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)

Leucocyte ascorbic acid was estimated in patients with abnormal leucocyte states and other haematological disorders. Levels below the normal range were found in most cases of chronic myeloid leukaemia and chronic lymphatic leukaemia. Subnormal levels were found in more than a third of patients with acute leukaemias, lymphomas, glandular fever, myelofibrosis, and polycythaemia, and in the same proportion of patients receiving cytotoxic drugs, and also in those with a polymorph leucocytosis and those with purpura. Most patients with anaemia but a normal leucocyte count, and those with myelomatosis had normal levels. The majority of pregnant women tested had subnormal levels. In a wide variety of leucocyte disorders the leucocyte ascorbic acid may not be an accurate index of the body's Vitamin C status. The results also support the supposition that leucocyte ascorbic acid is mostly carried by normal mature polymorphs.
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PMID:Leucocyte ascorbic acid in abnormal leucocyte states. 97 12

Adriamycin (ADR) is effective against a wide range of human neoplasms. However, its clinical use is compromised by serious cardiac toxicity, possibly through induction of peroxidation in cardiac lipids. Ascorbic acid, a potent antioxidant, was examined for effect in reducing ADR toxicity in mice and guinea pigs. Ascorbic acid had no effect on the antitumor activity of ADR in mice inoculated with leukemia L1210 or Ehrlich ascites carcinoma, but it significantly prolonged the life of animals treated with ADR. ADR elevated lipid peroxide levels in mouse heart, and ascorbic acid prevented the elevation. The significant prevention of ADR-induced cardiomyopathy in guinea pigs by ascorbic acid was proved by electron microscopy. Ascorbic acid and the derivatives may delay general toxicity of ADR and also prevent the cardiac toxicity. The results also suggest the clinical efficacy of the combined treatment of ADR and ascorbic acid or the derivatives.
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PMID:Ascorbic acid and adriamycin toxicity. 196 86

Dihydroambazone 1, a soluble derivative of ambazone, was tested with an admixture of ascorbic acid (0.1, 0.25, or 0.5% in distilled water) for antineoplastic activity by different routes (i.p., p.o., s.c., i.v.) against leukemia P388, and by s.c. application against Lewis lung carcinoma on B6D2F1-mice. The results were compared with that of ambazone. 1 was as active as ambazone upon the per os d 1-4 schedule only. Ascorbic acid, added for stabilization of 1, had no significant influence on the results. Intravenously given 1 was of low activity. It proved to be toxic at 100 mg/kg body mass. The i.v. toxicity was estimated approximately on B6D2F1-mice (LD50: 150 mg/kg; LD100: 175 mg/kg; maximum tolerated dose (MTD): 100 mg/kg. A comparison between the MTD's of 1 and ambazone in mice and rats (Wistar) showed partly a somewhat better p.o. compatibility of 1. The expectation of a favourable i.v. applicable derivative from the otherwise in water nearly insoluble ambazone could not be realized.
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PMID:[Antineoplastic activity and toxicity of dihydroambazone in comparison with ambazone (1,4-benzoquinone-guanylhydrazone-thiosemicarbazone)]. 233 15

Ascorbic acid (vitamin C) is an important intracellular reducing agent. It also has been suggested to be (i) a protective agent against development of cancer, (ii) a therapeutic agent for malignancies and (iii) a mutagen. We have found that high concentrations of ascorbate leads to DNA damage in several in vivo and in vitro situations. Guinea-pigs receiving oral 1-methyl-1-nitrosourea (MNU) were used as a whole animal model. Administration of sodium ascorbate prior to MNU increased strand breakage in pancreatic DNA. Concentrations of ascorbate greater than 0.5 mM increased the frequency of DNA strand breaks caused by MNU in both L1210 murine leukemia cells and guinea-pig pancreatic cells in tissue culture; ascorbate alone led to DNA strand breaks in the latter cells. Investigations of the mechanism of DNA damage were carried out with purified DNA. Ascorbate produced single- and double-strand breaks in plasmid DNA. Cleavage was catalyzed by copper(II), inhibited by catalase and blocked by the presence of thiols. We conclude that superoxide and hydrogen peroxide produced during the oxidation of ascorbate leads to generation of hydroxyl free radicals that can mediate DNA strand scissions and potentiate the effects of alkylating carcinogens.
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PMID:Ascorbate potentiates DNA damage by 1-methyl-1-nitrosourea in vivo and generates DNA strand breaks in vitro. 282 77

