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)

Plasma membrane preparations from KA31 (mouse) cells contained receptors for the binding of Rauscher murine leukemia virus (R-MuLV) envelope glycoprotein, gp70. This binding was demonstrated by gel filtration of a mixture of the microsomal fraction of the cells and 125I-labeled gp70. A rapid and convenient assay was developed to measure the complex formation between the membrane receptors and gp70 involving specific precipitation of the complex by 3 to 4% polyethylene glycol. The complex formation was responsive to the concentrations of both the receptor and gp70 and also to changes in temperature and pH. The gp70 binding was a noncooperative, saturable process, and an association constant of 3.5 X 10(8) M-1 was estimated from the binding data. The complex formation was reversible and a near-total exchange of 125I-labeled gp70 in the complex was achieved by incubation with excess of unlabeled gp70. The complex formation was inhibited by protein denaturing agents, guanidine-hydrochloride and urea. Pretreatment of the membrane fractions with either chymotrypsin or phospholipase C led to a loss of the membrane-associated receptor activity, indicating that a lipoprotein structure was important for the receptor function, consistent with the observation that nonionic detergents strongly inhibited the complex formation.
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PMID:Characterization of Rauscher murine leukemia virus envelope glycoprotein receptor in membranes from murine fibroblasts. 3 3

The cytotoxic effect of 5-azacytidine (AzaCR) on normal hematopoietic colony-forming units (NCFU) and L1210 leukemic colony-forming units (LCFU) in the femoral marrow of BALB/c x DBA/2 F1 mice was studied using the spleen colony assay. Dose-survival curves for LCFU and NCFU were biphasic. Repopulation of LCFU was rapid at a low dose of AzaCR (0.1 mg/mouse) but was delayed for greater than 6 days at higher doses (0.25 mg/mouse and above). Of the agents tested in this system, only AzaCR exhibited these properties. Survival of mice with L1210 leukemia following AzaCR administration was prolonged beyond that predicted by the degree of LCFU reduction alone, and reflected the delay in LCFU repopulation. In contrast, repopulation of NCFU in normal mice was not delayed at a high dose of AzaCR (0.5 mg/mouse). AzaCR produced a nine-fold greater reduction of NCFU in leukemic mice than in normal mice, measured 5 days after AzaCR injection. While divided doses of AzaCR produced LCFU cytotoxicity equivalent to a single dose, 24-hr infusions of high doses were inferior to single infections.
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PMID:Kinetics of both leukemic and normal cell population reduction following 5-azacytidine. 5 Jan 28

A dose of 10 or 20 mg of N-butylnitrosourea (BNU) dissolved in 50% ethanol was administered by a gastric tube to 6-week-old male ICR/JCL strain mice and they were sacrificed 15 months later. One of 18 animals developed a hepatoma, but none of the mice given CCl4 in 0.1 ml of 50% oliver oil subcutaneously at the right thigh developed hepatoma. However, a marked enhancement of hepatoma induction was observed in mice injected with CCl4 one day before the single intragastric administration of BNU, with 12 out of 28 mice developing one or more hepatomas (average 3.2/mouse) ranging in diameter from 0.5 to 1.5 cm. By extending the administration interval between CCl4 and BNU to 1 week or 1 month, or by reversing the order of administration, the hepatotumorigenic action was virtually lost. There was no occurrence of hepatoma but a predominant development of leukemia, of either thymic or nonthymic origin, was observed in mice of younger age treated with CCl4 one day before continuous oral administration of BNU (1 mg/day/mouse). It is thus concluded that the preparative (cocarcinogenic) action of CCl4 is indispensable for hepatotumorigenesis with a single large dose of BNU.
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PMID:Preparative action of carbon tetrachloride in liver tumorigenesis by a single application of N-butylnitrosourea in male ICR/JCL strain mice. 17 59

