• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.1121-1126
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• 2013

Background: Palliative chemotherapy with cisplatin/5-fluorouracil (5FU) is the commonest regimen employed for metastatic and recurrent head and neck squamous cell carcinoma (SCCHN) and nasopharyngeal carcinoma (NPC). However, this regimen is cumbersome requiring 5 days of admission to hospital. Carboplatin/5FU may be an alternative regimen without compromising survival and response rates. This study aimed to compare the efficacy and toxicity of carboplatin/5FU regimen with the cisplatin/5FU regimen. Materials and Methods: This retrospective study looked at patients who had palliative chemotherapy with either cisplatin/5FU or carboplatin/5FU for metastatic and recurrent SCCHN and NPC. It included patients who were treated at UKMMC from $1^{st}$ January 2004 to $31^{st}$ December 2009 with either palliative IV cispaltin 75 $mg/m^2$ D1 only plus IV 5FU 750 $mg/m^2$ D1-5 infusion or IV Carboplatin AUC 5 D1 only plus IV 5FU 500 $mg/m^2$ D1-2 infusion plus IV 5FU 500 $mg/m^2$ D1-2 bolus. The specific objectives were to determine the efficacy of palliative chemotherapy in terms of overall response rate (ORR), median progression free survival (PFS) and median overall survival (OS) and to evaluate the toxicities of both regimens. Results: A total of 41 patients were eligible for this study. There were 17 in the cisplatin/5FU arm and 24 in the carboplatin/5FU arm. The ORR was 17.7 % for cisplatin/5FU arm and 37.5 % for carboplatin/5FU arm (p-value=0.304). The median PFS was 7 months for cisplatin/5FU and 9 months for carboplatin/5FU (p-value=1.015). The median OS was 10 months for cisplatin/5FU arm and 12 months for carboplatin/5FU arm (p-value=0.110). There were 6 treatment-related deaths (6/41=14.6%), four in the carboplatin/5FU arm (4/24=16.7%) and 2 in the cisplatin/5FU arm (2/17=11.8%). Grade 3 and 4 hematologic toxicity was also more common with carboplatin/5FU group, this difference being predominantly due to grade 3-4 granulocytopenia (41.6% vs. 0), grade 3-4 anemia (37.5% vs. 0) and grade 3-4 thrombocytopenia (16.6% vs. 0). Conclusions: Carboplatin/5FU is not inferior to cisplatin/5FU with regard to its efficacy. However, there was a high rate of treatment-related deaths with both regimens. A better alternative needs to be considered.

• Journal of Digestive Cancer Research
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• 제5권1호
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• pp.58-61
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• 2017

5-FU로 인한 심장독성은 드물지만 협심증, 심근경색, 심지어 심장 돌연사까지 유발할 수 있다. 그러므로 약물치료를 계획하기 전 환자의 기저 심질환 여부를 정확히 평가해야 하며, 지연반응으로 인해 약물 투여와 증상 발생의 시간적 간격이 늘어날 수도 있으므로 증상과 EKG에서의 변화가 명확하다면 5-FU로 인한 관상동맥의 일시적인 연축으로 볼 수 있다. 심장효소의 상승과 관상동맥 조영술에서 심혈관의 협착 소견이 없더라도 약물을 중단하고 칼슘통로차단제 등의 혈관확장제를 사용하여야 한다. 그리고 재발의 위험성이 매우 높기 때문에 재투여는 피해야 한다.

• Journal of Pharmaceutical Investigation
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• 제24권3호spc1호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4807-4814
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• 2012

Purpose: The chemoresistance of human hepatocellular carcinoma (HCC) to cytotoxic drugs, especially intrinsic or acquired multidrug resistance (MDR), still remains a major challenge in the management of HCC. In the present study, possible mechanisms involved in MDR of HCC were identified using a 5-fluorouracil (5-FU)-resistant human HCC cell line. Methods: BEL-7402/5-FU cells were established through continuous culturing parental BEL-7402 cells, imitating the pattern of chemotherapy clinically. Growth curves and chemosensitivity to cytotoxic drugs were determined by MTT assay. Doubling times, colony formation and adherence rates were calculated after cell counting. Morphological alteration, karyotype morphology, and untrastructure were assessed under optical and electron microscopes. The distribution in the cell cycle and drug efflux pump activity were measured by flow cytometry. Furthermore, expression of potential genes involved in MDR of BEL-7402/5-FU cells were detected by immunocytochemistry. Results: Compared to its parental cells, BEL-7402/5-FU cells had a prolonged doubling time, a lower mitotic index, colony efficiency and adhesive ability, and a decreased drug efflux pump activity. The resistant cells tended to grow in clusters and apparent changes of ultrastructures occurred. BEL-7402/5-FU cells presented with an increased proportion in S and G2/M phases with a concomitant decrease in G0/G1 phase. The MDR phenotype of BEL-7402/5-FU might be partly attributed to increased drug efflux pump activity via multidrug resistance protein 1 (MRP1), overexpression of thymidylate synthase (TS), resistance to apoptosis by augmentation of the Bcl-xl/Bax ratio, and intracellular adhesion medicated by E-cadherin (E-cad). P-glycoprotein (P-gp) might play a limited role in the MDR of BEL-7402/5-FU. Conclusion: Increased activity or expression of MRP1, Bcl-xl, TS, and E-cad appear to be involved in the MDR mechanism of BEL-7402/5-FU.

