• Bulletin of the Korean Chemical Society
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• 제35권5호
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• pp.1294-1298
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• 2014

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer representing 85% of lung cancer patients. Despite several EGFR-targeted drugs have been developed in the treatment of NSCLC, the clinical efficacy of these EGFR-targeted therapies is being challenged by the occurrence of drug resistance. In this regard, Hsp90 represents great promise as a therapeutic target of cancerous diseases due to its role in modulating and stabilizing numerous oncogenic proteins. Accordingly, inhibition of single Hsp90 protein simultaneously disables multiple signaling networks so as to overcome drug resistance in cancer. In this study, we synthesized a series of 11 butein analogues and evaluated their biological activities against gefitinibresistant NSCLC cells (H1975). Our study indicated that analogue 1h inhibited the proliferation of H1975 cells, down-regulated the expression of Hsp90 client proteins, including EGFR, Met, Her2, Akt and Cdk4, and upregulated the expression of Hsp70. The result suggested that compound 1h disrupted Hsp90 chaperoning function and could serve a potential lead compound to overcome the drug resistance in cancer chemotherapy.

• 한국식품위생안전성학회지
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• 제21권1호
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• pp.23-30
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• 2006

2001년부터 2005년까지 서울 시내 식중독 환자에서 분리한 150주의 Sal. Enteritidis의 항생제 감수성 및 다재내성 양상을 조사한 결과 총 364주의 살모넬라속균 중 41.2%를 차지하였다. 가장 내성율이 높은 항생제는 streptomycin(46.7%), ampicillin(37.3%), ticarcillin(36.7%), tetracycline(36.0%), nalidixic acid(20.7%), chloramphenicol (13.3%), amoxicillin/clavulanic acid(6.7%) 및 ampicillin/sulbactam(4.0%). 분리균의 74.7%는 1제 이상의 항생제에 내성이 있다. 실험한 S. Enteritidis에 대한 nalidixic acid와 chloramphenicol에 대한 내성은 증가하였으나 tetracycline에 대한 내성율은 감소되었다. 가장 많이 검출된 내성 양상은 NA 단일 내성과 Streptomycin-tetrcyline 내성이 18.0%로 가장 높았으며, streptomycin-ampicillin-ticarcillin(10.0%) 및 ampicillin-ticarcillin(5.5%)순이었다. 전체적으로 1제 내성이 19.3%, 2제 내성 24.7%, 3제 내성 6.7%, 4제 내성 15.0% 그리고 5제 이상 내성은 6.0%이었다. 특히 2005년에는 1제 내성과 2제 내성이 증가하였다.

• Bulletin of the Korean Chemical Society
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• 제35권4호
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• pp.1154-1158
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• 2014

Hsp90 is an ubiquitous molecular chaperone protein, which plays an important role in regulating maturation and stabilization of many oncogenic proteins. Due to its potential to simultaneously disable multiple signaling pathways, Hsp90 represents great promise as a therapeutic target of cancer. In this study, we synthesized flavokawain analogues and evaluated their biological activities against drug-resistant cancer cells. The study indicated that compound 1i impaired the growth of gefitinib-resistant non-small cell lung cancer (H1975), down-regulated the expression of Hsp90 client proteins including EGFR, Her2, Met, Akt and Cdk4, and upregulated the expression of Hsp70. The result strongly suggested that compound 1i inhibited the proliferation of cancer cells through Hsp90 inhibition. Overall, compound 1i could serve as a potential lead compound to overcome the drug resistance in cancer chemotherapy.

• Journal of Chest Surgery
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• 제30권8호
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• pp.786-792
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• 1997

