• Title/Summary/Keyword: 5-fluorouracil

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A Forward Genetic Approach for Analyzing the Mechanism of Resistance to the Anti-Cancer Drug, 5-Fluorouracil, Using Caenorhabditis elegans

  • Kim, Seongseop;Shim, Jaegal
    • Molecules and Cells
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    • v.25 no.1
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    • pp.119-123
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    • 2008
  • Pyrimidine antagonists including 5-Fluorouracil (5-FU) have been used in chemotherapy for cancer patients for over 40 years. 5-FU, especially, is a mainstay treatment for colorectal cancer. It is a pro-drug that is converted to the active drug via the nucleic acid biosynthetic pathway. The metabolites of 5-FU inhibit normal RNA and DNA function, and induce apoptosis of cancer cells. One of the major obstacles to successful chemotherapy is the resistance of cancer cells to anti-cancer drugs. Therefore, it is important to elucidate resistance mechanisms to improve the efficacy of chemotherapy. We have used C. elegans as a model system to investigate the mechanism of resistance to 5-FU, which induces germ cell death and inhibits larval development in C. elegans. We screened 5-FU resistant mutants no longer arrested as larvae by 5-FU. We obtained 18 mutants out of 72,000 F1 individuals screened, and mapped them into three complementation groups. We propose that C. elegans could be a useful model system for studying mechanisms of resistance to anti-cancer drugs.

Controlled Release of Fluorouracil from Sodium Alginate Matrices (알긴산나트륨 마트릭스로부터 플루오로우라실의 제어 방출)

  • Kim, Sung-Ho;Jung, Yong-Jae;Ha, Chung-Hun
    • 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.

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Adsorption Kinetic Studies of 5-fluorouracil Molecules on Hydroxyapatite Surface

  • Yoon, Jiseol;Kwon, Ki-Young;Woo, Dong Kyun
    • Proceedings of the Korean Vacuum Society Conference
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    • 2014.02a
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    • pp.432.1-432.1
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    • 2014
  • Hydroxyapatite (Ca10(PO4)6(OH)2) is known as the main inorganic component of mature mammalian bones and teeth. Because of its biocompatibility, hydroxyapatite has attracted much attention due to its potential applications in many biomedical researches. Here, we tested a therapeutic potential for the use of hydroxyapatite as an anticancer drug delivery vector. We prepared various types of hydroxyapatite having different chemical contents and morphologies using hydrothermal synthesis. The capability of hydroxyapatite as drug delivery materials was examined by adsorption kinetics of 5-fluorouracil molecules, a common anticancer drug, in phosphate buffered saline. We find that hydroxyapatite with smaller crystal size and higher phosphate contents shows improved adsorption property. Given that hydroxyapatite provides a scaffold for bone regeneration, these results highlight a potential use of hydroxyapatite in therapies aimed at osteosarcoma.

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Factors Affecting the Rate of Release of 5-Fluorouracil from Ethylene-Vinyl Acetate Matrices

  • Oh, Seaung-Youl;Chung, Hee-Won;Cho, Sun-Hang;Lee, Hai-Bang
    • Journal of Pharmaceutical Investigation
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    • v.24 no.3
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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.

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Effect of Water-Soluble Carriers on Water-Absorption and Swelling of Polydimethylsiloxane-5-Fluorouracil Devices

  • O, Sung-Il;Lee, Chi-Young;Kim, Sung-Ho
    • Journal of Pharmaceutical Investigation
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    • v.16 no.3
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    • pp.101-105
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    • 1986
  • The changes of water absorption and surface area of polydimethylsiloxane-5-fluorouracil devices containing different water soluble additives such as sodium chloride, glycerine, poly-propylene glycol(PPG 400), and polyethylene oxide(PEO 400, 400 and 2000) were investigated. It was confirmed that carriers controlled water absorption and swelling of the devices in the aqueous solutions. The water absorption and the swelling were affected by the osmotic pressure and ionic strength of the aqueous solutions.

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Photocycloaddition of 5,7-Dimethoxycoumarin to 5-Fluorouracil

  • Shim, Sang-Chul;Ra, Choon-Sup;Chae, Kyu-Ho
    • Bulletin of the Korean Chemical Society
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    • v.1 no.4
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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.

