• Korean Journal of Veterinary Research
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• v.37 no.3
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• pp.509-523
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• 1997

This study was carried out for investigating antitumor effects of 5-fluorouracil(5-FU), methotrexate(MTX) and retinoic acid(RA) on hepatocellular carcinoma induced in Sprague-Dawley rat. Antitumor effects were examined a flow cytometric DNA distributions by flow cytometry and stuied ATP/Pi using nuclear magnetic resorance, and the enzymatic activity of thymidylate synthetase and dihydrofolate reductase as well as contents of total collagen and sialic acid were measured with spectrophotometer. In this study, S phase fraction, contents of sialic acid and total collagen were decreased in the induced hepatocellular carcinoma treated with 5-FU and MTX, and synergistic effects of anticancer drugs were exhibited in the hepatocellular carcinoma treated with 5-FU and MTX simultaneously, and the inhibition of thymidylate synthetic and dihydrofolate reductase activity were shown in the hepatocellular carcinoma treated with 5-FU, MTX, and 5-FU and MTX simultaneously. On the other hand, the ratio of ATP/Pi were increased in all groups except group treated with RA. The experimental results suggest that above method may be valuable for evaluating antitumor effect of anticancer drugs.

• Journal of the Korean Chemical Society
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• v.35 no.3
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• pp.233-239
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• 1991

$N_1-alkyl-5-fluorouracil$ derivatives from 2-chloro-ethylacrylate(CEA) were synthesized. The reaction of 5-fluorouracil(5-FU) with 2-chloroethyl acrylate gave 1-hydroxyethyl-5-fluorouracil(HEFU) in 70% yield. The treatment of HEFU with acryloyl chloride afforded 1-acryloyloxyethyl-5-fluorouracil (AOEFU). Poly(1-acryloyloxyethyl-5-fluorouracil)[Poly(AOEFU)] was also synthesized from 5-fluorouracil and Poly(CEA). The hydrolysis rates of $N_1-alkyl-5-fluorouracil$ derivatives were observed by means of UV spectrophotometer at 265 nm in ethanol-water(1 : 1); k = the constant of hydrolysis rate, $k=1.38{\times}10^{-4}$/sec for HEFU, $k=9.25{\times}10^{-5}$/sec for AOEFU, $k=4.16{\times}10^{-5}$k = 4.16 ${\times}$ $10-5}sec$ for Poly(AOEFU). The differential thermal analysis and thermogravimetry of 5-fluorouracil derivatives have been discussed.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7037-7041
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• 2014

Background: 5-Fluorouracil (5-FU) is the most commonly used drug in colon cancer therapy. However, despite impressive clinical responses initially, development of drug resistance to 5-Fu in human tumor cells is the primary cause of failure of chemotherapy. In this study, we established a 5-Fu-resistant human colon cancer cell line for comparative chemosensitivity studies. Materials and Methods: Real time PCR and Western blotting were used to determine gene expression levels. Cell viability was measured by MTT assay. Glucose uptake was assess using an Amplex Red Glucose/Glucose Oxidase assay kit. Results: We found that 5-Fu resistance was associated with the overexpression of Glut1 in colon cancer cells. 5-Fu treatment at low toxic concentration induced Glut1 expression. At the same time, upregulation of Glut1 was detected in 5-Fu resistant cells when compared with their parental cells. Importantly, inhibition of Glut1 by a specific inhibitor, WZB117, significantly increased the sensitivity of 5-Fu resistant cells to the drug. Conclusions: This study provides novel information for the future development of targeted therapies for the treatment of chemo-resistant colon cancer patients. In particular it demonstrated that Glut1 inhibitors such as WZB117 may be considered an additional treatment options for patients with 5-Fu resistant colon cancers.

• Analytical Science and Technology
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• v.11 no.1
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• pp.36-41
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• 1998

A gas chromatography-mass spectrometry method for the determination of 5-fluorourasil in human plasma is described. The method involves a single extraction procedure with 10 ml of isopropanol-ether(20:80) solution and pentafluoro-benzylation. Samples were injected using an automatic injector, followed by separation on a nonpolar capillary column and detection with a mass selective detector(MSD). No endogeneous compounds were found to interfere. The detection limit, based upon an assayed plasma volume of 0.5, was 3 ng/ml. The extraction yield was found to be above 80%. Plasma 5-FU concentrations were determined by this method in about 500 plasma samples from cancer patients undergoing treatment with 5-FU. This method is suitable for monitoring of 5-FU in plasma of cancer patients.

• Journal of Ginseng Research
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• v.27 no.2
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• pp.47-51
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• 2003

Synergistic anticancer activities of red ginseng acidic polysaccharide (RGAS) showing immunomodulatory activity were evaluated by combined treatment with anticancer agents such as Cyclophosphamide (CY) or 5-Fluorouracil (5-FU) in experimental tumor models. The combined treatment of RGAP (100 mg/kg) and CY (3 mg/kg) exhibited 71% of survival rate in lift span of sarcoma 180-bearing mice, while single treatment of RGAP (100 mg/kg) and CY (3 or 10 mg/kg) exhibited 43, 14 and 43% of survival rates, respectively. In addition, when RGAP (100 mg/kg) was administered in combination with 5-FU (2.5 mg/kg) to sarcoma 180 tumor-bearing mice, higher survival rate was found when compared with RGAP or 5-FU treatment alone. Moreover, tumor weights in LL/2 lung carcinoma-bearing mice treated combined with RGAP (100 mg/kg) and 5-FU (5 or 10 mg/kg) was obviously decreased when compared with 5-FU alone. These results suggest that clinical trials of RGAP as an adjuvant in cancer chemotheraphy can be higly feasible.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.20 no.2
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• pp.158-165
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• 1998

