• 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.

• Journal of Korean Library and Information Science Society
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• v.5
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• pp.67-89
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• 1978

This study is the third partial study of the 'A Bibliographical Study of the Toegye.' The contents of the study is divided into three chapters as following : In the first chapter, the authorship of Hsin-ching-fu-chu(心經附註) is described Hsin-ching(心經) was edited by Chen-Te-Hsiu(眞德秀), a scholar of the Sung Dynasty (1178-1235A.D.). He selected several articles on Hsin Study(心學) from classics of ancient China, with the view of spreading of Hsin thought of ancestor. Hsin-ching-fu-chu is an annotated work of Hsin-ching, which was edited by $Ch'\^{e}ng-Min-Ch\^{e}ng$(程敏政). $Ch'\^{e}ng-Min-Ch\^{e}ng$ was a scholar of the Ming Dynasty (died 1499 A.D). His annotation of Hsin-ching was according to the edition of Tuan-Ping (端平) 1st (1234 A.D.). Hsin-ching-fu-chu which was first published in 1492 A.D., by his student, named Wang-Tsu(汪祚). In the second chapter, the editions of Hsin-ching-fu-chu which was published in Korea before 1566 A.D., when Toe-gye's postscript was written, are described. In Korea, three editions were published. The first was published before 1523 A.D. in, kwang-ju(光州), by the wooden plate block. The second was published ca 1564 A.D. in Pyeong-yang(平壤), by the wooden plate, too. These two editions have remained. The last was published ca 1564 A.D., in Hae-ju(海州), but the method of printing couldn't be found out because I have not been able to get the book itself and records on the printing. In the last chapter, facts on Hsin-ching-fu-chu related to Toegye are described. Toegye found Kwang-ju edition of Hsin-ching-fu-chu in 1533 A.D., at Seong-gyun-gwan(成均館) in Seoul. He acquired the book from his friend. He read and studied very hard and remembered all the text. Also, he taught the Hsin-ching-fu-chu to his pupils and guided the reading of Hsin-ching-fu-chu to his followers and student. He read many proof sheets of the new publication of Hsin-ching-fy-chu, correcting then on detail and making notes on them.

• 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.

• Journal of Pharmaceutical Investigation
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• v.38 no.1
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• pp.45-50
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• 2008

5-Fluorouracil (5-FU) is an antimetabolic of the pyrimidine derivatives that is used in chemotherapy for the treatment of several types of cancer. 5-FU have poor oral absorption and short biological half-time and strong side effects. Microneedle introduced to find a solution of problems. Microneedle device with roll was manufactured for transdermal delivery of various drugs. 5-FU was mixed in non-ionic surfactant such as tween 20 and tween 80. Camscope was used to analysis the permeation magnitude of treated skin by microneedle and trypan blue staining. The 5-FU solution with surfactant measured by ZETA-potential analysis system for stability of solution. The skin permeation rate of 5-FU determined by HPLC. We confirmed that cross treated skin was dyed more deeply than parallel treated skin through trypan blue staining. The results indicate that skin permeation rate of 5-FU was increased with the treatment types and treatment times.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.185-196
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• 1992

To assess its suitability as a prodrug of 5-fluorouracil (5-FU), 1-glycyloxymethyl-5-FU HCl (GFU), a 5-fluorouracil derivative having a glycyloxymethyl group at the N-l position was synthetized. Its physicochemical properties and hydrolysis kinetics, in aqueous solution of pH $1{\sim}10$ and in the presence of human plasma or rat liver homogenate were studied. Its acute toxicity and antitumor activity against sarcoma 180 were also examined, GFU showed higher lipid/water partition coefficient than 5-FU. The calculated $pK_{\alpha}$ values of 5-FU and GFU were 8.02 and 7,20, respectively. The decomposition rates of GFU in aqueous solution showed a pH-dependence over the pH range used, which could be ascribed to solvent catalysed hydrolysis reaction at pH lower than 4,16 and to specific hydroxide ion hydrolysis reaction at pH higher than 4,16, The half-life of GFU was 6,9 min in 80% human plasma solution and less than 3 min in rat liver homogenate at $37^{\circ}C$, The $LD_{50}$ value of 5-FU was 240 mg/kg while that of GFU was 440.6 mg/kg (226 mg as 5-FU). Both of 5FU and GFU showed a strong antitumor activity, Therapeutic ratios of 5-FU and GFU were 3.07 and 3.55, respectively.