Human T-cell leukemia virus type I was induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 5-iodo-2'-deoxyuridine (ldUrd) in the MT-1 cell line. Virus expression was monitored by immunofluorescence microscopy with GIN-14, mouse monoclonal antibodies directed toward Mr 19,000 and Mr 28,000 protein-specific virus polypeptides. MNNG (0.1 micrograms/ml) and ldUrd (50 micrograms/ml) both induced virus synthesis in MT-1 cells. MNNG-induced virus expression peaked between 24 and 48 h of incubation, whereas ldUrd induced maximum virus expression between 48 and 72 h of incubation. Superinduction resulted when MNNG was added to cells induced 48 h previously with ldUrd, but not with concomitant treatment. 13-cis-Retinoic acid, retinol, retinol aldehyde, and retinol acetate (10(-6) to 10(-9)M) were concomitantly added with ldUrd to MT-1 cells for 24, 48, and 72 h incubation. All inhibited virus induction to various degrees. The retinoids were ranked as to inhibitory activity: retinol greater than retinoic acid greater than retinol aldehyde greater than retinol acetate. The most sensitive period for inhibiting ldUrd induction by retinoic acid was 24 h postinduction or with concomitant treatment. Vitamin C and vitamin E inhibited ldUrd induction most effectively with 48 h incubation. Retinol and vitamin C also inhibited virus induction by MNNG. None of the retinoids, vitamin C, or vitamin E significantly inhibited virus expression in noninduced cells or were toxic to the cells at the concentrations used in these experiments.
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PMID:Human T-cell leukemia virus I induction by 5-iodo-2'-deoxyuridine and N-methyl-N'-nitro-N-nitrosoguanidine: inhibition by retinoids, L-ascorbic acid, and DL-alpha-tocopherol. 299 Jun 71

Vitamin C was shown to be an essential requirement for the growth of mouse myeloma cells in an in vitro colony assay. Human leukemia (acute nonlymphocytic leukemia) cell colonies grow well in a similar in vitro culture system, and vitamin C has been shown to enhance the growth of leukemic cell colonies in 77 (35%) of 219 leukemic patients while none of 34 normal bone marrows tested simultaneously shows growth enhancement by this vitamin. This vitamin C effect is reproducible in repeated experiments in same patients, specific to this vitamin, selective for leukemic cells, and is proven to be biological in nature. Further, leukemic cells are mobilized back and forth between cycling and resting states with vitamin C supplementation/depletion. Our more recent study indicates that the preleukemia (myelodysplastic syndrome), generally known to be related to acute nonlymphocytic leukemia, has similar pattern in terms of vitamin C sensitivity, with 8 of 25 patients (32%) showing the growth enhancement with this vitamin.
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PMID:Vitamin C in leukemia and preleukemia cell growth. 336 76

