• The Korean Journal of Physiology and Pharmacology
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• v.26 no.2
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• pp.95-111
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• 2022

Chronic obstructive pulmonary disease (COPD) is an important healthcare problem worldwide. Often, glucocorticoid (GC) resistance develops during COPD treatment. As a classic hypoglycemic drug, metformin (MET) can be used as a treatment strategy for COPD due to its anti-inflammatory and antioxidant effects, but its specific mechanism of action is not known. We aimed to clarify the role of MET on COPD and cigarette smoke extract (CSE)-induced GC resistance. Through establishment of a COPD model in rats, we found that MET could improve lung function, reduce pathological injury, as well as reduce the level of inflammation and oxidative stress in COPD, and upregulate expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), multidrug resistance protein 1 (MRP1), and histone deacetylase 2 (HDAC2). By establishing a model of GC resistance in human bronchial epithelial cells stimulated by CSE, we found that MET reduced secretion of interleukin-8, and could upregulate expression of Nrf2, HO-1, MRP1, and HDAC2. MET could also increase the inhibition of MRP1 efflux by MK571 significantly, and increase expression of HDAC2 mRNA and protein. In conclusion, MET may upregulate MRP1 expression by activating the Nrf2/HO-1 signaling pathway, and then regulate expression of HDAC2 protein to reduce GC resistance.

• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.382-392
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• 2003

Purpose: Uptakes of Tc-99m MIBI (MIBI) and Tc-99m tetrofosmin (tetrofosmin) in human non-small cell lung cancer A549, multidrug-resistance associated protein (MRP) expressing cell, were investigated in vitro and in vivo. Materials and Methods: Western blot analysis and immunohistochemistry were used for detection of MRP in A549 cells with anti-MRPr1 antibody. Cellular uptakes of two tracers were evaluated at $100{\mu}M$ of verapamil (Vrp), $50{\mu}M$ of cyclosporin A (CsA) and $25{\mu}M$ of butoxysulfoximide (BSO) after incubation with MIBI and tetrofosmin for 30 and 50 min at $37^{\circ}C$, using single cell suspensions at $1{\times}10^6cells/ml$. Radioactivities in supernatants and pellets were measured with gamma well counter. A549 cells were inoculated in each flanks of 24 nude mice. Group 1 (Gr1) and Gr3 mice were treated with only MIBI or tetrofosmin, and Gr2 and Gr4 mice were treated with 70mg/kg of CsA i.p. for 1 hour before injection of 370KBq of MIBI or tetrofosmin. Mice were sacrificed at 10, 60 and 240 min. Radioactivities of organs and tumors were expressed as percentage injected dose per gram of tissue (%ID/gm). Results: Western blot analysis of the A549 cells detected expression of MRPr1 (190 kDa) and immunohistochemical staining of tumor tissue for MRPr1 revealed brownish staining in cell membrane but not P-gp. Upon incubating A549 cells for 60 min with MIBI and tetrofosmin, cellular uptake of MIBI was higher than that of tetrofosmin. Coincubation with modulators resulted in an increase in cellular uptakes of MIBI and tetrofosmin. Percentage increase of MIBI was higher than that of tetrofosmin with Vrp by 623% and 427%, CsA by 753% and 629% and BSO by 219% and 140%, respectively. There was no significant difference in tumoral uptakes of MIBI and tetrofosmin between Gr1 and Gr3. Percentage increases in MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively higher by the time up to 240 min with CsA. Conclusion: These results indicate that MIBI and tetrofosmin are suitable tracers for imaging MRP-mediated drug resistance in A549 tumors. MIBI may be a better tracer than tetrofosmin for evaluating MRP reversal effect of modulators.

• Korean Journal of Veterinary Research
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• v.38 no.4
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• pp.771-776
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• 1998

Synthetic oligonucleotide primers of 20 and 21 bases, respectively, were used in the polymerase chain reaction (PCR) to amplify a sequence of the mrp gene, which encodes the muramidase released protein of Streptococcus suis. Amplification was not recorded when 5 other streptococcal species were tested or when 9 different nonstreptococcal species were tested. A DNA fragment of 517bp was amplified from the genomic DNA of S suis. The lower detection limit was 100pg of the genomic DNA. The primers recognized 34 serotypes of S suis reference strains and 9 isolates from pneumonic lung, brain, nasal discharge, tonsil. This results suggest that the amplification of the mrp gene by PCR method is potential for the identification of S suis isolates.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1403-1410
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• 2014

Epigenetic regulators like histone deacetylases (1 and 2), and viral onco-proteins (E6/E7) are known to be overexpressed in cervical cancer cells. The present study was designed to investigate the effect of curcumin on HDACs (1 and 2) and HPV E6/E7 in the cervical cancer cell line SiHa and a drug resistant clone $SiHa^R$ (derived from SiHa). It was further intended to investigate whether curcumin could sensitize the cells towards cisplatin induced cell killing by modulation of multi drug resistant proteins like MRP1 and Pgp1. Curcumin inhibited HDACs, HPV expression and differentially increased acetylation and up-regulation of p53 in SiHa and $SiHa^R$, leading to cell cycle arrest at G1-S phase. Up-regulation of pRb, p21, p27 and corresponding inhibition of cyclin D1 and CDK4 were observed. Cisplatin resistance in $SiHa^R$ due to over-expression of MRP1 and Pgp1 was overcome by curcumin. Curcumin also sensitized both the cervical cancer cells towards cisplatin induced cell killing. Inhibition of HDACs and HPVs led to cell cycle arrest at G1/S phase by alteration of cell cycle regulatory proteins. Suppression of MRP1 and Pgp1 by curcumin resulted in sensitization of cervical cancer cells, lowering the chemotherapeutic dose of the drug cisplatin.