• Journal of the Korean Chemical Society
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• v.57 no.1
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• pp.88-93
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• 2013

In order to construct a controlled release system of drugs and to reduce toxic side effects of 5-fluorouracil, the novel ramose chitosan-based-5-fluorouracil microspheres (CS-FU-MS) were prepared. Firstly, using chitosan (CS) as carriers and 5-fluorouracil (5-FU) as a model drug, ramose chitosan-based-5-fluorouracil (CS-FU) was efciently synthesized by chemical crosslinking method through microwave irradiation, drug loading was 10.6%; Secondly, CS-FU-MS were prepared by CS-FU self-assembled under the dialysis conditions and the free 5-FU was encapsulated further at the same time. The size dispersivity of particles is uniform, and the average diameter of the CS-FU-MS was $4{\mu}m$. The drug encapsulation efficiency was 76.1%, and the drug loading was increased to 26.22%. CS-FU-MS maintain the zero-order release time in PBS (pH = 7.4) and HCl/KCl (pH = 1.2) dialysis medium was 40h and 34h respectively, and the cumulative release were 58.89% and 79.33% in 182 h. The results showed that CS-FU-MS have excellent sustained release properties.

• The Journal of Asian Finance, Economics and Business
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• v.8 no.2
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• pp.747-757
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• 2021

The primary purpose of the study is to investigate the volatility spillover from financial uncertainty (FU) of the United States (US) to the stock markets of SAARC member countries including India, Sri-Lanka, Pakistan, and Bangladesh. The empirical literature overlooked SAARC countries and the FU index. Based on the estimation method, the data of FU is available for three different forecast horizons including 1-month, 3-months, and 12-months. For empirical analysis, monthly data is used from February 2013 to September 2019. EGARCH model is employed to investigate the volatility spillover effects. The findings of the study show that the spillover effect of FU varies with the forecast horizon. The FU with a higher forecast horizon has a significant spillover effect on more countries. The spillover effect of US financial uncertainty is negative in most of the SAARC countries. Bangladesh stock market is influenced by FU with all three forecast horizons whereas the volatility of the Pakistan stock market is not influenced by FU with any forecast horizon. The findings are consistent with the concept of "limited trade openness" in the financial markets of emerging economies. The emerging economies avoid financial market openness to minimize the risk of spillover of other countries.

• Journal of Information Technology Services
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• v.4 no.2
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• pp.99-107
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• 2005

This paper describes a kernel function named FU(forced unmount) related to filesystem on linux system. FU is a function to forcibly unmount filesystems in despite of busy state of the filesystems. Our current implementation has been developed on linux-2.6.8 and tested in environments that are established by tools, POSTMAR and LTP. This contains considerations of FU and a algorithm to solve problems during developing FU.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.479-489
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• 2022

5-Fluorouracil (5-FU) remains to be an important chemotherapeutic drug for treating several cancers when targeted therapy is unavailable. Chemoresistance limits the clinical utility of 5-FU, and new strategies are required to overcome the resistance. Reactive oxygen species (ROS) and antioxidants are balanced differently in both normal and cancer cells. Modulating ROS can be one method of overcoming 5-FU resistance. This review summarizes selected compounds and endogenous cellular targets modulating ROS generation to overcome 5-FU resistance.

• KSBB Journal
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• v.23 no.5
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• pp.452-459
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• 2008

To obtain maximal efficacy with minimal systemic side-effects, many studies have been carried out to achieve the controlled release of 5-fluorouracil (5-FU). In this study, biodegradable poly(L-lactide) (L-PLA) microparticles containing 5-FU were prepared by a process, called aerosol solvent extraction system (ASES), utilizing supercritical carbon dioxide. The effects of various organic solvents, drug/polymer feeding ratio, polymer molecular weight, and blending with the same polymers with different molecular weights on the formation of 5-FU loaded microparticles were investigated under a predetermined operating condition from our previous study. The drug recovery, entrapment efficiency, and in vitro drug release kinetics were determined by HPLC assays. The drug recovery obtained from the ASES process was found to be very high, whereas the drug entrapment efficiency was considerably low in all the experiments due to the poor affinity between L-PLA and 5-FU. These results indicated that the precipitation rate of L-PLA might be quite different from that of 5-FU so that there was little chance to form 5-FU loaded L-PLA microparticles.