Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The novel endogenous cannabinoid 2-arachidonoylglycerol (2-AG) was rapidly inactivated by intact rat basophilic leukaemia (RBL-2H3) and mouse neuroblastoma (N18TG2) cells through diffusion/hydrolysis/reacylation processes. The hydrolysis of 2-AG was inhibited by typical esterase inhibitors and by more specific blockers of 'fatty acid amide hydrolase' (FAAH), the enzyme catalysing the hydrolysis of the other 'endocannabinoid', anandamide (AEA). No evidence for a facilitated-diffusion process was found. A 2-AG-hydrolysing activity was detected in homogenates from both cell lines, with the highest levels in membrane fractions. It exhibited an optimal pH at 10, and recognized both 2- and 1(3)- isomers of monoarachidonoylglycerol with similar efficiencies. The apparent Km and Vmax values for -3H-2-AG hydrolysis were 91 microM and 29 microM and 2.4 and 1.8 nmol.min-1.mg of protein-1 respectively in N18TG2 and RBL-2H3 cells. [3H]2-AG hydrolysis was inhibited by Cu2+, Zn2+ and p-hydroxymercuribenzoate, and by 2- or 1(3)-monolinoleoyl- and -linolenoyl-glycerols, but not by the oleoyl, palmitoyl and myristoyl congeners. Purified fractions from solubilized membrane proteins catalysed, at pH 9.5, the hydrolysis of 2-AG as well as AEA. Accordingly, AEA as well as FAAH inhibitors, including arachidonoyltrifluoromethyl ketone (ATFMK), blocked [3H]2-AG hydrolysis by N18TG2 and RBL-2H3 membranes, whereas 2-AG inhibited [14C]AEA hydrolysis. FAAH blockade by ATFMK preserved from inactivation the 2-AG synthesized de novo by intact N18TG2 cells stimulated with ionomycin. These data suggest that FAAH may be one of the enzymes deputed to the physiological inactivation of 2-AG, and create intriguing possibilities for the cross-regulation of 2-AG and AEA levels.
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PMID:The novel endogenous cannabinoid 2-arachidonoylglycerol is inactivated by neuronal- and basophil-like cells: connections with anandamide. 951 56

We investigated the effect of diphenylthiocarbazone (dithizone) and its structurally related compounds on the differentiation and apoptosis of two human myeloid leukemia cell lines. Dithizone caused a time- and concentration-dependent induction of differentiation in both the promyelocytic leukemia cell line HL-60 cells and the myeloblastic leukemia cell line ML-1 cells, as measured by nitroblue tetrazolium (NBT) reducing activity. Morphological changes and esterase activities confirmed that this differentiation took place. The induction of differentiation required the addition of dithizone to the culture medium for at least 12 h. The differentiation inducing activity was inhibited by the preincubation of dithizone with various metal ions such as Pb2+, Zn2+, Cu2+ and Mn2+ ions, but not with Fe3+ and Mg2+ ions. In addition, the DNA extracted from dithizone-treated HL-60 cells showed a typical ladder pattern characteristic of apoptosis in agarose gel electrophoresis. A quantitative analysis of DNA fragmentation revealed that this apoptosis was concentration- and time-dependent in both the HL-60 and ML-1 cells. Dithizone-induced apoptosis was also inhibited by preincubation with Mn2+ ions, but not with Mg2+ ions. These results indicate that dithizone induces both differentiation and apoptosis in HL-60 and ML-1 cells through a unique mechanism including metal chelation.
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PMID:Induction of differentiation and apoptosis by dithizone in human myeloid leukemia cell lines. 965 26

Tax-1, the transcriptional activation protein of human T-cell leukemia virus-1, increases transcription from the human T-cell leukemia virus-1 long terminal repeat and specific cellular promoters through interactions with cellular DNA-binding proteins. The Tax response elements (TxREs) of the long terminal repeat resemble cAMP response elements (CREs), the target of cAMP-responsive element-binding protein (CREB). CREB binds the TxRE with reduced affinity; however, the interaction is specifically enhanced by Tax. Using a fluorescence quenching method, we determined that CREB dimerizes in the absence of DNA, and that Tax does not enhance dimerization. DNA footprinting of the TxRE with 1, 10-phenanthroline-copper complex demonstrates that Tax contacts DNA and extends the footprint of CREB to GC-rich sequences flanking the core CRE-like element. The minor groove-binding drug chromomycin A3, but not distamycin A, disrupted Tax-enhanced CREB binding to the TxRE. Substitution of the guanine-rich sequences flanking the core of the TxRE with inosine residues also blocked the Tax effect. Finally, the IC-substituted TxRE binds CREB with increased affinity, suggesting flanking DNA influences the binding of CREB to the core CRE-like element. These data indicate that Tax does not regulate DNA binding of CREB by altering dimerization, but rather enhances DNA binding by additionally interacting with the minor groove of flanking DNA sequences.
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PMID:The human T-cell leukemia virus-1 transcriptional activator Tax enhances cAMP-responsive element-binding protein (CREB) binding activity through interactions with the DNA minor groove. 966 14

