• BMB Reports
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• v.53 no.12
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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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• v.15 no.7
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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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• v.15 no.7
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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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• v.79 no.4
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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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• v.64 no.2
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• pp.87-94
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• 2008

Background: Surveillance of TB drug resistance (DR) is essential for providing information on the magnitude and trends in resistance, for developing treatment guidelines and for monitoring the effect of interventions. Up to now national surveys of drug resistance of M. tuberculosis have been conducted four times since 1994 among patients registered at health centers. The purpose of this study is to estimate the prevalence of primary drug resistance among new cases identified in private sector, and to compare it with the previous national drug resistance surveys. Methods: The study collected results of drug susceptibility testing (DST) performed at the Korean Institute of Tuberculosis by the request of private sector from January 2003 to December 2005, and then finally selected new cases for the analysis from the database of Korean TB Surveillance (KTBS) by matching patients' name and social identification numbers. Results: Of the 5,132 new patients included in the study, 689 (13.4%) patients were found to have drug resistance at least one drug, 530 patients (10.3%) were isoniazid resistant, 195 patients (3.8%) were multi-drug resistant (MDR), and 21 patients (0.4%) were extensively drug resistant (XDR). The rate of drug resistance tended to decrease annually but it was not statistically significant. When compared with previous national DR surveys in 2003 and in 2004 respectively, they were not significantly different. Conclusion: The prevalence of DR among new cases managed in the private sector did not show significant difference from that of new patients registered in the public sector in the same year.

• Journal of Microbiology and Biotechnology
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• v.28 no.11
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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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• v.15 no.17
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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.

• Microbiology and Biotechnology Letters
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• v.49 no.4
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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.

• Korean Journal of Poultry Science
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• v.19 no.3
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• pp.151-160
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• 1992

Control of coccidiosis depends on medication, management, immunity, or some combination of these methods. Prophylactic medication with anticoccidials remains the primary method of control, although the development of drug resistance is a major problem. Shuttle and rotation programs are increasingly used to delay the onset of drug resistance. Sensitivity testing has become an important tool in the identification of what specific medications will be effective in specific poultry operations. Management techniques for the control of coccidiosis have not been totally effective because most disinfectants do not kill the coccidial oocysts. Present methods for vaccination are currently limited to the use of controlled doses of live coccidia. New vaccination methods under investigation include vaccination with attenuated strains or parasite antigens produced either by fractionating the parasites or genetically engineered sub unit vaccines.

• Genomics & Informatics
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• v.21 no.3
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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.