• Biomolecules & Therapeutics
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• 제30권6호
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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.

• Journal of Pharmaceutical Investigation
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• 제22권2호
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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.

• 대한치과의사협회지
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• 제10권6호
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• pp.359-367
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• 1972

• 대한치과의사협회지
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• 제19권4호통권143호
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• pp.361-367
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• 1981

• 대한치과의사협회지
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• 제13권3호
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• pp.211-220
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• 1975

• Journal of Pharmaceutical Investigation
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• 제22권3호
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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.

• 대한화학회지
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• 제57권1호
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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.

• Applied Microscopy
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• 제27권1호
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• pp.13-30
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• 1997

The experiment was performed to study the morphological responses of the thymus of the mice, to antitumour agents (5-Fluorouracil or mitomycin C). Healthy adult mice weighing 25 gm each were divided into normal and experimental groups. 5-Fluorouracil (60 mg/kg) or Mitomycin-C $(400{\mu}g/kg)$ were injected subcutaneously to the animals every other day. Animals were sacrificed at 4 days and 7 days following the first injection. Pieces of the tissue taken from the thymus were prefixed with 2.5% paraformaldehyde-l.5% glutaraldehyde, followed by post-fixation with 1% osmium tetroxide. Ultrathin sections stained with uranyl acetate and lead citrate were observed with a JEM 100 CX-II electron microscope. The observed results were as follow: 1. Apoptoses of T-lymphocytes were observed more frequently in the thymus of the experimental groups than in those of a normal group. 2. In the experimental group, the plasma cells with distended cisternae of the granular endoplasmic reticulum and the eosinophile leukocytes were observed frequently. 3. In the experimental group, newly forming Hassall's corpurscles were observed frequently. 4. In the mitomycin-treated group, the epithelial reticular cells containing distended perinuclear cisternae, distended the granular endoplasmic reticula and pyknotic nuclei were observed in the cortico-medullary junctional area. 5. In the mitomycin-treated group, nuclear bodies with medium electron dense materials were often observed in the T lymphocyte. 6. In the 5-fluorouracil-treated groups, fused and dissolved tonofilament bundles and apoptotic bodies were observed in the some epithelial reticular cells in the medullary area. 7. In the 5-fluorouracil-treated groups, some elongated and bar-shaped lysosomes with electron lucent gap were often observed in the macrophages. 8. In the 5-fluorouracil-treated group, membrane complex of the smooth endoplasmic reticulum were ofen observed in the macrophage. From the above results, it was suggested that 5-fluorouracil or mitomycin could induce rapid involution of the thymus, and disturb maturation and differentiation of T lymphocytes, and, in turn, supress immunity.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2669-2673
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• 2012

Purpose: Pancreatic carcinoma is one of the most malignant tumors of the alimentary system, with relatively high incidence rates. The purpose of this study was to assess the efficacy and safety of two regimens for advanced pancreatic carcinoma: continuous transarterial infusion versus systemic venous chemotherapy with gemcitabine and 5-fluorouracil. Methods: Of the 48 patients with advanced pancreatic carcinoma receiving chemotherapy with gemcitabine and 5-fluorouracil, 24 received the selective transarterial infusion, and 24 the systemic chemotherapy. For the continuous transarterial infusion group (experimental group), all patients received gemcitabine 1000 mg/$m^2$, given by 30-minute transarterial infusion, on day 1 of a 4-week cycle for 2 cycles, and a dose of 600 mg/$m^2$ 5-fluorouracil was infused on days 1~5 of a 4-week cycle for 2 cycles. For the systemic venous group (control group), gemcitabine and 5-fluorouracil were infused through a peripheral vein, a dose of 1000 mg/$m^2$ gemcitabine being administrated over 30 min on days 1 and 8 of a 4-week cycle for 2 cycles, and a dose of 600 mg/$m^2$ 5-fluorouracil was infused on days 1~5 of a 4-week cycle for 2 cycles. The effectiveness and safety were evaluated after 2 cyclesaccording to WHO criteria. Results:The objective effective rate in transarterial group was 33.3% versus 25% in the systemic group, the difference not being significant (P=0.626). Clinical benefit rates(CBR) in the transarterial and systemic groups were 83.3% and 58.3%, respectively (P=0.014). The means and medians for survival time in transarterial group were higher than those of the systemic group (P < 0.005). at the same time, the adverse effects did not significantly differ between the two groups (P > 0.05). Conclusion: Continuous transarterial infusion chemotherapy with gemcitabine and 5-fluorouracil could improve clinical benefit rate and survival time of patients with advanced pancreatic carcinoma, compared with systemic venous chemotherapy. Since adverse effects were limited in the transarterial group, the regimen of continuous transarterial infusion chemotherapy can be used more extensively in clinical practice. A CT and MRI conventional sequence can be used for efficacy evaluation after chemotherapy in pancreatic carcinoma.

• 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.