• 공업화학
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• 제2권1호
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• pp.56-63
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• 1991

1-(2-carbomethoxyacryloyl)-5-fluorouracil(CMAFU)을 trans-${\beta}$-carbomethoxyacryl chlocide와 2, 4-bis(trimethylsilyloxy)-5-fluoropyrimidine으로부터 합성하고, CMAFU와 메틸메타크릴레이트를 cyclohexanone을 용매로 사용하여 $60^{\circ}C$에서 라디칼공중합을 하였다. 5-FU, CMAFU 및 poly(CMAFU-Co-MMA)들이 노랑초파리에 미치는 생리유전학적 영향을 Lewis와 Bacher 방법에 의하여 조사한 결과, CMAFU와 그 중합체가 5-FU 보다 생리유전학적 영향이 약함을 알 수 있었다.

• 약학회지
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• 제37권1호
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• pp.89-94
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• 1993

In order to find out a proper connecting bridge between 5-fluorouracil(5-FU) and a macromolecule such as a polypeptide, potentially hydrolytic N$^{1}$-derivartives of 5-FU have been systhesized and evaluated for their biological activity. When tested with in vitro leukemic L$_{1210}$ cells all the obtained derivartives exhibited slightly higher antitumor activity than the parent 5FU. Among them the N$^{1}$ -carbamoyl analogue 2 and N$^{1}$-acetamido analogue 6b showed 50% inhibition of the L$_{1210}$ cell growth at the concentrations of 5.01$\times$10$^{-8}$M and 1.03$\times$10$^{-7}$M, respectively. When tested against sarcoma 180 tumor cells inoculated into mice, the compounds 2 and 6b exhibited, respectively, 62% and 54% inhibition of the solid tumor growth at the 5-time doses of 100 mg/kg/day. Both compounds, N$^{1}$-carbamoyl analogue 2 and N$^{1}$-acetamido analogue 6b, realeased the parent 5-FU when incubated in the L$_{1210}$ cell cultural media for 5 hrs.

• 생명과학회지
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• 제26권9호
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• pp.1015-1021
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• 2016

Pyrimidine 유도체의 일종인 5-fluorouracil (5-FU)은 광범위하게 사용되는 항암제의 일종으로, thymidylate synthase의 활성을 억제시켜 핵산의 합성 및 대사기능 자애 유발 물질이다. 본 연구에서는 Ewing′s 육종 CHP-100 세포에서 5-FU의 증식억제와 연관된 기전 해석으로 시도하였다. 본 연구의 결과에 의하면, 5-FU 처리 시간의 경과에 따른 CHP-100 세포의 증식억제가 세포주기 G1 arrest 유발에 따른 것임을 알 수 있었다. 5-FU에 의한 CHP-100 세포의 G1 arrest는 retinoblastoma protein (pRB)의 탈인산화에 따른 전사인자 E2F-1 및 E2F-4와의 결합 촉진과 연관성이 있었다. 비록 5-FU 처리가 cyclin-dependent kinases의 발현에는 크게 영향을 주지 않았으나, 정상배지에서 배양된 대조군에 비하여 cyclin A 및 B의 발현이 5-FU 처리 시간 의존적으로 억제되었다. 또한 5-FU에 의한 CHP-100 세포의 G1 arrest는 apoptosis 유도와 연관이 있음을 핵 내 염색질의 응축에 따른 apoptotic body의 형성증가, poly (ADP-ribose) polymerase의 단편화 및 annexin V 염색 등을 통하여 확인하였다. 아울러 5-FU는 pro-apoptotic Bax 단백질의 발현 증가 및 anti-apoptotic Bcl-2의 발현 감소를 통한 mitochondrial membrane potential의 소실을 촉진시켰으며, 이로 인하여 미토콘드리아에서 세포질로의 cytochrome c 유리가 증가시켰음을 알 수 있었다. 따라서 본 연구의 결과는 5-FU에 의한 CHP-100 세포의 증식억제와 연관된 G1 arrest 및 apoptosis 유도에는 pRB의 인산화 억제 및 미토콘드리아 기능의 손상이 최소한 관여하고 있음을 의미하는 것이다.

