• BMB Reports
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• 제53권12호
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• pp.622-627
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• 2020

Cancer stem cells (CSCs) or tumor-initiating cells are thought to play critical roles in tumorigenesis, metastasis, drug resistance, and tumor recurrence. For the diagnosis and targeted therapy of CSCs, the molecular identity of biomarkers or therapeutic targets for CSCs needs to be clarified. In this study, we identified CD166 as a novel marker expressed in the sphere-forming CSC population of A2780 epithelial ovarian cancer cells and primary ovarian cancer cells. The CD166+ cells isolated from A2780 cells and primary ovarian cancer cells highly expressed CSC markers, including ALDH1a1, OCT4, and SOX2, and ABC transporters, which are implicated in the drug resistance of CSCs. The CD166+ cells exhibited enhanced CSC-like properties, such as increased sphere-forming ability, cell migration and adhesion abilities, resistance to conventional anticancer drugs, and high tumorigenic potential in a xenograft mouse model. Knockdown of CD166 expression in the sphere-forming ovarian CSCs abrogated their CSC-like properties. Moreover, silencing of CD166 expression in the sphere-forming CSCs suppressed the phosphorylation of focal adhesion kinase, paxillin, and SRC. These results suggest that CD166 plays a key role in the regulation of CSC-like properties and focal adhesion kinase signaling in ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3093-3097
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• 2014

Background: Cancer is a major threat to the public health whether in developed or in developing countries. As the most common primary malignant tumor, the morbidity and mortality rate of lung cancer continues to rise in recent ten years worldwide. Chemotherapy is one of the main methods in the treatment of lung cancer, but this is hampered by chemotherapy drug resistance, especially MDR. As a component of the 60S large ribosomal subunit, ribosomal protein L39-L gene was reported to be expressed specifically in the human testis and human cancer samples of various tissue origins. Materials and Methods: Total RNA of cultured drug-resistant and susceptible A549 cells was isolated, and real time quantitative RT-PCR were used to indicate the transcribe difference between amycin resistant and susceptible strain of A549 cells. Viability assay were used to show the amycin resistance difference in RPL39-L transfected A549 cell line than control vector and null-transfected A549 cell line. Results: The ribosomal protein L39-L transcription level was 8.2 times higher in drug-resistant human lung cancer A549 cell line than in susceptible A549 cell line by quantitative RT-PCR analysis. The ribosomal protein L39-L transfected cells showed enhanced drug resistance compared to plasmid vector-transfected or null-transfected cells as determined by methyl tritiated thymidine (3H-TdR) incorporation. Conclusions and Implications for Practice: The ribosomal protein L39-L gene may have effects on the drug resistance mechanism of lung cancer A549 cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3219-3226
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• 2014

Chemotherapy continues to be a mainstay of cancer treatment, although drug resistance is a major obstacle. Lipid metabolism plays a critical role in cancer pathology, with elevated ether lipid levels. Recently, alkylglyceronephosphate synthase (AGPS), an enzyme that catalyzes the critical step in ether lipid synthesis, was shown to be up-regulated in multiple types of cancer cells and primary tumors. Here, we demonstrated that silencing of AGPS in chemotherapy resistance glioma U87MG/DDP and hepatic carcinoma HepG2/ADM cell lines resulted in reduced cell proliferation, increased drug sensitivity, cell cycle arrest and cell apoptosis through reducing the intracellular concentration of lysophosphatidic acid (LPA), lysophosphatidic acid-ether (LPAe) and prostaglandin E2 (PGE2), resulting in reduction of LPA receptor and EP receptors mediated PI3K/AKT signaling pathways and the expression of several multi-drug resistance genes, like MDR1, MRP1 and ABCG2. ${\beta}$-catenin, caspase-3/8, Bcl-2 and survivin were also found to be involved. In summary, our studies indicate that AGPS plays a role in cancer chemotherapy resistance by mediating signaling lipid metabolism in cancer cells.

