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)

Exposure to nitrous oxide interferes selectively with the coenzyme function of vitamin B12 and causes inactivation of methionine synthetase, with subsequent impairment of folate metabolism and reduction of cellular proliferation. In a rat leukemia model (BNML) we investigated the combined administration of nitrous oxide, inactivating vitamin B12, and methotrexate (MTX), a folate antagonist inhibiting the enzyme dihydrofolate reductase. Through different mechanisms, both agents decrease the availability of tetrahydrofolate, and subsequently of other reduced folates, with increased impairment of folate-dependent synthesis of thymidylate. Effects on leukemic growth and on hematological values in rats demonstrated enhancement of the therapeutic effect of MTX by exposure to nitrous oxide. With several treatment schedules, the results of combined treatment were seen to be better than additive when compared with the effects of single agents. In particular, pretreatment of leukemic rats with nitrous oxide for 3 days before administration of MTX appeared effective. With higher doses of MTX, concomitant exposure to nitrous oxide even resulted in toxic effects. These findings were in accordance with the results of some metabolic studies performed in leukemic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhanced therapeutic effect of methotrexate in experimental rat leukemia after inactivation of cobalamin (vitamin B12) by nitrous oxide. 371 92

The cytostatic activity of 5-fluorouracil (5-FU) can be modified by the addition of reduced folates, as well as antifolates. This is indicative of the complex involvement of folate metabolism in the effects of 5-FU. In the BN rat leukemia model, 5-FU treatment was combined with the inactivation of cobalamin (vitamin B12) by nitrous oxide (N2O). Exposure to nitrous oxide causes severe disturbance of folate metabolism through the inhibition of the cobalamin-dependent enzyme methionine synthetase, and leads to loss of folates from the cell. With regard to the effects on growth of leukemia, the addition of nitrous oxide did not antagonize 5-FU. On the contrary, therapeutic effects were enhanced by combined treatment, as was evident from a further reduction of leukemic infiltration in spleen and liver, from a decrease or even disappearance of leukemic cells in the peripheral blood, and from extended survival of rats. These findings were in accordance with metabolic studies in isolated leukemic cells of treated rats, in which combined treatment caused further impairment of thymidylate and DNA synthesis. Pretreatment with nitrous oxide, for a period of 3 days, was more effective than treatment after the administration of 5-FU. Folate levels, in plasma and intracellular, were reduced after combined treatment. It is concluded that in this leukemia, unlike observations in some models of solid tumors, the activity of 5-FU is enhanced with a depletion of folates. This effect is probably comparable to the combination of methotrexate pretreatment with 5-FU, and might be important to applications of 5-FU in combination chemotherapy of hematological neoplasms.
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PMID:Effects of 5-fluorouracil treatment of rat leukemia with concomitant inactivation of cobalamin. 375 54

The preleukemic syndrome occurs mainly after middle age. We report 11 patients, aged 62 to 92 years, who presented with weakness, fatigue, malaise and pallor. Eight patients died; survival from the time of diagnosis was between 2 and 21 months. Two of them developed acute myelomonocytic leukemia. A third patient developed Philadelphia chromosome-negative chronic myeloid leukemia within 9 months. Serum unsaturated B12 binding capacity and transcobalamin I were elevated in this patient, preceding the transformation to chronic myeloid leukemia. Five other patients died from sepsis or pneumonia. All patients were anemic, and 10 were leukopenic. Bone marrow was hypocellular in 1 and hypercellular in 10 cases. Chromosomal studies were performed in five patients, with three showing abnormal findings: 47xx, trisomy 8 and a tetraploid karyotype 92xxyy5q-. No cytotoxic treatment should be given during the preleukemic phase until transformation to acute leukemia occurs. Since preleukemic patients are very susceptible to infections, early diagnosis of the condition is important, as is supportive care in the case of surgery.
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PMID:Preleukemic syndrome in elderly patients--report of 11 cases. 385 73