• 약학회지
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• 제40권5호
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• pp.532-538
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• 1996

In cancer chemotherapy, it is necessary to control the phamacokinetic behavior of an antitumor drug for effective treatment. Therefore, two 5-fluorouracil derivatives synthesize d with N-a-cyloxycarbonyl derivatives {1-(N-t-butyloxycarbonyl)leucyloxymethyl-5-FU(BLFU) and 1-(N-t-carbobenzyloxymethyl)leucyloxymethyl-5-FU(CLFU)}. prodrugs of 5-fluorouracil, antitumor agent, were loaded into liposome of different lipid compositions. After liposomal drugs were injected intramuscularly, their pharmacokinetics and tissue distribution were assessed. The $AUC_{0{\to}{\infty}$ values were 1.29, 72.50, 85.57, 66.40 and 103.60${\mu}$g.hr/ml for 5-FU, BLFU, CLFU, BLFU- and CLFU-loaded liposome, respectively. 5-FU was distributed to spleen and liver with a maximal concentration after 1 hr and eliminated after 24 hr. But both prodrugs and dimyristoylphosphatidylcholine liposome entrapped prodrugs were distributed to spleen and liver at a lower concentration but maintained for a long time with a relatively high concentration in lung. Especially, liposome-entrapped CLFU was distributed to lung with a maximal concentration after 1 hr and redistributed to spleen increasingly, while the concentration of liposome-entrapped BLFU in lung reached a maximal level after 12 hr.

• Archives of Pharmacal Research
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• 제26권12호
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• pp.1096-1101
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• 2003

To enhance the liver targeting and reduce the side effects of 5-fluorouracil (5-Fu), it was acylated by stearyl chloride to obtain .$\b{N}_{\b{1}}$stearyl-5-Fu (5-FuS). The chemical structure of the prodrug was confirmed by Nuclear Magnetic Resonance and Infrared Spectrometry. 5-FuS was incorporated into solid lipid nanoparticles (SLN), which were prepared by the physical agglomeration method. The mean diameter of 5-FuS-SLN was 240.19 nm and the drug loading was 20.53%. The release characteristics in vitro of 5-FuS-SLN were fitted to the first-order pharmacokinetic model. Compared with 5-Fu injection, a study on the distribution of 5-FuS-SLN in mice showed that 5-FuS-SLN could double 5-Fu concentration in mice livers. The main pharmacokinetic parameters of 5-FuS-SLN in rabbits is shown as follows: $V_d$=0.04336L/kg, $T_{1/2} \beta$=1.2834h, CL=0.1632 L/h. In conclusion, 5-FuS-SLN has significant liver targeting properties. The employment of a prodrug to enhance drug liposoluble properties and the preparation method presented in this paper, seem to be an alternative strategy to the traditional colloidal delivery system.

• Molecules and Cells
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• 제26권4호
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• pp.344-349
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• 2008

5-Fluorouracil (5-FU), a pyrimidine antagonist, has a long history in cancer treatment. The targeted pyrimidine biosynthesis pathway includes dihydropyrimidine dehydrogenase (DPD), which converts 5-FU to an inactive metabolite, and thymidylate synthase (TS), which is a major target of 5-FU. Using Caenorhabditis elegans as a model system to study the functional and resistance mechanisms of anti-cancer drugs, we examined these two genes in order to determine the extent of molecular conservation between C. elegans and humans. Overexpression of the worm DPD and TS homologs (DPYD-1 and Y110A7A.4, respectively) suppressed germ cell death following 5-FU exposure. In addition, DPYD-1 depletion by RNAi resulted in 5-FU sensitivity, while treatment with Y110A7A.4 RNAi and 5-FU resulted in similar patterns of embryonic death. Thus, the pathway of 5-FU function appears to be highly conserved between C. elegans and humans at the molecular level.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7611-7615
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• 2014

Aims: To prepare 5-fluorouracil (5-Fu) nanoparticles with higher encapsulation efficiency and drug loading, and then investigate interaction with the SGC-7901 gastric cancer cell line. Materials and Methods: Prescription was optimized by orthogonal experiments, the encapsulation efficiency and loading capacity were tested by high-performance liquid chromatography, and inhibition of proliferation by 5-Fu nanoparticles and 5-Fu given to cells for 24, 48 and 72 hours was investigated by methyl thiazolyl tetrazolium assay (MTT). In addition, 5-Fu nanoparticles were labeled by fluorescein isothiocyanate (FITC), and absorption into cells was tested by flow cytometry. Results: The optimal conditions for preparation were concentrations of 5-Fu of 5mg/ml, of $CaCl_2$ of 60 mg/ml and of chitosan of 2 mg/ml. With a stirring speed of 1200rpm, encapsulation efficiency of 5-Fu nanoparticles was $55.4{\pm}1.10%$ and loading capacity was $4.22{\pm}0.14%$; gastric cancer cells were significantly inhibited by 5-Fu nanoparticles in a time and concentration dependent manner, and compared to 5-Fu with slower drug release, in a certain concentration range, inhibition with 5-Fu nanoparticles was stronger. 5-Fu nanoparticles were absorbed by the cells in line with the concentration. Conclusions: 5-Fu nanoparticles can inhibit growth of gastric cancer cells in vitro to a greater extent than with 5-Fu with good adsorption characteristics, supporting feasibility as a carrier.

