• International Journal of Oral Biology
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• v.37 no.3
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• pp.91-102
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• 2012

Bcl-2 protects tumor cells from the apoptotic effects of various anti-neoplastic agents. Increased expression of Bcl-2 has been associated with a poor response to chemotherapy in various malignancies, including leukemia. Hence, bypassing the resistance conferred by anti-apoptotic factors such as Bcl-2 represents an attractive therapeutic strategy against cancer cells, including leukemic cells. This study was undertaken to examine whether the anticancer drug, cisplatin and the synthetic chenodeoxycholic acid (CDCA) derivative, HS-1200 show anti-tumor activity in U937 and U937/Bcl-2 cells. Viability assays revealed that HS-1200 overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells. Various apoptosis assessment assays further demonstrated that HS-1200 overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells by inducing apoptosis. In addition HS-1200, but not cisplatin, overcomes the anti-apoptotic effects of Bcl-2 in Bcl-2 over-expressing human leukemic cells (U937/Bcl-2 cells). Notably, we observed that the HS-1200-induced formation of mature promyelocytic leukemia (PML) nuclear bodies (NBs) correlates with a suppression of the anti-apoptotic effects of Bcl-2 in human leukemic cells over-expressing this protein (U937/Bcl-2 cells). Furthermore, HS-1200 was found to induce the association between PML and SUMO-1, Daxx, Sp100, p53 or CBP in the aggregated PML-NBs of U937/Bcl-2 cells. Thus, PML protein and the formation of mature PML-NBs could be considered as therapeutic targets that may help to bypass the resistance to apoptosis conferred by Bcl-2. Elucidating the exact mechanism by which PML regulates Bcl-2 will require further work.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4807-4814
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• 2012

Purpose: The chemoresistance of human hepatocellular carcinoma (HCC) to cytotoxic drugs, especially intrinsic or acquired multidrug resistance (MDR), still remains a major challenge in the management of HCC. In the present study, possible mechanisms involved in MDR of HCC were identified using a 5-fluorouracil (5-FU)-resistant human HCC cell line. Methods: BEL-7402/5-FU cells were established through continuous culturing parental BEL-7402 cells, imitating the pattern of chemotherapy clinically. Growth curves and chemosensitivity to cytotoxic drugs were determined by MTT assay. Doubling times, colony formation and adherence rates were calculated after cell counting. Morphological alteration, karyotype morphology, and untrastructure were assessed under optical and electron microscopes. The distribution in the cell cycle and drug efflux pump activity were measured by flow cytometry. Furthermore, expression of potential genes involved in MDR of BEL-7402/5-FU cells were detected by immunocytochemistry. Results: Compared to its parental cells, BEL-7402/5-FU cells had a prolonged doubling time, a lower mitotic index, colony efficiency and adhesive ability, and a decreased drug efflux pump activity. The resistant cells tended to grow in clusters and apparent changes of ultrastructures occurred. BEL-7402/5-FU cells presented with an increased proportion in S and G2/M phases with a concomitant decrease in G0/G1 phase. The MDR phenotype of BEL-7402/5-FU might be partly attributed to increased drug efflux pump activity via multidrug resistance protein 1 (MRP1), overexpression of thymidylate synthase (TS), resistance to apoptosis by augmentation of the Bcl-xl/Bax ratio, and intracellular adhesion medicated by E-cadherin (E-cad). P-glycoprotein (P-gp) might play a limited role in the MDR of BEL-7402/5-FU. Conclusion: Increased activity or expression of MRP1, Bcl-xl, TS, and E-cad appear to be involved in the MDR mechanism of BEL-7402/5-FU.

• The Korean Journal of Physiology
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• v.25 no.2
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• pp.147-158
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• 1991

The effects of noradrenaline on the spontaneous contraction recorded from a strip of mucosa-free antral circular muscle were studied in the guinea-pig stomach, and the changes in slow waves and membrane resistance were analyzed in order to elucidate the mechanism for the excitatory response to noradrenaline. Electrical responses of circular muscle cells were recorded using glass microelectrodes filled with 3 M KCI. Electrotonic potentials were produced to estimate membrane resistance by the partition stimulating method. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% $O_2$ and kept at $35^{\circ}C$. The results obtained were as follows: 1) The spontaneous contractions were potentiated dose-dependently by the application of noradrenaline. 2) Through the experiments using adrenoceptor-blockers, the strong excitatory effect via $[\alpha}-adrenoceptors$ and the weak inhibitory efffect via ${\beta}-adrenoceptors$ were noted. 3) Noradrenaline produced hyperpolarization of membrane potential, and increases in the amplitude and the maximum rate of rise of slow waves. 4) In the presence of apamin, Ca-dependent K channel blocker, the characteristic hyperpolarization was not developed. However, the excitatory effect of noradrenaline on spontaneous contraction remained. 5) Membrane resistance was reduced during the hyperpolarized state by the application of noradrenaline, and the change of membrane resistance and the hyperpolarized state were completely abolished by apamin. From the above results, following conclusions could be made: Excitatory responses to noradrenaline result from the dominant ${\alpha}-excitatory$, and the weak ${\beta}-inhibitory$ action of noradrenaline. Hyperpolarization of membrane potential by noradrenaline is due to the activation of Ca-dependent K channel.

