Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Relationship between the survival time of L-1210-bearing mice and myelosuppression of normal mice after combination chemotherapy was studied. In a variety of combinations of 6-mercaptopurine, 6-thioguanine, and cyclophosphamide, a combination of cyclophosphamide and 6-thioguanine produced the highest increase in life span (ILS) and the highest number of 60-day survivors of all. In contrast, a combination of 6-mercaptopurine and 6-thioguanine showed as low as ILS as did single agents. A combination of 6-mercaptopurine, cyclophosphamide, and 6-thioguanine exhibited the second best effect on survival time of leukemic mice. However, in myelosuppression as measured by changes in the total number of nucleated cells, in the number of hematopoietic colony-forming cell, and in peroxidase level of femoral bone-marrow, the combination of 6-mercaptopurine and 6-thioguanine showed no more toxicity than the other 2-drug combinations. In addition to these findings, the presence of a striking difference in the cell number in ascitic fluid of leukemic mice among the animals given 6-thioguanine, and those given other 2- or 3-drug combinations may suggest that the difference in the antileukemic activity is not due to the difference in the toxicity against the host, but due to the difference in the activity of direct action of combined drugs on leukemic cells in the peritoneal cavity or in other sites.
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PMID:Effect of drug combination of antitumor activity and myelotoxicity. 96 53

A 30-year-old female was admitted to our hospital complaining of high fever and fatigue. Laboratory findings showed as follows; WBC 41,500/microliter (40% of blasts), Hb 8.5g/dl, platelets 4.4 x 10(4)/microliter. Cytochemical staining of blasts was positive for peroxidase and non-specific esterase with NaF inhibition. Chromosome analysis showed 46, XX, inv (16p+,q-). AML with eosinophilia was diagnosed. During myelosuppression after remission induction therapy, she developed high fever, and did not respond to transfusions. Marrow smears showed the presence of phagocytic histiocytes consisting of 18% total nuclear cells. A diagnosis of reactive histiocytosis (RH) was made. She recovered spontaneously, but suffered two episode of recurrence during subsequent chemotherapy. Reactive histiocytosis is characterized by proliferation of histiocytes which phagocyte blood cells in immunodeficient cases, e.g. a myelosuppressive state after chemotherapy. RH causes high fever and prolonged myelosuppression. It is considered to be one of the poor prognostic factors in AML during chemotherapy, and spontaneous recovery is rare. In this report, the effect of hydrocortisone on histiocytes derived from patient marrow was also investigated in vitro.
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PMID:[A case with AML (M4EO) accompanied by recurrent reactive histiocytosis which showed spontaneous remission]. 802 88

Anthracycline-induced cardiotoxicity is believed to be related to the generation of reactive oxygen species by at least two mechanisms: enzymatic reduction of the quinone with subsequent redox cycling and/or formation of an iron-anthracycline complex capable of intramolecular reduction and redox cycling. Both pathways may lead to the production of superoxide anions and highly reactive metabolites, such as hydroxyl radicals and hydrogen peroxide. As a result, membrane lipid peroxidation may ensue, producing damage in tissues like the heart, which have low antioxidant defenses (superoxide dismutase glutathione and especially, glutathione-peroxidase). Pharmacologic methods of interrupting this cycle have involved numerous antioxidants, such as the sulfhydryls N-acetylcysteine and cysteamine, and the lipophilic vitamin alpha tocopherol. Unfortunately, none of these compounds has been proven to be cardioprotective in patients receiving doxorubicin. In contrast, the water-soluble d-isomer of the iron chelator razoxane, dexrazoxane or ICRF-187, has been shown to reduce doxorubicin-induced cardiomyopathy. This has afforded greater cumulative doses of doxorubicin to be safely administered. The cytoprotective effect is apparently limited to the heart since there is no effect on antitumor efficacy and, unfortunately, no reduction in gastrointestinal toxicity, and with a slight increase in myelosuppression. More recent preclinical studies have also demonstrated cardioprotective activity for the aminothiol amifostine (WR-2721). In vitro, this agent has been shown to scavenge superoxide anions and hydroxyl radicals, the latter effect mediated by the active (dephosphorylated) metabolite, WR-1065. In tumor-bearing mice, amifostine reduces the lethality of high doses of doxorubicin without affecting antitumor activity. Finally, in vitro studies in neonatal rat heart cells have shown direct evidence of anthracycline cardioprotection for both amifostine and WR-1065. Cytoprotective drug levels of either agent were limited to 2.0 microg/mL, which is one tenth of the achievable peak plasma levels in humans. At this concentration, a 15-minute sulfhydryl pretreatment significantly prevented doxorubicin-induced depressions of myocyte adenosine triphosphate levels. Overall, these studies suggest that amifostine may have cytoprotective activity against doxorubicin-induced cardiac damage. Animal studies in a chronically dosed doxorubicin model are indicated; if positive, clinical trials testing this hypothesis will be warranted.
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PMID:Cytoprotective agents for anthracyclines. 878 63

