• 제목/요약/키워드: Resistant Genes

검색결과 852건 처리시간 0.027초

Silencing of Suppressor of Cytokine Signaling-3 due to Methylation Results in Phosphorylation of STAT3 in Imatinib Resistant BCR-ABL Positive Chronic Myeloid Leukemia Cells

  • Al-Jamal, Hamid AN;Jusoh, Siti Asmaa Mat;Yong, Ang Cheng;Asan, Jamaruddin Mat;Hassan, Rosline;Johan, Muhammad Farid
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권11호
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    • pp.4555-4561
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    • 2014
  • Background: Silencing due to methylation of suppressor of cytokine signaling-3 (SOCS-3), a negative regulator gene for the JAK/STAT signaling pathway has been reported to play important roles in leukemogenesis. Imatinib mesylate is a tyrosine kinase inhibitor that specifically targets the BCR-ABL protein and induces hematological remission in patients with chronic myeloid leukemia (CML). Unfortunately, the majority of CML patients treated with imatinib develop resistance under prolonged therapy. We here investigated the methylation profile of SOCS-3 gene and its downstream effects in a BCR-ABL positive CML cells resistant to imatinib. Materials and Methods: BCR-ABL positive CML cells resistant to imatinib (K562-R) were developed by overexposure of K562 cell lines to the drug. Cytotoxicity was determined by MTS assays and $IC_{50}$ values calculated. Apoptosis assays were performed using annexin V-FITC binding assays and analyzed by flow cytometry. Methylation profiles were investigated using methylation specific PCR and sequencing analysis of SOCS-1 and SOCS-3 genes. Gene expression was assessed by quantitative real-time PCR, and protein expression and phosphorylation of STAT1, 2 and 3 were examined by Western blotting. Results: The $IC_{50}$ for imatinib on K562 was 362nM compared to 3,952nM for K562-R (p=0.001). Percentage of apoptotic cells in K562 increased upto 50% by increasing the concentration of imatinib, in contrast to only 20% in K562-R (p<0.001). A change from non-methylation of the SOCS-3 gene in K562 to complete methylation in K562-R was observed. Gene expression revealed down-regulation of both SOCS-1 and SOCS-3 genes in resistant cells. STAT3 was phosphorylated in K562-R but not K562. Conclusions: Development of cells resistant to imatinib is feasible by overexposure of the drug to the cells. Activation of STAT3 protein leads to uncontrolled cell proliferation in imatinib resistant BCR-ABL due to DNA methylation of the SOCS-3 gene. Thus SOCS-3 provides a suitable candidate for mechanisms underlying the development of imatinib resistant in CML patients.

충청지역의 임상검체로부터 분리된 Acinetobacter calcoaceticus-baumannii Complex를 대상으로 항균제 내성 유전자 비교분석 (Distribution of Antimicrobial Resistant Genes in Acinetobacter calcoaceticus-baumannii Complex Isolated from Clinical Specimens in Chungcheong, Korea)

