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)

1 A simple, specific assay for 6-mercaptopurine (6-MP) in human plasma with a sensitivity of 10 ng/ml (66 nmol/1) has been developed. 2 6-MP was extracted directly from plasma into toluene using a novel extraction procedure. This involves conversion of 6-MP into a phenyl mercury derivative by its reaction with phenyl mercuric acetate in alkaline plasma and extracting into toluene. Back-extraction of the toluene layer with 0.1N HCl regenerates 6-MP, which is then oxidised to purine-6-sulphonate and assayed fluorimetrically. 3 This assay has been modified to measure azathioprine and a new thiopurine metabolite in plasma. 4 In a kidney transplant patient given azathioprine, 50 mg i.v., conversion to 6-MP was rapid and the plasma half-life of 6-MP was 36 min. 5 These assays are suitable for studying the pharmacokinetics of azathioprine in patients with kidney transplants. The 6-MP assay should also prove useful for studying the pharmacokinetics of the drug in patients with leukaemia.
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PMID:Assay of azathioprine, 6-mercaptopurine and a novel thiopurine metabolite in human plasma. 4 May 85

When cells are infected by C-type viruses such as Moloney sarcoma/leukaemia virus, new antigens appear on the cell membrane. Mice and rats will respond immunologically to the antigen(s). It was uncertain whether the antigens were related to the viral structural proteins or to non-virion, tumour-specific surface antigens (TSSA) or both. In an 125I-antiglobulin binding assay, Moloney virus completely blocked the binding of mouse and rat sera to virus shedding target cells, thus suggesting that mice and rats recognise only viral proteins. Mice responded to type-specific and rats mainly to group-specific determinants on the virus. Individual Moloney viral proteins were prepared using the guanidine HCl method and were used to block the binding of the rat anti-Moloney immune serum to Moloney virus shedding target cells. By this method, it was demonstrated that the rat serum contains specificities for the viral proteins gp70 and p30, but it was not possible to detect any antibodies directed towards non-virion or TSSA-like molecules.
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PMID:Specificity of serum from rodents immune to Moloney C-type virus-induced tumours. 6 44

The RNA components of two C-type RNA viruses, avian myeloblastosis virus and Friend leukaemia virus, have been isolated by treatment of the viruses with 6 M-guanidine-HCl and precipitation with ethanol. The virus proteins were recovered by lyophilization of the guanidine-HCl-ethanol supernatant after thorough dialysis against 0.5 mM-dithiothreitol. This simple method yielded RNA of similar quality to the phenol and sodium dodecyl sulphate (SDS) extraction methods, and the same amount of 60-70S RNA, although a fraction of the smaller (4S) species remained in the protein fraction. The sedimentation patterns of heat-denatured RNA extracted by either method were similar. Electrophoretic analyses of the extracted proteins in polyacrylamide gel gradients containing SDS gave patterns that were very similar to those obtained by direct analysis of SDS disrupted viruses.
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PMID:The use of guanidine-HCl for the isolation of both RNA and protein from RNA tumour viruses. 21 Nov 81

The pharmacological and therapeutic effects of the daunomycin (DNM):DNA complex were compared with those of free DNM in mice. A complex formation between dnm and DNA (1:11.7, w/w) resulted in a 79% decrease in DNM complex was dialyzable. The DNM fluorescence was completely recovered from the complex in 0.3 N HCl and 50% ethanol solution, and a short contact with biological tissues studied did not quench DNM fluorescence after extraction. The plasma fluorescence (DNM equivalent) 5 min after the i.v. injection of DNM:DNA complex at a dose of 20 mg/kg was 60-fold higher than that of an equivalent amount of free DNM. The complex was cleared for plasma with an initial half-life of 20 min. In spite of an initally higher blood generally similar except in liver and spleen, where DNM equivalent were significantly higher than those of free DNM. The uptake of DNM:DNA into L1210 cells in vitro was low and, at 1 hr, was about one-twentieth of that from DNM. Treatment of DBA/2 mice bearing i.p. L1210 leukemia transplant (initial cell number, 10-3) with DNM:DNA complex resulted in identical increases in life-span as occurred with free DNM. When routes of cell transplant and treatment were different, no therapeutic advantage of DNM:DNA over DNM was seen.
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PMID:Pharmacological and therapeutic efficacy of daunomycin:DNA complex in mice. 113 31