• Journal of Nutrition and Health
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• v.53 no.4
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• pp.356-368
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• 2020

Purpose: Histidine-containing dipeptides, which are rich in chicken, have been reported to reduce the risk of metabolic abnormalities via anticarbonylation mechanism in animal models. To determine the effect of dietary histidine-containing dipeptides on metabolic risk factors in humans, the relation between chicken consumption and insulin resistance were determined in a population consuming high carbohydrate and low protein. Methods: A total of 7,183 subjects (2,929 men and 4,254 women) aged ≥ 50 years from the Korea National Health and Nutrition Examination Survey (KNHANES) were divided into three groups according to chicken consumption (rarely, monthly, and weekly), and evaluated for the metabolic risk factors using homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) in this cross-sectional study. The fourth and fifth (IV-1-3 & V-1) KNHANES, which had blood insulin data, were chosen for the current study. Results: The chicken consumption was significantly associated with insulin (p for trend = 0.018) and HOMA-IR (p for trend = 0.023) in men. In particular, the 'weekly' chicken consuming men in the lowest tertile (< 65.0%) of carbohydrate intake group had significantly lower HOMA-IR (p for trend = 0.033) and higher QUICKI (p for trend = 0.043) than the 'rarely' intake group. In addition, the odds ratio for abnormal HOMA-IR was 0.55 (95% confidence interval [CI], 0.31-0.99) and QUICKI was 0.47 (95% CI, 0.26-0.86) for the 'weekly' chicken consuming group. Conclusion: The 'weekly' chicken consumption had a beneficial effect on insulin resistance and it may partially be due to the major bioactive components in chicken, histidine-containing dipeptides.

• YAKHAK HOEJI
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• v.34 no.2
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• pp.139-146
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• 1990

Streptococcus sp. TR-1 which has inducible resistance to MLS antibiotics was isolated from soil samples in Korea. Streptococcus sp. TR-1 was cultured in Lysis broth, then a plasmid was isolated by modified Elliker method. Bacillus subtilis UOTO277 was transformed with that plasmid. This result showed that the plasmid has the gene relating with inducible resistance to MLS antibiotics. It was named pMB4 and its size was determined about 2.4 Kb by results of digestion with various restriction enzymes. Restriction endonuclease cleavage site map of pMB4 plasmid was made by double digestion of the plasmid. pMB4 plasmid has different restriction endonuclease site map from the other plasmids that have been discovered in Streptococcus sp. so far. And it could be identified that pMB4 plasmid does not have homology with ermK of Bacillus licheniformis EMR but has homology with ermC of Staphylococcus aureus from the results of Southern hybridization.

• Geotechnical Engineering
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• v.14 no.6
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• pp.139-151
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• 1998

SI anchor means the soil improvement anchor. The ground for supporting anchor is improved by JSP, and as a result, SI anchor body has about 80cm in diameter. SI anchor shows high pullout resistance by the frictional force between anchor body and ground, and the bearing capacity of anchor body. Especially the frictional force increases very much with increasing diameter of anchor body improved by JBP. In this study, model and field tests are made to analyse the mechanism of pullout resistance of SI anchor. Through model tests for the SI anchor in air dried sandy ground, strain fields of ground around SI anchor surface are analysed by a photo analysis method using the latex membrane on the wall of soil tank. The results of field tests are analysed by the strains measured by 10 strain gages attached on the inner wall of specially designed PVC pipe embedded in anchor body, and the strains of anchor body are also measured in the model tests.

