DNA flow cytometric study of 5-fluorouracil used to treat end stage non-Hodgkin's lymphoma

Hedley, David W.

doi:10.1038/bjc.1987.22

Cited by 3 publications

(1 citation statement)

References 7 publications

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“…Monoparametric or multiparametric analysis of the cell cycle, as well as kinetic studies, can be interesting to evaluate in vitro drug effects [51,93]. It allows to emphasize the drug cytotoxicity, its specific phase of action [78], its influence on cellular metabolism or the position in the cycle where cells are killed [60]. This technique permits in vitro characterization of drugs employed in chemotherapy to inhibit cell growth and division [96,156], or for chemical agents used in antitumoral hormonetherapy [88,144].…”

Section: Pharmacology-toxicologymentioning

confidence: 99%

Cell cycle analysis by flow cytometry: Principles and applications

Jayat

Ratinaud²

1993

Biology of the Cell

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Numerous flow cytometric analyses are based on DNA content studies. We have considered firstly monoparametric cell cycle analyses, which only take DNA content into account, but are sometimes of limited interest. Then, we have presented multiparametric analyses, which can be used to improve cycle phase identification by taking simultaneously into account DNA and other cellular components, or by considering some events occurring during cell cycle. Finally, we have discussed monoparametric and multiparametric cell cycle analysis interest in various application fields, particularly in pharmacology, toxicology, tumoral pathology and higher plant system studies.

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Section: Pharmacology-toxicologymentioning

confidence: 99%

Cell cycle analysis by flow cytometry: Principles and applications

Jayat

Ratinaud²

1993

Biology of the Cell

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Enhancement of the antitumor effects of 5-fluorouracil by folinic acid

Mini

Trave

Rustum

et al. 1990

Pharmacology & Therapeutics

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Biochemical Modulation of Fluoropyrimidines by Antifolates and Folates in anIn VitroModel of Human Leukemia

Mini

Coronnello

Carotti

et al. 1990

Journal of Chemotherapy

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Although 5-fluorouracil (FUra) is one of the most effective cytotoxic agents in the treatment of various solid tumors (carcinomas of the gastro-intestinal tract, breast, head and neck), remissions occur in only 20 to 30% of cases and usually are of short duration. Recently, preclinical studies have shown that the antitumor activity of FUra can be potentiated by modulating the metabolism of this drug by using other substances, in particular antifolates of folates. Pretreatment with antifolates may, by blocking de novo purine biosynthesis and consequently increasing phosphoribosyl pyrophosphate (PRPP) pools, enhance the conversion of FUra to active fluoronucleotide pools via orotate phosphoribosyltransferase. Methotrexate (MTX) pretreatment may also enhance binding of the fluoropyrimidine inhibitor, 5-fluodeoxyuridylate (FdUMP), to the target enzyme, thymidylate synthase (TS), indirectly by increasing dihydrofolate polyglutamates or directly, as MTX polyglutamates, by enhancing the formation of ternary complexes with FdUMP and TS. Exogenous folates, in particular 5-formyltetrahydrofolate (folinate, leucovorin, LV), can, by raising the intracellular levels of 5, 10-methylenetetrahydrofolate, lead to increased formation and stabilization of the ternary complex formed by TS, the folate coenzyme, and FdUMP. In vitro studies have also shown potentiation of FUra cytotoxicity by antifolates and folates against human lymphoblastic leukemia cell lines. Thus, while FUra may have little or no single agent activity in leukemias and lymphomas, it may be converted to an active drug in these neoplasms by appropriate modulation. Clinical studies of sequential MTX-FUra or combined LV-FUra based upon experimental tumor results reviewed herein, are warranted.

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DNA flow cytometric study of 5-fluorouracil used to treat end stage non-Hodgkin's lymphoma

Cited by 3 publications

References 7 publications

Cell cycle analysis by flow cytometry: Principles and applications

Cell cycle analysis by flow cytometry: Principles and applications

Enhancement of the antitumor effects of 5-fluorouracil by folinic acid

Biochemical Modulation of Fluoropyrimidines by Antifolates and Folates in anIn VitroModel of Human Leukemia

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