  • 성지연
    • 대한임상검사과학회지
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    • 제49권4호
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    • pp.427-434
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    • 2017
  • Acinetobacter calcoaceticus-baumannii (Acb) complex에 속한 종들은 빈번하게 병원감염 및 기회감염을 일으킨다. 또한 다제내성인 경우가 많아 이 균들의 감염증 치료를 위한 항균제 선택이 매우 제한적이다. 본 연구에서는 ciprofloxacin 내성 Acinetobacter species 53균주를 대상으로 fluoroquinolone 내성기전을 조사했다. 항균제 감수성 양상을 조사하기 위해 디스크확산법이 시행되었다. Fluoroquinolone 내성과 관련된 유전자 및 돌연변이 검출을 위해 PCR과 염기서열분석이 이루어졌다. 본 연구에서 수집된 53균주의 ciprofloxacin 내성 Acinetobacter 중 47균주가 gyrA 유전자의 83번째 serine 아미노산 잔기와 parC 유전자의 80번째 serine 아미노산 잔기가 leucine 잔기로 치환된 sense mutations 가지고 있는 것으로 나타났다. gyrA와 parC 유전자에 sense mutations을 가지고 있는 47균주 중 44균주가 A. baumannii 였고 3균주는 A. pittii였다. 본 연구에서 조사대상이 되었던 Acb complex 균주들 중 plasmid-mediated quinolone resistance (PMQR) determinants를 가지고 있는 균주는 한나도 없었다. 46 균주의 ciprofloxacin 내성 A. baumannii 는 A, B, 또는 F형의 banding pattern을 보였는데 이는 충청지역에 위치한 일개의 병원에 ciprofloxacin 내성 A. baumannii가 수평확산 되어 있음을 의미한다. Fluoroquinolone 내성 Acb complex 균주의 집락화 및 확산을 막기 위해서 다제내성 균주들을 대상으로 항균제 내성인자들을 지속적으로 조사하고 모니터링할 필요가 있을 것으로 사료된다.

1981年度 韓國動物學會 秋季學術大會 特別講演 要旨: Resistance to Carcinogens at Early Developmental Stages and the Latent Period of Induced Neoplasms

  • 근등종평
    • 한국동물학회지
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    • 제25권1호
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    • pp.29-29
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    • 1982
  • Carcinogenesis is extremely complex. Therefore, it is paradoxical but nonetheless important in cancer research if, in an animal whose parental strains are normally sensitive to cancer induction, we could find mutant strains which are resistant to various carcinogens as a result of mutations in one or two genes. No such mutants have been reported so far as I am aware but we do know that at early stages in their development, fish, mice, and humans are highly resistant to cancer induction by chemicals and radiation. I will give a brief overview of the stage-dependent resistance of fish, mice and humans to cancer induction and discuss the stem-cell mutation theory to explain the cancer-resistant stages. Finally, the latent period of induced neoplasms will be discussed in relation to the stem-cell mutation theory.

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Insulin Resistance Does Not Influence Gene Expression in Skeletal Muscle

  • Nguyen, Lisa L.;Kriketos, Adamandia D.;Hancock, Dale P.;Caterson, Ian D.;Denyer, Gareth S.
    • BMB Reports
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    • 제39권4호
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    • pp.457-463
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    • 2006
  • Insulin resistance is commonly observed in patients prior to the development of type 2 diabetes and may predict the onset of the disease. We tested the hypothesis that impairment in insulin stimulated glucose-disposal in insulin resistant patients would be reflected in the gene expression profile of skeletal muscle. We performed gene expression profiling on skeletal muscle of insulin resistant and insulin sensitive subjects using microarrays. Microarray analysis of 19,000 genes in skeletal muscle did not display a significant difference between insulin resistant and insulin sensitive muscle. This was confirmed with real-time PCR. Our results suggest that insulin resistance is not reflected by changes in the gene expression profile in skeletal muscle.

항생제 내성 제어를 위한 소독 기법간의 비교 ; 염소, 오존 및 전자빔 (The Comparison of Disinfection Technologies for Managing Antibiotic Resistance ; Chlrorination, Ozonation and Electron Beam)

  • 오준식;김성표
    • 상하수도학회지
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    • 제27권6호
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    • pp.797-803
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    • 2013
  • Recently, a number of countries are now considering the reuse of effluents from wastewater treatment for various water applications. To improve the reuse of wastewater effluent, the development of appropriate micro-pollutant removal technology is necessary. Although several researche have been studied for removing micro-pollutants in water, little study has been conducted for the removal of emerging contaminant such as antibiotic resistant genes (ARGs) by disinfection processes. Therefore, the aim of this study is to compare the capacity of disinfection technologies such as chlorination, ozone, and electron beam, for removing antibiotic resistant bacteria (ARB) and ARGs. Based on this study, better ARG removal can be achieved by ozonation and electron beam. Relatively, high CT values of chlorination or ozonation are needed to remove ARB and ARG compared to conventional pathogens.

