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)

To establish which constituents of blood influence the NMR relaxation time T1 of water protons in malignant blood diseases, 55 blood samples were studied (20 from healthy donors and 35 from patients with leukaemia, myelofibrosis and multiple myeloma). Relaxation time measurements were performed at 19.8 MHz resonance frequency and at a temperature of 33 +/- 1 degree C. There is a significant elevation of T1 over the normal level in whole blood, packed cells, and plasma of patients with blood disease. The relaxation rate R1 (= 1/T1) depends very strongly on the ratio of dry solids to water, which is in accordance with the three-state fast-exchange relaxation model.
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PMID:The spin-lattice relaxation time in the blood of healthy subjects and patients with malignant blood disease. 711 98

A novel antibiotic, prothracarcin was isolated from the culture broth of Streptomyces umbrosus subsp. raffinophilus DO-62. The antibiotic has the molecular formula of C14H14N2O and belongs to the pyrrolo [1,4]benzodiazepine antibiotics. Its structure has been elucidated by mass and NMR spectra. It is active against Gram-positive and Gram-negative bacteria and experimental murine tumor sarcoma 180 and leukemia P388.
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PMID:Prothracarcin, a novel antitumor antibiotic. 714 14

7-(2,3-Epoxypropoxy)actinomycin D has been synthesized along with its major companion product, 7-(2,3-dihydroxypropoxy)actinomycin D. They were characterized by UV-visible and CD spectra and by NMR studies. According to UV-visible absorptiometry, circular dichroism, and thermal denaturation studies, they bind to DNA in a manner that is comparable to actinomycin D. The analogues are, like actinomycin D, extremely cytotoxic to human lymphoblastic leukemic cells (CCRF-CEM) in vitro but are significantly less toxic than actinomycin D to normal CDF1 mice is vivo. Unlike actinomycin, these analogues are metabolized in rats, and the metabolites are excreted in rat urine at a rapid rate. Compared to actinomycin D, the antitumor activity of the 7-(2,3-epoxypropoxy)actinomycin analogue against P-388 leukemia in mice is decidedly superior, and the therapeutic index is improved several fold.
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PMID:Carbon-7 substituted actinomycin D analogues as improved antitumor agents: synthesis and DNA-binding and biological properties. 714 58

The antitumor activity of various platinum(II) complexes of 1,2-cyclohexanediamine and 2-(aminomethyl)cyclohexylamine isomers against leukemia P388 was evaluated by means of the platinum analogue study protocol recommended by the National Cancer Institute. For the former complexes, trans isomers are more efficacious than the corresponding cis isomers. For the latter complexes, cis isomers seem to be somewhat more active than trans isomers. 2-(Aminomethyl)cyclohexylamine platinum complexes exhibited higher activity than 1,2-cyclohexanediamine complexes in this tumor system. These findings encouraged us to determine the structural differences between 1,2-cyclohexanediamine and 2-(aminomethyl)cyclohexylamine complexes. Their structures of platinum complexes were elucidated from circular dichroism and 13C NMR spectral analyses, and it has been concluded that the cyclohexane ring of cis-1,2-cyclohexanediamine is nearly perpendicular to the chelate ring, while both rings of trans-1,2-cyclohexanediamine and trans-2-(aminomethyl)cyclohexylamine complexes lie in a common plane. The structure of cis-2-(aminomethyl)cyclohexylamine complexes is flexible, and the cyclohexane ring is not perpendicular to the chelate ring. The coplanarity of trans isomers and the flexibility of cis-2-(aminomethyl)cyclohexylamine complexes allow them easy approach to the target DNA. However, the perpendicular ring of cis-1,2-cyclohexanediamine complexes would prevent their interactions with dna molecules due to the steric hindrance.
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PMID:Relation of conformation to antitumor activity of platinum(II) complexes of 1,2-cyclohexanediamine and 2-(aminomethyl)cyclohexylamine isomers against leukemia P388. 724 8

