• 약학회지
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• 제40권3호
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• pp.279-292
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• 1996

To assess their stability as a prodrug of 5-fluorouracil (5-FU), four N-acyloxycarbonyl derivatives (1-(N-tert-butyloxycarbonyl)glycyloxymethyl-5-FU :BGFU, 1-(N-tert-butyloxycar bonyl)-leucyloxymethyl-5-FU:BLFU, 1-(N-tert-carbobenzyloxymethyl) glycyloxymethyl-5-FU:CGFU and 1-(N-tert-carbobenzlyoxymethyl)leucyloxymethyl-5-FU:CLFU) possessing differently protected amino acids, and two acetic acid derivatives (5FU-1-acetylpentane:FUAP and 5-FU-1-acetylhexane:FUAH) were synthesized and their physicochemical properties, hydrolysis kinetics, acute toxicity and antitumor activity were evaluated. The lipid-water partition coefficients of six 5-FU prodrugs were higher than that of 5-FU and their aqueous solubilities were in the following rank order; BGFU>FUAP>CGFU>BLFU>CLFU${\simeq}$FUAH. The hydrolysis of N-acyloxycarboyl derivatives, greater at higher pH, was enhanced in presence of liver homogenate or human plasma. Meanwhile, acetic acid ester derivatives, very stable, were hydrolyzed by liver homogenate. Absorption rate constants were 0.181, 0.121, 0.111, 0.168, 0.168, 0.116 and 0.125 $hr^{-1}$ for 5-FU, BGFU, BLFU, CGFU, CLFU, FUAP and FUAH, respectively. The cytotoxicity of N-acyloxycarbonyl derivatives was 4 to 5 times lower than that of 5-FU, but that of acetic acid ester derivatives was negligeble. The $LD_{50}$ values were 204, 325.97 (133.59, amount as 5-FU), 708.16 (262.13), 663.50 (211.77), 382.33 (192.54) and 272.33 (130.09) mg/kg for 5-FU, BGFU, CGFU, CLFU, FUAP and FUAH, respectively. While N-acyloxycarbonyl derivatives showed enhanced antitumor activity and therapeutic ratio (3.30, 3.06, 4.19, 3.11 and 1.81 for BGFU, BLFU, CGFU, CLFU and 5-FU, respectively), FUAH and FUAP showed a smaller therapeutic ratio (0.79 and 0.83).

• 약학회지
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• 제40권5호
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• pp.522-531
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• 1996

5-fluorouracil(5-FU) derivatives synthesized with four N-acyloxycarbonyl group such as 1-(N-t-butyloxycarbonyl)glycyloxymethyl-5-FU(BGFU), 1-(N-t-butyloxycarbonyl)leucyloxymethy l-5-FU(BLFU), 1-(N-t-carbobenzyloxymethyl)glycyoxymethyl-5-FU(CGFU) and 1-(N-t-carbobenzyloxymethyl)leucyloxymethyl-5-FU(CLFU) were entrapped into liposomes with different lipid compositions. The entrapment efficiency and release rate of drugs from each liposomes were evaluated. The particle size of liposomes, cytotoxicity and stability of drug-entrapped in liposomes were evaluated. The entrapment efficiency in 5-FU derivatives liposomes was dependent on the lipophilicity of N-acyloxymethyl derivatives. The drug entrapment efficiency also increased on the content of lipid increased up to 200mcmol of lipid per milliliter of liposomal solution. However, inclusion of additives such as cholesterol, dicetylphosphate and stearylamine decreased the entrapment efficiency. The mean particle size and size distribution were varied with lipid compositions and lipophilicity of prodrugs. The release rates of drugs from liposomes were not affected by additives, but those of BGFU and CGFU entrapped in liposomes with cholesterol decreased. Cytotoxicity of BLFU and CLFU entrapped in liposomes decreased by 3~5 fold compared with those of free two prodrugs. Liposome-entrapped 5-FU prodrugs were more stable either at pH 7.4 or in human plasma. Especially, 5-FU prodrugs entrapped in liposome with dipalmitoylphosphatidylcholine(DMPC) was the most stable in human plasma. Compared with free BLFU, BLFU entrapped in DMPC liposome showed a superior antitumor activity at all doses used. In contrast, CLFU entapped in liposomes were more toxic than free prodrug.

