Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The characteristics of cyclophosphamide-induced suppression of established ccll mediated immunity were studied in guinea pigs previously senstized to tuberculin. Cyclophosphamide treatment for 5 days produced a dose-dependent peripheral lymphoctopenia and disproportionatley greater neutrophenia which was particularly striking at high doses of 20 mg/kg per day(approximaetly 200 mg/kg-2 per day). Lymphoctes remianing in the circulation of cyclophosphamide treeated aniamls showed a doses-dependent reduction to both in vitro proliferactive and macrophage migration inhibitory factor responses to tuberculin compared to lymphocte responses of controls. Proliferative responses to phytohemaggultinin and concanavalin a were not significatly suppressed. Additional studies showed that cyclophosphamide suppressed the porliferactive and migration inhibitroy factor responses to tuberculin of lymph node and splenic as well as cirulating lymphocte populations. These studies showed that relatively short-term cyclophospamide administration produced immunosuppresion by quantitative as well as qualitative changes in lymphocyte populations. Significant suppresion of lymphocte function, howerver, was achived only with doses of cyclophoshamide which also produced a severe neutropenia.
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PMID:Cyclophosphamide suppression of established cell-mediated immunity. Quantitative vs. qualitative changes in lymphocyte populations. 109 12

Variability in the efficacies and toxicities of anticancer agents is a major problem. We hypothesized that polymorphisms in cytokine gene promoters may underlie genetic susceptibility to chemotherapy-induced toxicities in the Japanese. DNA was extracted from 100 patients undergoing 5-fluorouracil plus cisplatin chemotherapy. We used a case-only design to evaluate the relation between toxicities and cytokine promoter gene polymorphisms. The following polymorphisms were genotyped: tumor necrosis factor (TNF)-alpha-1031T/C, interleukin (IL)-1beta-511C/T, IL-6-634C/G, IL-10-819T/C, IL-18-137G/C, macrophage migration inhibitory factor -173G/C, and 86-basepair variable numbers of tandem repeat in intron 2 of the IL-1 receptor antagonist. The frequency of the IL-6-634 GC and GG genotypes was significantly higher in patients with grades 1-4 leukopenia (P=0.003; Crude-odds ratios (Cr-OR) =4.0), neutropenia (P=0.0051; Cr-OR=3.6), or thrombocytopenia (P<0.0001; Cr-OR=6.1) than in patients without these toxicities. Similarly, the frequency of the IL-1beta-511 TC and TT genotypes and the frequency of the TNF-alpha-1031 TT genotype were significantly higher in patients with grades 1-4 thrombocytopenia (P=0.015; Cr-OR=2.9) and stomatitis (P=0.02; Cr-OR=3.1), respectively. Multivariate analysis of factors such as age, sex, disease type, purpose of the chemotherapy, use of radiotherapy, and cytokine promoter gene polymorphisms showed polymorphisms to be significant predictors of toxicity. Our results suggest that polymorphisms in cytokine gene promoters may be associated with susceptibilities to leukopenia, neutropenia, thrombocytopenia and stomatitis in patients treated with 5-fluorouracil plus cisplatin.
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PMID:Relation between cytokine promoter gene polymorphism and toxicity of 5-fluorouracil plus cisplatin chemotherapy. 1682 Sep 19