The Photoaddition Reaction of 1,4-Diphenyl-1,3-butadiyne with 5-Fluorouracil

  • Shim, Sang-Chul;Lee, Tae-Suk;Kim, Sung-Sik
    • Bulletin of the Korean Chemical Society
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    • v.7 no.3
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    • pp.228-230
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    • 1986
  • Diacetylene compound, 1,4-diphenyl-1,3-butadiyne, was photolyzed with 5-fluorouracil as a model reaction of the phototoxic conjugated poly-ynes with DNA or RNA and obtained a [2 + 2] photocycloadduct. The structure of the photoadduct was determined by spectral methods and compared with the [2 + 2] photoadducts of 1,4-diphenyl-1,3-butadiyne with tetramethylethylene and dimethyl fumarate.

The Effect of Combination of Radiation with 5-Fluorouracil on Mouse Jejunal Crypt Cells (5-Fluorouracil 투여가 마우스 공장 소낭선세포의 방사선조사 효과에 미치는 영향)

  • Huh, Seung-Jae;Park, Charn-Il
    • Radiation Oncology Journal
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    • v.3 no.2
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    • pp.87-93
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    • 1985
  • The interaction of radiation and 5-Fluorouracil (5-FU) on mouse jejunal crypt cells was studied using the microcolony survival assay. 150mg/kg of 5-FU was injected intraperitoneally 15 minutes before irradiation and 6 hours after irradiation. Jejunal crypt cells of mouse survived more when 5-FU was given 15 minutes before irradiation than giving it 6 hours after irradiation. The mean lethal doses (Do) of each of irradiation alone group, 5-FU injection group of 15 minutes preceding irradiation, and 5-FU injection group of 6 hours post irradiation were, 135, 135, and 114 rad respectively. The dose effect factor (DEF) of each of 5-FU injection groups of 15 minutes preceding irradiation and of 6 hours post irradiation were 1.13 and 1.27

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THE EFFECT OF THE 5-FLUOROURACIL ON THE HAIR OF RAT : SCANNING ELECTRONMICROSCOPIC STUDY (5-Fluorouracil이 백서 체모에 미치는 영향에 관한 실험적 연구)

  • Choi, Yong-Chul;Kim, Kyung-Wook;Lee, Jae-Hoon
    • 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.

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Clinical Effects of the Combination Chemotherapy of Heptaplatin and 5-Fluorouracil in Advanced Gastric Cancer (진행성 위암 환자에서 Heptaplatin과 5-Fluorouracil 복합요법의 임상효과)

  • Shin, Gashil;Oh, Jung Mi
    • Korean Journal of Clinical Pharmacy
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    • v.14 no.2
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    • pp.61-70
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    • 2004
  • Heptaplatin is a new platinum derivative with antitumor activity against gastric cancer. Preclinical studies showed that it is less toxic than other platinum analogues. The purpose of this study is to evaluate the efficacy and toxicity of the combination therapy of heptaplatin and 5-fluorouracil in Korean advanced gastric cancer patients. This study was investigated retrospectively. The patients group consisted of 65 advanced gastric cancer patients with no prior radiotherapy. All patients received heptaplatin $400\;mg/m^2$ by 2-3 hour infusion on Day 1 and 5-FU $1000\;mg/m^2by 12-24 hour continuous infusion for 5 days. After the first cycle, subsequent doses were adjusted according to the toxicity. Courses were repeated every 28 days. As results, objective response occurred in 16 patients $(24.6\%)$. Two were complete and 14 were partial response. Median progression free survival was 32 weeks with $29\%$ of patients progression free at 1 year. The most common hematologic toxicity was anemia. Grade 3 or 4 anemia was seen at $2.7\%$ of treatment cycles. Grade 3 or higher leucopenia was seen at $1.2\%$ of cycles. Grade 3 or 4 neutropenia and thrombocytopenia occurred at $6.1\%\;and\;1.5\%$ of cycles, respectively. The most common nonhematologic toxicity was proteinuria. Though no patients experienced grade 3 or 4 proteinuria, proteinuria was a considerable factor for this chemotherapy. Grade 3 or higher gastrointestinal toxicities were nausea and vomiting ($4.6\%$ of patients) and diarrhea ($1.5\%$ of patients). Grade 2 renal toxicity with elevation of serum creatinine was seen in $0.3\%$ of cycles, which is less than that of other platinum analogues. This study showed that combination therapy of heptaplatin and 5-FU have modest antitumor activity against advanced gastric cancer without severe renal toxicity.

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