• Proceedings of the Korea Inteligent Information System Society Conference
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• 2002.05a
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• pp.429-434
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• 2002

For companies assembling end products from sub assemblies or components, MRP (Material Requirement Planning) logic is frequently used to synchronize and pace the production activities for the required parts. However, in MRP, the planning of operational-level activities is left to short term scheduling. So, we need a good scheduling algorithm to generate feasible schedules taking into account shop floor characteristics and multi-level job structures used in MRP. In this paper, we present a GA (Genetic Algorithm) solution for this complex scheduling problem based on a new gene to reflect the machine assignment, operation sequences and the levels of the operations relative to final operation. The relative operation level is the control parameter that paces the completion timing of the components belonging to the same branch in the multi-level job hierarchy. In order to revise the fixed relative level which solutions are confined to, we apply large step transition in the first step and GA in the second step. We compare the genetic algorithm and 2-phase optimization with several dispatching rules in terms of tardiness for about forty modified standard job-shop problem instances.

• Industrial Engineering and Management Systems
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• v.11 no.3
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• pp.255-265
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• 2012

Environments surrounding production sites have changed greatly in recent years. Accommodating environmental changes calls for the design and development of information systems that center on production lines. There is a need for a training program that teaches learners to understand the particulars of an operation and apply that knowledge to an information system. In this research, we used material requirements planning (MRP) as the subject for which basic skills are to be taught and developed an MRP exercise-based training program. The program is designed for 13 lectures of 90 minutes each, and it consists of MRP exercises, modeling methods to represent them, the use of a programming language for system development, and finally, evaluation of the exercises. Lecture materials are described in 505 lecture slides using Microsoft PowerPoint to allow visualization of topics through graphs and models. The developed training program was then delivered to 86 college students, and its results were measured through quizzes to verify educational effectiveness.

• Journal of the Korea Institute of Building Construction
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• v.4 no.1
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• pp.105-110
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• 2004

Resource procurement is an important management area because cost of resource covers 40％ of total construction project cost and resource delivery has direct relationship with project performance. Integration of cost provides various potentials for effective and efficient project control. This study investigates the usefulness of time in resource procurement management focused on materials. These days, construction projects have characterized manufacture because of industrialization and component. Therefore, application of systematic resource planning has been requested in the construction. There are many companies conducting procurement of resource on the web by applying MRP, ERP etc. in the construction. However, in applying them in the construction yet, there is obstruction. MRP has the character doing its function under accurate cost prediction of resource. But prediction of resource is difficult in industry mechanism of the construction. If accurate cost prediction of resource is possible in the construction, it will be expected to reduce cost of procurement of resource substantially by applying successful resource planning model in the manufacture. On the basis of recent current, the purpose of study is to present procurement of resource system that period observance of construction and minimization of stock is possible by reflecting accurate lead-time to apply proactive thought to be able to cope with alteration of construction schedule efficiently in analyzing resource planning of the construction site.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4597-4606
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• 2012

Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma which arises from the epithelial cells of the bile ducts. The aim of the study was to investigate the cytotoxicity, toxicity, and anticancer activity of a crude ethanolic extract of ginger (Zingiber officinale Roscoe) against CCA. Cytotoxic activity against a CCA cell line (CL-6) was assessed by calcein-AM and Hoechst 33342 assays and anti-oxidant activity was evaluated using the DPPH assay. Investigation of apoptotic activity was performed by DNA fragmentation assay and induction of genes that may be involved in the resistance of CCA to anticancer drugs (MDR1, MRP1, MRP2, and MRP3) was examined by real-time PCR. To investigate anti-CCA activity in vivo, a total of 80 OV and nitrosamine (OV/DMN)-induced CCA hamsters were fed with the ginger extract at doses of 1000, 3000, and 5000 mg/kg body weight daily or every alternate day for 30 days. Control groups consisting of 10 hamsters for each group were fed with 5-fluorouracil (positive control) or distilled water (untreated control). Median $IC_{50}$ (concentration that inhibits cell growth by 50%) values for cytotoxicity and anti-oxidant activities of the crude ethanolic extract of ginger were 10.95, 53.15, and $27.86{\mu}g/ml$, respectively. More than ten DNA fragments were visualized and up to 7-9 fold up-regulation of MDR1 and MRP3 genes was observed following exposure to the ethanolic extract of ginger. Acute and subacute toxicity tests indicated absence of any significant toxicity at the maximum dose of 5,000 mg/kg body weight given by intragastric gavage. The survival time and survival rate of the CCA-bearing hamsters were significantly prolonged compared to the control group (median of 54 vs 17 weeks). Results from these in vitro and in vivo studies thus indicate promising anticancer activity of the crude ethanolic extract of ginger against CCA with the absence of any significant toxicity. Moreover, MDR1 and MRP3 may be involved in conferring resistance of CCA to the ginger extract.

• Proceedings of the Korean Operations and Management Science Society Conference
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• 1999.04a
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• pp.7-8
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• 1999

• Proceedings of the Korean Operations and Management Science Society Conference
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• 1988.10a
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• pp.7-7
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• 1988