Linked Life Data

9548417

Source:http://linkedlifedata.com/resource/pubmed/id/9548417

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-4-28
pubmed:abstractText
The hematologic toxicity of arabinosylcytosine (Ara-C) and carboplatin (CBDCA) as well as the stimulating effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on murine bone marrow vary according to their dosing time along the 24-h time scale. In the present study, we investigated whether the tolerability of Ara-C or CBDCA, given at their least toxic circadian time, could be improved further with AcSDKP, a negative regulator of hemopoiesis, rhG-CSF or both. A total of 228 B6D2F1 mice received once-daily injection of either Ara-C (42 mg/kg/d s.c.) for 7 d (d 0-6) at 8 hours after light onset - HALO) or CBDCA (40 mg/kg/d i.p.) for 5 d (d 2-6) at 16 HALO. AcSDKP (24 microg/d) was continuously infused for 7 d (d 0-6), using an osmotic minipump. rhG-CSF (400 microg/kg/d s.c.) was injected for 4 d (d 9-12) at 9 HALO. Subgroups of mice were sacrificed at 3 HALO on various days following treatment. AcSDKP significantly increased CFU-GM count on d 7 and leukocyte, neutrophil and monocyte counts on d 13 and d 16 compared to Ara-C alone. Also, rhG-CSF produced similar protective effects to those of AcSDKP with regard to leukocyte and CFU-GM counts. The combination of AcSDKP with rhG-CSF induced a further increase in total leukocytes and their subsets as compared to either agent alone, but did not alter the CFU-GM counts. Neither AcSDKP nor rhG-CSF nor their combination reduced CBD CA-induced hematological toxicity. In conclusion, AcSDKP or rhG-CSF administration further improved the tolerability of Ara-C beyond that already achieved with optimal circadian timing, while no such effect was observed in mice receiving CBDCA at the dose used. The results warrant further exploration of chronopharmacologic delivery schedules combining Ara-C with AcSDKP.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0902-4441
pubmed:author
pubmed:issnType
Print
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
181-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Circadian-based effects of AcSDKP, with or without rhG-CSF on hematologic toxicity of chemotherapy in mice.
pubmed:affiliation
Laboratoire Rythmes Biologiques & Chronothérapeutique (Université Paris XI), ICIG, Hôpital Paul-Brousse, Villejuif, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't