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

The protective action of amifostine (Ethyol, US Bioscience, Inc. West Conshohocken, PA) against the toxic effects of cyclophosphamide derivatives on the normal progenitor/stem cell pool was investigated. Early and late normal progenitor/stem cells were studied in the presence of placenta-conditioned medium (placenta-conditioned medium-granulocyte-macrophage colony-forming units); in the presence of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin-3, erythropoietin, stem cell factor (5R-CFU-GM); stimulated granulocyte-macrophage colony-forming and in a long-term culture-initiating cell assay. The preservation of an antileukemic effect was investigated by growing leukemic progenitor cells in the presence of phytohemagglutinin and leukocyte feeder layer with or without 25u interleukin-2. In 10 of 13 cases, a statistically significant (P < .05) protective effect was found on PCM-granulocyte-macrophage colony-forming units, in four of 10 cases on factor-stimulated granulocyte-macrophage colony-forming units, and in two of six cases on long-term culture-initiating cell. In contrast, amifostine exhibited no protective effect (none of nine cases) on leukemic progenitor cells. From the experimental data, it seems that amifostine is able to protect human normal progenitor/stem cells from cyclophosphamide derivative toxicity, while preserving their antileukemic effects. The therapeutic usefulness of such protection in autologous bone marrow transplantation with purged marrow is obvious.
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PMID:Comparative effects of amifostine (Ethyol) on normal hematopoietic stem cells versus human leukemic cells during ex vivo purging in autologous bone marrow transplants. 797 73

Thrombocytopenia is a manifestation of hematopoietic toxicity that, at present, can be treated only with platelet transfusions. Thrombocytopenia is a dose-limiting toxicity for carboplatin, mitomycin-C, and other agents, and becomes dose limiting when granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor are used with some chemotherapeutic regimens; thus, strategies to reduce thrombocytopenia are needed. While clinical trials have begun using hematopoietic growth factors that have shown promising preclinical effects on thrombocytopenia, alternative approaches to modifying therapy-related thrombocytopenia are also being developed. Amifostine is a pro-drug that is metabolized to a thiol, WR-1065, which functions to selectively protect normal tissues from the toxic effects of ionizing radiation, alkylating agents, platinating agents, and other cytotoxic compounds. Results from a randomized clinical trial have shown that amifostine reduces mitomycin-induced thrombocytopenia in patients with refractory colorectal cancer. The results of phase I studies of the combination of amifostine and carboplatin suggest that amifostine could modify the toxicity of the platinum compound. Two randomized clinical trials using amifostine and carboplatin have also been reported. In one, the median platelet nadir of all cycles was lower in the amifostine-treated patients; in the other, more profound thrombocytopenia was produced by a higher carboplatin dose, but platelet recovery was more rapid in the amifostine-treated patients. In both of these trials, survival of non-small cell lung cancer patients who received both amifostine and carboplatin was longer than in those treated with carboplatin alone, suggesting that amifostine does not inhibit the antitumor effects of carboplatin. Further studies of amifostine with carboplatin and combination chemotherapy regimens in which thrombocytopenia is dose limiting should be undertaken, as should clinical investigations of amifostine in conjunction with hematopoietic growth factors.
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PMID:Amifostine and chemotherapy-related thrombocytopenia. 878 67