• Journal of Gastric Cancer
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• 제16권3호
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• pp.177-181
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• 2016

Purpose: The International Organization for Standardization-5fluorouracil (FU) 10 trial found that bolus 5-FU and l-leucovorin was not inferior to S-1 in the treatment of gastric cancer (GC). Continuous 5-FU and the rapid injection of 5-FU have different anti-cancer effects. Thus, bolus 5-FU and l-leucovorin treatment might be useful for oral FU-resistant GC. Materials and Methods: We retrospectively analyzed the medical records of all patients with S-1 or capecitabine-resistant, unresectable, or recurrent GC treated with bolus 5-FU and l-leucovorin between January 2010 and December 2015 at Hokkaido University Hospital. The bolus 5-FU and l-leucovorin regimen consisted of intravenous l-leucovorin ($250mg/m^2/2h$) and bolus 5-FU ($600mg/m^2$) administered once weekly followed by a 2-week rest period; each cycle was repeated every 8 weeks. Results: A total of 14 patients were identified. The disease control rate was 35.7%. The median progression-free survival was 1.6 months (95% confidence interval [CI], 1.3~2.0 months), and the median overall survival was 6.3 months (95% CI, 4.7~7.9 months). No patient died from treatment-related causes. The most common severe adverse event associated with bolus 5-FU and l-leucovorin was neutropenia, which occurred in 21.4% of patients. Conclusions: Bolus 5-FU and l-leucovorin treatment might be useful for oral FU-resistant GC. We are planning a multi-center prospective phase II trial to evaluate the efficacy and safety of bolus 5-FU and l-leucovorin treatment for pre-treated unresectable or recurrent GC to confirm the results of this limited, retrospective study.

• 한국안전학회지
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• 제24권4호
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• pp.47-52
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• 2009

이 연구는 Fluorouracil(5-FU)가 병원에서 암치료제로 쓰이는 세포독성약제의 한 종류이기 때문에 병원내부에 5-FU의 폭로 정도와 그 관리를 위한 가장 효율적인 세척약제를 조사하기 위한 것이다. 이러한 세포독성 약제실이나 종약학 병동에서 근무하는 실무자들은 세포독성약제로 오염된 표면에 빈번하게 접촉하게 되면 세포유전성이나 DNA손상에 대한 위험이 높게 된다. 따라서 이러한 약제의 세척제실험을 위하여 4가지 약제로서 시행한분해시험에서 0.5%(w/v) NaClO 용액만이 5-FU를 즉시 분해시켰으므로 이 용액은 오염표면의 잔유물을 분해시키는데 사용될 수 있다. 세포독성 약제실의 오염표면에서 확인된 농도범위는 2.0에서 $13.8{\mu}g/m^2$까지이고, 종약학 병동의 오염표면에서 측정한 농도범위는 5.39에서 $11.53{\mu}g/m^2$이었다. 5-FU와 같은 세포독성약제로부터 피부오염을 피하기 위하여 작업장의 노출허용기준과 같은 법적인 조치, 완벽한 표면세척제 및 보호구사용과 같은 엄격한 관리기준이 마련되어야 할 것이다.

• 약학회지
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• 제53권3호
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• pp.145-150
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• 2009

We evaluated cytotoxic effect based on the MTT assay and identified altered proteins in 5-FU(fluorouracil) treated HT29 cells using two-dimensional gel electrophoresis and MALDI-TOF/TOF-MS. As proteins inducing apoptosis, siah binding protein 1 and p47 protein isoform a were up-regulated and tumor protein translationally-controlled 1 was down-regulated by 5-FU treatment. And mannose 6 phosphate receptor binding protein 1 controls DNA mismatch repair system was increased. We suggest 5-FU promotes a cytotoxicity under the action of these proteins in colon cancer cells.