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

AKR mice, which have a short mean survival time and usually die with leukaemia, were studied from one month of age for correlation between these two parameters. For untreated animals we found the same mean survival time whether or not leukaemia occurred. By treating sucklings with the polycations diethylaminoethyl-dextran or hexadimethrine bromide the leukaemia incidence was significantly reduced. However, the mean survival time was unchanged, and remained the same in leukaemic and non-leukaemic animals. It is therefore suggested that the early death of AKR mice results from an ageing process and does not require leukaemia for implementation. Our prophylactic polycation treatment was furthermore found to induce spleen amyloid in some but not all of the mice that remained non-leukaemic.
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PMID:Life span, leukaemia and amyloid incidences of untreated and polycation-treated AKR mice. 61 59

Moloney leukemia virus activated both the classical and alternative pathways of human complement. About 500,000 virions were required to detect activation of the classical pathway whereas 5,000 times as many virions were necessary to initiate the alternative pathway, indicating that in this system only the former is of biological significance. Disruption of the virus with Triton X-100 destroyed its ability to initiate the alternative pathway without affecting its ability to activate the classical pathway. After ultracentrifugation of disrupted virus the active component could be recovered in the supernate and was isolated by isoelectric focusing in granulated gels. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic and analysis and cyanogen bromide digestion studies revealed that the activity resided in a methionine-containing protein having a pI of 7.5 and a molecular weight of approximately equal to 15,000 daltons. The purified protein interacts strongly with Clq and efficiently activates Cl. RNase and lipolytic enzymes had no effect on the isolated protein but incubation with trypsin resulted in loss of activity. Enzymatic digestion studies of surface-labeled virus indicate that the active protein is a viral membrane protein. On the basis of these results it is concluded that the complement receptor of Moloney leukemia virus is the surface protein p15E.
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PMID:Lysis of oncornaviruses by human serum. Isolation of the viral complement (C1) receptor and identification as p15E. 63 50

Treatment of a methanolic solution of 4-hydroxy-1-beta-D-ribofuranosyl-2-pyridinone (3-deazauridine, 1) with diazomethane gave 2-methoxy-1-beta-D-ribofuranosyl-4-pyridinone (2) and 4-methoxy-1-beta-D-ribofuranosyl-2-pyridinone (3a) in an approximate ratio of 1:2. Analogous treatment of 1 with diazomethane in the presence of stannous chloride dihydrate gave eight detected products including 2, 2-methoxy-1-(2-O-methyl-beta-D-ribofuranosyl)-4-phridinone (4), 2-methoxy-1-(3-O-methyl-beta-D-ribofuranosyl)-4-pyridinone (5), 3a, 4-methoxy-1-(2-O-methyl-beta-D-ribofuranosyl)-2-pyridinone (6a), 4-methoxy-1-(3-O-methoxy-beta-D-ribofuranosyl)-2-pyridinone (7a), 2'-O-methyl-3-deazauridine (6b), and 3'-O-methyl-3-deazauridine (7b). For comparison, the 2'-O-methyl derivatives of 2 )4 and 5) and of 3a (6a and 7a), respectively, were prepared in good overall yields by stannous chloride catalyzed methylation of 2 and 3a. Treatment of 1 with benzyl bromide gave 4-benzyloxy-1-beta-D-ribofuranosyl-2-pyridinone (3b). Stannous chloride catalyzed methylation of 4-pivaloxy-1-beta-D-ribofuranosyl-2-pyridinone (3c) gave the corresponding 2'-O-methyl derivative 6c. These compounds were tested in leukemia L1210 culture and against three bacterial strains and were found to be uniformly inactive. This provides a striking example of nucleoside structure specificity and also adds support to the depot storage-enzymic cleavage mode of antileukemic activity of 4-(adamantane-1-carbonyloxy)-1-beta-D-ribofuranosyl-2-pyridinone (3d).
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PMID:Nucleic acid related compounds. 17.3-Deazuridine. Stannous chloride catalysis of cis-diol vs. phenolic base methylation with diazomethane. 80 80

