• Tuberculosis and Respiratory Diseases
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• 제75권2호
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• pp.59-66
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• 2013

Background: This study was conducted in order to elucidate the effects of docetaxel on the growth of peroxiredoxin 1 (Prx1) knockdown A549 xenograft tumors and further tested the role of Prx1 as a predictor for how a patient would respond to docetaxel treatment. Methods: Effects of docetaxel on the growth of scrambled- and shPrx1-infected A549 xenograft tumors in nude mice were measured. Moreover, immunohistochemical expression of Prx1 was evaluated in paraffin-embedded tissues from 24 non-small cell lung cancer patients who had received docetaxel-cisplatin regimens as a first-line treatment. Results: Docetaxel treatment in Prx1 knockdown xenograft tumor resulted in reduced tumors growth compared with other groups. Prx1 knockdown increased the production of cleaved caspases-8 and -9 in the control itself compared to scramble tumors. Moreover, docetaxel treatment in Prx1 knockdown tissue led to an increased protein band. Phosphorylated Akt was found in Prx1 scramble tissues. Phosphorylated FOXO1 was detected in the docetaxel treatment group. On the other hand, Prx1 knockdown completely suppressed the Akt-FOXO1 axis. The median progression-free survival (PFS) of patients with low Prx1 expression was 7 months (95% confidence interval [CI], 6.0-7.7), whereas the median progression-free survival of patients with high Prx1 expression was 4 months (95% CI, 4.0-5.0). However, high Prx1 expression was not associated with decreased PFS (p=0.114). Conclusion: Our findings suggest that elevated Prx1 provides resistance to docetaxel treatment through suppression of FOXO1-induced apoptosis in A549 xenograft tumors, but may not be related with the predictive significance for response to docetaxel treatment.

• Tuberculosis and Respiratory Diseases
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• 제85권1호
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• pp.18-24
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• 2022

Background: Neutrophilic asthma (NeuA) is usually resistant to corticosteroids. Tiotropium bromide (TIO) is a bronchodilator that is used as an add-on therapy to inhaled corticosteroid and long-acting β2 agonist in asthma treatment. However, the role of TIO in NeuA is not fully known. Thus, the aim of this study was to evaluate the effect of TIO on NeuA compared to that of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin and lipopolysaccharide to induce neutrophilic inflammation. Dexamethasone (DEX) was administered on days 14, 17, 20, and 23. TIO was inhaled on days 21, 21, and 23. On day 24, mice were sacrificed. Airway hyper-responsiveness, levels of cytokines in bronchoalveolar lavage (BAL) and lung homogenates, and lung tissue histopathology were compared between the two groups. Results: Neutrophil counts, T helper 2 cells (T_H2)/T_H17 cytokines, and pro-inflammatory cytokine in BAL fluids were elevated in the NeuA group. TIO group showed lower total cells, neutrophil counts, and eosinophil counts in BAL fluids than the DEX group (p<0.001, p<0.05, and p<0.001, respectively). Airway resistance was attenuated in the TIO group but elevated in the NeuA group (p<0.001). Total protein, interleukin (IL)-5, and IL-17A levels in BAL fluids were lower in the TIO group than in the NeuA group (all p<0.05). Conclusion: TIO showed more potent effects than DEX in improving airway inflammation and attenuating airway resistance in NeuA.

• Membrane and Water Treatment
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• 제2권2호
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• pp.91-103
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• 2011

The flux behavior in the separation of equimolar bovine serum albumin (BSA) and bovine hemoglobin (HB) in aqueous solutions by cross-flow ultrafiltration (UF) was investigated, in which polyacylonitrile membrane with a molecular weight cut-off (MWCO) of 100 kDa was used. BSA and HB have comparable molar mass (67,000 vs. 68,000) but different isoelectric points (4.7 vs. 7.1). The effects of process variables including solution pH (6.5, 7.1, and 7.5), total protein concentration (1.48 and 7.40 ${\mu}M$), transmembrane pressure (69, 207, and 345 kPa), and solution ionic strength (with or without 0.01 M NaCl) on the separation were examined. It was shown that the ionic strength had a negligible effect on separation performance under the conditions studied. Although BSA and HB are not rigid bodies, the flux decline in the present cross-flow UF did not result from the mechanism of cake filtration with compression. In this regard, the specific cake resistance when pseudo steady-state was reached was evaluated and discussed.