Kanamycin Acetyltransferase Gene from Kanamycin-producing Streptomyces kanamyceticus IFO 13414

  • Joe, Young-Ae;Goo, Yang-Mo
    • Archives of Pharmacal Research
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    • 제21권4호
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    • pp.470-474
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    • 1998
  • A kanamycin producer, Streptomyces kanamyceticus IFO 13414 is highly resistant to kanamycin. Cloning of the kanamycin resistance genes in S. lividans 1326 with pIJ702 gave several kanamycin resistant transformants. Two transformants, S. lividans SNUS 90041 and S. lividan. SNUS 91051 showed similar resistance patterns to various aminoglycoside antibiotics. Gene mapping experiments revealed that plasmids pSJ5030 and pSJ2131 isolated from the transformants have common resistant gene fragments. Subcloning of pSJ5030 gave a 1.8 Kb gene fragment which showed resistance to kanamycin. Cell free extracts of S. lividans SNUS 90041, S. lividans SNUS 91051 and subclone a S. lividans SNUS 91064 showed kanamycin acetyltransferase activity. The detailed gene map is included.

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거세저항성전립선암에서 정밀의학에 대한 고찰 (Precision Medicine in Castration-Resistant Prostate Cancer)

  • 김원태;윤석중;김원재
    • 대한비뇨기종양학회지
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    • 제16권3호
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    • pp.97-102
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    • 2018
  • Prostate cancer is usually managed by androgen deprivation therapy after failure of primary treatment. However, such therapies are only temporarily effective in prostate cancer patients, and the most patients experience the progression to castration-resistant prostate cancer (CRPC). Docetaxel chemotherapy is conventional effective treatment for CRPC but has many adverse effects. In CRPC patients, treatment decisions were not typically base on the recognitions of inter-individual differences. Therefore, there are growing interests for precision medicine in CRPC. In this review, we summarized the precision medicine such as candidate target genes and potential therapies in CRPC.

Virus-resistant and susceptible transgenic Nicotiana benthamiana plants expressing coat protein gene of Zochini green mottle mosaic virus for LMO safety assessment

  • Park, M.H.;B.E. Min;K.H. Ryu
    • 한국식물병리학회:학술대회논문집
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    • 한국식물병리학회 2003년도 정기총회 및 추계학술발표회
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    • pp.146.1-146
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    • 2003
  • Transgenic Nicotiana benthmiana plants harboring and expressing coat protein (CP) gene of Zucchini green mottle mosaic virus (ZGMMV) were generated for both virus-resistant screening and complementation analysis of related viruses and environmental safety assessment (SA) of living modified organism (LMO) purposes. Transformation of leaf disc of N. benthamiana was performed using Agrobacterium-mediated method and the pZGCPPGA748 containing the ZGMMV CP and NPTII genes. Two kinds of transgenic homozygous groups, virus-resistant and -susceptible lines, were obtained by screening of challenging homologous virus for T1 generations. Complementation of CP-deficient related virus was analyzed using the susceptible line of ZGMMV. These two pathologically different lines can be useful for host-virus interactions and LMO environmental SA.

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Complete Genome Sequence of Colistin-Resistant Salmonella enterica Serotype Enteritidis Strain CRSE-01 Isolated from Poultry Carcass in South Korea

  • Jun Bong Lee;Yewon Cheong;Se Kye Kim;Jang Won Yoon
    • 한국미생물·생명공학회지
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    • 제51권3호
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    • pp.314-316
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    • 2023
  • Colistin is one of the last-resort antibiotics used to treat multidrug-resistant Gram-negative bacterial infection in both human and animals. Here, we report the complete genome sequence of colistin-resistant Salmonella enterica serotype Enteritidis strain CRSE-01 isolated from poultry carcass in South Korea. The assembled genome consists of a 4,783,907-bp circular chromosome containing numerous antimicrobial resistance genes and a 59,372-bp plasmid.