Haloacetamido analogues (fluoro, chloro, and bromo) of 2-deoxy-2acetamido-D-mannose and their tetra-O-acetates were prepared from D-mannosamine hydrochloride, with either chloroacetic or bromoacetic anhydride or by dicyclohexylcarbodiimide-activated condensation with fluoroacetate followed by acetylation. Comparative specific rotations and 13C and 1H NMR spectra were consistent with a beta configuration for the tetra-O-acetylated derivatives, 1,3,4,6-Tetra-O-acetyl-2-deoxy-2-(bromoacetamido)-beta-D-mannose and the corresponding analogue of glucose inhibited [3H]thymidine incorporation into mouse L1210 leukemia cells by 50% (IC50) at concentrations between 6 and 9 microM. 1,3,4,6-Tetra-O-acetyl-2-deoxy-2-(chloroacetamido)-beta-D-mannose was 3-fold more active in the thymidine-incorporation assay (143 +/- 24 microM, IC50) than was the corresponding analogue in the glucose series (425 +/- 62 microM; p = 0.05). All of the haloacetamido free sugars, as well as the tetra-O-acetates of the fluoroacetamido analogues in the glucose, galactose, and mannose series, were inactive in the thymidine incorporation assay at 1mM. In the mannose series the tetra-O-acetylated chloroacetamido and bromoacetamido analogues, as well as the bromoacetamido free sugar, could be administered at relatively high in vivo tolerated doses compared to the corresponding analogues in the galactose and glucose series. These three mannose analogues produced high proportions of cures of Ehrlich tumor-bearing B6D2F1 mice, whereas in the galactose and glucose series only the tetra-O-acetylated bromoacetamido analogues had previously produced in vivo chemotherapeutic activity.
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PMID:Haloacetamido analogues of 2-amino-2-deoxy-D-mannose. Syntheses and effects on tumor-bearing mice. 727 92

Hydrogenolysis of 3-(benzyloxy)cyclophosphamide (10) using Pd/C catalyst and ethyl acetate as solvent leads to the formation of 3-hydroxycyclophosphamide (3, approximately 20%) and cyclophosphamide (1, approximately 10%), accompanied by regioselective hydrogen-exchange reactions at the C-4 and C-5 positions in 3 and 1. A variety of oxidizing reagents and liver microsomal incubation failed to provide evidence (31P NMR) for conversion of 1 into 3, whereas identical incubation of 3 led to its reduction to 1. Compound 3 is stable at pH 6.5-8.2, 37 degrees C, and exhibits anticancer activity comparable to 1 when tested against L1210 leukemia in mice. Data are discussed with regard to a previously reported suggestion that metabolism of 1 may involved oxidation to give 3 followed by rearrangement of 3 to 2.
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PMID:Synthesis of 3-hydroxycyclophosphamide and studies related to its possible role in the metabolism of cyclophosphamide. 731 Aug 17

A new class of tricyclic nucleosides in which the aglycon has a linear [6:5:6] geometry has been synthesized using certain pyrrolo[2,3-d]pyrimidine nucleosides as the starting materials. An adenosine-adenosine analogue (12) has been prepared from 6-aminotoyocamycin using two different synthetic routes. An adenosine-guanosine analogue (4) and several adenosine-6-mercaptopurine ribonucleoside-type tricyclic nucleoside derivatives have also been synthesized. Structural assignments have been based on 1H NMR spectral studies, as well as an unequivocal chemical proof of structure. An interesting chemical shift for the 2' hydrogen of certain tricyclic nucleosides was observed and is discussed. The in vitro cytotoxicity of these nucleosides against leukemia L-1210 has been determined. The in vivo evaluation of these tricyclic nucleosides against mouse leukemia will also be discussed.
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PMID:Synthesis of certain [6:5:6] linear tricyclic nucleosides as potential antitumor agents. 745 64

Human T-lymphotropic virus type 1 (HTLV-I) is a retrovirus associated with adult T-cell leukemia/lymphoma, and the virus infection constitutes a growing public health problem. In a continuing effort to engineer conformationally dependent HTLV-I epitopes that elicit a protective immune response, we have examined the role and functional importance of carbohydrate moieties in specific immune recognition and antibody responses. There have been several reports of the importance of N-linked virus glycosylation in the formation of neutralizing antibodies. Residues 230-257 is predicted to encode two beta-turn/loop regions at 240-244 (LYGPN), 248-257 (VPSSSSTPL) and a glycosylation site at N-244 (NVS). We have successfully engineered and synthesized the 233-253 sequence of gp46 of HTLV-1 with and without GlcNAC at Asn244. Circular dichroism spectroscopy and proton NMR showed the presence of beta-turn conformation in both peptide constructs. Chimeras of the glycosylated and non-glycosylated epitope with promiscuous T-cell epitope were synthesized and shown to elicit high titered antibodies in rabbits specific for the immunogen (SC1MVF and SC2MVF) and the B cell epitope 233-253. Additionally, antibodies to the glycosylated form of the peptide recognized the HTLV-I envelope precursor in radioimmunoassay precipitation assay and react with HTLV-I whole virus preparations in ELISA.
Leukemia 1995 Oct
PMID:Glycosylation-dependent peptide antigenic determinants of env gp46 HTLV-1. 747 6