Reverse transcriptase plays an essential role in the early steps of the replicative cycle of retroviruses. Because of the resistance against nucleoside analogue inhibitors such as 3'-azido-2',3'-dideoxythymidine, the importance of the investigation of non-nucleoside analogue inhibitors is increasing. We have investigated the influence of trifluoperazine (TFP--a species of phenothiazines) and its newly prepared TFP-metal complexes (TFP-VO(IV), TFP-Cu(II), TFP-Ni(II), TFP-Pd(II), TFP-Sn(IV)). The compounds were tested on Moloney murine leukemia virus reverse transcriptase assay. The inhibitory effect of metal complexes was higher than that of TFP. TFP-VO(IV) showed higher effectiveness compared the added effect of parent tricyclic chemical and metal. Therefore we concluded that the improved biological action depends on the formation of metal complexes. This phenothiazine and its metal coordination complexes could become a new non-nucleoside analogue group of compounds inhibiting the retrovirus replication.
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PMID:Trifluoperazine and its metal complexes inhibit the Moloney leukemia virus reverse transcriptase. 967 43

Contraception selection poses special challenges to women with pre-existing medical problems and clinicians often lack the knowledge to counsel these women. The IUD represents an excellent option for many US women with medical problems. Because IUDs have no direct systemic effects other than increasing circulating immunoglobulins and possibly copper ions, they are unlikely to affect a woman's underlying disease process or to interact with medications used in disease treatment. Currently available IUDs may be appropriate for women with cardiovascular disease, diabetes mellitus with vascular disease, hematologic disorders, neurologic conditions, and psychiatric disorders. Other candidates for IUD use include women with a history of breast cancer or other hormone-sensitive cancers, active liver disease, hypertriglyceridemia, a sensitivity to hormonal contraception, and smokers over 40 years old. IUDs are contraindicated in women with diseases that increase their vulnerability to infection (e.g., AIDS, leukemia, and intravenous drug abuse), diseases or medications that produce profuse uterine bleeding, and conditions that distort the uterine cavity. Given the deleterious impact of unintended pregnancy on the clinical course of many diseases, information on contraception for women with pre-existing medical conditions should be more broadly disseminated among clinicians.
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PMID:Intrauterine device practice guidelines: medical conditions. 980 94

Although N-acetylcysteine is an antioxidant which has been expected to be a cancer chemopreventive agent, its safety and risk assessment have not been evaluated. N-acetylcysteine increased the amount of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic oxidative DNA lesion, in human leukemia cell line HL-60, whereas the amount of 8-oxodG in HP100, which is a hydrogen peroxide (H(2)O(2))-resistant cell line derived from HL-60, was not increased. To clarify the mechanism of cellular DNA damage, we investigated DNA damage and its site specificity induced by N-acetylcysteine, using (32)P-labeled DNA fragments obtained from the human p53 tumor suppressor gene and the c-Ha-ras-1 protooncogene. N-acetylcysteine induced extensive DNA damage in the presence of Cu(II). The DNA cleavage was enhanced by piperidine treatment, suggesting that N-acetylcysteine plus Cu(II) caused not only deoxyribose phosphate backbone breakage but also base modification. N-acetylcysteine plus Cu(II) frequently modified thymine and guanine residues. Bathocuproine, a specific Cu(I) chelator, and catalase inhibited the DNA damage, indicating the participation of Cu(I) and H(2)O(2) in the DNA damage. Typical hydroxyl radical scavengers did not inhibit N-acetylcysteine plus Cu(II)-induced DNA damage, whereas methional completely inhibited it. These results suggest that reactive species derived from the reaction of H(2)O(2) with Cu(I) participates in N-acetylcysteine plus Cu(II)-induced DNA damage. The content of 8-oxodG in calf thymus DNA was increased by N-acetylcysteine in the presence of Cu(II). The present study has demonstrated that N-acetylcysteine could induce metal-dependent H(2)O(2) generation and, subsequently, damage to cellular and isolated DNA. Therefore, it is reasonable to consider that N-acetylcysteine may have the dual function of carcinogenic and anti-carcinogenic potentials. This work requires further studies on safety and risk assessment of N-acetylcysteine.
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PMID:N-acetylcysteine, a cancer chemopreventive agent, causes oxidative damage to cellular and isolated DNA. 1042 96

