Platelet factor 4 (PF4) has been recognized as an inhibitor of myeloid progenitors. However, the mechanism of action of this chemokine remains poorly understood. The present study was designed to determine its structure/function relationship. A series of peptides overlapping the C-terminal and central regions of PF4 were analyzed in vitro for their action on murine hematopoietic progenitor grow...

We have investigated the effects of in vivo treatment with flt3 ligand (FL) on murine hematopoiesis, including mobilization of progenitors into the peripheral blood (PB). Mice were injected once daily with 10 micrograms recombinant human FL for 15 days. On days 3, 5, 8, 10, 15, and 22, mice were killed and analyzed for the number of leukocytes and colony-forming units (CFU) in bone marrow (BM),...

Interferons (IFNs) have been shown to suppress the proliferation of human pluripotent hematopoietic progenitor cells, CFU-GEMM, and committed erythroid (BFU-E, CFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. However, no information is yet available concerning the effect of IFNs on human megakaryocytic progenitor cells CFU-Mk. Furthermore the mechanisms underlying the inhibitory act...

Erythropoietin (EPO) is the principal growth factor regulating the production of circulating erythrocytes. We introduced null mutations into both Epo and the EPO receptor (EpoR) gene. Both heterozygotes appeared normal. Homozygous animals exhibited reduced primitive erythropoiesis and died around embryonic day 13, owing to failure of definitive fetal liver erythropoiesis. Both types of mutation...

8-Carbamoyl-3-methylimidazo(5,1-d)-1,2,3,5-tetrazin-4(3H)-one (temozolomide) is a new imidazole tetrazinone compound with promising preclinical and clinical activity in nitrosourea-sensitive and -resistant models and manageable toxicity in Phase I and II clinical trials. In this study, we investigated the antiproliferative activity of temozolomide against a large variety of human tumors taken d...

Erythropoietin (Epo) response and binding was assessed in purified murine CFU-E and their descendants. Several features emerged. First, Epo on CFU-E is in rapid flux: Half-time for 125I-Epo internalization is approximately four to five minutes. Second, computer-aided Scatchard analyses indicate that greater than 70 high-affinity Epo-receptor sites on anemic animal CFU-E are sometimes already oc...

Peripheral blood progenitor cells (PBPC) are increasingly being used in the clinic as a replacement for bone marrow (BM) in the transplantation setting. We investigated the capacity of several different growth factors, including human flt3 ligand (FL), alone and in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF ) or granulocyte colony-stimulating factor (G-CSF ), to m...

This study was conducted to identify tumor types warranting Phase II clinical trials of oxaliplatin using the human tumor cloning assay. Oxaliplatin was tested at concentrations ranging from 0.5 to 50.0 microg/ml in 1-h and 14-day continuous exposures along with 1.4 microg/ml carboplatin and 0.2 microg/ml cisplatin for comparison. We defined in vitro response as tumor growth inhibition >50% of ...

BACKGROUND Several bone marrow-derived cell populations may have angiogenic activity, including cells termed endothelial progenitor cells. Decreased numbers of circulating angiogenic cell populations have been associated with increased cardiovascular risk. However, few data exist from large, unselected samples, and the genetic determinants of these traits are unclear. METHODS AND RESULTS We e...