Although cellular drug resistance is considered to be an important cause of the poor prognosis of children with relapsed acute lymphoblastic leukaemia (ALL), the knowledge of drug resistance in these patients is very limited. Different aspects of drug resistance were studied in 17 children with relapsed ALL. The in vitro sensitivity profile was determined using the MTT assay. Cells from relapsed children were significantly more resistant to 6-thioguanine, prednisolone, cytosine arabinoside, daunorubicin (DNR), mustine-HCl and mafosfamide but not to L-asparaginase and vincristine (VCR) than cells from 41 children with ALL at initial diagnosis. Some relapsed patients showed a general drug resistance while others were resistant to only 1-3 drugs. The relevance of the multidrug resistance (MDR) model was analysed: In all DNR- and VCR resistant cases a co-resistance to drugs not involved in the MDR model was found. P-glycoprotein was not detected in any of 28 untreated and 14 relapsed samples tested. VCR- and DNR accumulation in the most resistant cells were not lower than in sensitive cells. Resistance modifiers did not potentiate the cytotoxicity of VCR and DNR. We conclude that resistance to anthracyclines and vinca alkaloids in childhood relapsed ALL is not due to P-glycoprotein mediated MDR. Different types of drug resistance varying from a resistance to only one drug to a general chemoresistance, can be detected in children with relapsed ALL. VCR and L-asparaginase seemed to be only infrequently involved in drug resistance. Knowledge of drug resistance might lead to more effective and less toxic therapies for children with relapsed ALL.
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PMID:Different types of non-P-glycoprotein mediated multiple drug resistance in children with relapsed acute lymphoblastic leukaemia. 135 Feb 7

Serum and aqueous humor samples, collected from 14 clinically normal cats and 96 cats with clinical evidence of intraocular inflammation, were assayed with ELISA for Toxoplasma gondii-specific immunoglobulin M (IgM), T gondii-specific IgG, T gondii-specific antigens, total IgG, and total IgM. Additionally, serum was assayed with ELISA for feline leukemia virus p27 antigen and antibodies against the feline immunodeficiency virus as well as with an immunofluorescent antibody assay for antibodies against feline coronaviruses. Calculation of the Goldmann-Witmer coefficient (C-value) for the T gondii-specific antibodies detected in aqueous humor established the likelihood of local antibody production. Serologic evidence of present or prior infection by an infectious agent was found in 81.9% of the clinically affected cats from which serologic results were available (77/94 cats). Seropositive results for toxoplasmosis were found in 74.0% of the clinically affected cats. Anterior segment inflammation was found in 93.1% (81/87 cats from which information was available) of the clinically affected cats, most of which were older males. Toxoplasma gondii-specific antibodies were not detected in the aqueous humor of 6 seropositive, clinically normal cats. The C-values for aqueous T gondii antibodies were greater than 1 in 44.8% of the cats and greater than 8 in 24.0% of the cats. Response to treatment with clindamycin HCl was positive in 15/20 (75%) of the T gondii-seropositive, clinically affected cats treated with this drug. In 13/15 (86.7%) T gondii-seropositive, clinically affected cats having a C-value greater than 1, response to treatment with clindamycin HCl was positive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enzyme-linked immunosorbent assays for the detection of Toxoplasma gondii-specific antibodies and antigens in the aqueous humor of cats. 142 23

In our hands, benzene proved to be a valuable drug for the treatment of chronic leukaemia. When correctly administered it did not provoke the harmful side effects reported by several authors in accord with the first description of von Koranyi in 1912. In many cases benzene induced complete remission persisting for over 18 months. This compound was found to be active even in patients who had not responded to busulphan, although the contrary was also observed for certain subjects. In accordance with previous investigations carried out in the rabbit, concomitant administration of cysteine-HCl blocked the leucopenic effect of benzene in 5 of 6 cases whereas ethionine, an antimetabolite of methionine and/or cysteine, appeared to enhance its therapeutic action. It is worthy of note that in at least one case ethionine administered alone led to complete clinical and haematological remission of the leukaemic state.
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PMID:Ethionine: a new antileukaemic drug? 144 55

