PMID- 11007917
OWN - NLM
STAT- MEDLINE
DCOM- 20001013
LR  - 20131121
IS  - 1066-5099 (Print)
IS  - 1066-5099 (Linking)
VI  - 18
IP  - 5
DP  - 2000
TI  - Thrombopoietin and chemokine mRNA expression in patient post-chemotherapy and in 
      vitro cytokine-treated marrow stromal cell layers.
PG  - 331-42
AB  - CD34(+) cells and megakaryocyte progenitors were lower in marrow from patients 
      after hematological recovery from the first cycle of 5-fluorouracil, leucovorin, 
      adriamycin, cyclophosphamide (FLAC) chemotherapy plus PIXY321 (GM-CSF/interleukin 
      3; IL-3 hybrid) than in FLAC + GM-CSF or pre-FLAC marrows. Marrow stromal layers, 
      an in vitro model of the marrow microenvironment, express a combination of 
      stimulatory and inhibitory factors that modulate hematopoietic progenitor cell 
      proliferation and differentiation. The TaqMan assay and quantitative reverse 
      transcriptase-polymerase chain reaction were used to measure monocyte 
      chemoattractant protein-1 (MCP-1), melanoma stimulatory growth activity, and 
      monokine inducible by interferon-gamma (Mig) (inhibitory chemokines for primitive 
      or megakaryocyte progenitors) mRNA levels in in vitro PIXY and GM-CSF-treated and 
      patient post-FLAC marrow stromal layers. Chemokine mRNA was increased after in 
      vitro GM-CSF and to a lesser extent after PIXY treatment. MCP-1 mRNA levels were 
      fivefold higher in FLAC + PIXY than in FLAC + GM-CSF layers, and Mig mRNA was 
      elevated in FLAC + GM-CSF layers. Thrombopoietin (TPO), insulin-like growth 
      factor I (IGF-I), and IGF-II (stimulatory factors for primitive and megakaryocyte 
      progenitors) mRNA were also measured. TPO mRNA levels were 30% lower in GM-CSF 
      and PIXY-pretreated than in control layers with no decrease in IGF mRNA. TPO mRNA 
      in stromal layers of patients who developed grade 3 thrombocytopenia (platelets < 
      20 x 10(9)/l) during the third cycle of FLAC was only 24% of levels in stromal 
      layers of marrow from other post-FLAC patients. Results demonstrate that patient 
      and in vitro treatment had modulatory effects on TPO and chemokine mRNA 
      expression in marrow stromal layers.
FAU - Schwartz, G N
AU  - Schwartz GN
AD  - Department of Experimental Transplantation and Immunology, Medicine Branch and 
      Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA. 
      gnschwar@cpcug.org
FAU - Kammula, U
AU  - Kammula U
FAU - Warren, M K
AU  - Warren MK
FAU - Park, M K
AU  - Park MK
FAU - Yan, X Y
AU  - Yan XY
FAU - Marincola, F M
AU  - Marincola FM
FAU - Gress, R E
AU  - Gress RE
LA  - eng
PT  - Journal Article
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-3)
RN  - 0 (PIXY321 fusion protein, recombinant)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 67763-97-7 (Insulin-Like Growth Factor II)
RN  - 80168379AG (Doxorubicin)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - 9014-42-0 (Thrombopoietin)
RN  - Q573I9DVLP (Leucovorin)
RN  - U3P01618RT (Fluorouracil)
RN  - CALF protocol
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Bone Marrow Cells/cytology/pathology/*physiology
MH  - Breast Neoplasms/*drug therapy/*pathology
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics
MH  - Chemokines/*genetics
MH  - Cyclophosphamide/administration & dosage
MH  - Cytokines/*pharmacology
MH  - Doxorubicin/administration & dosage
MH  - Female
MH  - Fluorouracil/administration & dosage
MH  - *Gene Expression Regulation/drug effects/immunology
MH  - Granulocyte Colony-Stimulating Factor/pharmacology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology/*therapeutic use
MH  - Humans
MH  - Insulin-Like Growth Factor I/genetics
MH  - Insulin-Like Growth Factor II/genetics
MH  - Interleukin-3/pharmacology/*therapeutic use
MH  - Leucovorin/administration & dosage
MH  - RNA, Messenger/genetics
MH  - Recombinant Fusion Proteins/therapeutic use
MH  - Recombinant Proteins
MH  - Stromal Cells/cytology/drug effects/*physiology
MH  - Thrombopoietin/*genetics
MH  - *Transcription, Genetic/drug effects/immunology
EDAT- 2000/09/29 11:00
MHDA- 2000/10/21 11:01
CRDT- 2000/09/29 11:00
PHST- 2000/09/29 11:00 [pubmed]
PHST- 2000/10/21 11:01 [medline]
PHST- 2000/09/29 11:00 [entrez]
AID - 10.1634/stemcells.18-5-331 [doi]
PST - ppublish
SO  - Stem Cells. 2000;18(5):331-42. doi: 10.1634/stemcells.18-5-331.