• Archives of Pharmacal Research
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• v.29 no.11
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• pp.1018-1023
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• 2006

Chemoresistance remains the major obstacle to successful therapy of cancer. In order to understand the mechanism of multidrug resistance (MDR) that is frequently observed in lung cancer patients, here we studied the contribution of MDR-related proteins by establishing lung cancer cell lines with acquired resistance against etoposide. We found that human H460 lung cancer cells responded to etoposide more sensitively than A549 cells. Among MDR-related proteins, the expression of p-glycoprotein (Pgp) and lung resistance protein (LRP) were much higher in A549 cells compared with that in H460 cells. When we established H460-R1 and -R2 cell lines by progressive exposure of H460 cells to increasing doses of etoposide, the response against etopbside as well as doxorubicin was greatly reduced in R1 and R2 cells, suggesting MDR induction. Induction of MDR was not accompanied by a decrease in the intracellular accumulation of etoposide and the expression of MDR-related proteins that function as drug efflux pumps such as Pgp and MRP1 was not changed. We found that the acquired resistance paralleled an increased expression of LRP in H460 cells. Taken together, our data suggest the implicative role of LRP in mediating MDR in lung cancer.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.68-72
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• 2014

When chemotherapy is administered during pregnancy, it is important to consider the fetus chemotherapy exposure, because it may lead to fetal consequences. Paclitaxel has become widely used in the metastatic and adjuvant settings for woman with cancer including breast and ovarian cancer. Therefore, we attempted to clarify the transport mechanisms of paclitaxel through blood-placenta barrier using rat conditionally immortalized syncytiotrophoblast cell lines (TR-TBTs). The uptake of paclitaxel was time- and temperature-dependent. Paclitaxel was eliminated about 50% from the cells within 30 min. The uptake of paclitaxel was saturable with $K_m$ of $168{\mu}M$ and $371{\mu}M$ in TR-TBT 18d-1 and TR-TBT 18d-2, respectively. [$^3H$]Paclitaxel uptake was markedly inhibited by cyclosporine and verapamil, well-known substrates of P-glycoprotein (P-gp) transporter. However, several MRP substrates and organic anions had no effect on [$^3H$]paclitaxel uptake in TR-TBT cells. These results suggest that P-gp may be involved in paclitaxel transport at the placenta. TR-TBT cells expressed mRNA of P-gp. These findings are important for therapy of breast and ovarian cancer of pregnant women, and should be useful data in elucidating teratogenicity of paclitaxel during pregnancy.

• Transactions of the Korean Society of Pressure Vessels and Piping
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• v.15 no.2
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• pp.58-63
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• 2019

This paper presents preliminary analysis and results on IASCC sensitivity of a core shroud in the reactor pressure vessel. First, neutron irradiation flux distribution of the reactor internals was calculated by using the Monte Carlo simulation code, MCNP6.1 and the nuclear data library, ENDF/B-VII.1. Second, based on the neutron irradiation flux distribution, temperature and stress distributions of the core shroud during normal operation were determined by performing finite element analysis using the commercial finite element analysis program, ABAQUS, considering irradiation aging-related degradation mechanisms. Last, IASCC sensitivity of the core shroud was assessed by using the IASCC sensitivity definition of EPRI MRP-211 and the finite element analysis results. As a result of the preliminary analysis, it was found that the point at which the maximum IASCC sensitivity is derived varies over operating time, initially moving from the shroud plate located in the center of the core to the top shroud plate-ring connection brace over operating time. In addition, it was concluded that IASCC will not occur on the core shroud even after 60 years of operation (40EFPYs) because the maximum IASCC sensitivity is less than 0.5.