공동성 병소나 파괴된 폐를 적절한 시기에 제거하므로 다제내성환자와 중증환자의 양산을 감소시킬 수 있으리라는 관점에서 1989년 1월부터 1996년 6월 사이 7년 5개월간 본원에서 시행한 폐결핵환자 70명에대한 폐절제수술 71례를 대상으로 임상적으로 분석하였다. 1. 3~6개월간의 약물치료에도 불구하고 수술전 균음전화 실패을은 66.2%였고 균음전화 실패환자의 87.2%가 다제내성환자였다. 2. 다제내성군의 경우, 술전 균음전화 실패율은 71.9%였다. 3. 방사선 소견에 따른 폐절제술의 적응증은 공동성 병변이 43례(60.6%), 파괴폐가 24례(33.8%)였다. 4. 수술후 합병증은 20례(28.2%)에서 나타났으며 전례가 다제내성군이었다. 합병증 중에서 가장 흔한 것은 결 핵병변 확산이었다. 5. 양측성 병변에서,술후 결핵병변 확산은 7례(25%)에서 나타났으며 이 중 65례(85.7%)는 공동성 병변이었다. 6. 술전 균음전화에 실패한 47례의 폐절제술후 36례에서 균음전화(76.6%)되었으며, 다제내성군에서는 균음전 율이 73.2%였다. 약제내성군이면서 양측성 폐결핵의 경우 균음전율이 가장 낮았다(60%). 반면 약제 감수 성군에서의 균음전율은 위치에 관계없이 100%였다. 결국, 다제약제내성환자는 장기적인 약물치료에도 불구하고 술전에 균음전화 시키기가 어려울뿐 아니라, 술후 적절한 약제의 부족으로 재발등.수술후 합병증의 발생율을 높이고,술후 균음전화율을 감소시킨다. 여러 가지 이유로 다제내성환자의 증가가 문제인 우리나라\ulcorner서 다제내성환자에 대한 수술과 함께 다제내성환 자와 중증환자의 양산을 막는 것이 근본적인 해결책이라 생각되며 그 방법 중의 하나로 1차 결핵약제에 치 료를 실패했거나 내성을 가진 경우 2차 치료와 함께 수술을 고려해야 하며, 1차 치료 중이라도 수술 .적응이 되면 적극적으로 수술 치료를 시도해야 할 것으로 생각된다.

• Bulletin of the Korean Chemical Society
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• 제34권12호
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• pp.3782-3786
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• 2013

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and that accounts for 85% of lung cancer patients. Although several EGFR-targeted drugs have been developed in the treatment of NSCLC, the clinical efficacy of EGFR-targeted drugs in NSCLC is limited by the occurrence of drug resistance. In this regard, Hsp90 represents great promise as a therapeutic target of cancer due to its potential to simultaneously disable multiple signaling pathways. In this study, we discovered that a natural product, flavokawain B disrupted Hsp90 chaperoning function and impaired the growth of gefitinib-resistant non-small cell lung cancer (H1975). The result suggested that flavokawain B could serve as a potential lead compound to overcome the drug resistance in cancer chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2619-2623
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• 2014

Aim: To investigate signaling pathways for reversal of EGF-mediated multi-drug resistance (MDR) in hepatocellular carcinoma (HCC) models. Materials and Methods: HCC MDR cell strain HepG2/adriamycin (ADM) and SMMC7721/ADM models were established using a method of exposure to medium with ADM between low and high concentration with gradually increasing concentration. Drug sensitivity and reversal of multi-drug resistance by EGF were determined and the cell cycle distribution and apoptosis were analyzed by flow cytometry. Phosphorylation of ERK1, ERK2, ERK5 and expression of Bim were detected by Western blotting. Results: The results showed that HepG2/ADM and SMMC7721/ADM cells were resistant not only to ADM, but also to multiple anticancer drugs. When used alone, EGF had no anti-tumor activity in HepG2/ADM and SMMC7721/ADM cells in vitro, while it increased the cytotoxicity of ADM. EGF induced cell apoptosis and G0/G1 phase cell cycle arrest in HepG2/ADM And SMMC7721/ADM cells, while enhancing activity of p-ERKs and up-regulated expression of BimEL. Conclusions: EGF might enhance the chemosensitivity of HepG2/ADM and SMMC7721/ADM cells via up-regulating p-ERKs and BimEL protein.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6663-6668
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• 2015

Background: Treatment failure in leukemia is due to either pharmacokinetic resistance or cell resistance to drugs. Materials and Methods: Gene expression of multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP) and low resistance protein (LRP) was assessed in 45 pediatric ALL cases and 7 healthy controls by real time PCR. The expression was scored as negative, weak, moderate and strong. Results: The male female ratio of cases was 2.75:1 and the mean age was 5.2 years. Some 26/45 (58%) were in standard risk, 17/45(38%) intermediate and 2/45 (4%) in high risk categorie, 42/45 (93%) being B-ALL and recurrent translocations being noted in 5/45 (11.0%). Rapid early response (RER) at day 14 was seen in 37/45 (82.3%) and slow early response (SER) in 8/45 (17.7%) cases. Positive expression of MDR-1, LRP and MRP was noted in 14/45 (31%), 15/45 (33%) and 27/45 (60%) cases and strong expression in 3/14 (21%), 11/27 (40.7%) and 8/15 (53.3%) cases respectively. Dual or more gene positivity was noted in 17/45 (38%) cases. 46.5 % (7/15) of LRP positive cases at day 14 were in RER as compared to 100% (30/30) of LRP negative cases (p<0.05). All 8 (100%) LRP positive cases in SER had strong LRP expression (p=<0.05). Moreover, only 53.3% of LRP positive cases were in haematological remission at day 30 as compared to 100% of LRP negative cases (p=<0.05). Conclusions: Our study indicated that increased LRP expression at diagnosis in pediatric ALL predicts poor response to early treatment and hence can be used as a prognostic marker. However, larger prospective studies with longer follow up are needed, to understand the clinical relevance of drug resistance proteins.