• Macromolecular Research
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• 제9권5호
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• pp.277-284
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• 2001

Poly(exo-3,6-epoxy-1,2,3,6-tetrahydrophthalic anhydride)s [poly(ETA)s] and poly($\alpha$-ethoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil)s [poly(EETFU)s ] with various average molecular weights were prepared by photopolymerizations. The number average molecular weights of the fractionated poly(ETA)s and poly(EETFU)s determined by GPC were in the range of 3,600∼21,000 and 3,600-33,400, respectively. The release rate of 5-FU from poly(EETFU) decreased with increasing average molecular weight. The in vitro cytotoxicity of poly(ETA) against a normal cell line was lower than that of 5-fluorouracil(5-FU), The in vivo antitumor activities of the synthesized samples at dosage of 0.8 mg/kg against mice bearing sarcoma 180 tumor cell line decreased in the following order: poly(EETFU) > poly(ETA) > EETFU > ETA > 5-FU. The antiangiogenic activities of the poly(ETA)s were better than those of 5-FU.

• Bulletin of the Korean Chemical Society
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• 제1권4호
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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.

• 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).

• 동의생리병리학회지
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• 제16권1호
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• pp.146-149
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• 2002

To evaluate the protective effect of Ziziphi Jujubae Semen(ZJS) on 5-Fluorouracil(5-Fu) in cultured vestibular neurons(VN), neurotoxicity was assessed by XTT assay after VN was exposed to 3-24ug/ml 5-Fu for 48 hours. and also, the neuroprotective effect of ZJS was measured by XTT assay in these cultrures. Cell viability was remarkably decreased dose-dependently, after the treatment with 12ug/ml 5-Fu to cultured VN for 48 hours. In the neuroprotective effect of ZJS on the toxicity induced by 5-Fu, ZJS prevented the neurotoxicity induced by 5-Fu in these cultures. From above the results, it suggests that 5-Fu is toxic in cultured VN and herb extract, ZJS has protective effect over the neurotoxicity induced by 5-Fu.

• Toxicological Research
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• 제7권1호
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• pp.13-20
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• 1991

To investigate the cytotoxicity and genotoxicity of the DNA alkylating agnet, mitomycin C and the antimetabolite, 5-Fluorouracil (5-FU) in cultured rat fibroblasts, the colorimetric assay of netural red (NR) for cytotoxicity and for genotoxicity, sister chromatid exchange (SCE) assay and the measurement of the rate of DNA synthesis were performed in cells cultured in media containing various concentrations of mitomycin C and 5-FU. The uptake ability of neutral red decreased does-dependently. NR90 and NR50 values of mitomycin C were 1.49 nM and 6.87mM and 5-FU were 38.4mM AND 284.4Mm respectively.

• Applied Microscopy
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• 제40권4호
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• pp.229-235
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• 2010

암은 전 세계적으로 사망률이 높은 질병으로 현재 자궁암 치료는 cisplatin, 5-fluorouracil (5FU) 등의 항암화학요법과 방사선 요법 등을 복합적으로 병행하고 있다. 최근 항암효과를 가지고 있는 자연식품의 섭취에 관심이 커지면서 커리의 주성분인 curcumin (CMN), 녹차의 주성분인 카테킨, 토마토의 주성분인 리코펜 등의 약리효과에 대한 연구가 활성화되고 있다. CMN은 동물실험 결과 항염증의 활성이 있고, 피부, 대장, 유방, 전립선 등에서 암으로의 진행을 억제한다는 보고가 있으나 인체 자궁암에서는 그 효과가 밝혀져 있지않다. 본 연구는 항암제 5FU와 CMN이 인체 자궁암세포 HeLa에 미치는 영향을 apoptosis의 유도로 평가하고, p53유전자 발현율과의 상관관계로 확인하고자 시행하였다. CMN은 HeLa 세포의 성장을 억제하였으며, 5FU로 유도된 apoptosis의 발생률과 p53유전자의 발현률을 현저하게 증가시키는 것으로 나타났다(p<0.05). 이러한 연구결과는 CMN이 자궁암 치료제의 가능성이 있으며, 또한 5FU와 복합적으로 사용하면 항암제를 단독으로 투여하는 경우보다 자궁암 치료에 보다 효과적임을 강력히 시사하는 것이다.