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dc.contributor.authorLord, Brian Ien
dc.contributor.authorGurney, Hen
dc.contributor.authorChang, Jamesen
dc.contributor.authorThatcher, Nicken
dc.contributor.authorCrowther, Dereken
dc.contributor.authorDexter, T Michaelen
dc.date.accessioned2010-07-22T09:08:01Z
dc.date.available2010-07-22T09:08:01Z
dc.date.issued1992-01-02
dc.identifier.citationHaemopoietic cell kinetics in humans treated with rGM-CSF. 1992, 50 (1):26-31 Int J Canceren
dc.identifier.issn0020-7136
dc.identifier.pmid1370226
dc.identifier.urihttp://hdl.handle.net/10541/108142
dc.description.abstractWe have investigated the kinetics of myeloid cell proliferation in the marrow of patients with small-cell lung cancer and treated with 10 daily subcutaneous injections of granulocyte/macrophage colony-stimulating factor (GM-CSF). Bone marrow, obtained before and during treatment with the growth factor, was labelled in vitro with tritiated thymidine (3H-TdR). A 3rd bone-marrow sample was obtained 1 hr following an intravenous injection of 3H-TdR. Subsequent daily blood samples were also collected, and 3H-TdR labelling was assessed on these and the marrow preparations by autoradiography. GM-CSF treatment increased the peripheral granulocytic cells nearly 5-fold, but this included significant eosinophilia, so that the neutrophilic granulocytes increased only 3.3-fold. These cells were released from the marrow over a normal time scale, but their peripheral half-life was about 6 times longer than normal and they were probably functionally defective. Furthermore, significant numbers of immature cells were released from the marrow. Neutrophil production stimulated by GM-CSF was thus overestimated by measurement of the apparent peripheral granulocytosis. Increased labelling indices and grain counts in the proliferating granulocytic cells of the marrow indicate shortened cell-cycle times, and the excess granulocyte production appears to be the result of extra amplification divisions in the proliferative compartments.
dc.language.isoenen
dc.subjectHaematopoiesisen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshCarcinoma, Small Cell
dc.subject.meshCell Cycle
dc.subject.meshGranulocyte Colony-Stimulating Factor
dc.subject.meshGranulocyte-Macrophage Colony-Stimulating Factor
dc.subject.meshGranulocytes
dc.subject.meshHematopoiesis
dc.subject.meshHematopoietic Stem Cells
dc.subject.meshHumans
dc.subject.meshLeukocyte Count
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshMonocytes
dc.subject.meshRecombinant Proteins
dc.titleHaemopoietic cell kinetics in humans treated with rGM-CSF.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Department of Experimental Haematology, Paterson Institute for Cancer Research, Manchester, UK.en
dc.identifier.journalInternational Journal of Canceren
html.description.abstractWe have investigated the kinetics of myeloid cell proliferation in the marrow of patients with small-cell lung cancer and treated with 10 daily subcutaneous injections of granulocyte/macrophage colony-stimulating factor (GM-CSF). Bone marrow, obtained before and during treatment with the growth factor, was labelled in vitro with tritiated thymidine (3H-TdR). A 3rd bone-marrow sample was obtained 1 hr following an intravenous injection of 3H-TdR. Subsequent daily blood samples were also collected, and 3H-TdR labelling was assessed on these and the marrow preparations by autoradiography. GM-CSF treatment increased the peripheral granulocytic cells nearly 5-fold, but this included significant eosinophilia, so that the neutrophilic granulocytes increased only 3.3-fold. These cells were released from the marrow over a normal time scale, but their peripheral half-life was about 6 times longer than normal and they were probably functionally defective. Furthermore, significant numbers of immature cells were released from the marrow. Neutrophil production stimulated by GM-CSF was thus overestimated by measurement of the apparent peripheral granulocytosis. Increased labelling indices and grain counts in the proliferating granulocytic cells of the marrow indicate shortened cell-cycle times, and the excess granulocyte production appears to be the result of extra amplification divisions in the proliferative compartments.


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