Murine mammary tumor virus (MuMTV), produced from a glucocorticoid-stimulated C3H mouse mammary adenocarcinoma cell line, was free of murine leukemia virus and oncogenic for weanling BALB/c mice. Adenocarcinomas were induced by MuMTV as early as 136 days post inoculation and with as low as 5 X 10(3) virus particles/mouse. Tumor incidence did not correlate directly with virus dose; rather, it was low at higher MuMTV concentrations (1.2 X 10(8) particles/mouse), reached and optimum at 1.3 X 10(5) particles/mouse, and decreased with virus dilution.
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PMID:Oncogenicity of murine mammary tumor virus produced in tissue culture: brief communication. 20 21

The spleen colony assay was used to examine the effect of thymidine (dThd) on 5-fluorouracil (FUra) cytotoxicity in two transplantable leukemias, AKR (in AKR mice) and L1210 [in (BALB/c x DBA/2)F1 mice], in vivo. A large dose of dThd (10 mg/mouse) could not rescue these cell lines from FUra toxicity. Instead, when dThd was given within 1 hour before FUra, it enhanced FUra cytotoxicity by a factor between 100 and 1,000 in AKR leukemia. That dThd increased the cytotoxicity of FUra only by a factor of 3 in L1210 leukemia suggested a different mechanism of interaction of the two drugs in the two cell lines. Examination in hybrid mice capable of supporting the growth of both leukemias showed the enhancement to be tumor related rather than host related. We also demonstrated a dose-dependent effect of dThd injection 15 minutes before FUra in AKR leukemia. Concerning the kinetics of killing of AKR leukemia colony-forming units (LCFU) following the administration of dThd 15 minutes before FUra, LCFU survival continued to decrease for 24--36 hours following drug administration.
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PMID:In vivo enhancement of 5-fluorouracil cytotoxicity to AKR leukemia cells by thymidine in mice. 27 62

The in vivo effects of VM-26 and VP-16-213 upon hematopoietic stem cells and L1210 leukemia cells were quantitated using the spleen-colony assay technique. The effect of VM-26 on leukemia cells was further quantitated using an endpoint dilution assay. The dose-response curves for leukemic clonogenic cells for both agents when given by iv injection were exponential and biphasic, indicating the existence of two populations. The survival of leukemia cells when VM-26 was administered as a 24-hour infusion was less than that found for equivalent doses administered as single injections. The survival kinetics with respect to time for a low dose (0.02 mg/mouse) and a high dose (0.15 mg/mouse) of VM-26 were similar in that the decrease in survival was rapid, reaching a maximum effect within 4 hours after administration. With the low dose, repopulation of the femoral marrow started immediately, whereas with the high dose, there was a 20-hour delay in repopulation. The data from the increase in lifespan studies were in excellent agreement with the quantitative assays. The dose-response curves for the normal hematopoietic clonogenic cells were also exponential, but these cells were much less sensitive to the agents than were the leukemia cells.
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PMID:Kinetics of cytotoxicity of VM-26 and VP-16-213 on L1210 leukemia and hematopoietic stem cells. 68 75

We have studied the quantitative pharmacokinetic differences of individual metabolites and unchanged cyclophosphamide (CPA) in control and phenobarbital-treated animals, using radiolabelled CPA together with thin-layer chromatography. On Day 0, one group was started on phenobarbital drinking water and one group stayed on regular acid water. P388 leukaemia, (10(6) cells i.p.) was administered to all mice on Day 8, and 2 days later both groups of mice were given i.p. CPA (200 mg/kg) with 14C-CPA (0.2 muCi per mouse). At 5--60 min after CPA administration, groups of 10 mice were killed and their blood collected for assay of parent compound and metabolites in plasma. Phenobarbital pretreatment reduced CPA and phosphoramide mustard CXT (concentration x time) by 66+% and 27+%, respectively. Assuming that phosphoramide mustard is both the ultimate cytotoxic form of CPA and the blood-transport form, the reduction of CPA by phenobarbital would predict a decreased therapeutic effect. The assay methods in this study will be used in the future to determine the importance of this potential drug interaction in man.
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PMID:Effect of phenobarbital on plasma levels of cyclophosphamide and its metabolites in the mouse. 69 48