• 분석과학
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• 제11권1호
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• pp.36-41
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• 1998

GC-MS를 이용한 사람의 혈중 5-fluorouracil(5-FU)의 정량법이 연구되었다. 5-FU은 isopropanol-ether(20:80) 혼합용매 10ml로서 추출하였고 pentafluoro-benzylation에 의해 유도체화 하였다. 시료주입은 자동으로 수행하였으며 분리에 사용한 칼럼은 비극성 capillary column이었고 검출은 MSD로 하였다. 위의 조건하에서 내인성 물질들의 방해현상은 없었고 검출한계는 0.5 ml의 혈액시료를 사용하였을 때 3 ng/ml이었으며 추출효율은 80%이상을 나타냈다. 5-FU로 항암치료를 받는 환자의 시료 500개중에 혈중 5-FU의 농도 측정에 적용하였으며 이 방법이 우수한 monitoring법임을 알 수 있었다.

• Macromolecular Research
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• 제16권6호
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• pp.510-516
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• 2008

New antitumor active polymers, poly(methacryloyl-2-oxy-1,2,3-propanetricarboxylic acid-co-exo-3,6-epoxy-l,2,3,6-tetrahydrophthalic acid) [poly(MTCA-co-ETAc)], poly(methacryloyl-2-oxy-l,2,3-propanetricarboxylic acid-co-hydrogen ethyl-exo-3,6-epoxy-l,2,3,6-tetrahydrophthalate) [poly(MTCA-co-HEET)], and poly(methacryloyl-2-oxy-l,2,3-propanetricarboxylic acid-co-a-ethoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil) [poly(MTCA-co-EETFU)] were synthesized and characterized. Their antitumor activity, inhibition of DNA replication and antiangiogenesis were examined. The structures of the polymers were identified by FT-IR, $^1H$ and $^{13}C$-NMR spectroscopy. The number average molecular weights of the fractionated polymers determined by GPC ranged from 9,400 to 14,900, and polydispersity indices were less than 1.7. The in vitro cytotoxicity of these polymers was determined and their antitumor activity was evaluated. The $IC_{50}$ values (the drug concentration at inhibition of 50% tumor growth) indicated that the synthesized polymers were much better inhibitors of cancer cells and showed lower cytotoxicity than the free 5-FU. The in vivo antitumor activity of the conjugates was examined using mice bearing the sarcoma 180 tumor cell line. The life spans (TIC) of the mice treated with the conjugates were higher than those treated with the free 5-FU. In addition, the synthesized conjugates showed excellent antiangiogenic activity based on an embryo chorioallantoic membrane assay.

• Radiation Oncology Journal
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• 제4권2호
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• pp.141-145
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• 1986

1981년 1월부터 1985년 12월까지 서울대학교병원 치료방사선과에서 운2명의 극소적으로 절제 불가능한 췌장암 환자를 방사선과 악물요법으로 치료하였다. 방사선은 2주의 간격을 두고 2000cGy씩 총 4000cGy를 조사하였으며 5-FU (5-fluorouracil)는 방사선 조사의 각 course의 첫 3일에 걸쳐 주입하였다. 방사선치료 종료 4주 후부터 FAM (5-FU, Adriamycin, Mitomycin)을 지속요법으로 사용하였다. 통증 완화는 $22\%(4/18)$에서 완전관해를, $39\%(7/18)$에서 부분관해를 보였다. 생존기간의 중앙치는 31주였으며 치료 전 Performance status가 중요한 예후인자였다. 국소적으로 절제불가능한 췌장암의 치료에 있어서 방사선과 FAM regimen의 병용은 통증완화 및 생존기간의 연장에 기여할 수 있는 바 이에 대한 보다 많은 연구와 고찰이 없어야 차겠다.