• Tuberculosis and Respiratory Diseases
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• 제79권4호
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• pp.248-256
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• 2016

Somatic mutations that lead to hyperactivation of epidermal growth factor receptor (EGFR) signaling are detected in approximately 50% of lung adenocarcinoma in people from the Far East population and tyrosine kinase inhibitors are now the standard first line treatment for advanced disease. They have led to a doubling of progression-free survival and an increase in overall survival by more than 2 years. However, emergence of resistant clones has become the primary cause for treatment failure, and has created a new challenge in the daily management of patients with EGFR mutations. Identification of mechanisms leading to inhibitor resistance has led to new therapeutic modalities, some of which have now been adapted for patients with unsuccessful tyrosine kinase inhibitor treatment. In this review, we describe mechanisms of tyrosine kinase inhibitor resistance and the available strategies to overcoming resistance.

• Tuberculosis and Respiratory Diseases
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• 제64권2호
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• pp.87-94
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• 2008

연구배경: 항결핵 약제내성률은 국가결핵관리 사업을 평가하는 중요한 지표 중 하나이다. 최근 보건소보다 민간병의원에서 신고되는 결핵 신환자가 증가하는 추세에서, 이들을 대상으로 초회(일차) 내성률을 조사하고자 하였다. 방법: 2003년에서 2005년까지 민간병의원에서 결핵연구원에 약제감수성 검사를 의뢰한 환자와 결핵감시체계에 신고된 환자 중에서 성명과 주민등록번호가 일치하는 결핵 신환자를 선정하여 그 약제감수성 검사 결과를 조사 하였다. 결과: 3년간 조사 대상자는 5,132명이었고 이 중 내성환자는 689명으로 13.4%이었고, 다제 내성환자는 195명으로 3.8%이었으며, 광역 내성환자는 21명으로 0.4%이었다. 항결핵 약제 내성률이나 다제내성률에 있어서 3년간 통계적으로 유의할만한 내성률의 증감현상은 없었다. 약제별 내성에서는 이소니아지드 내성은 10.3%, 리팜핀 내성은 4.5%이었다. 결핵환자의 남녀 성비에 따른 차이는 남자가 60%, 여성은 40%로 있었지만, 성비에 따른 내성률의 차이는 없었다. 연령대 별로는 20대에서 19.6%로 가장 높았으며, 연령별 내성률은 50대에서 15.8%로 가장 높았고, 10대에서 9.6%로 가장 낮았다. 다제 내성률은 30대에서 5.3%로 가장 높았으며, 70대에서 1.4%로 가장 낮았다. 결론: 본 조사는 민간병의원 환자를 대상으로 검사실 자료를 이용한 최초의 항결핵 약제내성률 조사이며, 보건소 환자를 대상으로 실시한 약제내성률 조사 결과와 통계학적인 유의성을 보이지는 않았다.

• Journal of Microbiology and Biotechnology
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• 제28권11호
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• pp.1771-1781
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• 2018

The emergence of multidrug-resistant microorganisms, as well as fungal infectious diseases that further threaten health, especially in immunodeficient populations, is a major global problem. The development of new antifungal agents in clinical trials is inferior to the incidence of drug resistance, and the available antifungal agents are restricted. Their mechanisms aim at certain characteristics of the fungus in order to avoid biological similarities with the host. Synthesis of the cell wall and ergosterol are mainly targeted in clinical use. The need for new approaches to antifungal therapeutic agents or development alternatives has increased. This review explores new perspectives on mechanisms to effectively combat fungal infections and effective antifungal activity. The clinical drug have a common feature that ultimately causes caspase-dependent cell death. The drugs-induced cell death pathway is associated with mitochondrial dysfunction, including mitochondrial membrane depolarization and cytochrome c release. This mechanism of action also reveals antimicrobial peptides, the primary effector molecules of innate systems, to highlight new alternatives. Furthermore, drug combination therapy is suggested as another strategy to combat fungal infection. The proposal for a new approach to antifungal agents is not only important from a basic scientific point of view, but will also assist in the selection of molecules for combination therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7037-7041
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• 2014

