• Journal of Pharmaceutical Investigation
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• v.24 no.3
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• pp.33-39
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• 1994

We have studied the effect of loading amount and particle size on the rate of release of 5-fluorouracil (5-FU) from ethylene-vinyl acetate (EVA) matrix. Release rate increased as the loading amount and particle size increase. We also studied the effect of additives (lactose and algin) on the rate of release of 5-FU. Both algin and lactose promoted the rate of release. The ability to increase the rate is in the order of algin>lactose>5-FU. Scanning electron microscope study clearly shows that large cavities and cracks are created. The results imply that, by the proper combinations of the amount of the additive, $EVA_c$ and drug, the rate of drug release can be modulated over a wide range of values.

• 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.

• Journal of Society of Preventive Korean Medicine
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• v.2 no.1
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• pp.13-30
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• 1998

Geraniol (1), olivetol (2), cannabinoids (3 and 4) and 5-fluorou.a.il (5). were tested for their growth inhibitory effects against SK-MEL-3 cell lines using two different 3-(4,5-dimethylthiazol- 2yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and sulforhodamine B protein (SRB) assay. These compounds showed inhibitory activity in vitro in the micromolar range against SK-MEL-3 cell lines. In general, the antitumor activity of these compounds (1, 2, 3, 4 and 5) was in a dose-dependent over the micromolar concentration range $1\;to\;100{\mu}M$. The comparison of $IC_{50}$ values of these compounds in tumor cell lines shows that their susceptibility to these compounds decrease in the following order : OLVTL > CBG > CBD > 5-FU > CRNL in MTT assay, CBG > OLVTL > CBD > GRNL > 5-FU in SRB assay. Cannabinoids (3 and 4) and 5-fluorouracil (5) were tested for their cytotoxic effects on NIH 373 fibroblasts using two different MTT assay and SRB assay. These compounds exhibited potent cytotoxic activities in vitro in the micromolar range against NIH 373 fibroblasts. In general, the cytotoxic activities of these compounds (3, 4 and 5) were in a dose-dependent over the micromolar concentration range $1\;to\;100{\mu}M$. The comparison of $CD_{50}$ values of these compounds on NIH 373 fibroblasts shows that their susceptibility to these compounds decrease on the following order ; CBD > 5-FU > CBG in MTT assay and SRB assay. Cannabigerol (3) was shown the least cytotoxic activity on NIH 373 fibroblasts. Cannabigerol (3) exhibited the most growth-inhibitory activity against SK-MEL-3 cell lines.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2503-2508
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• 2013

Histone deacetylation mediated by histone deacetylases (HDACs) has been reported as one of the epigenetic mechanisms associated with tumorigenesis. The poor responsiveness of anticancer drugs found with cholangiocarcinoma (CCA) leads to short survival rate. We aimed to investigate mRNA expression of HDACs class I and II, and the effect of HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA), in CCA in vitro. Expression of HDACs was studied in CCA cell lines (M213, M214 and KKU-100) and an immortal cholangiocyte (MMNK1) by semi-quantitative reverse transcription-PCR. SAHA and VPA, as well as a classical chemotherapeutic drug 5 -fluorouacil (5-FU) were used in this study. Cell proliferation was determined by sulforhodamine assay. $IC_{50}$ and $IC_{20}$ were then analyzed for each agent and cell line. Moreover, synergistic potentional of VPA or SAHA in combination with 5-FU at sub toxic does ($IC_{20}$) of each agent was also evaluated. Statistic difference of HDACs expression or cell proliferation in each experimental condition was analyzed by Student's t-test. The result demonstrated that HDACs were expressed in all studied cell types. Both SAHA and VPA inhibited cell proliferation in a dose-dependent manner. Interestingly, KKU-100 which was less senstitive to classical chemotheraoeutic 5-FU was highly was sensitive to HDAC inhibitors. Simultaneous combination of subtoxic doses of HDAC inhibitors and 5-FU signiicantly inhibited cell proliferation in CCA cell lines compared to single sgent treatment($P{\leq}0.01$), while sequentially combined treatments were less effective. The present study showed inhibitory effects of HDACIs on cell proliferation in CCA cell lines, with synergistic antitumor potential demonstrated by simultaneous combination of VPA or SAHA with 5-FU, suggesting a novel alternative therapeutic strategy in effective treatment of CCA.

• Molecular & Cellular Toxicology
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• v.3 no.2
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• pp.137-144
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• 2007

The mechanism of cytotoxicity of doxifluridine, a prodrug fluorouracil (5-FU), has been ascribed to the misincorporation of fluoropyrimidine into RNA and DNA and to the inhibition of the nucleotide synthetic enzyme thymidylate synthase. Increased understanding of the mechanism of 5-FU has led to the development of strategies that increases its anticancer activity or predicts its sensitivity to patients. Using GeneChip?? Rhesus Macaque Genome arrays, we analyzed gene expression profiles of doxifluridine after two weeks repeated administration in cynomolgus monkey. Kegg pathway analysis suggested that cytoskeletal rearrangement and cell adhesion remodeling were commonly occurred in colon, jejunum, and liver. However, expression of genes encoding extracellular matrix was distinguished colon from others. In colon, COL6A2, COL18A1, ELN, and LAMA5 were over-expressed. In contrast, genes included in same category were down-regulated in jejunum and liver. Interestingly, MMP7 and TIMP1, the key enzymes responsible for ECM regulation, were overexpressed in colon. Several studies were reported that both gene reduced cell sensitivity to chemotherapy-induced apoptosis. Therefore, we suggest they have potential as target for modulation of 5-FU action. In addition, the expression of genes which have been previously known to involve in 5-FU pathway, were examined in three organs. Particularly, there were more remarkable changes in colon than in others. In colon, ECGF1, DYPD, TYMS, DHFR, FPGS, DUT, BCL2, BAX, and BAK1 except CAD were expressed in the direction that was good response to doxifluridine. These results may provide that colon is a prominent target of doxifluridine and transcriptional profiling is useful to find new targets affecting the response to the drug.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.114-114
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• 1993