• Proceedings of the Korean Operations and Management Science Society Conference
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• 1994.04a
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• pp.728-736
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• 1994

본 연구는 MRP(Material Requirement System) 시스템의 기본 요소인 BOM(Bill of Material)의 효과성 분석을 목적으로 한다. BOM은 부품의 구성 관계를 나타내는 표로서, 근자에는 모듈화의 개념이 도입된 Modular BOM이 제시되고 있다. Modular BOM은 부품의 구성 관계를 모듈화 함으로써 이들을 보다 편리하게 관리하고, 기존에 사용되어 오던 구조형 BOM의 불편함, 단점 등을 보완한다. 본 연구는 기존의 구조형 BOM과 modular BOM을 데이타베이스 관리면에서 분석함으로서, 모듈화한 BOM이 데이타 관리면에서 지니는 효과성을 분석하였다. 데이타 관리의 효과성 분석은 BOM 데이타 관리면에서 지니는 효과성을 분석하였다. 데이타 관리의 효과성 분석은 BOM 데이타베이스의 제품구성을 관계형 데이타베이스의 레코드 (또는 tuple)로 표현 함으로서, 특정 부분품으로 구성된 완제품들을 나타내기 위해 필요한 레코드 수를 기초로 하여 수행되었다. 이상의 논리에 근거하여 본 연구는 다음과 같은 데이타 관리 관점에서 분석한다. 1. 제품구성 표시를 위한 BOM 데이타베이스의 구성 레코드 수의 비교, 2. 새로운 제품의 추가나 기 제품의 제품구성 변경에 따른 갱신의 용이성 본 연구에서는 분석의 편의를 위하여 BOM 구성이 레벨을 무시한 단순형태의 2단계 BOM을 분석 대상으로 한다. BOM데이타 베이스 관리의 효과성은 제시된 레코드 수에 기초하여 데이타베이스의 규모와 변경 용이성의 측정 모형을 수립하고, 이들 모형을 modular BOM과 구조형 BOM에 적용함으로서 수행 되었다.

• Industrial Engineering and Management Systems
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• v.4 no.1
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• pp.23-35
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• 2005

This paper aims to develop a practical finite capacity MRP (FCMRP) system based on the needs of an automotive parts manufacturing company in Thailand. The approach includes a linear goal programming model to determine the optimal start time of each operation to minimize the sum of penalty points incurred by exceeding the goals of total earliness, total tardiness, and average flow-time considering the finite capacity of all work centers and precedence of operations. Important factors of the proposed FCMRP system are penalty weights and dispatching rules. Effects of these factors on the performance measures are statistically analyzed based on a real situation of an auto-part factory. Statistical results show that the dispatching rules and penalty weights have significant effects on the performance measures. The proposed FCMRP system offers a good tradeoff between conflicting performance measures and results in the best weighted average performance measures when compared to conventional forward and forward-backward finite capacity scheduling systems.

• Journal of Veterinary Science
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• v.22 no.3
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• pp.25.1-25.16
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• 2021

Background: Malignant lymphoma is the most common hematopoietic malignancy in dogs, and relapse is frequently seen despite aggressive initial treatment. In order for the treatment of these recurrent lymphomas in dogs to be effective, it is important to choose a personalized and sensitive anticancer agent. To provide a reliable tool for drug development and for personalized cancer therapy, it is critical to maintain key characteristics of the original tumor. Objectives: In this study, we established a model of hybrid tumor/stromal spheroids and investigated the association between canine lymphoma cell line (GL-1) and canine lymph node (LN)-derived stromal cells (SCs). Methods: A hybrid spheroid model consisting of GL-1 cells and LN-derived SC was created using ultra low attachment plate. The relationship between SCs and tumor cells (TCs) was investigated using a coculture system. Results: TCs cocultured with SCs were found to have significantly upregulated multidrug resistance genes, such as P-qp, MRP1, and BCRP, compared with TC monocultures. Additionally, it was revealed that coculture with SCs reduced doxorubicin-induced apoptosis and G2/M cell cycle arrest of GL-1 cells. Conclusions: SCs upregulated multidrug resistance genes in TCs and influenced apoptosis and the cell cycle of TCs in the presence of anticancer drugs. This study revealed that understanding the interaction between the tumor microenvironment and TCs is essential in designing experimental approaches to personalized medicine and to predict the effect of drugs.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.490-496
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• 2017

