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dc.contributor.authorLord, Brian Ien
dc.contributor.authorWoolford, Lorna Ben
dc.contributor.authorMolineux, Grahamen
dc.date.accessioned2009-11-10T09:29:04Z
dc.date.available2009-11-10T09:29:04Z
dc.date.issued2001-07
dc.identifier.citationKinetics of neutrophil production in normal and neutropenic animals during the response to filgrastim (r-metHu G-CSF) or filgrastim SD/01 (PEG-r-metHu G-CSF). 2001, 7 (7):2085-90 Clin. Cancer Res.en
dc.identifier.issn1078-0432
dc.identifier.pmid11448927
dc.identifier.urihttp://hdl.handle.net/10541/85717
dc.description.abstractFilgrastim G-CSF has a short, biologically active half-life, and its effective use depends on repeated inoculations. A major aim, therefore, has been to develop a once-per-chemotherapy cycle formulation. To this end, a polyethylene glycolylated form of Filgrastim, known as SD/01, has been developed. In this study, we compared the cellular kinetics of granulocyte production in mice stimulated with SD/01 and granulocyte colony-stimulating factor (G-CSF). Mice were injected with a single dose of SD/01 (1 mg/kg) or G-CSF (125 microg/kg) twice per day for 4 days. Mice rendered leukopenic with a single injection of cyclophosphamide (200 mg/kg) and temozolomide (90 mg/kg) were similarly treated at their 3-day neutrophil nadir. Tritiated thymidine was injected for autoradiographic labeling studies. Bone marrow labeling indices and the release of labeled neutrophils and monocytes into the peripheral blood were assessed. Granulocytopoiesis was stimulated similarly by both SD/01 and G-CSF in both normal and neutropenic animals, with counts rising to >20 x 10(9) polymorphonuclear neutrophils/l in both cases. Bone marrow thymidine labeling indices were increased, indicating a greater proportion of cells in DNA synthesis and an elevated proliferative activity. Compared with the normally slow release of neutrophils into the peripheral blood, labeled neutrophils (and monocytes) were rapidly released, increasing to peak levels at approximately 24 h. The peripheral half-life of neutrophils was not significantly different from normal, and the mitotic amplification factors for increase in granulocytopoiesis, accounted for by 3-3.9 extra cell divisions, were comparable for both factors. We conclude that neutrophil kinetics are stimulated in the same way and to the same extent by both SD/01 and G-CSF.
dc.language.isoenen
dc.subject.meshAnimals
dc.subject.meshBone Marrow Cells
dc.subject.meshCell Division
dc.subject.meshFemale
dc.subject.meshFilgrastim
dc.subject.meshKinetics
dc.subject.meshLeukocyte Count
dc.subject.meshMale
dc.subject.meshMice
dc.subject.meshMice, Inbred C57BL
dc.subject.meshMice, Inbred DBA
dc.subject.meshMice, Inbred Strains
dc.subject.meshMonocytes
dc.subject.meshNeutropenia
dc.subject.meshNeutrophils
dc.subject.meshPolyethylene Glycols
dc.subject.meshThymidine
dc.subject.meshTime Factors
dc.subject.meshTritium
dc.titleKinetics of neutrophil production in normal and neutropenic animals during the response to filgrastim (r-metHu G-CSF) or filgrastim SD/01 (PEG-r-metHu G-CSF).en
dc.typeArticleen
dc.contributor.departmentCRC Experimental Haematology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, United Kingdom. blord@picr.man.ac.uken
dc.identifier.journalClinical Cancer Researchen
html.description.abstractFilgrastim G-CSF has a short, biologically active half-life, and its effective use depends on repeated inoculations. A major aim, therefore, has been to develop a once-per-chemotherapy cycle formulation. To this end, a polyethylene glycolylated form of Filgrastim, known as SD/01, has been developed. In this study, we compared the cellular kinetics of granulocyte production in mice stimulated with SD/01 and granulocyte colony-stimulating factor (G-CSF). Mice were injected with a single dose of SD/01 (1 mg/kg) or G-CSF (125 microg/kg) twice per day for 4 days. Mice rendered leukopenic with a single injection of cyclophosphamide (200 mg/kg) and temozolomide (90 mg/kg) were similarly treated at their 3-day neutrophil nadir. Tritiated thymidine was injected for autoradiographic labeling studies. Bone marrow labeling indices and the release of labeled neutrophils and monocytes into the peripheral blood were assessed. Granulocytopoiesis was stimulated similarly by both SD/01 and G-CSF in both normal and neutropenic animals, with counts rising to >20 x 10(9) polymorphonuclear neutrophils/l in both cases. Bone marrow thymidine labeling indices were increased, indicating a greater proportion of cells in DNA synthesis and an elevated proliferative activity. Compared with the normally slow release of neutrophils into the peripheral blood, labeled neutrophils (and monocytes) were rapidly released, increasing to peak levels at approximately 24 h. The peripheral half-life of neutrophils was not significantly different from normal, and the mitotic amplification factors for increase in granulocytopoiesis, accounted for by 3-3.9 extra cell divisions, were comparable for both factors. We conclude that neutrophil kinetics are stimulated in the same way and to the same extent by both SD/01 and G-CSF.


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