Benzene is a carcinogen in rodents and a cause of bone marrow toxicity and leukemia in humans. p-Benzoquinone (p-BQ) is one of the stable metabolites of benzene, as well as of a number of drugs and other chemicals. 2'-Deoxycytidine (dC) and 2'-deoxyadenosine (dA) were allowed to react with p-BQ in aqueous solution at pH 7.4 and 4.5. The yields were considerably higher at pH 4.5 than at pH 7.4, as indicated by HPLC analysis. The desired products were isolated by column chromatography on silica gel or cellulose. Identification was done by FAB-MS, 1H NMR, and UV spectroscopy. The reaction of p-BQ with dC and dA at pH 4.5 produced the exocyclic compounds 3-hydroxy-1,N4-benzetheno-2'-deoxycytidine (p-BQ-dC), and 9-hydroxy-1,N6-benzetheno-2'-deoxyadenosine (p-BQ-dA), respectively, in a large scale and high yield. These adducts have been previously made in a microgram scale as the 3'-phosphate for 32P-postlabeling studies of their incidence in DNA. The p-BQ-dC and p-BQ-dA adducts have, in addition to the two hydroxyl groups of deoxyribose, one newly formed hydroxyl group at the C-3 or C-9 of the exocyclic base of each product respectively. Incorporation of these adducts into oligonucleotides as the phosphoramidite requires the protection of all three hydroxyl groups in these compounds. The exocyclic hydroxyl on the base has been successfully protected by acylation after protecting the 5'- and the 3'-hydroxyl groups of the sugar moiety with a 4,4'-dimethoxytrityl group and a cyanoethyl N,N-diisopropylphosphoramidite group, respectively. For the first time, to our knowledge, the fully protected phosphoramidites of p-BQ-dC and p-BQ-dA were prepared and incorporated site-specifically into a series of oligonucleotides. The coupling efficiency was very high (> 98%). However, deprotection of the DNA oligomers with ammonia produced only 50% of the desired oligomers containing the adduct. In contrast, when 10% of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in methanol at room temperature was used, only the desired oligomers were detected by HPLC. Thus, by deprotecting the oligomers with methoxide ions (DBU/methanol) and avoiding the use of ammonia, a high yield of modified DNA was obtained. After purification of these oligomers by HPLC, they were hydrolyzed enzymatically and analyzed by HPLC, which confirmed the base composition and the incorporation of the adducts. The mass spectroscopic analysis of the DNA oligomers was confirmed by electrospray MS. These oligomers are now under investigation for their biochemical properties.
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PMID:Large scale synthesis of p-benzoquinone-2'-deoxycytidine and p-benzoquinone-2'-deoxyadenosine adducts and their site-specific incorporation into DNA oligonucleotides. 749 36

Human leukaemia inhibitory factor (LIF) is a glycoprotein with a diverse range of activities on many cell types. A molecular model of LIF has been constructed based mainly on the structure of the related cytokine granulocyte colony-stimulating factor, and refined using simulated annealing and molecular dynamics in water. The model was stable during molecular dynamics refinement and is consistent with known stereochemical data on proteins. It has been assessed by comparison with 1H NMR data on the ionization behaviour of the six histidine residues in LIF, the imidazolium pKa values of which range from 3.6 to 7.4. These pKa values were assigned to individual histidine residues from NMR studies on a series of His-->Ala mutants. The environments of the histidine residues in the model account very well for their observed ionization behaviour. Furthermore, the model is consistent with mutagenesis studies which have defined a group of amino acid residues involved in receptor binding.
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PMID:Homology modelling and 1H NMR studies of human leukaemia inhibitory factor. 752 Aug 73


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