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)

Synthesis of 8-phosphorus substituted isosteres of purine [pyrimidino (4,5-d)-1,3,2-diazaphosphole], 1-deazapurine [pyridino (2,3-d)-1,3,2-diazaphosphole] and 3-deazapurine [pyridino (4,5-d)-1,3,2-diazaphosphole] has been achieved by the reaction of equimolar amounts of triphenylphosphite and 4,5-diaminopyrimidine, 2,3-diaminopyridine and 3,4-diaminopyridine, respectively. These compounds hydrolyzed (cleavage of the phosphorus-nitrogen bounds) in aqueous solutions to provide the corresponding diaminopyrimidine or diaminopyridines. These three new basic ring systems constitute the first reported synthesis of purines in which ring carbon atom is substituted with a phosphorus atom. 8-Phosphorus substituted purine at a concentration of 4 X 10(-4)M caused a 50% inhibition in the growth of leukemia L1210 cells in culture. The biochemical rationale for the synthesis of these compounds is discussed.
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PMID:8-Phosphorus substituted isosteres of purine and deazapurines. 49 40

Studies were made on the maximal non-carcinogenic dose of dimethylnitrosamine (DMN) in rats. Groups of Wistar strain rats of both sexes, 6 weeks old, were given standard diet without DMN (group 1), or containing 0.1 ppm DMN (group 2), 1.0 ppm DMN (group 3), or 10 ppm DMN (group 4) for 96 weeks and then sacrificed for hematological, serum-biochemical, and histopathological examinations. After 96 weeks, the weights of the body and main organs in the different groups were not significantly different. The leucocyte count and blood urea-nitrogen (BUN) in group 4 were slightly increased, but other serum findings were not significantly different in different groups. Hepatocellular carcinomas were found in group 3 (1 male and 3 females), but not in group 2. Hemangioendotheliomas of the liver, adrenal adenomas, pituitary adenomas, interstitial cell tumors of the testis, ovarian tumors, and leukemia were also found. Pyelonephritis was found in both experimental and control animals, but no kidney tumors developed with these dose levels of DMN. These results show that on long-term oral administration to rats, 1.0 ppm DMN is the minimum carcinogenic dose, while a level of about 0.1 ppm DMN is non-carcinogenic.
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PMID:Long-term experiment of maximal non-carcinogenic dose of dimethylnitrosamine for carcinogenesis in rats. 51 Aug 53

A structure-activity relationship study was conducted on a number of bis(substituted aminoalkylamino)anthraquinones. These compounds were prepared by the condensation of substituted or unsubstituted leucoquinizarin with appropriate amines, followed by air oxidation. Both the position and the nature of the center nitrogen atom of the side chain are vital to the antineoplastic activity. The possible mode of action of these aminoquinones was discussed. 1,4-Dihydroxy-5,8-bis[[2-(hydroxyethyl)amino]ethyl]amino-9,10-anthracenedione (DHAQ) was found to possess potent inhibitory activity against both the P-388 leukemia system (T/C of 299 at 0.5 mg/kg with 4/6 cures) and the B-16 melanoma system (T/C of 503 at 1 mg/kg with 7/10 cures).
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PMID:Antineoplastic agents. Structure-activity relationship study of bis(substituted aminoalkylamino)anthraquinones. 62 5

Platelets were removed from 25 patients with leukemia during remission and were frozen for subsequent transfusion. With 5 per cent dimethyl sulfoxide as a cryoprotective agent, we froze 3 to 5 units of pooled platelet concentrate by simply placing the platelets in the vapor phase of a liquid nitrogen freezer. Ninety-one transfusions of platelets stored for 13 to 400 days were administered. The mean freeze-thaw loss was 13 percent, and the corrected one-hour increment in platelet count was 13,700 per microliter, corresponding to a recovery of 53 per cent of the predicted value. In many patients most or all of the transfusion requirements were met with frozen platelets. Our results indicate that frozen platelets can circulate and function hemostatically. Autologous frozen platelets are of particular value in the management of alloimmunized patients and have become an integral part of our transfusion support program.
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PMID:Frozen autologous platelet transfusion for patients with leukemia. 66 55