1. BCG (1 mg/mouse) administered i.v. on day 5 after chemotherapy by cyclophosphamide (CPM), given itself at the dose of 80 or 134 or 403 mg/kg one day after the inoculation of L 1210 leukaemia 10(3) cells, increases the effect of the non-optimal doses: i.e. 80 mg/kg, which is insufficient to cure mice, and 403 mg/kg, which is toxic. It does not change the effect of the optimal dose of CPM (134 mg/kg) which cures most of the mice. 2. BCG (1 mg/mouse i.v.) given on day 15 before CPM decreases the effect of the latter at the dose of 134 mg/kg. These results suggest that: a. BCG given after chemotherapy is not only able to eradicate the residual disease, but can decrease chemotherapy toxicity; b BCG given before an optimal dose of chemotherapy may decrease its antileukaemic effect, via the enhancement of the chemotherapy immunodepressive action, as demonstrated by skin graft experiments; this deterioration of the effect of chemotherapy by immunodepression was also suggested when the combination of CPM and antithymocyte serum was used.
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PMID:[Immune manipulation of BCG administered before or after cyclophosphamide for chemo-immunotherapy of L1210 leukemia]. 81 77

A modified recombinant human granulocyte colony-stimulating factor (rhG-CSF), KW-2228, has some excellent properties such as high specific activity in stimulating granulocyte colony-formation in vitro, great biological stability in plasma, good pharmacokinetic profile and high potency in granulopoiesis in normal mice in vivo. Recently, the application of G-CSF against infectious diseases has been considered, and some animal experiments have been carried out to support its in clinical applications. Patients with underlying diseases such as leukemia or cancer often have recurrent infections because of reduced number and functions of neutrophils, which mediate an early stage of host defense. We investigated the prophylactic effect of KW-2228 against an experimental systemic infection with Pseudomonas aeruginosa in tumor-bearing mice (colon 26: BALB/c) treated with cyclophosphamide. KW-2228 (0.25-2.0 micrograms/mouse) was administered (s.c.) once a day for 4 days before the experimental bacterial infection. As a result of KW-2228 administration, the reduction in peripheral blood neutrophils usually caused by the injection with cyclophosphamide was prevented markedly. KW-2228 displayed excellent protective potency dose-dependently against the infection with P. aeruginosa in tumor-bearing mice. These data show the possibility that prophylactic therapy with KW-2228 may augment the host defense of immunocompromised patients to infections. It present, clinical efficacy studies on KW-2228 are under way.
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PMID:[Protective effect of KW-2228 in a systemic infection model of CPA-treated tumor-bearing mice]. 137 51

The purpose of the study was to characterize in vivo an immunodepressive murine retroviral 'model' for the possible testing of drugs against HIV infection. Urethane leukaemia virus (ULV) injected into adult BALB/c mice (10(5) focus-forming units/mouse) caused a small, significant splenomegaly from 2 to at least 9 weeks after virus inoculation. Virus was also present in up to 60% nucleated splenocytes (XC 'infectious centre assay'). Effects on splenomegaly and virus in splenocytes were assayed following various regimens of zidovudine given as 0.5 mg/ml or 0.25 mg/ml in drinking water. Regimens included continuous treatment both before and after ULV, only before, and only after ULV inoculation. Zidovudine was also given for a limited period immediately after virus, or initiated after virus infection was established. Zidovudine given continuously at and following ULV infection completely prevented splenomegaly and virus expression in splenocytes. No other regimen was as effective; however, limited zidovudine treatment immediately after virus inoculation greatly reduced the effects of virus, while the same dose initiated after virus infection was established had only a small ameliorating effect. We conclude that ULV may prove to be a useful addition to other available murine systems, and this is discussed.
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PMID:Inhibition of urethane leukaemia virus, a murine retrovirus, in mice by zidovudine. 196 87


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