The present study was conducted to clarify the mechanism responsible for enhancement of the anti-melanoma activity of levodopa methylester by supplemental ascorbate in vivo. 5-Hydroxydopa, a known cytotoxic agent and the major metabolite formed from levodopa in the presence of ascorbate and mushroom tyrosinase in vitro, was assessed for its antitumor activity against i.p. and s.c. inoculated B16 melanoma, P388 leukemia, and L1210 leukemia in mice with and without supplemental ascorbate. Treatment with 5-hydroxydopa failed to significantly increase survival of mice bearing i.p. or s.c. pigmented and non-pigmented B16 melanomas even though it inhibited local tumor growth. Treatment increased survival of both P388 and L1210 leukemias, and this increase was more pronounced in mice bearing i.p. tumors than in mice bearing s.c. tumors. This treatment significantly decreased final tumor weight of both leukemias implanted s.c., and inhibited ascites formation in mice inoculated with i.p. tumors. Ascorbate supplementation decreased or abrogated the effect of 5-hydroxydopa on survival in mice bearing i.p. or s.c. leukemia tumors and decreased survival relative to control mice bearing i.p. or s.c. pigmented and s.c. non-pigmented tumors. It did not affect survival of treated mice bearing i.p. non-pigmented melanoma tumors. Ascorbate supplementation did not modify the effect of 5-hydroxydopa treatment on primary s.c. tumor growth in mice bearing melanoma or leukemia tumors nor did it affect ascites formation in treated mice bearing i.p. leukemia tumors. The lack of correlation between the observed inhibition of primary tumor growth and the absence of an effect on survival in 5-hydroxydopa treated mice bearing i.p. melanoma may relate to an inability of this drug to interfere with tumor metastasis. These data argue against a role for 5-hydroxydopa as a metabolically derived cytotoxic formed in situ during concurrent treatment with levodopa methylester and supplemental ascorbate.
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PMID:Influence of supplemental ascorbate on the antitumor activity of 5-hydroxydopa, a purported cytotoxic metabolite. 393 10

L-Ascorbic acid (0.57 mM) and dimethylsulfoxide (14.1 mM) were found to potentiate four times the antibacterial activities of daunomycin and adriamycin in the Staphylococcus aureus test. This effect, however, could not be demonstrated against eukaryotic cells and leukemia P 388 in mice.
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PMID:Potentiation of the biological activities of daunomycin and adriamycin by ascorbic acid and dimethylsulfoxide. 680 12

Two infants with recurrent infections and a history of delay in separation of the umbilical cord (1 month and 17 days) had severely impaired neutrophil mobility. In addition very poor natural killer cell (NK) activity of blood lymphocytes against a leukaemia cell line (Molt 4F) was found. Incubation of lymphocytes with lymphoblastoid interferon increased NK activity in the one case tested. No immune (gamma) interferon production was detected in Raji cell and phytohaemagglutinin (PHA) stimulated cultures from the other case. Apart from an abnormal dose-response curve in thymidine uptake after PHA stimulation of blood lymphocytes, no other abnormalities were found in a range of immunological tests. Ascorbic acid improved neutrophil mobility but had no effect, on NK activity. Both children have subsequently died from septicaemic illnesses.
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PMID:Defective immune interferon production and natural killer activity associated with poor neutrophil mobility and delayed umbilical cord separation. 681 56

6-Hydroxydopamine (6-OHDA) is a neurotoxin for catecholaminergic neurons and neuroblasts. Since frequent marrow involvement in neuroblastoma restricts the exploitation of stored autologous bone marrow for rescue postchemotherapy, the potential for tumor-specific in vitro specificity of 6-OHDA was studied. The cytotoxic effect of 6-OHDA on 12 human neuroblastoma cell lines was compared to the effect on nonneuroblastoma cell lines. Most neuroblastoma cell lines were very sensitive to 6-OHDA (average concentration killing 50% of cells, 22 microgram/ml; range, 2.8 to 65.4). Cells derived from catecholamine-producing tumors were more sensitive to 6-OHDA than were those from non-catecholamine producers. By contrast, human fibroblasts, lymphoblastoid cell lines, and normal marrow were relatively insensitive to 6-OHDA; the concentration needed to kill 50% of cells for most of these cells exceeded 100 microgram/ml. Leukemia cell lines and a rhabdomyosarcoma cell line were intermediate in sensitivity. Ascorbate and 6-OHDA were synergistic in toxicity for human neuroblastoma cells. Thus, in vitro addition of 6-OHDA and ascorbate was rapidly lethal for human neuroblastoma cells at concentrations which were minimally toxic for hematopoietic cells. This differential toxicity provides a possible means for selective destruction of neuroblastoma cells in bone marrow harvested for autologous transplantation.
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PMID:Selective toxicity of 6-hydroxydopamine and ascorbate for human neuroblastoma in vitro: a model for clearing marrow prior to autologous transplant. 703 75


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