This study was undertaken to observe the effects of the antineoplastic agent, 5-Fluorouracil(5 FU) on the hair in Sprague-Dawley white rats. Twenty four sprague-Dawley strain white rats, each weighing about 150-200 grams were used and divided into control and experimental groups. In the experimental group, eighteen rats were injected intraperitonially with 60 mg of 5-FU per killogram body weight with one time per two days, Six rats were injected with 0.5 cc of normal saline solution intraperitoneally as a placebo on this control group. Rats were serially sacrificed on the first, third, fifth, seventh, tenth and fourteenth day after 2 times of injection of 5-FU and saline. The hair were obtained and observed SEM. After examination and comparision of all specimens, the results of this study were as follows: 1. In the control group, the scale and cuticle of hair was observed smooth surface and equal interval 2. In the experimental group, the first day, scale change was seen from body of hair and crack was seen. from fifth day, and irregular scale and cuticle of hair was seen from 10, 14 days 3. The apperance of root of hair was not almost change From above results, 5-Fluorouracil was more effective on the hair body. The change was begun from first day and crack of scale was seen from fifth day and irregular scale and cuticle of hair was seen from 10,14 days. The.

• Korean Journal of Clinical Pharmacy
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• v.7 no.1
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• pp.45-49
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• 1997

The effect of the light on the stability of 5-fluorouracil admixture was investigated. Four sets of 5-fluorouracil admixture were prepared using 50 mg/ml injection in $5\%$ dextrose solution in PVC bags and glass bottles: (1) 5-fluorouracil 1 mg/ml concentration in glass bottles, (2) 5-fluorouracil 1 mg/ml in PVC bags, (3) 5-fluorouracil 10 mg/ml in glass bottles, and (4) 5-fluorouracil 10 mg/ml in PVC bags. In each set, one group was protected from the light (control group) and the other group was exposed to the fluorescent light (study group). All admixtures were stored at room temperature for 72 hours. Also, 5-fluorouracil injections (50 mg/ml) were prepared in plastic syringes. Half of the samples of 50 mg/ml concentration were protected from the light (control group) and the other half were exposed to the fluorescent light (study group). These were stored at room temperature for 48 hours. After visual inspection, the pHs of each admixture were determined. The 5-fluorouracil concentrations were measured by high-performance liquid chromatography with UV detection, with 5-bromouracil as an internal standard. Over the study period, no visual changes were observed. The pHs of 5-fluorouracil admixtures were in the range of $8.2\~8.5$. The peak area ratios (5-FU/5-BrU) of 5-fluorouracil admixtures protected from the light were compared with those of the admixtures exposed to the light. There was no statistically significant difference between two groups during the study period (p>0.05). In conclusion, 5-fluorouracil admixtures in $5\%$ dextrose solution exposed to the light were stable for 72 hours.

• Molecules and Cells
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• v.37 no.7
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• pp.540-546
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• 2014

Several types of genetic and epigenetic regulation have been implicated in the development of drug resistance, one significant challenge for cancer therapy. Although changes in the expression of non-coding RNA are also responsible for drug resistance, the specific identities and roles of them remain to be elucidated. Long non-coding RNAs (lncRNAs) are a type of ncRNA (> 200 nt) that influence the regulation of gene expression in various ways. In this study, we aimed to identify differentially expressed lncRNAs in 5-fluorouracil-resistant colon cancer cells. Using two pairs of 5-FU-resistant cells derived from the human colon cancer cell lines SNU-C4 and SNU-C5, we analyzed the expression of 90 lncRNAs by qPCR-based profiling and found that 19 and 23 lncRNAs were differentially expressed in SNU-C4R and SNU-C5R cells, respectively. We confirmed that snaR and BACE1AS were down-regulated in resistant cells. To further investigate the effects of snaR on cell growth, cell viability and cell cycle were analyzed after transfection of siRNAs targeting snaR. Down-regulation of snaR decreased cell death after 5-FU treatment, which indicates that snaR loss decreases in vitro sensitivity to 5-FU. Our results provide an important insight into the involvement of lncRNAs in 5-FU resistance in colon cancer cells.

• YAKHAK HOEJI
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• v.34 no.6
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• pp.395-400
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• 1990

The FU-fat conjugates(4a-e) as a prodrug have been synthesized by condensing various fatty acids(1a-e) via isocyanates(2a-e) as carbamoyl group at $N^1-position$ of 5-fluorouracil and their structures characterized. Preliminary testing for their antitumor effect was carried out on leukemia L1210 cells in culture. Most of them(4a-d) like the parent FU exhibited less than 50% inhibition on grouth of the cultrued cells at the concentration of $1\;{\times\;10^{-7}M$. Only a dicarboxylic acid derivative, 4e, showed over 50% inhibition at the same level.

• Molecules and Cells
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• v.42 no.2
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• pp.175-182
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• 2019

microRNAs regulate a diverse spectrum of cancer biology, including tumorigenesis, metastasis, stemness, and drug resistance. To investigate miRNA-mediated regulation of drug resistance, we characterized the resistant cell lines to 5-fluorouracil by inducing stable expression of miRNAs using lenti-miRNA library. Here, we demonstrate miR-551a as a novel factor regulating cell survival after 5-FU treatment. miR-551a-expressing cells (Hep3B-lenti-miR-551a) were resistant to 5-FU-induced cell death, and after 5-FU treatment, and showed significant increases in cell viability, cell survival, and sphere formation. It was further shown that myocyte-specific factor 2C is the direct target of miR-551a. Our results suggest that miR-551a plays a novel function in regulating 5-FU-induced cell death, and targeting miR-551a might be helpful to sensitize cells to anti-cancer drugs.