Background: 5-Fluorouracil (5-FU) is the most commonly used drug in colon cancer therapy. However, despite impressive clinical responses initially, development of drug resistance to 5-Fu in human tumor cells is the primary cause of failure of chemotherapy. In this study, we established a 5-Fu-resistant human colon cancer cell line for comparative chemosensitivity studies. Materials and Methods: Real time PCR and Western blotting were used to determine gene expression levels. Cell viability was measured by MTT assay. Glucose uptake was assess using an Amplex Red Glucose/Glucose Oxidase assay kit. Results: We found that 5-Fu resistance was associated with the overexpression of Glut1 in colon cancer cells. 5-Fu treatment at low toxic concentration induced Glut1 expression. At the same time, upregulation of Glut1 was detected in 5-Fu resistant cells when compared with their parental cells. Importantly, inhibition of Glut1 by a specific inhibitor, WZB117, significantly increased the sensitivity of 5-Fu resistant cells to the drug. Conclusions: This study provides novel information for the future development of targeted therapies for the treatment of chemo-resistant colon cancer patients. In particular it demonstrated that Glut1 inhibitors such as WZB117 may be considered an additional treatment options for patients with 5-Fu resistant colon cancers.

• 한국미생물·생명공학회지
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• 제49권4호
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• pp.587-593
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• 2021

Infertility is a key issue affecting mood and behavior in men. Microorganisms are one of the primary etiological agents that may be associated with infertility. The objective of the present study was to identify bacterial causative agents from the semen of infertile subjects and determine the effect of bacterial infection on sperm quality, as well as determine the susceptibility of these bacteria to drugs. Forty semen samples from 30 infertile patients and 10 fertile individuals were collected. The pH, volume, motility, and concentration of semen were analyzed. The samples were processed and identified by biochemical testing using API identification kits. The antibiotic susceptibility pattern was determined using the disc diffusion method. Abnormal sperm quality was observed. The mean age of the individual and their sperm morphology, concentration, progressive motility, pH level, and pus cell content were 31.9 years, 2.7%, 10.4 million/ml, 27.3%, 8.3, and 5.7, respectively. Among the tested samples, oligoasthenozoospermia was found to show the highest occurrence, at 27/30 samples, followed by teratozoospermia, at 25/30 samples, and asthenozoospermia, at 22/30 samples. Of the tested infertile patients' sperm, 19, 6, and 5 isolates were identified as Escherichia coli, Klebsiella pneumonia, and Staphylococcus epidermidis, respectively. The results also revealed multi-drug resistance in the bacteria. Compared to that shown by the other tested antibiotics, amikacin showed higher activity against all isolated bacteria. However, the bacteria exhibited maximum resistance against gentamicin, cefotaxime, levofloxacin, and ampicillin. In conclusion, leukocytospermia and bacterial infections are possibly responsible for sperm abnormalities. Multi-drug resistant bacteria were detected. Gentamicin, cefotaxime, levofloxacin and ampicillin were shown the highest resistance, while amikacin was the most effective antimicrobial agent against the isolated bacteria.

• 한국가금학회지
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• 제19권3호
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• pp.151-160
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• 1992

현재 콕시듐 병의 방제는 약제 투여, 사육관리, 백신을 이용하거나 혹은 이들 방법을 적당히 혼합하여 실시하고 있다. 약제 투여 방법은 약의 내성이라는 문제점을 내재하고 있지만 아직도 콕시듐 방제에 최우선 방법으로 쓰고 있으며 이러한 약제 내성을 조금이나마 지연시키기 위하여 shuttle, 혹은 rotation program을 쓰고 있다. 따라서 약제 내성 검사는 각 농장에 어떠한 약제가 효과가 있는지를 알아보는데 가장 중요한 방법이 되어 왔던 것이다. 콕시듐 방제에 있어서 사육관리에 의한 방법은 아직은 완전한 효과적인 방법으로 정착되지 않았는데 그 이우는 소독제만으로는 콕시듐의 원충을 죽일 수 없기 때문이다. 백신에 의한 방법은 현재까지 살아있는 콕시듐 원충을 제한적으로 쓰고 있는 단계이다. 새로운 형태의 백신개발이 요즈음 연구가 되고 있는데 이 백신은 순화시킨 콕시듐 원충을 사용하거나 유전공학적 방법 혹은 원충의 일부분에 대한 항원을 추출하여 백신으로 이용하는 것이다.

• Genomics & Informatics
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• 제21권3호
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• pp.42.1-42.23
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• 2023

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Tolllike receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.