A 30-year-old man with a diagnosis of acute promyelocytic leukemia (APL) was admitted. Laboratory findings were as follows: WBC 32,900/microliter with 88% promyelocytes, Hb 10.4 g/dl, platelets 2.6 x 10(4)/microliter. Coagulation tests revealed DIC. Bone marrow was hypercellular with 91.8% promyelocytes which were strongly positive for peroxidase and positive for alpha-naphthyl butyrate esterase. Cytogenetic study revealed 46, XY, t(15;17) (q22:q11). He was treated with all-trans retinoic acid (ATRA) along with hydroxyurea (HU) and low-molecular weight heparin (LMH). Because his WBC increased to 93,700/microliter on day 6 of ATRA therapy, DCMP chemotherapy was given, while ATRA was withheld. He developed enterocolitis due to myelosuppression. ATRA was restarted along with granulocyte-colony stimulating factor (G-CSF). His WBC rose to 10,400/microliter with a marked, but temporary predominance of myelomonocytes both in peripheral blood and in bone marrow. These myelomonocytoid cells were positive for specific and nonspecific esterase double stainings. Then he entered complete remission. It was of interest that myelomonocytoid differentiation of APL cells was induced by ATRA. The etiology was discussed.
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PMID:[All-trans retinoic acid-induced myelomonocytoid differentiation in acute promyelocytic leukemia]. 919 90

The transfer of drug resistance genes into hematopoietic cells is an experimental approach to protect patients from drug-induced myelosuppression. Because anti-cancer drugs are often administered in combination to increase their clinical efficacy, vectors that express two drug resistance genes are being developed to broaden the spectrum of chemoprotection. We have constructed a bicistronic vector, MFG/GST-IRES-CD (MFG/GIC) coexpressing rat glutathione S-transferase (GST) A3 isoform (rGST Yc1) and human cytidine deaminase (CD). Murine NIH 3T3 fibroblast cells transduced with this vector were evaluated for their resistance to nitrogen mustards and cytosine nucleoside analogs. GIC-transduced polyclonal cell populations (GIC cells) demonstrated marked increases in selenium-independent glutathione peroxidase (peroxidase) and CD activities, as well as increased resistance to melphalan (2.3-fold), chlorambucil (3.4-fold), and cytosine arabinoside (Ara-C) (8.1-fold). After selection with Ara-C, the peroxidase and CD activities of GIC cells were augmented 2.6- and 2.9-fold, respectively, in comparison with unselected cells, and the resistance to melphalan, chlorambucil, and Ara-C was further increased to 3.7-, 5.9-, and 53-fold, respectively. Melphalan selection of GIC cells likewise augmented their peroxidase (2.3-fold) and CD (1.9-fold) activities. GIC cells proliferated in the simultaneous presence of melphalan and Ara-C at drug concentrations that completely inhibited the growth of untransduced cells. The growth rate of unselected GIC cells exposed to the drug combination averaged 18% that of drug-free cultures. The growth rate of GIC cells exposed to the drug combination increased to 30% of controls after Ara-C selection and to 50% after melphalan selection. Our results suggest that retroviral transfer of MFG/GIC may be useful for chemoprotection against the toxicities of nitrogen mustards and cytosine nucleoside analogs.
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PMID:Coexpression of rat glutathione S-transferase A3 and human cytidine deaminase by a bicistronic retroviral vector confers in vitro resistance to nitrogen mustards and cytosine arabinoside in murine fibroblasts. 1083 Jul 23