• BMB Reports
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• v.40 no.6
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• pp.853-860
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• 2007

Resistance to anticancer drugs is a major obstacle in the effective treatment of tumors. To understand the mechanisms responsible for multidrug resistance (MDR), a proteomic approach was used to identify proteins that were expressed in different levels by the adriamycinresistant human gastric cancer cell line, SGC7901/ADR, and its parental cell line, SGC7901. Two-dimensional gel electrophoresis (2-DE) and image analysis was used to determine which protein spots were expressed in different levels by the two cell lines. These spots were then partially identified using ESI-Q-TOF mass spectrometry, and the differential expressional levels of the partially identified proteins were then determined by western blot analysis and real-time RT-PCR. Additionally, the association of Nucleophosmin (NPM1), a protein that was highly expressed by SGC7901/ADR, with MDR was analyzed using siRNA. As a result of this study, well-resolved, reproducible 2-DE patterns of SGC7901/ADR and SGC7901 were established, and 16 proteins that may playa role in the development of thermo resistance were identified. Additionally, suppression of NPMl expression was found to enhance adriamycin chemosensitivity in SGC7901/ADR. These results provide a fundamental basis for the elucidation of the molecular mechanism of MDR, which may assist in the treatment of gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6435-6439
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• 2012

Chemoresistance to cancer therapy is a major obstacle to the effective treatment of human cancers with cisplatin (DDP), but the mechanisms of cisplatin-resistance are not clear. In this study, we established a cisplatin-resistant human ovarian cancer cell line (COC1/DDP) and identified differentially expressed proteins related to cisplatin resistance. The proteomic expression profiles in COC1 before and after DDP treatment were examined using 2-dimensional electrophoresis technology. Differentially expressed proteins were identified using matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and high performance liquid chromatography-electrospray tandem MS (NanoUPLC-ESI-MS/MS). 5 protein spots, for cytokeratin 9, keratin 1, deoxyuridine triphosphatase (dUTPase), aarF domain containing kinase 4 (ADCK 4) and cofilin1, were identified to be significantly changed in COC1/DDP compared with its parental cells. The expression of these five proteins was further validated by quantitative PCR and Western blotting, confirming the results of proteomic analysis. Further research on these proteins may help to identify novel resistant biomarkers or reveal the mechanism of cisplatin-resistance in human ovarian cancers.

• Geomechanics and Engineering
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• v.12 no.2
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• pp.295-312
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• 2017

Cast in situ and grouted concrete helical piles with 150-200 mm diameter half cylindrical ribs have become an economical and effective choice in Shanghai, China for uplift piles in deep soft soils. Though this type of pile has been successful used in practice, the reinforcing mechanism and the contribution of the ribs to the total resistance is not clear, and there is no clear guideline for the design of such piles. To study the inclusion of ribs to the contribution of shear resistance, the shear behaviour between silty sand and concrete slabs with parallel ribs at different spacing and angles were tested in a large direct shear box ($600mm{\times}400mm{\times}200mm$). The front panels of the shear box are detachable to observe the soil deformation after the test. The tests were modelled with three-dimensional finite element method in ABAQUS. It was found that, passive zones can be developed ahead of the ribs to form undulated failure surfaces. The shear resistance and failure mode are affected by the ratio of rib spacing to rib diameter. Based on the shape and continuity of the failure zones at the interface, the failure modes at the interface can be classified as "punching", "local" or "general" shear failure respectively. With the inclusion of the ribs, the pull out resistance can increase up to 17%. The optimum rib spacing to rib diameter ratio was found to be around 7 based on the observed experimental results and the numerical modelling.

• Microbiology and Biotechnology Letters
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• v.22 no.3
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• pp.240-245
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• 1994

Relation the phage defense mechanism of phage resistant Lactococcus lactis subsp. cremoris ATCC 11602-A1 to its cell wall components was investigated. To determine whether teichoic acid which is known to be one of the phage receptor site present on the cell wall, phage adsorption was examined after treatment 5% TCA(60%$\CIRC $C) and concanavalin A to the cell wall of A1 and parent strain. However, the adsorption rate of two strains did not change. Total amount of phosphate after TCA treatment did not change in both strains, but a difference between the two strains was observed. Ribitol and glycerol, components of teichoic acid, could not be detected in the cell walls of two strains by GC analysis. These results suggest that although teichoic acid was not present in the cell walls of both strains, the composition of cell wall of two strains was not identical. Measurement of amount of protein and SDS-polyacryamide gel electrophoresis were carried out to examine the involvement of cell wall protein in phage resistance, showing that protein is nothing to do with phage adsorption of parent strain, but phage resistance of A1 is related to protein. Cell wall carbohydrates of A1 contained rhamnose, glucose, and galactose. Total amount of carbohydrate of 1% SDS-treated A1 cell wall was reduced to the level of parent strain. The results suggest that phage resistance of A1 was due to the presence of a higher level of carbohydrates then parent strain, and to interaction of carbohydrate and protein.