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

The essential role of Rauscher leukemia virus (RLV) multiplication in viral-chemical co-carcinogenesis was investigated by the use of ethidium bromide (EtBr) as an inhibitor of viral complementary DNA (cDNA) integration in the host genome. EtBr inhibited co-carcinogenic transformation when present at the time of RLV inoculation but was ineffective when added to preinfected cells. Inhibitors of protein synthesis, puromycin and cyclohexamide also inhibited co-carcinogenic transformation of chronically infected cells. Purified rat interferon used at a concentration which inhibited 85% of RLV production did not modify the course of co-carcinogenic transformation. The implications of these observations in terms of the possible role of the virus-specific protein (s) in the co-carcinogenic process are discussed.
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PMID:Chemical-viral co-carcinogenesis: requirement for leukemia virus expression in accelerated transformation. 99 12

Synthesis and biological activities of 12 analogs of N6-benzyladenosine are described. The compounds were prepared by two methods: (1) direct alkylation of adenosine with an appropriately substituted benzyl bromide to give the N1-substituted derivative which was then rearranged in base to give the N6-substituted compound, and (2) by nucleophilic displacement of chlorine in 6-chloropurine ribonucleoside, 6-chloro-2-aminopurine ribonucleoside, and 6-chloro-2-aminopurine with an amine. These analogs were examined for their growth inhibitory effect in cultured leukemic cells and also for their effect on adenosine aminohydrolase activity. N6-p-Nitrobenzyladenosine and its 2'-deoxy analog were competitive inhibitors (K1 65, 22 MUM). The 2-amino-N6-p-nitrobenzyladenine and its ribonucleoside were found to be noncompetitive inhibitors of adenosine aminohydrolase. In cultured L1210 leukemia, 2-amino-6-p-nitrobenzylaminopurine and the corresponding ribonucleoside were better growth inhibitors than N6-benzyladenosine, while N6-p-nitrobenzyladenosine, its 2'-deoxy analog, and N6-p-fluorobenzyladenosine were as active as N6-benzyladenosine.
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PMID:Synthesis and biological activities of some N6-(nitro- and -aminobenzyl)adenosines. 105 53

Feline immunodeficiency virus (FIV) proviral DNA was detected by the polymerase chain reaction method (PCR). PCR products were detected by gel electrophoresis and ethidium bromide staining. The P-10, P-15 and P-24 regions of the gag gene of FIV were chosen as the target sequences for amplification, and three primer pairs were prepared. The PCR products subjected to amplification with each primer pair were found to possess sites of digestion by a restriction enzyme, as hypothesized. They did not react with feline leukemia virus (FeLV)-infected or feline syncytium-forming virus (FeSFV)-infected cell-derived DNA, and specifically amplified FIV-infected cell-derived DNA. FIV proviral DNA was detected by the PCR method with either primer pair (one-step amplification: single PCR) in DNA derived from peripheral blood lymphocytes (PBL) from 7 of 12 FIV antibody-positive cats. When PCR products in each of the 12 cats were subjected to a second amplification using the same primer pair (two-step amplification: double PCR), FIV proviral DNA was detected in all of the cats. When PBL samples collected from three cats that were negative and three that were positive in the single PCR were cultured for a few weeks in the presence of interleukin 2, FIV proviral DNA was detected in all six cats by the single PCR method. The results suggest that either the use of cultured PBL as the sample or the performance of the double PCR method enables simple and specific detection of FIV proviral DNA in PBL.
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PMID:Detection of feline immunodeficiency proviral DNA in peripheral blood lymphocytes by the polymerase chain reaction. 131 18

