High-dose methotrexate therapy with leucovorin rescue: in vitro investigations on human osteosarcoma cell lines

Diddens, H.; Teufel, T.; Niethammer, D.

doi:10.1007/bf00253966

Cited by 12 publications

(15 citation statements)

References 12 publications

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“…Among the clinically relevant conclusions which can be drawn from the present study, the optimum time interval between MTX and FA appears to be around 18-24 h; a marked reduction in MTX cytotoxicity occurs during shorter intervals. This observation concurs well with the similar conclusions of a comparable study on human osteosarcoma cell lines (Diddens et al, 1987) and with the data reported by Sirotnak et al (1978) (Stoller et al, 1979). This finding may explain why patients treated by standard dose MTX plus FA rescue, exhibited a significantly lower response rate than those receiving only MTX, in a randomised placebo-controlled study (Browman et al, 1990).…”

Section: Discussionsupporting

confidence: 94%

Critical factors for the reversal of methotrexate cytotoxicity by folinic acid

Bernard

Etienne²,

Fischel³

et al. 1991

Br J Cancer

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Summary The cytotoxicity of methotrexate (MTX) on representative human tumour cell lines (two cell lines from head and neck carcinomas, two from breast carcinomas, two from osteosarcomas and one lymphoblastoid cell line) was evaluated to: (1) examine the optimal time interval between MTX and folinic acid (FA) administration; (2) (FBS) were from Gibco (Paisley, UK). Penicillin and streptomycin were from Merieux (Lyons, France). Transferrin was from Flow Laboratories (Irvin, UK). The MTT test was performed with 3-(4-5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and DMSO, both from Sigma. Cell culturesThe eight human tumour cell lines used are described in Table I. Cells were routinely cultured in a humidified incubator (Sanyo) at 37'C with an atmosphere containing 8% CO2 in air. The head and neck cancer cell lines and the osteosarcoma cell lines were grown in DMEM medium supplemented with 10% FBS, penicillin (50,000 IU I1), streptomycin (86 tLM), and 1-glutamine (2 mM). The breast cancer cell lines were grown in the same medium supplemented with insulin (0.1 jIM) and transferrin (0.64 liM). The lymphoblastoid cell line was grown in RPMI 1640 medium supplemented with 10% FBS, penicillin (50,000 IU 1'), streptomycin (86 fLM) and 1-glutamine (2 mM). In brief, cells were grown in 96-well microtitration plates in their respective culture medium; 24 h later, they were exposed to MTX for 24 h. The respective initial cellular densities (Table I) were determined by a preliminary study in order to obtain optimal logarithmic growth. The MTX concentrations used (Table I)

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Section: Discussionsupporting

confidence: 94%

Critical factors for the reversal of methotrexate cytotoxicity by folinic acid

Bernard

Etienne²,

Fischel³

et al. 1991

Br J Cancer

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“…Standard doses (0.5 gm-2) and high doses (2.5 gm-2) of MTX generate median MTX CSF values of 8 x 10-8 M and 6 x I0 -7 M respectively (Thyss et al, 1987). Diddens et al (1987) established in a lymphoblastoid cell line that the cytotoxic effect of high concentrations of MTX was reversed by relatively low concentrations of simultaneously added leucovorin. There is thus a potential risk of competition between folates and antifolates in CSF during standard or even high dose MTX plus FA rescue in the treatment of childhood ALL.…”

Section: Resultsmentioning

confidence: 99%

Evidence for CSF accumulation of 5-methyltetrahydrofolate during repeated courses of methotrexate plus folinic acid rescue

Thyss

Milano²,

Etienne³

et al. 1989

Br J Cancer

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“…Clarke et al 27 demonstrated that folinic acid (leucovorin TM /folate) administered in drinking water prevented the development of MTX-induced mucositis entirely. It has been shown in humans that folate (leucovorin) administered intravenously has the potential to reinitiate tumor cell survival if given within 24 h. 34,35 Sepehr et al (2003), reported that cecal bacteria-synthesized folate was not absorbed or stored in substantial amounts in the liver, indicating that systemic folate distribution is limited. The mechanism of protection by TH-4 in non-tumor bearing animals may have been the result of delivering a micro dose of folate to the site of damage, suggesting that a dose of 10 9 cfu/mL was insufficient DAR ( Table 4; p < 0.001) for "Net" small intestinal sucrase activity (average).…”

confidence: 99%