• 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.

• YAKHAK HOEJI
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• v.26 no.1
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• pp.25-27
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• 1982

We had reported that s-triazine can readily be converted into the corresponding 5-substituted pyrimide. In order to develop new synthetic method of 5-fluorouracil, we tried to replace eliminating fragment, 1, 3-dimethylurea, by fluoroacetamide, which was expected to undergo nucleophilic attack by proton extraction of both .alpha.-hydrogen and aminohydrogen by lithium diisopropylamide (LDA). We found that 5-fluorouracil could be transformed from s-triazine under strong base condition like LDA as well as other 5-substituted pyrimidines.

• Applied Microscopy
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• v.29 no.1
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• pp.25-41
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• 1999

The experiment was performed to study the morphological responses of the renal glomeruli of the mice after administration of 5-fluorouracil or mitomycin C. 5-fluorouracil (60 mg/kg) or mitomycin-C $(400{\mu}g/kg)$ were injected subcutaneously to the animals every other day, and animals were sacrificed at 4 days or 7 days following the first injections. Pieces of tissues were observed with a JEM 100CX-II electron microscope. The observed results were as follows: 1. In the fourth day following the first injection of 5-fluorouracil or mitomycin C, components of the renal glomeruli of the mice are looked compact since they were filled with the widened the mesangium, and showed narrowing lumen of glomerular capillaries and of urinary spaces. The changes were more significant in the mitomycin C treated mice. 2. In the 5-fluorouracil treated mice, morphological changes of glomeruli were generally recovered in the seventh day, whereas the glomeruli of the mitomycin C treated mice have not shown general recovery. 3. In the fourth and seventh days following the first injection of mitomycin C, in the renal glomeruli of the mice, swollen endothelial cells, and protruded mesangeal cells into the capillary lumen are frequently observed. 4. In the fourth day following the first injection of mitomycin C, in the glomerular basal lamina of the mice, the electron densities of the lamina rara interna and the lamina rara externa were similar to the density of the lamina densa and the expanded lamina rara interna were often seen. From the above results, it is suggested that the cytotoxic effects of the mitomycin C on renal glomeruli are more severe as compared with those of 5-fluorouracil.

• 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.

• Macromolecular Research
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• v.11 no.5
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• pp.317-321
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• 2003

In order to prepare a prodrug, poly(polyethylene glycol methacrylate-co-methacryloyloxymethyl-5-fluorouracil) (poly(PEGM-co-MAOFU)) prodrug particles were prepared by precipitation polymerization of MAOFU and PEGM in polyacrylic acid solution. The size of prodrug particles were 0.2-0.35 ${\mu}{\textrm}{m}$. The antitumor activity of prodrugs against sarcoma-l80 tumor cell in mice was demonstrated and the polymer particles themselves showed low toxicity and good biocompatibility when they were administrated into mice.

• Applied Microscopy
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• v.41 no.1
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• pp.1-11
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• 2011

This experiment was performed to evaluate the morphological responses of the gastric epithelial cells of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of 5-fluorouracil, mitomycin C or Acriflavine-Guanosine compound (AG60). In this study, each mouse was inoculated with $1{\times}10^7$ Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.2 mL of saline, 5-fluorouracil (30 mg/kg), mitomycin C ($400{\mu}g/kg$) or AG60 (30 mg/kg) were injected to the animals every other day, respectively. Each animals were sacrificed after 7th injection and tissue were taken from the gastric mucosa. Thereafter, the ultrathin sections were stained with uranyl acetate and lead citrate. In the 5-fluorouracil-, mitomycin C- or AG60-treated mice, myelin figures and multivesicular bodies within the gastric mucous epithelial cells were observed more frequently than those of the normal control. In the 5-fluorouracil-treated mice, membrane structures containing a few mucous granules in the luminal space were observed. Indeed, bulging cytoplasmic process containing mucous granules protruding into the gastric lumen were observed in the mitomycin Ctreated mice. Therefore, this study suggested that AG60 as compared with 5-fluorourail and mitomycin C may effective medicine without damage to the secretion ability of gastric mucous epithelial cells.

• Polymer(Korea)
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• v.36 no.2
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• pp.149-154
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• 2012

The amphiphilic copolymer by the conjugation of biocompatible chitosan and antioxidant lipoic acid was studied as a drug delivery carrier. The amphiphilic copolymer was self-assembled to form nanoparticles in the aqueous solution. 5-Fluorouracil widely used as an anticancer drug was encapsulated inside the nanoparticles by a solid dispersion method. The degree of branching of lipoic acid on chitosan was controlled to obtain the optimal condition for the drug delivery carrier. The sizes of nanoparticles were about 250 nm by the dynamic light scattering. The encapsulation efficiency of nanoparticles were about 10%. The copolymer with 42% degree of branching showed the best performance as a drug delivery carrier.

• Korean Journal of Clinical Pharmacy
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• v.19 no.1
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• pp.65-68
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• 2009

Disposal infusion device is known to be useful for chemotherapy. Anti-cancer drug can be released by the force of carbon dioxide or balloon. In this study, we compared the$Anapa^{(R)}$ (LC0020) with B Company (LV2 ml) in terms of infusion rate and stability. Infusion rate was determined every six minute using software, MSI08IH. Stability of 5-fluorouracil was examined periodically using a High Performance Liquid Chromatography. Infusion rates of gas-derived $Anapa^{(R)}$ device were 2.29, 1.86, 1.98 ml/hr and those of balloon-derived B Company device were 1.71, 1.58, 1.37 ml/min. There were no significant differences in stability of 5-fluorouracil between $Anapa^{(R)}$ and B Company devices. In summary, gas-derived $Anapa^{(R)}$ device is thought to be comparable or superior to balloon-derived B Company device as far as infusion rate and stability are concerned. We expect that $Anapa^{(R)}$ as a home infusion device can be employed to improve a quality of life and compliance of cancer patients.

• Journal of Pharmaceutical Investigation
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• v.16 no.1
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• pp.1-7
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• 1986

The influences of sodium chloride, polyethylene glycol 4000 and 20000 on 5-fluorouracil release from disk type silicone polymer devices were examined in isotonic phosphate buffer. These water soluble cosolvent and sodium chloride caused devices to swell in aqueous media. Sodium chloride exerted the greatest influence on drug release. The addition of water soluble cosolvent or sodium chloride to silicone polymeric devices permitted controlled release of 5-fluorouracil, presumably due to the change of the physical microstructure of silicone network, and the solubility and diffusivity of 5-fluorouracil. It seemed that the water soluble drug was released through the hydrophilic pores or pathways formed in the device by the incorporation of a water soluble cosolvent or sodium chloride.

• Journal of Pharmaceutical Investigation
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• v.22 no.2
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• pp.149-153
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• 1992

The applicability of sodium alginate as a carrier of 5-fluorouracil as an oral delivery system was investigated. Hydrophobicity of sodium alginate was controlled by introducing cetyl group to this polymer. The effects of degree of esterification for n-cetyl partial ester on the rate of release of 5-fluorouracil in artificial gastric juice and artificial intestinal juice were examined. The release rete of the drug in the gastric juice was mainly affected by the diffusion of the drug. The release rate of the drug in the intestinal juice could be controlled by the degree of esterification. The alginate matrices may be a valuable addition as the carrier of 5-fluorouracil for an oral delivery system.