• Genomics & Informatics
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• 제15권3호
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• pp.87-97
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• 2017

Multiple myeloma (MM) is a malignant disease caused by an abnormal proliferation of plasma cells, of which the prognostic factors include chromosomal abnormality, ${\beta}$-2 microglobulin, and albumin. Recently, the term chromothripsis has emerged, which is the massive but highly localized chromosomal rearrangement in response to a one-step catastrophic event. Many studies have shown an association of chromothripsis with the prognosis in several cancers; however, few studies have investigated it in MM. Here, we studied the association between chromothripsis-like patterns and treatment resistance or prognosis. First, we analyzed nine MM cell lines (U266, MM.1S, RPMI8226, KMS-11, KMS-12-BM, KMS-12-PE, KMS-28-BM, KMS-28-PE, and NCI-H929) and bone marrow samples of four patients who were diagnosed with MM by next-generation sequencing-based copy number variation analysis. The frequency of the chromothripsis-like pattern was observed in seven cell lines. We analyzed the treatment-induced chromothripsis-like patterns in KMS-12-BM and KMS-12-PE cells. As a result, breakpoints and chromothripsis-like patterns were increased after drug treatment in the relatively resistant KMS-12-BM. We further analyzed the patients' results according to the therapeutic response, which was divided into sensitive and resistant, as suggested by the International Myeloma Working Group. The chromothripsis-like pattern was more frequently observed in the resistant group. In the sensitive group, the frequency of the chromothripsis-like pattern decreased after treatment, whereas the resistant group showed increased chromothripsis-like patterns after the treatment. These results suggest that the chromothripsis-like pattern is associated with treatment response in MM.

• 대한수의학회지
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• 제48권3호
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• pp.275-285
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• 2008

Antimicrobial drugs are widely used in poultry industry as growth promoters or to control infectious diseases. However, this practice is reported to have caused high resistance to antimicrobial drugs in normal chicken flora and pathogens. Antimicrobial resistance to Escherichia coli (E. coli) from chicken has been mainly reported in normal flora, but rare in pathogenic organism in Korea, recently. Therefore, this study was conducted to investigate prevalence of antimicrobials resistance, transfer of R plasmid, and association between antimicrobial drug resistance and O serotype of 203 pathogenic E. coli from poultry in Korea during the period from April 2003 to December 2005. These isolates showed a high resistance to tetracycline (Tc, 93.6%), nalidixic acid (Na, 92.6%), streptomycin (Sm, 81.8%), ampicillin (Ap, 77.3%), ciprofloxacin (Ci, 70.9%), sulfisoxazole (Su, 66.5%), and trimethoprim (Tp, 58.1%). Two hundred-one (99.0%) of the isolates were resistant to one or more drugs. They showed 57 different resistant patterns, and the most prevalent resistant pattern among them was Tc, Sin, Su, Ap, Tp, Ci, Na. Sixty-eight (33.8%) of the isolates transferred all or a part of their antimicrobial resistant pattern to the recipient strain by R plasmid. The most common antimicrobial resistant pattern was Tc, Sm, Su, Ap, Tp, Ci, Na in serotype O78, O88 and O15, respectively. These results exhibit high individual and multiple resistance to antimicrobials of pathogenic E. coli from poultry in Korea. They also suggest the needs for surveillance to monitor antimicrobial resistance in pathogenic bacteria that can be potentially transmitted to humans from food animals and to regulate the abuse of antimicrobials on food-producing animals in Korea.

• Tuberculosis and Respiratory Diseases
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• 제71권2호
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• pp.120-125
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• 2011

Background: Although the prevalence of pulmonary tuberculosis has progressively decreased all over the world, drug-resistant tuberculosis is major obstacle in treating tuberculosis. This study was performed to examine the current prevalence and risk factors of drug resistant tuberculosis in a single tertiary hospital in Busan, Korea. Methods: We enrolled 367 patients with active pulmonary tuberculosis on a retrospective basis who had undergone mycobacterium culture and drug sensitivity tests between January 2005 and December 2009. We analyzed all clinical and radiographic parameters to find predictors related to drug resistant tuberculosis. Results: At least one incident of drug resistance was found in 75 (20.4%) patients. Isoniazid (18.8%) was the most frequent resistant drug, followed by rifampin (10.9%), ethambutol (7.1%), streptomycin (4.9%), and fluoroquinolone (2.7%). Resistance to second-line drugs was found in 37 (10.1%) patients. Multidrug resistance and extensively drug resistance was evident in 39 (10.6%) and 4 (1.1%) patients, respectively. Using multiple logistic regression analysis, history of previous treatment including relapse (odd ratio [OR], 11.3; 95% confidence interval [CI], 4.92~26.08; p<0.01), treatment failure (OR, 24.1; 95% CI, 5.65~102.79; p<0.01) and an age of below 46 years-old (OR, 3.8; 95% CI, 1.62~8.65; p<0.01) were found to be independent predictors of multidrug resistant tuberculosis. Conclusion: We found that the prevalence of drug resistant tuberculosis was considerably high. A careful consideration for possible drug resistant tuberculosis is warranted in patients with a history of previous treatment or for younger patients.