항암성 또는 항 virus성 약물개발 목적으로 천연의 pyrimidine nucleoside의 구조유사체로 pyrimidine acyclonucleoside들을 합성하였다. Pyrimidine acyclonucleoside를 염기 uracil, thymine 및 5-fluorouracil을 원료로 하여 합성하고 구조를 NMR, IR data를 써서 확인하였다. 이들 합성 화합물들은 L$_{1210}$ 암세포를 이용하여 in vitro 항암성 작용을 검색하였다. 합성된 화합물들 중 5-fluorouraoil-acyclonucleoside들은 약간이나마 모 5FU보다 높은 항암성 작용을 보였다. 유도체들은 5-FU의 N$^1$에 glycosidic 결합이 아닌 alkyl 결합을 하고있어, 모 5FU를 그리 쉽게 유리시키리라 보아지지 않으므로 이들의 작용성은 acyclonucleoside형태일 것 같아 이들의 작용기전 연구가 필요하다고 보아진다. 한편 얻은 유도체들은 HSV-1 및 HSV-2를 이용하여 항 virus성 작용을 검색한 결과 2500$\mu\textrm{g}$/ml 농도에서 유의성 있는 억제 작용성을 보이지 않았다.

• Korean Journal of Clinical Pharmacy
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• v.16 no.2
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• pp.131-138
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• 2006

Heptaplatin, a new platinum derivative, has several contradicting reports on the nephrotoxicity. Therefore, the aim of this study is to compare the toxicities of heptaplatin-containing regimens in the chemotherapy. This study was performed retrospectively on seventy-seven patients with advanced gastric cancer who did not receive chemotherapy within the last 1 months before taking of heptaplatin- or cisplatin-containing chemotherapy. The 38 patients among total patients was received heptaplatin-containing regimens (26 with SEF regimens: heptaplatin/epirubicin/5-FU, 12 with SF regimens: heptaplatin/5-FU) and the rest 39 patients was received cisplatin-containg regimens (11 with CEF regimens: cisplatin/epirubicin/5-FU, 28 with ELF regimens: epirubicin/leucovorin/5-FU). Before and after the chemotherapy serum creatinine (Scr) and proteinuria were measured by urine stick test in all patient groups. Also Scr was measured a day before the second cycle and did not vary significantly between groups. However Scr on cycle 3 were significantly higher in SEF and SF groups. In case of proteinuria, it was more frequent on cycle 1 in heptaplatin/5-FU group. Proteinuria before and after on cycle 2 was not different between the two cisplatin -containing groups, but was more frequent in heptaplatin-containing groups. The reason why the Scr measured was not so different could be because we excluded the patients who received only one cycle of heptaplatin and changed the regimen due to signs of nephrotoxcity. As the results nephrotoxicity such as protienuria was appeared to be more frequent with heptaplatin-treated patients. It suggests that the clinical consequences of the toxicity need to further evaluation and also the modalities to prevent or minimize nephrotoxicity of heptaplatin should be studied for future utilization of the drug.

• Bulletin of the Korean Chemical Society
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• v.1 no.4
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• pp.121-123
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• 1980

$C_4$-Photocycloaddition of 5,7-dimethoxycoumarin(DMC) to 5-fluorouracil(5-FU) was studied in frozen aqueous solution. The major photoproduct was diagnosed and isolated by TLC and column chromatography. The structure of isolated photoproduct was identified as a $C_4$-cycloaddition product of DMC and 5-FU by the characteristics of its UV, IR, NMR, mass spectra, elemental analysis, and photosplitting.

• Macromolecular Research
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• v.14 no.4
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• pp.461-465
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• 2006

Two types of injectable system using thermosensitive chitosan (chitosan-g-NIPAAm), hydrogel and microparticles (MPs)-embedded hydrogel were developed as drug carriers for controlled release and their pharmaceutical potentials were investigated. 5-Fluorouracil (5-FU)-loaded, biodegradable PLGA MPs were prepared by a double emulsion method and then simply mixed with an aqueous solution of thermosensitive chitosan at room temperature. All 5-FU release rates from the hydrogel matrix were faster than bovine serum albumin (BSA), possibly due to the difference in the molecular weight of the drugs. The 5-FU release profile from MPs-embedded hydrogel was shown to reduce the burst effect and exhibit nearly zero-order release behavior from the beginning of each initial stage. Thus, these MPs-embedded hydrogels, as well as thermosensitive chitosan hydrogel, have promising potential as an injectable drug carrier for pharmaceutical applications.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1987.05a
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• pp.20.1-20
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• 1987

후두 유두종은 후두에서 발생하는 가장 흔한 양성종양이나 임상적으로는 이비인후과영역에서 치유하기 어려운 질환중 하나이다. 1817년 Cheesmann이 성대에서 발생한 유두종을 처음 보고한 이래 많은 보고가 있었으나 아직도 결정적인 치료법이 없는 실정이다. 연자는 수술적 제거후 재발을 방지할 목적으로 Interferon을 술후 7일간은 300,000IU을 매일 피하주사하고 이후는 주 3회에 걸쳐 주사하였으며 동시에 5-FU l00mg을 주 5회 국소분무요법으로 3개월간 병합 실시하여 치료후 평균 3개월 이상 관찰 결과 대상환자 10명중 6명에서는 전혀 재발이 없었고 2명은 현저한 감소, 2명은 재발의 양상을 나타내었다.