Three pediatric patients with refractory anemia with ringed sideroblasts (RARS) are presented. Bone marrow aspirates were examined using Romanowsky and Prussian blue iron stains in all three patients, and electron microscopic analysis was performed in one patient. All three patients had cytogenetic analysis of the bone marrow. Other studies included analysis of serum iron, total iron-binding capacity, ferritin, copper, vitamins B6 and B12, and folate levels. Antibody titers to Parvovirus, HIV, and other viruses were measured. The patients had contrasting clinical courses. Patients 1 and 2 had dysplastic hematopoietic features and cytogenetic findings (with either partial or one allele loss of chromosome 7), suggestive of myelodysplastic syndrome. Patient 1 experienced acute myeloid leukemia (AML) and had a good response to AML-directed therapy. Patient 2 had prolonged cytopenias and underwent bone marrow transplantation (BMT). Patient 3 had features suggestive of refractory anemia associated with mitochondrial cytopathy, including normal cytogenetics with pronounced vacuolization of marrow precursors. His anemia regressed spontaneously a few months after diagnosis. These patients represent two subgroups of pediatric RARS. Patients with the myelodysplastic syndrome (MDS) type may progress to cytopenias or leukemia and may require aggressive therapy; the type is characterized by clonal cytogenetic findings. The non-MDS type, which may relate to mitochondrial cytopathy, often shows spontaneous regression and requires only supportive treatment; it has normal cytogenetic findings.
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PMID:Refractory anemia with ringed sideroblasts in children: two diseases with a similar phenotype? 1052 57

The activity of casiopeina II [Cu(1,4-dimethyl-1, 10-phenanthroline)(glycine)NO(3)], a novel anticancer agent, was tested in two cell lines, L1210 murine leukaemia, CH1 human ovarian carcinoma, cisplatin-resistant and sensitive. Exposure of the cells to a range of concentrations of casiopeina II indicates that this copper complex kills cells by apoptosis and necrosis. Condensed chromatin and nuclear fragmentation were observed after exposure to casiopeina II. The caspase inhibitor Z-Val-Ala-DL-Asp-fluoromethylketone (Z-VAD-FMK) almost completely inhibited apoptosis induced by cisplatin; however, casiopeina II-induced apoptosis was inhibited only by 50-70%. These data are consistent with caspase activation (measured by Z-Asp-Glu-Val-Asp-7-amino-4-trifluoromethylcoumarin; Z-DEVD-AFC) by casiopeina II and cisplatin and confirm that caspases are activated in the apoptotic cell death induced by casiopeina II. DNA fragmentation was observed in L1210 cells, but not in CH1 cells. No difference in susceptibility to induction of apoptosis by casiopeina II was found between sensitive and cisplatin resistant cells. In this work we show that the novel copper-based antineoplastic agent casiopeina II is highly active against murine and human cancer cell lines, including cell lines resistant to cisplatin.
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PMID:Induction of apoptosis by a novel copper-based anticancer compound, casiopeina II, in L1210 murine leukaemia and CH1 human ovarian carcinoma cells. 1069 55

Free radicals are highly reactive species that have been implicated in the pathogenesis of many diseases. Reactive oxygen species can initiate lipid peroxidation and DNA damage leading to mutagenesis, carcinogenesis and cell death, if the antioxidant system is impaired. This study was undertaken to examine the prevalence of oxidative stress and the role of antioxidant defence in untreated leukemia patients. The generation of superoxide anion and hydrogen peroxide by leukocytes, plasma malondialdehyde levels, red cell copper zinc superoxide dismutase (Cu-Zn SOD) and glutathione peroxidase (GSH-PX) activities were determined in 30 patients with different types of leukemias prior to therapy. The superoxide anion generation by polymorphonuclear leukocytes was found to be significantly increased in leukemia patients especially those with acute lymphocytic and nonlymphocytic leukemias, while the hydrogen peroxide levels were comparable to the control values. Plasma lipid peroxidation products in untreated leukemia patients were in the normal range. Red cell Cu-Zn SOD and GSH-PX activities were significantly increased and showed no correlation with the hemoglobin content. Although superoxide generation was high, lipid peroxide levels were normal in these patients. This might be due to the increased activities of the antioxidant enzymes (SOD, GSH-PX) which counteract lipid peroxidation. Increased free radical generation, especially superoxide anion in leukemia patients and increased antioxidant defence enzymes, which is an adaptive protective response, are indicative of mild oxidative stress. There were no significant differences for the parameters cited above between different types of leukemias, suggesting that the changes are not specific to the type of leukemia.
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PMID:Free radicals antioxidant enzymes and lipid peroxidation in different types of leukemias. 1069 22

Wilson disease is an autosomal recessively inherited disease of copper metabolism and is characterized by liver and central nervous system dysfunction. The heterozygote carrier state rate is about one in 90 persons and the incidence of the disease is about 30 in 1,000,000. Although leukemia is the most common form of childhood malignancies, the probability of the presence of Wilson disease and acute lymphoblastic leukemia in the same patient is very low. We report an unusual case of a child with Wilson disease who developed acute lymphoblastic leukemia in three months.
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PMID:Acute lymphoblastic leukemia in a child with Wilson disease. 1110 31


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