• 한국동물위생학회지
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• 제43권1호
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• pp.31-37
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• 2020

Clostridial bacteria are zoonotic agents, which cause severe necrotizing enteritis, pseudo-membrane colitis, enterotoxemia to both humans and animals. The objective of this study was to monitor the antibiotic resistance of Clostridium isolates on clinical specimens from wild animals in Seoul zoo for 5 years. Clostridium isolates were verified by using Vitek2 compact machine. Antibiotic susceptibility was assessed by antibiotic disc diffusion test, which was followed by Kirby-Bauer disc diffusion test method. The frequency of Antimicrobial resistance of Clostridium isolate was the greatest in gentamicin (87%), then in order of amikacin (80%). There were 55.6% of Clostridium isolates showed multiple drug resistance (MDR). These results showed that a lot of Clostridial bacteria from wild animals in Seoul zoo were acquired antibiotic resistance. Because of the wild animal's aggressive manner, it has been hard to collect clinical samples from wild animals in a zoo to exam antibiotic susceptibility. For these reasons, empirical use of antibiotics has been performed in frequently. It may cause to increase the emergence of antibiotic resistance bacteria. In addition, the antibiotic resistance bacteria from zoo animals can be spread to other wild animals which inhabit around the zoo. Therefore, regular monitoring of antibiotic resistance Clostridial bacteria is important to protect animals and humans from Clostridial diseases.

• 한국어병학회지
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• 제12권2호
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• pp.115-121
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• 1999

양식넙치에서 분리된 Edwardsiella tarda가 갖는 약제내성을 전달하는 R plasmid의 특성을 알아보기 위하여, 16종의 화학요법제에 대한 E. tarda의 감수성 정도를 비교하였으며, 내성형태 및 내성전달을 확인하고 transferable R plasmid를 분리하였다. E. tarda는 ampicillin, amoxicillin, erythromycin, flumequine, doxycycline(DOXY), nalidixic acid, novobiocin, oxolinic acid, oxytetracycline(OTC), thiamphenicol(TP) 그리고 sulfonamide의 11약제에 대하여 다양한 조합으로 복합내성을 보였으며, DOXY, OTC, TP 내성이 Escherichia coli로 전달되었다. 복합내성의 두 균주에서 transconjugant가 형성되었으며 이들로부터 분리된 transferable R plasmid는 서로 상이한 DNA 구조였다. 이는 넙치에서 분리되는 E. tarda에는 적어도 두 종류 이상의 thansferable R plasmid가 분포한다는 것을 의미한다.

• 대한수의학회지
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• 제16권2호
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• pp.159-163
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• 1976

One hundred and sixty one Escherichia coli strains isolated from 24 swine (11 swine fed with feedstuffs containing 7.5mg/kg of tetracycline and 13 swine not received antibiotic) were studied for the drug resistance and distribution of R factors. About 42 per cent of E. coli strains isolated from pigs of a herd fed with tetracycline (TC)-containing feeds were resistant to TC, streptomycin(SM), sulfisomidine(SA), ampicillin (AP) and kanamycin (KM), alone or in combination thereof, but none of the swine not receiving antibiotic containing feedstuffs excreted E. coli resistant to these drugs, Among resistant strains, 18.2% were found to be singly resistant to TC, whereas 81.8% were resistant to two or more antibiotics. The most common pattern was the triple resistant to TC, SM and SA(30.3%), and follolwed by double ones to TC and SM(24.2%). About one half of resistant strains carried R factors which were tranferable to the recipients by conjugation. In spite of feeding with feedstuffs containing only TC, high incidences of multiple resistance and R factors were observed in the E. coli isolated from these swine.

• Molecules and Cells
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• 제46권3호
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• pp.153-164
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• 2023

Cancer stem cells (CSCs) are a small population of tumor cells characterized by self-renewal and differentiation capacity. CSCs are currently postulated as the driving force that induces intra-tumor heterogeneity leading to tumor initiation, metastasis, and eventually tumor relapse. Notably, CSCs are inherently resistant to environmental stress, chemotherapy, and radiotherapy due to high levels of antioxidant systems and drug efflux transporters. In this context, a therapeutic strategy targeting the CSC-specific pathway holds a promising cure for cancer. NRF2 (nuclear factor erythroid 2-like 2; NFE2L2) is a master transcription factor that regulates an array of genes involved in the detoxification of reactive oxygen species/electrophiles. Accumulating evidence suggests that persistent NRF2 activation, observed in multiple types of cancer, supports tumor growth, aggressive malignancy, and therapy resistance. Herein, we describe the core properties of CSCs, focusing on treatment resistance, and review the evidence that demonstrates the roles of NRF2 signaling in conferring unique properties of CSCs and the associated signaling pathways.