The SAL rat leukaemia, which resembles acute myeloblastic leukaemia, appeared initially to be non-immunogenic since resistance to an i.p. challenge with as few as 100 cells could not be obtained using stimulation of the RES or by immunization with SAL cells exposed to x-rays, nitrogen mustard, iodoacetate or glutaraldehyde. However, immunization with SAL cells exposed to low doses of mitomycin-C slowed the growth of the challenge inoculum. Cells treated with high doses of mitomycin-C did not immunize. The results are interpreted in terms of rapid shedding of a tumour-specific antigen from the membrane of SAL cells.
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PMID:Immunogenicity of a rat leukaemia of spontaneous origin (SAL). 76 14

cis-1-Acetamido-2-acetoxy-7-methoxy-N-methylmitosene was prepared in 11 steps from 7-methoxy-6-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-one by a route involving bromination of the pyrrolidineenamine or trimethylsilyl enol ether of starting material, displacement of bromide by acetate, oxime formation, and reductive acetylation, followed by elaboration of the quinone and methyl carbamate functions according to previously established methods. An unsubstituted carbamate could not be prepared. The mitosene thus synthesized differs from previously reported 1,2-disubstituted mitosenes, which are derived from the solvolysis of mitomycins, in that it has the opposite arrangement of oxygen and nitrogen substituents at the 1 and 2 positions. It showed antibacterial activities in disk-plate assays superior to those of cis-diacetylapomitomycin A and equivalent to those of certain 1-substituted mitosenes; however, it was less active than mitomycin A in these assays. It was inactive in inducing lambda-bacteriophage in Escherichia coli and inactive against P388 leukemia in mice. In contrast, certain 1-substituted mitosenes were active in prophage induction and 2b and mitomycin A were active in both assays.
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PMID:Mitomycin antibiotics. Synthesis and activity of 1,2-disubstituted mitosenes. 83 12

Several derivatives of 2-indolyl 5-(1,2,3,6-tetrahydropyridyl) ketone with various substituents on the pyridine nitrogen and with or without a benzenesulfonyl group on the indole nitrogen were synthesized and characterized by spectroscopic and analytical data. Only one showed erratic but confirmed activity in the P-388 screen. The other derivatives were inactive in the L-1210 leukemia screen.
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PMID:Synthesis and anticancer screening of 2-indolyl 5-(1,2,3,6-tetrahydropyridyl) ketones. 83 25

The quinazoline couterpart of folic acid (5,8-deazafolic acid) as well as its 10-methyl analogue has been shown to be an effective inhibitor of thymidylate synthetase from several different sources. This paper describes the synthesis of modifications in which the nitrogen atom at position 10 is replaced by sulfur, oxygen, or methylene affording 10-thia-5,8-deazafolic acid, 10-oxa-5,8-deazafolic acid, and 5,8,10-deazafolic acid, respectively. In preliminary testing, each of the target compounds displayed marginal activity against L1210 leukemia in mice.
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PMID:Sycnthesis of quinazoline analogues of folic acid modified at postion 10. 91 99

The N-nitrosoureas are the most active of a variety of N-nitroso compounds tested against L1210 leukemia in mice. Structure-activity studies show that the N-(2-chloro(or fluoro)ethyl)-N-nitrosoureido grouping is necessary for high-level activity in this test system, but a variety of carrier groups can be attached to the N'-nitrogen of the urea. For high-level activity against solid tumors in rodents, eg, the Lewis lung adenocarcinoma, the N'-substituent must be a cyclohexane ring, and the most active of these compounds are substituted at position 4 of the ring. The chemistry involved in the synthesis and reactions of the nitrosoureas is described. The possible relationship of the chemically reactive species generated by the decomposition of the nitrosoureas under in vivo conditions to biologic activity is discussed.
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PMID:Chemistry and structure-activity studies of the nitrosoureas. 95 7

The effect of morphine and cocaine on the transport of hydrolyzed nitrogen mustard (NH2-OH) and choline by peripheral blood cells of normal subjects and patients with chronic lymphocytic leukemia, acute lymphoblastic leukemia, and acute myeloblastic leukemia was determined. Transport of HN2-OH by lymphocytes from normal individuals and patients with chronic lymphocytic leukemia was stimulated by morphine and cocaine and, in each case, the effect was statistically significant (P less than 0.05 or greater). However, choline transport by normal lymphocytes was not altered by cocaine and was only slightly stimulated by morphine; choline transport by lymphocytes from patients with chronic lymphocytic leukemia was not stimulated by either morphine or cocaine. HN2-OH and choline transport by cells from patients with either acute lymphoblastic or myeloblastic leukemia was stimulated to a comparable degree by both drugs. Stimulation of HN2-OH transport by morphine and cocaine was greater in normal lymphocytes than in acute leukemic cells and the differences were highly significant (p less than 0.001). Conversely, stimulation of choline transport was more marked in acute leukemic cells than in normal lymphocytes, and these differences were also highly significant (p less than 0.001). It was previously shown that transport of nitrogen mustard by normal and leukemic human cells was biphasic in nature, consisting of a choline-independent component at "high" drug concentrations and a choline-dependent system at "low" substrate concentrations. The preferential stimulation of the low-dose, choline-dependent system by morphine and cocaine in acute leukemic cells relative to that observed in normal lymphocytes suggests a possible mechanism of increasing the therapeutic index of nitrogen mustard.
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PMID:Drug-induced stimulation of transport of hydrolyzed nitrogen mustard and choline by normal and leukemic human cells in vitro. 106 33


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