed, Ashraf S.A.
    • Journal of Microbiology and Biotechnology
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    • v.30 no.2
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    • pp.226-236
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    • 2020
  • Antibiotic resistance by pathogenic bacteria and fungi is one of the most serious global public health problems in the 21st century, directly affecting human health and lifestyle. Pseudomonas aeruginosa and Staphylococcus aureus with strong resistance to the common antibiotics have been isolated from Intensive Care Unit patients at Zagazig Hospital. Thus, in this study we assessed the biocidal activity of nanoparticles of silver, copper and zinc synthesized by Fusarium solani KJ 623702 against these multidrug resistant-bacteria. The synthesized Metal Nano-particles (MNPs) were characterized by UV-Vis spectroscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and Zeta potential. The Fourier transform infrared spectroscopy (FTIR) result showed the presence of different functional groups such as carboxyl, amino and thiol, ester and peptide bonds in addition to glycosidic bonds that might stabilize the dispersity of MNPs from aggregation. The antimicrobial potential of MNPs by F. solani against the multidrug-resistant (MDR) P. aeruginosa and S. aureus in addition to the mycotoxigenic Aspergillus awamori, A. fumigatus and F. oxysporum was investigated, based on the visual growth by diameter of inhibition zone. Among the synthesized MNPs, the spherical AgNPs (13.70 nm) displayed significant effect against P. aeruginosa (Zone of Inhibition 22.4 mm and Minimum Inhibitory Concentration 21.33 ㎍/ml), while ZINC oxide Nano-Particles were the most effective against F. oxysporum (ZOI, 18.5 mm and MIC 24.7 ㎍/ml). Transmission Electron Microscope micrographs of AgNP-treated P. aeruginosa showed cracks and pits in the cell wall, with internalization of NPs. Production of pyocyanin pigment was significantly inhibited by AgNPs in a concentration-dependent manner, and at 5-20 ㎍ of AgNPs/ml, the pigment production was reduced by about 15-100%, respectively.

Isolation of Antibiotics Effective to Multidrug-Resistant Cancer Cells from Sorangium cellulosum(Myxobacteria). (점액세균 Sorangium cellulosum이 생산하는 약제내성 암세포의 증식억제물질)

  • 안종웅;이정옥
    • Microbiology and Biotechnology Letters
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    • v.32 no.1
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    • pp.47-51
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    • 2004
  • Drug resistance is one of the most significant impediments to successful chemotherapy of cancer. Multidrug-resistance Is characterized by decreased cellular sensitivity to anticancer agents due to the overexpression of P-glycoprotein. By using adriamycin-resistance CL02 cancer cells, we undertook the screening fur agents which were effective to multidrug-resistant cancer cells from strains of the species Sorangium cellulosum isolated in our laboratory. Sorangium cellulose, cellulose-degrading myxobacteria have recently proved to be a rich source of novel anticancer agents. One of the significant examples is the promising anticancer agent epothilone. JW 1006 is the first strain of Sorangium cellulosum which was selected by us for the isolation of a metabolite by a biological screening because of a high cytotoxic activity against the CL02 cancer cells. Cytotoxicity-guided chromatographic fractionation of the culture broth led to the Isolation of two active principles, disorazole $A_1$ and $A_2$. They showed potent cytotoxicity against CL02 cancer cells with $IC_{50}$ values in the picomolar range, and were as active against drug-resistant cancer cells CL02 and CP70 as against the corresponding sensitive cells.