Patients with the autosomal recessive disorder Fanconi anemia (FA) present with progressive pancytopenia, skeletal abnormalities and a predisposition to leukemia. In addition to elevated rates of spontaneous chromosome aberrations occurring in cultured fibroblasts and lymphoblastoid cell lines, an increased susceptibility to DNA cross-linking agents and oxygen has been found. To explain this hypersensitivity to clastogenic agents a defective function of DNA topoisomerase I or II could be invoked, a suggestion which is supported by the co-localization of the DNA topoisomerase I gene and a putative FA gene to chromosome 20q. In order to investigate the function of DNA topoisomerases in FA, the sensitivity of lymphoid B-cell lines derived from FA patients and control cell lines to inhibitors of DNA topoisomerases I and II was compared using continuous bromodeoxyuridine labeling and bivariate Hoechst/ethidium bromide flow cytometry. Both agents inhibited cell proliferation mainly by arresting cells in the G2 phase of the cell cycle. However, no difference was found in sensitivity towards both DNA topoisomerase inhibitors between control and FA cell lines.
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PMID:Cell cycle effects of the DNA topoisomerase inhibitors camptothecin and m-AMSA in lymphoblastoid cell lines from patients with Fanconi anemia. 138 35

After activation by interferon-gamma (INF-gamma) and lipopolysaccharide(LPS), mouse peritoneal macrophages were cocultured with P388 parental cell line (P388/PRT) and its adriamycin (ADM)-, cisplatin(CDDP)-, cyclophosphamide(CPM)-, and mitomycin-C(MMC)-resistant cell lines for one day at effector:target ratios (E:T) of 10:1, 5:1, and 2:1. The direct 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) cleavage assay and a new indirect MTT assay as well as clonogenic assay were used to quantitate activated macrophage-mediated cytotoxicity to these non-adherent leukemia targets. The results revealed that all the P388 cell lines can be suppressed efficiently by activated macrophages, but P388 CPM- and MMC-resistant cell lines (P388/CPM, P388/MMC) were more susceptible than P388/PRT while P388 ADM- and CDDP-resistant cell lines (P388/ADM, P388/CDDP) shared equal level of survival rates with P388/PRT. This study also showed that both non-activated and activated macrophages can produce formazan in a high level, which can interfere with the final results of direct MTT assay. The new indirect MTT assay can avoid such interference by separating the effectors from the targets before performing the MTT assay and reflects the real viability of the targets so the indirect MTT assay developed in this study could be a better way to examine cytostatic and cytotoxic effect of activated macrophages on non-adherent tumor cells in vitro.
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PMID:Differential macrophage-mediated cytotoxicity to P388 leukemia cells and its drug-resistant cells examined by a new MTT assay. 146 25

The antitumor effects of mitoxantrone (MITO) and the various mechanisms involved therein were investigated in the adriamycin sensitive (P388/S) and resistant (P388/ADR) P388 leukemia cells. Utilizing the MTT (3-[4,5/dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay, MITO concentration less than 100 ng elicited 50% inhibition of P388/S tumor cell survival, while a 10 times greater dose of MITO was required to inhibit the P388/ADR cell survival by 50%. A MITO dose dependent inhibition of DNA, RNA and protein biosynthesis was observed in the sensitive cells, while MITO elucidated a negligible effect on the macromolecular biosynthesis in the resistant tumor cells. Induction of DNA strand scission was observed in P388/S cells exposed to 0.1 and 1 microgram/ml MITO, while a minimal formation of DNA lesions was evident in the P388/ADR cells treated with 5 micrograms/ml MITO. These strand breaks were found to be not associated with proteins in either P388/S or P388/ADR cells. Generation of free radicals due to MITO and formation of alkylating metabolites of MITO were found to be not involved in the cytotoxic response of MITO against P388/S and P388/ADR cells. MITO did not affect the glutathione based detoxification mechanism of the sensitive and resistant tumor cells. Results indicate that in spite of reduced intracellular drug retention and induction of DNA strand breaks in P388/ADR cells other hitherto unknown mechanisms besides DNA binding might be involved in the antitumorigenic potential of MITO.
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PMID:Antineoplastic activity of mitoxantrone and its biological interactions in parental and multidrug resistant subline of P388 murine leukemia cells. 152 4


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