• 생명과학회지
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• 제31권5호
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• pp.527-535
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• 2021

라이소좀은 산성가수분해 효소를 가진 세포 내 소기관으로 단백질 및 고분자를 분해한다. 영양분 상태에 따라 세포 내 다양한 신호 전달 경로를 조절하는 신호 경로 중추로, 세포 항상성 조절에 중요한 역할을 한다. 따라서 이러한 라이소좀의 기능 이상은 라이소좀 저장질환, 퇴행성 신경질환 및 암을 발생시킬 수 있다. 암세포에서는 다양한 자극에 의한 lysosomal membrane permeabilization (LMP)가 일어날 수 있으며, 카텝신과 같은 라이소좀 내 효소 및 내용물이 세포질로 유출되어 다양한 형태의 라이소좀 의존적인 암세포사멸을 유도한다. 본 보고에서는 LMP 증가를 통한 다양한 형태의 세포사멸 유도 기전 및 항암제 민감성 증진에 대해 서술하였다. 미미한 LMP 유도는 일부 카텝신이 세포질로 유출되어 전형적인 세포사멸(apoptosis)을 일으키는 반면 강력한 LMP 유도는 라이소좀의 파열로 많은 카텝신 및 활성산소의 유출로 non-apoptotic 세포사멸을 일으킨다. 이러한 LMP 유도는 라이조솜 내에 포획된 항암제가 세포질로 유출되어 다른 타겟 소기관으로 작용하여 항암제에 대한 내성을 극복하고 민감성을 증진시킬 수 있다. 따라서, LMP 유도제 및 라이소좀 항성 작용제(lysosomotropic agent)에 의한 라이소좀 막 분열은 종양치료에 있어 새로운 전략이 될 수 있다.

• 미생물학회지
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• 제48권1호
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• pp.22-28
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• 2012

장염비브리오는 우리나라에서 하절기에 발생하는 식중독의 주요 원인균으로 주로 해수 및 어패류를 통해 인체에 감염된다. 최근 지구 온난화로 해수의 온도가 상승하면서 해양환경 중 세균들의 분포도가 증가하고 또 다양한 항생제에 대한 내성을 보이는 병원균들이 확산되고 있어 국민보건 및 수산양식 등의 분야에 큰 문제로 대두되고 있다. 이에 본 연구에서는 경기, 인천지역 7곳에서 해수 및 어패류 시료를 채취하여 장염비브리오균의 분포도를 모니터링하고 이들의 항생제 내성 양상을 분석하였다. 총 966건의 시료를 $CHROMagar^{TM}$ 및 TCBS 평판배지와 multiplex PCR기법으로 동정했을 때 전체 해수 시료의 61.9%, 어패류 시료의 41.8% 등 총 47.7%의 시료에서 장염비브리오균이 검출되었다. 이들 분리균주들의 항생제 내성을 13종의 항생제에 대해 분석한 결과 97.3%와 87.3%가 각각 vancomycin과 ampicillin에 대해 내성을 보였고 cephalothin (48.8%)과 rifampin (46.1%)에 대한 내성비율도 기타 다른 항생제들에 비해 상대적으로 높은 것으로 나타났다. 분리균주들의 항생제 감수성은 chloramphenicol (91.7%)과 trimethoprim-sulfamethoxazole (91.8%)에 대해 가장 높았고, gentamycin (82.3%), tobramycin (74.8%), nalidixic acid (71.6%), tetracyclin (69.4%), cefotaxime (63.0%) 등의 순서로 감수성 비율이 높았다. 분리균주들의 약 69%가 vancomycin과 ampicillin을 포함하여 3개 이상의 항생제에 대해 다중내성을 보였고 특히 11개 항생제에 대해 내성을 보이는 균주도 2개 검색되었다. 항생제 내성 장염비브리오 분리균주들의 플라스미드 프로파일을 분석한 결과 55.1%가 플라스미드를 보유하고 있었으며, 이들은 총 24가지 유형으로 분류되었으나 플라스미드 프로파일과 항생제 내성 간의 뚜렷한 상관관계는 관찰되지 않았다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2793-2800
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• 2015

In molecular-targeted cancer therapy, acquired resistance to gemcitabine is a major clinical problem that reduces its effectiveness, resulting in recurrence and metastasis of cancers. In spite of great efforts to reveal the overall mechanism of acquired gemcitabine resistance, no definitive genetic factors have been identified that are absolutely responsible for the resistance process. Therefore, we performed a cross-platform meta-analysis of three publically available microarray datasets for cancer cell lines with acquired gemcitabine resistance, using the R-based RankProd algorithm, and were able to identify a total of 158 differentially expressed genes (DEGs; 76 up- and 82 down-regulated) that are potentially involved in acquired resistance to gemcitabine. Indeed, the top 20 up- and down-regulated DEGs are largely associated with a common process of carcinogenesis in many cells. For the top 50 up- and down-regulated DEGs, we conducted integrated analyses of a gene regulatory network, a gene co-expression network, and a protein-protein interaction network. The identified DEGs were functionally enriched via Gene Ontology hierarchy and Kyoto Encyclopedia of Genes and Genomes pathway analyses. By systemic combinational analysis of the three molecular networks, we could condense the total number of DEGs to final seven genes. Notably, GJA1, LEF1, and CCND2 were contained within the lists of the top 20 up- or down-regulated DEGs. Our study represents a comprehensive overview of the gene expression patterns associated with acquired gemcitabine resistance and theoretical support for further clinical therapeutic studies.