Subject(s)
Amphotericin B/pharmacology , Antifungal Agents/pharmacology , Candidiasis/drug therapy , Fungemia/drug therapy , Child, Preschool , Female , Humans , Immunocompromised Host/drug effects , Microbial Sensitivity Tests/methods , Neutropenia , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/microbiologyABSTRACT
The aim of this study was to see whether pleiotropic or myeloid hematopoietic growth factors, which do not stimulate normal lymphoid cells, can induce proliferation of blast cells of the acute lymphoid leukemia (ALL) of childhood. Bone marrow cells of 13 children with untreated ALL (nine common ALL, two myeloid antigen positive ALL and two early T-cell ALL) formed colonies of leukemic blast cells in primary methylcellulose cultures. Spontaneous growth was observed in three of 13 cases, whereas phytohemagglutinin-stimulated leukocyte conditioned medium (PHA-LCM), a conventional source of various natural human cytokines, induced colony formation in ten of 13 cases. A similar rate of responsiveness was seen with recombinant human granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF); a combination of these three cytokines induced colony formation in all cases studied. The effect of these growth factors on colony formation seemed to be dose-dependent in some cases. Of the stimuli studied, GM-CSF induced the smallest number of colonies, whereas the effects of G-CSF, SCF and PHA-LCM were similar in this respect. Combination of cytokines proved to be even more efficient in inducing clonal proliferation of leukemic lymphoblasts. In double combinations, G-CSF and GM-CSF as well as G-CSF and SCF were able to potentiate each other's effects. Triple combination of these cytokines mediated the most potent growth stimulus. Our results demonstrate that myeloid and pleiotropic cytokines are able to stimulate clonal proliferation of pediatric leukemic lymphoblasts. This may present a potential hazard to children with ALL while on adjuvant therapy with hematopoietic growth factors. In vitro colony assays performed prior to or in parallel with the administration of hematopoietic growth factors to ALL patients may help to forecast their possible effects on leukemic cells in vivo.
Subject(s)
Bone Marrow Cells/pathology , Carrier Proteins/pharmacology , Cytokines/pharmacology , Growth Substances/pharmacology , Hematopoietic Cell Growth Factors/pharmacology , Neoplastic Stem Cells/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Recombinant Fusion Proteins , Adolescent , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Cells, Cultured , Child , Child, Preschool , Dose-Response Relationship, Drug , Female , Granulocyte Colony-Stimulating Factor/pharmacology , Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , Humans , Infant , Interleukin-3 , Male , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Recombinant Proteins , Tumor Stem Cell AssaySubject(s)
Blood Platelet Disorders/diagnosis , Platelet Function Tests/instrumentation , Thrombasthenia/diagnosis , von Willebrand Diseases/diagnosis , Adenosine Diphosphate , Adolescent , Albinism/blood , Bleeding Time , Blood Platelet Disorders/blood , Child , Collagen , Epinephrine , Evaluation Studies as Topic , Humans , Male , Sensitivity and Specificity , Thrombasthenia/blood , von Willebrand Diseases/bloodABSTRACT
We have examined in mice the effects of mixed ligand treatments with desferrioxamine B (DFOA), Na3Ca-diethylenetriamine pentaacetic acid (DTPA), and DL-penicillamine (PA) on the retention of a mixture of 95Nb and 144Ce. The results show that 95Nb + 144Ce could be mobilized effectively by simultaneous application of specific agents (i.e., DFOA, DTPA) with no decrease in their efficiencies.
Subject(s)
Cerium Radioisotopes/metabolism , Chelating Agents/therapeutic use , Decontamination , Niobium/metabolism , Animals , Deferoxamine/administration & dosage , Drug Therapy, Combination , Male , Mice , Penicillamine/administration & dosage , Pentetic Acid/administration & dosage , Radioisotopes/metabolismABSTRACT
The individual effects of desferrioxamine B (DFOA), Na3Ca diethylenetriaminepentaacetic acid (DTPA), Na-salicylate, DL-penicillamine, and 2-aminoethylisothiouronium bromide hydrobromide, as well as the effect of mixed-ligand treatment on the retention and elimination of 95Nb in mice have been examined. It was found that 95Nb could easily be mobilized by a single dose of DFOA, but the best result was obtained with the DFOA and DTPA combination. Mixed-ligand treatment did not change the deposition characteristics and translocation kinetics of 95Nb.
Subject(s)
Chelating Agents/administration & dosage , Niobium/pharmacokinetics , Radioisotopes/pharmacokinetics , Animals , Chelating Agents/pharmacology , Decontamination/methods , Deferoxamine/administration & dosage , Deferoxamine/pharmacology , Drug Therapy, Combination , Male , Mice , Penicillamine/administration & dosage , Penicillamine/pharmacology , Pentetic Acid/administration & dosage , Pentetic Acid/pharmacology , Sodium Salicylate/administration & dosage , Sodium Salicylate/pharmacology , beta-Aminoethyl Isothiourea/administration & dosage , beta-Aminoethyl Isothiourea/pharmacologyABSTRACT
The individual effect of desferrioxamine-B (DFOA), Na3Ca-diethylene-triaminepentaacetic acid (DTPA), DL-penicillamine (PA) and Na-salicylate (SA) has been examined as well as the effect of mixed-ligand treatment on the retention and elimination of 144Ce in mice. It was found that 144Ce could easily be mobilized by a single dose of DTPA. Mixed-ligand (MLCs) treatment did not change the deposition characteristics and translocation kinetics of 144Ce.
