Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia

I. Hubeek; G. J. Peters; A. J.F. Broekhuizen; J. Sargent; B. E.S. Gibson; U. Creutzig; G. J.L. Kaspers

doi:10.1111/j.1365-2141.2005.05760.x

Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia

I. Hubeek, G. J. Peters, A. J.F. Broekhuizen, J. Sargent, B. E.S. Gibson, U. Creutzig, G. J.L. Kaspers

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10 Citaten (Scopus)

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To modulate in vitro cytarabine (ara-C) resistance we combined ara-C with six potential resistance modifiers in 10 paediatric acute myeloid leukaemia (AML) patient samples (methyl thiazol tetrazolium assay). Drug interactions were determined by median drug effect analysis. Co-incubation of ara-C/aphidicolin showed strong synergism. The combinations of ara-C/cladribine and ara-C/gemcitabine were synergistic. Nearly additive and moderately synergistic interactions were observed between ara-C/flavopiridol and ara-C/UCN-01. The combination of ara-C/decitabine was antagonistic. In conclusion, favourable interactions were observed between ara-C and aphidicolin, cladribine, gemcitabine and also with flavopiridol and UCN-01, supporting the evaluation of these combinations in clinical trials with AML patients.

Originele taal-2	Engels
Pagina's (van-tot)	219-222
Aantal pagina's	4
Tijdschrift	British Journal of Haematology
Volume	131
Nummer van het tijdschrift	2
DOI's	https://doi.org/10.1111/j.1365-2141.2005.05760.x
Status	Gepubliceerd - okt. 2005
Extern gepubliceerd	Ja

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10.1111/j.1365-2141.2005.05760.x

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Hubeek, I., Peters, G. J., Broekhuizen, A. J. F., Sargent, J., Gibson, B. E. S., Creutzig, U., & Kaspers, G. J. L. (2005). Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia. British Journal of Haematology, 131(2), 219-222. https://doi.org/10.1111/j.1365-2141.2005.05760.x

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title = "Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia",

abstract = "To modulate in vitro cytarabine (ara-C) resistance we combined ara-C with six potential resistance modifiers in 10 paediatric acute myeloid leukaemia (AML) patient samples (methyl thiazol tetrazolium assay). Drug interactions were determined by median drug effect analysis. Co-incubation of ara-C/aphidicolin showed strong synergism. The combinations of ara-C/cladribine and ara-C/gemcitabine were synergistic. Nearly additive and moderately synergistic interactions were observed between ara-C/flavopiridol and ara-C/UCN-01. The combination of ara-C/decitabine was antagonistic. In conclusion, favourable interactions were observed between ara-C and aphidicolin, cladribine, gemcitabine and also with flavopiridol and UCN-01, supporting the evaluation of these combinations in clinical trials with AML patients.",

keywords = "Acute myeloid leukaemia, Childhood leukaemia, Drug resistance",

author = "I. Hubeek and Peters, {G. J.} and Broekhuizen, {A. J.F.} and J. Sargent and Gibson, {B. E.S.} and U. Creutzig and Kaspers, {G. J.L.}",

year = "2005",

month = oct,

doi = "10.1111/j.1365-2141.2005.05760.x",

language = "English",

volume = "131",

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Hubeek, I, Peters, GJ, Broekhuizen, AJF, Sargent, J, Gibson, BES, Creutzig, U & Kaspers, GJL 2005, 'Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia', British Journal of Haematology, vol. 131, nr. 2, blz. 219-222. https://doi.org/10.1111/j.1365-2141.2005.05760.x

Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia. / Hubeek, I.; Peters, G. J.; Broekhuizen, A. J.F. et al.

In: British Journal of Haematology, Vol. 131, Nr. 2, 10.2005, blz. 219-222.

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

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T1 - Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia

AU - Hubeek, I.

AU - Peters, G. J.

AU - Broekhuizen, A. J.F.

AU - Sargent, J.

AU - Gibson, B. E.S.

AU - Creutzig, U.

AU - Kaspers, G. J.L.

PY - 2005/10

Y1 - 2005/10

N2 - To modulate in vitro cytarabine (ara-C) resistance we combined ara-C with six potential resistance modifiers in 10 paediatric acute myeloid leukaemia (AML) patient samples (methyl thiazol tetrazolium assay). Drug interactions were determined by median drug effect analysis. Co-incubation of ara-C/aphidicolin showed strong synergism. The combinations of ara-C/cladribine and ara-C/gemcitabine were synergistic. Nearly additive and moderately synergistic interactions were observed between ara-C/flavopiridol and ara-C/UCN-01. The combination of ara-C/decitabine was antagonistic. In conclusion, favourable interactions were observed between ara-C and aphidicolin, cladribine, gemcitabine and also with flavopiridol and UCN-01, supporting the evaluation of these combinations in clinical trials with AML patients.

AB - To modulate in vitro cytarabine (ara-C) resistance we combined ara-C with six potential resistance modifiers in 10 paediatric acute myeloid leukaemia (AML) patient samples (methyl thiazol tetrazolium assay). Drug interactions were determined by median drug effect analysis. Co-incubation of ara-C/aphidicolin showed strong synergism. The combinations of ara-C/cladribine and ara-C/gemcitabine were synergistic. Nearly additive and moderately synergistic interactions were observed between ara-C/flavopiridol and ara-C/UCN-01. The combination of ara-C/decitabine was antagonistic. In conclusion, favourable interactions were observed between ara-C and aphidicolin, cladribine, gemcitabine and also with flavopiridol and UCN-01, supporting the evaluation of these combinations in clinical trials with AML patients.

KW - Acute myeloid leukaemia

KW - Childhood leukaemia

KW - Drug resistance

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Hubeek I, Peters GJ, Broekhuizen AJF, Sargent J, Gibson BES, Creutzig U et al. Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia. British Journal of Haematology. 2005 okt.;131(2):219-222. doi: 10.1111/j.1365-2141.2005.05760.x

Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia

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