• 임상간호연구
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• 제28권1호
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• pp.76-87
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• 2022

Purpose: The purpose of this study was to examine the psychological distress related to quality of life (QoL) of patients with colorectal cancer receiving 5-fluorouracil (5-FU) chemotherapy at home with disposable Elastomeric infusion pumps. Methods: In this study, 179 colorectal outpatients were recruited between September 2019 and January 2021. National Cancer Center Psychological Symptom Inventory scores, general self-efficacy, and the EORTC QLQ-C30 scores were measured. Data were analyzed using Independent t-test, One-way ANOVA with Bonferroni post hoc analysis, and hierarchical multiple linear regression with the SPSS/WIN 26.0 programs. Results: The overall prevalence of psychological distress was 52.0% in colorectal patients. In multiple regression, psychological distress (β=-.20, p=.005), appetite loss (β=-.20, p=.001), chemotherapy cycles (β= .19, p=.002), fatigue (β=-.16, p=.035), physical functioning (β=-.16, p=.024), and emotional functioning (β=-.15, p=.025) were significant factors of QoL, and the final model explained 45.0% of the total variance of QoL. Conclusion: Supporting patients toward decreased psychological distress and increased physical and emotional functioning, especially in the first or second cycle of chemotherapy, could be used to improve their QoL. To consider the thresholds for clinical importance, it is necessary to increase the interpretation of psychological distress in clinical practice and further research.

• Composites Research
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• 제21권3호
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• pp.18-23
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• 2008

쾌속 조형(Rapid Prototyping; RP) 기술은 다양한 분야에서 활용되고 있다. 본 연구에서는 RP 기술을 이용한 나노복합재 적층장치(Nano Composite Deposition System, NCDS)를 사용하여 이식 가능한 약물전달시스템을 제작하였다. 약물전달시스템 복합재는 약물 입자로 5-fluorouracil (5-FU)를 사용하였으며, 생분해 고분자 매트릭스로 PLGA85/15를 사용하였다. 제작된 약물전달시스템은 넓은 표면적을 가질 수 있도록 지지체(scaffold) 형상으로 제작되었으며, in vitro 환경에서의 약물방출실험이 수행되었다. 약물방출제어를 위하여 생체적합재료인 수산화아파타이트(Hydroxyapatite, HA)를 약물-고분자 복합재에 첨가하였다. 약 50일간의 방출실험을 통하여 약물방출의 가능성을 보임을 확인하였다.

• Journal of Digestive Cancer Research
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• 제6권2호
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• pp.73-77
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• 2018

췌장암으로 진단된 70세 여자 환자가 유문보존 췌십이지장 절제술 및 5-fluorouracil 동시항암화학요법으로 치료받았다. 수술 후 병리학적으로 pT3N0 (stage IIA)의 췌장선암이 확진되었다. 14개월 뒤 복부 전산화단층촬영에서 10 mm 크기의 단일 간 재발 병소가 간 3번 분엽에서 발견되었다. Gemcitabine 12주기 및 capecitabine plus oxaliplatin 9주기 항암치료를 시행했으나 전이병소는 27mm로 크기가 증가하였다. 이에 간 3번 분엽의 종양절제술을 시행하였다. 종양절제술 시행 25개월 뒤 흉부 전산화단층촬영에서 23 mm 크기의 단일 공동성 폐결절이 발견되었고, 조직검사에서 전이성 선암으로 확인되었다. 환자는 두 차례의 정위적 체부 방사선 치료 후 질병의 진행 없이 진단 후 6년 이상 장기 생존 중이다. 본 증례를 통해 수술 후 단일 간 전이 혹은 폐 전이가 발견된 일부 환자들에서 수술적 절제를 비롯한 국소 치료가 장기생존에 도움이 될 것으로 사료된다.

• Natural Product Sciences
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• 제13권3호
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• pp.234-240
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• 2007

The present study investigated the anti-tumor activity of ethyl acetate extract of Acanthospermum hispidum DC against daltons ascites lymphoma in mice. The extract was prepared by cold maceration with ethyl acetate for 3 - 7 days and evaporated in vacuum to dry. (Yield : 14.2 g, 1.42% w/w). The extract was fractionated by column chromatography by using gradient elution technique and the diterpenes fraction isolated (0.649 g). Both extract and the fraction were administered as oral suspension with tween 20 in water to tumor bearing mice (DAL) and changes in dead cell count, histopathology of tumor cells, hematological parameters and median survival time (MST) were examined and compared with that of tumor control or 5-Fluorouracil (5-FU). The results indicate that both ethyl acetate extract and fraction possess anti-tumor activity. The study suggests that Acanthospermum hispidum DC seems promising as a source of diterpenes for potential anti-tumor activity.

• Bulletin of the Korean Chemical Society
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• 제26권11호
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• pp.1865-1868
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• 2005