Effects of UFT (Mixed Compound of Tegafur and Uracil) on Cell Kinetics and Inhibition of Thymidylate Synthase in L1210 Ascites Tumor

Kagawa, Yoshiyuki; Ohkubo, Toshiki; Higashigawa, Masamune; Ido, Masaru; Kakito, Hideshi; Inagaki, Shoji; Kojima, Michio; Ooi, Kazuya; Sakurai, Minoru

doi:10.3109/07357909509024909

Cited by 4 publications

(1 citation statement)

References 5 publications

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“…1,2,6,7,14) They have been used clinically by oral administration. 19) In this study, we examined the antitumor effect and 5-FU concentration in the intestine, plasma and tumor after oral equimolar administrations of each drug using BDF1 mice bearing L1210 ascites tumor.…”

Section: Discussionmentioning

confidence: 99%

Plasma, Intestine and Tumor Levels of 5-Fluorouracil in Mice Bearing L1210 Ascites Tumor Following Oral Administration of 5-Fluorouracil, UFT (Mixed Compound of Tegafur and Uracil), Carmofur and 5'-Deoxy-5-fluorouridine.

Ooi

Ohkubo

Higashigawa

et al. 2001

Biological & Pharmaceutical Bulletin

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Section: Discussionmentioning

confidence: 99%

Plasma, Intestine and Tumor Levels of 5-Fluorouracil in Mice Bearing L1210 Ascites Tumor Following Oral Administration of 5-Fluorouracil, UFT (Mixed Compound of Tegafur and Uracil), Carmofur and 5'-Deoxy-5-fluorouridine.

Ooi

Ohkubo

Higashigawa

et al. 2001

Biological & Pharmaceutical Bulletin

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Phase II Study of Oral Tegafur-Uracil and Folinic Acid as First-line Therapy for Metastatic Colorectal Cancer: Taiwan Experience

Lin¹

2000

Japanese Journal of Clinical Oncology

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Combined Antitumor Effect of Cyclophosphamide and Bromodeoxyuridine in BDF1 Mice Bearing L1210 Ascites Tumors

Kagawa

Noge

Higashigawa

et al. 2008

Biological & Pharmaceutical Bulletin

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Halogenated pyrimidines are incorporated in place of thymidine in DNA of replicating cells, making the cells more susceptible to the effects of radiation. 5-Bromo-2Ј-deoxyuridine (BrdUrd) has been clinically used as a radiosensitizer to enhance the tumor killing effect of radiation therapy. [1][2][3][4] The radiosensitizing effect of halogenated pyrimidines on mammalian cells in vitro is closely associated with the amount of drug incorporated into DNA. 5) Alkylating agents, such as cyclophosphamide (CPA), are widely used to treat a broad spectrum of malignancies, including both solid tumors and hematological malignancies. 6,7) CPA is converted by hepatic cytochrome P450 metabolic enzymes via two major pathways. 8) The first involves 4-hydroxylation to the active metabolite, 4-hydroxycyclophosphamide (4-OH-CPA). This conversion is carried out predominantly by cytochrome P450 CYP2B6 in humans. 9,10) 4-OH-CPA exists in equilibrium with aldophosphamide, which is broken down to form the DNA cross-linking agent phosphoramide mustard and the toxic metabolite acrolein. [11][12][13] The alternative pathway involves a CYP3A4-mediated N-dechloroethylation of CPA to form the inactive metabolite 3-dechloroethylcyclophosphamide (DECP) and the toxic byproduct chloroacetaldehyde. 11,14,15) In humans, this pathway is secondary to the activation pathway and accounts for less than 10% of the dose. 13) Alkylating agents undergo a transformation to produce highly reactive and positively charged ions. These ions can then form covalent bonds with electron-rich sites on biological molecules, such as nucleic acids, proteins, and amino acids. 16) Irradiation may cause the ablation of both singleand double-stranded DNA, degeneration or loss of bases, and intercalation of DNA and/or chromosomal protein. The actions of alkylating agents appear to have some similarities to those of gamma ray radiation. A previous in vitro report showed that pretreatment with iododeoxyuridine (IdUrd) or BrdUrd enhanced the cytotoxicity of various antineoplasmic agents, such as melphalan, cisplatin, doxorubicin, and bleomycin. 17) However, the mechanism of halopyrimidine's chemosensitizing effect is still unclear. There have been few in vivo studies on the combined antitumor effects of halogenated pyrimidines and alkylating agents. We investigated here the combined effect of BrdUrd and CPA, a bifunctional alkylating agent, on life span in L1210 ascites tumor-bearing mice and cytotoxicity in cultured L1210 cells using an MTT assay. Life Prolongation Study Male BDF1 mice were purchased from Shionogi Pharmaceutical Co., Ltd. and kept at Mie University Animal Center under constant conditions (a 12 h light : 12 h dark regimen with Oriental Chow pellet food and water freely available). L1210 leukemia cells were obtained from Shionogi Pharmacological Laboratory, Osaka, Japan and maintained in BDF1 mice by weekly intraperitoneal (i.p.) passage as previously described. 18) Experimental mice received an i.p. injection of 1ϫ10 6 ascites tumor cells in saline on Day 0. Se...

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Effects of UFT (Mixed Compound of Tegafur and Uracil) on Cell Kinetics and Inhibition of Thymidylate Synthase in L1210 Ascites Tumor

Cited by 4 publications

References 5 publications

Plasma, Intestine and Tumor Levels of 5-Fluorouracil in Mice Bearing L1210 Ascites Tumor Following Oral Administration of 5-Fluorouracil, UFT (Mixed Compound of Tegafur and Uracil), Carmofur and 5'-Deoxy-5-fluorouridine.

Plasma, Intestine and Tumor Levels of 5-Fluorouracil in Mice Bearing L1210 Ascites Tumor Following Oral Administration of 5-Fluorouracil, UFT (Mixed Compound of Tegafur and Uracil), Carmofur and 5'-Deoxy-5-fluorouridine.

Phase II Study of Oral Tegafur-Uracil and Folinic Acid as First-line Therapy for Metastatic Colorectal Cancer: Taiwan Experience

Combined Antitumor Effect of Cyclophosphamide and Bromodeoxyuridine in BDF1 Mice Bearing L1210 Ascites Tumors

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