• 통합자연과학논문집
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• 제15권4호
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• pp.171-177
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• 2022

ROS1 (c-ros oncogene) is one of the gene with mutation in NSCLC (non-small cell lung cancer). The increased expression of ROS1 is leading to the increase proliferation of cell, cell migration and survival. Crizotinib and Entrectinib are the drugs that have been approved by FDA against ROS1 protein, but recently patients started to develop resistance against Crizotinib and there is a need of new drug that could act as an effective drug against ROS1 for NSCLC. In this study, we have performed virtual screening, where compounds are taken from Zinc 15 dataset and molecular docking was performed. The top compounds were taken based upon their binding affinity and their interactions with the residues. The compounds stability and chemical reactivity was also studied through Density Functional theory and their properties. Further study of these compounds could reveal the required information of ROS1-inhibitor complex and in the discovery of potent inhibitors.

• Tuberculosis and Respiratory Diseases
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• 제51권2호
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• pp.122-134
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• 2001

연구배경 : 종양 세포들이 항암제에 대하여 저항을 나타내는 기전인 'apoptosis에 대한 저항'에 NF-${\kappa}B$의 활성이 중요한 역할을 하리라 생각되고 있다. 즉, NF-${\kappa}B$가 종양세포의 apoptosis를 억제하는 작용을 일으킴으로써 종양 세포의 생존에 유리하게 작용하고 있음이 제시되 고 있다. 방 법 : 본 연구에서는 비소세포폐암에 대한 항암 치료의 내성에 대하여 외부 자극으로 분해되지 않는 $I{\kappa}B{\alpha}$-SR의 삽입으로 NF-${\kappa}B$의 활성을 억제시키고 이로 인해 항암제에 대한 폐암세포주의 감수성이 증가하는지 여부를 밝혀 보고자 하였다. 결 과 : 비소세포폐암 세포주로 NCI H157, NCI H460 세포주를 이용하였고, Ad-$I{\kappa}B{\alpha}$-SR를 transduction 한 후 cisplatin을 처치한 군에서 NF-${\kappa}B$의 핵 내로의 이동이 억제되었으며 대조군과 비교시 $IC_{50}$이 2-3배 정도 유의하게 낮아짐을 관찰하였다. 또한 paclitaxel의 경우에도 Ad-$I{\kappa}B{\alpha}$-SR로 감염된 폐암세포주는 대조군과 비교시 IC50이 2배 정도 유의하게 낮아짐을 관찰하였다. 이러한 항암제에 대한 감수성의 증가의 기전으로 cisplatin의 경우는 $I{\kappa}B{\alpha}$-SR의 이입이 NF-${\kappa}B$의 활성을 억제 함으로 인한 apoptosis의 증대 때문인 것으로보인다. 결 론 : 폐암세포주에서 Ad-$I{\kappa}B{\alpha}$-SR transduction은 Clsplatin, paclitaxel에 대한 폐암세포주의 감수성을 증가시킴으로 앞으로 폐암을 치료하는데 있어 새로운 치료 방법이 될 수 있을 것으로 보인다.

• 생약학회지
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• 제45권1호
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• pp.1-10
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• 2014

Ginsenoside Rg3 (G-Rg3) is one of protopanaxadiol ginsenosides characteristic of red ginseng, steamed and dried ginseng (Panax ginseng), which has recently attracted much attention for its antitumor properties in vitro and in vivo animal models. Experimental studies have demonstrated that it could promote cancer cell apoptosis, inhibit cancer cell growth, the apoptosis of cancer cells, adhesion, invasion and metastasis, and also prevent an angiogenetic formation in prostate, breast, ovarian, colorectal, gastric, liver and lung cancer etc. It has shown the antitumor activities by modulation of diverse signaling pathways, including regulation of cell proliferation mediators (CDKs and cyclins), growth factors (vascular endothelial growth factor), tumor suppressors (p53 and p21), cell death mediators (caspases, Bcl-2, Bax), inflammatory response molecules ($NF-{\kappa}B$ and COX-2), protein kinases (JNK, Akt, and AMP-activated protein kinase) and Wnt/${\beta}$-catenin signaling. In addition, the combination of Rg3 and chemotherapeutic agents have synergistically enhanced therapeutic efficacy and reduced antagonistically side effects. Furthermore, it can reverse the multidrug resistance of cancer cells, prolong the survival duration and improve life quality of cancer patients. Taken together, accumulating evidences could provide the potential of G-Rg3 in the treatment of cancers and the feasibility of further randomized placebo controlled clinical trials.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7719-7724
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• 2013

