Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite significant advances in the treatment of acute myeloid leukemia (AML), the majority of patients will succumb to drug-resistant AML. To overcome this resistance, we have developed a novel fusion toxin consisting of the catalytic and translocation subunits of diphtheria toxin (DT388) linked to human granulocyte-macrophage colony-stimulating factor (GM-CSF). In vitro, DT388-GM-CSF demonstrated significant activity against numerous AML cell lines and fresh AML blasts. To determine its in vivo efficacy, we developed an in vivo model of human AML in severe combined immunodeficiency (SCID) mice injected intravenously with 1 x 10(7) HL-60 cells (AML-M2 cell line). The SCID mice developed abdominal masses, infiltration of the liver and bone marrow, and peripheral blasts with a median survival of 42.5 days. We tested DT388-GM-CSF, ara-C, human GM-CSF, and DAB389IL-2, which were injected intraperitoneally on days 2-6 in this model. DT3-GM-CSF significantly improved survival of the SCID mice over Ara-C, DAB389IL-2, or control (P < 0.001). DT388-GM-CSF-treated mice who developed leukemia exhibited no difference in the number of GM-CSF receptors (P = 0.39), ligand affinity (P = 0.77), or sensitivity (P = 0.56) to DT388-GM-CSF as compared to the controls. Frank leukemia in DT388-GM-CSF-treated mice may be due to incomplete penetration of drug into tissues rather than cellular resistance. DT388-GM-CSF is an active therapeutic agent in our SCID mouse model of AML with a unique mechanism of action and differing toxicities than current cytotoxic agents.
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PMID:DT388-GM-CSF, a novel fusion toxin consisting of a truncated diphtheria toxin fused to human granulocyte-macrophage colony-stimulating factor, prolongs host survival in a SCID mouse model of acute myeloid leukemia. 1021 72

The objective of this study was to investigate the possible effects of dexamethasone treatment on the immunoreactivity of dendritic cells in patients with chronic idiopathic thrombocytopenic purpura (ITP). Thirty-six newly diagnosed patients with chronic ITP received an oral high dose of dexamethasone (HD-DXM) at single daily doses of 40 mg for 4 consecutive days. The CD14 leukocytes isolated from the 21 remission patients and 10 normal controls were stimulated by recombinant human granulocyte-macrophage colony-stimulating factor and rhIL-4. The surface antigens of the dendritic cells were analyzed by flow cytometry and the level of IL-12p70 in the supernatant was detected by enzyme-linked immunosorbent assay. In ITP patients, the expression of both CD80 and CD86 in dendritic cells were significantly increased compared with those of the normal controls (51.60 +/- 13.47 vs. 36.03 +/- 15.43%, 61.50 +/- 15.93 vs. 40.28 +/- 11.49%, respectively; P < 0.05). After HD-DXM treatment, both CD80 and CD86 were decreased to levels comparable to normal controls (P > 0.05). The level of IL-12p70 in ITP patients was significantly higher (67.52 +/- 14.43 pg/ml) than the controls (39.78 +/- 10.03 pg/ml, P < 0.05). After treatment, IL-12p70 was reduced to 43.90 +/- 8.49 pg/ml with no significant differences between ITP group and control (P > 0.05). Dendritic cells and their cytokine secretion play important roles in ITP, and DXM may achieve its therapeutic effect on ITP by inhibiting immune responses through suppressing the function of dendritic cells.
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PMID:Dexamethasone inhibits immunoreactivity of dendritic cells in patients with chronic idiopathic thrombocytopenic purpura. 2058 60