Various 2'- and 3'-methylidene-substituted nucleoside analogues have been synthesized and evaluated as potential anticancer and/or antiviral agents. Among these compounds, 2'-deoxy-2'-methylidene-5-fluorocytidine (22) and 2'-deoxy-2'-methylidenecytidine (23) not only demonstrated potent anticancer activity in culture against murine L1210 and P388 leukemias, Sarcoma 180, and human CCRF-CEM lymphoblastic leukemia, producing ED50 values of 1.2 and 0.3 microM, 0.6 and 0.4 microM, 1.5 and 1.5 microM, and 0.05 and 0.03 microM, respectively, but also were active in mice against murine L1210 leukemia. Of all the tested drug dosage levels (25, 50, and 75 mg/kg, respectively) compound 23 had no toxic deaths and compound 22 yielded only one toxic death at the highest dosage level. On the contrary, in the same study, 1-beta-D-arabinofuranosylcytosine (ara-C) resulted in 2/5, 5/5, and 5/5 toxic deaths, respectively. Both compounds 22 and 23 have shown better anticancer activity than ara-C, yielding higher T/C x 100 values and some long-term survivors (greater than 60 days). In addition, compounds 22 and 23 were found to have, respectively, approximately 130 and 40 times lower binding affinity for cytidine/deoxycytidine deaminase derived from human KB cells compared to ara-C, suggesting that the two 2'-methylidene-substituted analogues may be more resistant to deamination. Cytoplasmic deoxycytidine kinase (dCK) was required for compounds 22 and 23 action. Furthermore, compounds 14, 22, 23, and 24 also have antiherpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) activity in cell culture. In addition, the crystal structure of 2'-deoxy-2'-methylidenecytidine hydrochloride (23-HCl) was determined by X-ray crystallography.
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PMID:Synthesis and anticancer and antiviral activities of various 2'- and 3'-methylidene-substituted nucleoside analogues and crystal structure of 2'-deoxy-2'-methylidenecytidine hydrochloride. 165 24

The basic biochemical characteristics of cyclocytidine hydrochloride (cC.HCl) and arabinosylcytosine (araC) were compared. It was demonstrated that despite different lipophilicity and different pK (4.15 for araC and 6.60 for cC.HCl), the mechanism of inhibition of DNA synthesis by both compounds is the same (ID50 for araC was 0.048 mumol/l and for cC. HCl 0.23 mumol/l). The compounds had a different mechanism of inhibition of RNA synthesis (ID50 for araC was 2.69 mmol/l and for cC.HCl 1.08 mmol/l) and showed a marginal effect on protein synthesis. Hydrolysis of the 0(2),2'-anhydro bond in cC.HCl and formation of araC in vivo was characterized by a Km = 280 mumol/l using HPLC. Deamination of araC in vivo was studied in healthy mice (Km = 247 mumol/l), 8.6% of arabinosyluracil 15 minutes after araC administration) and in mice with sensitive and araC resistant leukemia L1210 (15.5% and 8.5% of arabinosyluracil 15 minutes after araC administration, respectively). On the basis of different physico-chemical properties of cC.HCl and different mechanisms of inhibition of RNA synthesis it can be assumed that cC.HCl, when therapeutically used, may have its own mechanism of biological effect(s) and that its application may be therapeutically advantageous in some aspects as compared to araC.
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PMID:Comparison of some biochemical parameters of arabinosylcytosine and cyclocytidine in L1210 murine leukemia cells. 169 Aug 64

Since 1978, over 50 clinically useful antitumor drugs or new candidate antitumor agents have been evaluated in vivo against cisplatin-resistant P388 leukemia (P388/DDPt) in our laboratories. Analysis of this data base has yielded insights into the cross-resistance, collateral sensitivity, and mechanisms of resistance of P388/DDPt. P388/DDPt was cross-resistant or marginally cross-resistant to eight agents [carmethizole.HCl, rhizoxin, dibromodulcitol, spirohydantoin mustard, hepsulfam, arabinosyl-5-azacytosine (ara-AC), tiazofurin, and deoxyspergualin]. Of these eight agents, the latter six have entered various phases of clinical trials. For these trials, it may be important to exclude or to monitor with extra care patients who have previously been treated with cisplatin. P388/DDPt was collaterally sensitive to six agents [fludarabine phosphate (2-F-ara-AMP), amsacrine (AMSA), mitoxantrone, etoposide (VP-16), batracylin, and flavone acetic acid] and, possibly, to two others (merbarone and echinomycin). These observations of collateral sensitivity suggest that a combination of cisplatin plus any one of these drugs might exhibit therapeutic synergism. Therapeutic synergism has been observed in animal models for combinations of cisplatin plus VP-16, AMSA, or mitoxantrone. The observation of collateral sensitivity for P388/DDPt to four agents (AMSA, mitoxantrone, merbarone, and VP-16) that have been reported to interact with DNA topoisomerase II suggests the possible involvement of the latter in cisplatin resistance. Both the increased sensitivity of P388/DDPt to these agents and a portion of its resistance to cisplatin could be the result of an increase in DNA topoisomerase II activity.
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PMID:Antitumor drug cross-resistance in vivo in a cisplatin-resistant murine P388 leukemia. 184 65


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