Background: Overexpression of survivin, a known inhibitor of apoptosis, is associated with tumor progression and drug resistance in numerous malignancies, including leukemias. The aim of this study was to investigate the effect of a specific survivin small interference RNA (siRNA) on proliferation and the sensitivity of HL-60 acute myeloid leukemia (AML) cells to the chemotherapeutic drug etoposide. Materials and Methods: The cells were transfected with siRNAs using Lipofectamine $^{TM}2000$ transfection reagent. Relative survivin mRNA and protein levels were measured by quantitative real-time PCR and Western blotting, respectively. Trypan blue exclusion assays were performed to monitor tumor cell proliferation after siRNA transfection. The cytotoxic effects of etoposide and survivin siRNA, alone and in combination, on leukemic cells were determined using MTT assay. Apoptosis was assessed by ELISA cell death assay. Results: Survivin siRNA markedly reduced both mRNA and protein expression levels in a time-dependent manner, leading to distinct inhibition of cell proliferation and increased spontaneous apoptosis. Surprisingly, survivin siRNA synergistically increased the cell toxic effects of etoposide. Moreover, survivin down-regulation significantly enhanced its induction of apoptosis. Conclusions: Our study suggests that down-regulation of survivin by siRNA can trigger apoptosis and overcome drug resistance of leukemia cells. Therefore, survivin siRNA may be an effective adjuvant in AML chemotherapy.

• Tuberculosis and Respiratory Diseases
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• 제48권6호
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• pp.909-921
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• 2000

연구배경 : 최근 아포프토시스를 억제하는 단백질들에 대한 관심이 증가하고 있다. 이 중 IAP(inhibitor of apoptosis protein) 가족군의 일원인 survivin은 태아 사기에는 높은 발현율을 보이지만 생후 정상 분화된 조직에서는 거의 발현이 되지 않고 암세포로 변환이 되면 그 발현이 증가하는 것이 보고되고 있다. 대장암 및 위암을 대상으로 한 연구에서 survivin의 발현이 아포프토시스 지수의 감소와 연관이 있으며 대장암에서 survivin의 과발현이 나쁜 예후와 연관성이 있다고 보고한 바 있으나 추후 보완 연구가 필요한 상황이며, 폐암을 대상으로 한 연구결과는 아직 보고되지 않고 있다. 이에 수술적으로 절제된 비소세포폐암 병리조직 29예를 대상으로 survivin에 대한 면역조직화학적 연구를 시행하여 survivin의 종양특이적 발현 및 임상적 의의에 대한 분석을 시행하였다. 방법 : 수술절제된 29예의 비소세포폐암의 포르말린 고정조직을 파라핀 포매한후 $4{\mu}m$ 절편으로 잘라 면역조직화학 염색을 시행하였다. 일차항체로 antisurvivin polyclonal antibody를 이용하였고, 아포프토시스에 중요한 역할을 하는 p53과의 관련성을 분석하기 위하여 anti-p53 monoclonal antibody를 이용한 면역조직화학 염색도 병행 시행하였다. 발현 정도는 양성염색부위의 면적과 염색 강도에 따라 점수화한 뒤 합산한 접수로 판정하였다. 사용된 sntisurvivin antibody의 특이성 및 암특이적 발현을 확인하기 위하여 폐암부위와 주변 정상 폐부위로 분리되어 보존되어 있는 신선동결조직에서 단백질올 추출하여 Western blot을 시행하였다. 각각의 임상적 지표들과 survivin 발현과의 연관성은 chi-square test를 이용하여 비교하였고 Kaplan-Meier 방법으로 생존 곡선을 얻었으며 이 두 군간의 생존함수의 통계적 분석은 generalized Wilcoxon test로 하였다. 결과 : 면역조직화학 염색을 시행한 29예 중 20예(69.0%)에서 암세포 특이적 survivin의 발현이 관찰되었다. 폐암 조직과 정상 폐 조직으로 시행한 Western blot으로 암특이적 survivin의 발현을 확인하였다. 그러나 survivin의 발현 여부에 따른 연령, 조직학적 분류, 병기, 재발율 등과는 유의한 차이가 없었으며 생존 곡선에서도 통계적 유의성은 없었다. p53 발현과 survivin 발현 정도와도 통계적 유의성을 확인할 수 없었다. 결론 : 연역조직화학적 분석과 Western blot을 이용하여 비소세포폐암에서 survivin의 암 특이적 발현을 확인할 수 있었지만 survivin의 발현정도와 조직학적 분류, 병기, 재발율, 생존율 등 임상지표들과는 통계적 유의성올 관찰할 수 없었으며 p53 발현과도 유의한 상관성이 없었다.