Imatinib resistance has become a major clinical problem for chronic myeloid leukemia. The aim of the present study was to investigate the involvement of MEG3, a lncRNA, in imatinib resistance and demonstrate its underlying mechanisms. RNAs were extracted from CML patients' peripheral blood cells and human leukemic K562 cells, and the expression of MEG3 was measured by RT-qPCR. Cell proliferation and cell apoptosis were evaluated. Western blotting was used to measure the protein expression of several multidrug resistant transporters. Luciferase reporter assay was performed to determine the binding between MEG3 and miR-21. Our results showed that MEG3 was significantly decreased in imatinib-resistant CML patients and imatinib-resistant K562 cells. Overexpression of MEG3 in imatinib-resistant K562 cells markedly decreased cell proliferation, increased cell apoptosis, reversed imatinib resistance, and reduced the expression of MRP1, MDR1, and ABCG2. Interestingly, MEG3 binds to miR-21. MEG3 and miR-21 were negatively correlated in CML patients. In addition, miR-21 mimics reversed the phenotype of MEG3-overexpression in imatinib-resistant K562 cells. Taken together, MEG3 is involved in imatinib resistance in CML and possibly contributes to imatinib resistance through regulating miR-21, and subsequent cell proliferation, apoptosis and expression of multidrug resistant transporters.

• 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.

• JSTS:Journal of Semiconductor Technology and Science
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• v.17 no.3
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• pp.446-457
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• 2017

In order to reduce the size of frame memory or bus bandwidth, frame memory compression (FMC) recompresses reconstructed or reference frames of video codecs. This paper proposes a novel FMC design based on discrete wavelet transform (DWT) - set partitioning in hierarchical trees (SPIHT), which supports fine-scalable throughput and is area-efficient. In the proposed design, multi-cores with small block sizes are used in parallel instead of a single core with a large block size. In addition, an appropriate pipelining schedule is proposed. Compared to the previous design, the proposed design achieves the processing speed which is closer to the target system speed, and therefore it is more efficient in hardware utilization. In addition, a scheme in which two passes of SPIHT are merged into one pass called merged refinement pass (MRP) is proposed. As the number of shifters decreases and the bit-width of remained shifters is reduced, the size of SPIHT hardware significantly decreases. The proposed FMC encoder and decoder designs achieve the throughputs of 4,448 and 4,000 Mpixels/s, respectively, and their gate counts are 76.5K and 107.8K. When the proposed design is applied to high efficiency video codec (HEVC), it achieves 1.96% lower average BDBR and 0.05 dB higher average BDPSNR than the previous FMC design.

• Asia pacific journal of information systems
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• v.14 no.1
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• pp.143-163
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• 2004

Management is under constant pressures to achieve competitiveness in production in most manufacturing companies. The adoption of management techniques(MT) such as TQM, MRP, ERP and so on has been a logical response for better performance to many companies. Besides, these companies commonly adopt a number of such techniques with high expectation for performance improvement. However, expected improvement in performance is not guaranteed unless necessary ingredients exist for those techniques. Many research studies have focused on the nature of successful adoption of management techniques in the past. However, most studies have been related to a single technique and its effects. When more than one techniques are in use in a company, focusing on a single technique limits the value of analysis. This paper focuses the value of MTs adopted in a company in multiplicity and compares the relative characteristics of MTs one another. Especially, the purpose of this paper is to examine the comparative nature of MTs adopted In manufacturing companies and the elements of MT success in relationship with information systems and organizational adjustment for adoption of MTs. The result of the analysis shows that the more efforts are exhorted for the adjustment of information systems and organizational structures to accommodate the MTs, the more success from the adopted techniques results. However, the extent of adjustment for different management techniques differs one another due to the nature of each technique. With regard to the comparative impact of adjustment of information systems and that of organizational structures, the result shows that the latter has more direct and greater impact than the former.