• 대한수의학회지
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• 제34권2호
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• pp.267-273
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• 1994

Feces samples, obtained from zoo animals around Seoul, were examined for the isolation of Salmonella species, bioserotype and drug resistance for the prevention and treatment of salmonellosis, Salmonella spp were isolated 19(4.7%) from 408 samples of zoo animals. The subspecies in 19 Salmonella were all subspecies 1. The serological identification of Salmonella isolated were 31.6% in Sal typhimurium, 26.3% in Sal hadar, 21.1% in Sal muenchen, 15.8% in Sal enteritidis and 5.3% in Sal ayinde. The antibiotic resistance of Salmonella isolated were 13(68.4%) strains. The multiple resistant patterns of antibiotics in Salmonella were 2 drugs- and 3 drugs-resistance 30.8% respectively. The transferred rate of resistance to recipients(E coli ML 1410 $NA^r$) in Salmonella was 38.5%.

• Parasites, Hosts and Diseases
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• 제60권2호
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• pp.109-116
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• 2022

Drug resistance is an important problem hindering malaria elimination in tropical areas. Point mutations in Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes confer resistance to antifolate drug, sulfadoxine-pyrimethamine (SP) while P. falciparum chloroquine-resistant transporter (Pfcrt) genes caused resistance to chloroquine (CQ). Decline in Pfdhfr/Pfdhps and Pfcrt mutations after withdrawal of SP and CQ has been reported. The aim of present study was to investigate the prevalence of Pfdhfr, Pfdhps, and Pfcrt mutation from 2 endemic areas of Thailand. All of 200 blood samples collected from western area (Thai-Myanmar) and southern area (Thai-Malaysian) contained multiple mutations in Pfdhfr and Pfdhps genes. The most prevalent haplotypes for Pfdhfr and Pfdhps were quadruple and double mutations, respectively. The quadruple and triple mutations of Pfdhfr and Pfdhps were common in western samples, whereas low frequency of triple and double mutations was found in southern samples, respectively. The Pfcrt 76T mutation was present in all samples examined. Malaria isolated from 2 different endemic regions of Thailand had high mutation rates in the Pfdhfr, Pfdhps, and Pfcrt genes. These findings highlighted the fixation of mutant alleles causing resistance of SP and CQ in this area. It is necessary to monitor the re-emergence of SP and CQ sensitive parasites in this area.

• 미생물학회지
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• 제49권2호
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• pp.146-149
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• 2013

비브리오균은 해양 및 하구 환경에서 상재하는 균으로 그람 음성 간균, 호염성, 비포자형성의 특징을 가지고 있다. 질병과 관련된 균주로는 Vibrio parahaemolyticus, Vibrio vulnificus, Vibrio cholera 등이 있다. 매년 어패류의 섭취 등을 통해 식중독 사고가 빈번하게 발생하고 있으며, 이에 본 연구에서는 서해안 6곳에서 패류를 채취하여 비브리오균의 분포도를 모니터링하고, 이들의 항생제 내성을 분석하였다. 총 120건의 패류를 TCBS 평판배지와 API 20E kit 기법으로 동정하였을 때 23.3%의 시료에서 비브리오균이 검출되었다. 이들 분리균주들의 항생제 내성을 16종의 항생제에 대해 분석한 결과 82.1%가 각각 vancomycin과 ampicillin에 대해 내성을 보였고, rifampin (71.4%)과 cephalothin (53.6%)에 대한 내성비율도 다른 항생제들에 비해 상대적으로 높은 것으로 나타났다. 분리균주들의 항생제 감수성은 chloramphenicol (92.9%), sulfamethoxazole/trimethoprim (92.9%)과 tetracycline (96.4%)에 대해 가장 높았다. 분리균주들의 약 71.4%가 vancomycin과 ampicillin을 포함하여 3개 이상의 항생제에 대해 다중내성을 보였다.