• Tuberculosis and Respiratory Diseases
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• 제53권1호
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• pp.36-45
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• 2002

배 경 :포유동물은 고산소 노출되면 이에 적응하기 위해 성숙 폐장의 항산화 효소의 활성도가 증가하는 것으로 알려져 있다. 신생 폐장에서는 이들의 활성도가 뚜렷이 증가하고 이는 고산소 노출에 내성을 보이는 중요한 기전으로 알려져 있다. Peroxiredoxin은 세포내 항산화 효소로 세포내 많은 양이 존재하고 다양한 세포에 분포하고 있다. 그중 Prx I 및 II는 세포질에 존재하는 주된 동종 효소이다.본 연구는 고산소를 투여하여 성숙 백서의 폐장에서 Prx I과 Prx II mRNA 및 단백의 발현을 평가하여 신생 백서의 폐장에서의 발현과 비교하고자 하였다. 방 법 :성숙 백서와 임신 백서로부터 분만하여 얻은 신생 백서를 무작위로 고산소를 시간별로 투여후에 폐조직과 기관지폐포세척액을 얻었다. Prx I 및 Prx II mRNA는 Northernblot 방법으로 구하였으며 Actin mRNA을 내부 기준으로 하여 상대 발현을 평가하였다. Prx I 및 Prx II 단백은 Westernblot 방법으로 구하였으며 Actin 단백을 내부 기준으로 하여 상대 발현을 평가하였다. 결 과 : 성숙 백서에서 고산소 노출 후 24 시간에 Prx I mRNA 발현이 약간의 증가가 유도되었으며 신생 백서에서 고산소 노출 후 24 시간에 Prx I mRNA 발현이 현저한 증가가 유도되었다. 그러나 Prx II mRNA는 고산소 노출 내내 발현이 변화가 없었다. 성숙 및 신생 백서에서 고산소 노출 내내 Prx I 및 Prx II 단백의 발현이 변화가 없었으며 성숙 백서에서 고산소 노출 내내 기관지폐포세척액내 Prx I 및 Prx II 단백의 양의 변화가 없었다. 결 론 : 성숙 및 신생 백서에서 고산소 노출에 의해 Prx I 및 II의 발현이 전사 과정 에서 서로 다르게 조절된다. 성숙 백서보다 신생 백서에서 고산소 노출에 의한 Prx I mRNA의 뚜렷한 발현 증가는 신생 백서가 고산소에 내성을 보이는 하나의 기전으로 생각된다.

• 대한의생명과학회지
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• 제15권4호
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• pp.301-307
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• 2009

Whole-body insulin resistance results largely from impaired insulin-stimulated glucose disposal in skeletal muscle. Our previous studies using differential display and quantitative real-time RT-PCR have shown that a novel cDNA band (DD23) had a higher level of expression in insulin resistant skeletal muscle and it was correlated with whole-body insulin action, independent of age, sex, and percent body fat. In this study, we cloned and characterized DD23. The DD23 sequence is part of the 3'UTR region of the RNA binding motif, single stranded interacting protein (RBMS3). We have cloned the full length cDNA for RBMS3 and identified two splice variants. These variants named DD23-L and DD23-S have 15 and 14 exons respectively and differ from RBMS3 in the 3'UTR significantly. Northern blot analyses showed that an ~8.8 kb mRNA transcript of DD23 was predominantly expressed in skeletal muscle and to a lesser extent in placenta, but not in heart, brain, lung, liver, or kidney, unlike RBMS3. Elevated expression levels of these novel alternatively spliced variants of RBMS3 in skeletal muscle may play a role in whole body insulin resistance.