The present study was designed to test the effect of a combination of dehydroascorbic acid (DHA) and hydroxycobalamin (vitamin B12) on the survival of mice bearing L1210 leukemia. Results showed a significant increase in survival of treated mice compared with controls (p less than or equal to 0.0001) (Student's t-test). This positive effect was significantly lost when DHA was substituted by ascorbic acid (AA) in the same experimental conditions. In vitro findings also revealed that the DHA-B12 combination specifically inhibited mitoses of L1210 cells while non-neoplastic L929 cells were not affected.
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PMID:Mitogenic inhibition and effect on survival of mice bearing L1210 leukemia using a combination of dehydroascorbic acid and hydroxycobalamin. 405 Jul 46

Virus infected cells can carry HLA antigens not demonstrated in uninfected cells. In a wider context, it is known that tumour cells in the mouse can exhibit H2-like antigens of foreign haplotypes which they resemble. Our aim was to investigate, using an absorption method, the HLA antigens of ten leukaemic cells and to compare these results with those of normal lymphocytes. The following sera was used for absorption: anti-B5 serum, anti-B7 serum, anti-B12 serum. These sera were absorbed on the ten leukaemic cells and fifteen healthy lymphocytes. An anti-A1 + B8 serum and an anti-A2 serum were absorbed on the ten leukaemic cells, but there was not enough serum to carry out the similar absorption with the healty lymphocytes. Two points emerged from these results. (1) Leukaemia cells absorbed anti-HLA antibodies as effectively as healthy lymphocytes when the cells carried the antigen corresponding to the serum specificity. The curves obtained with leukaemia cells were comparable to those of healthy cells. (2) When the cells were not carriers of the antigens corresponding to the antibody's specificity, leukaemia cells were also capable of absorbing antibodies, unlike healthy lymphocytes which had no or poor absorption.
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PMID:Expression of HLA antigens on leukaemia cells. 617 97

Membrane transport of vitamin B12 (cyanocobalamin; Cbl) into mammalian cells is mediated by the serum protein transcobalamin II (TCII). In mouse leukaemia L1210 cells, TCII-Cbl binds to membrane receptors in a rapid, temperature-independent step and is internalized by a slow, temperature-dependent process. To delineate the location of receptors on these cells, we have constructed a visual probe by covalently coupling purified TCII-Cbl to submicrometre latex particles (minibeads). We report here that when L1210 cells are incubated with minibeads containing TCII-Cbl at 4 degrees C and examined by scanning electron microscopy (SEM), the particles are found attached predominantly to microvilli. Incubation of the cells at 37 degrees C results in the internalization of the minibeads. As visualized by transmission electron microscopy (TEM), this endocytotic process seems to occur in clathrin-coated pits and vesicles at the cell surface.
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PMID:Receptor binding and internalization of immobilized transcobalamin II by mouse leukaemia cells. 625 39

Uninfected, as well as feline leukemia virus (FeLV) infected human cells cultured under high cell density conditions undergo changes in the expression of major histocompatibility complex (MHC) antigens, as determined by indirect trace binding radio immunoassay (RIA) using monoclonal anti-HLA antibodies and by decreased sensitivity to complement mediated cytotoxicity by anti-HLA alloantibodies. FeLV particles produced by the viral infected cells are also sensitive to neutralization by anti-HLA antibodies, suggesting that enveloped viral particles incorporated MHC antigens in the viral envelope. The amount of HLA antigens expressed in the viral enveloped, closely reflects the expression of HLA antigens by the virus-producer lymphoid cells. FeLV-infected HsB-2 (T) and SB (B) lymphoid cells cultured under high cell concentration condition show decreased expression of some HLA antigens (A2, B12, B17), and the viral particles produced by those cells also incorporate lower amounts of such antigens. Our results, based on the findings that human lymphoid cells (uninfected, as well as FeLV infected) show decreased expression of some HLA membrane determinants when grown under high cell density conditions, indicate that no viral selective mechanism operates in the incorporation of HLA determinants by enveloped viruses. Instead, our results suggest that viruses pick up MHC antigens from the host cell membrane according to the concentration of those antigens on the surface of the cells at the time of virus budding.
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PMID:Cell culture density modulates the incorporation of HLA antigens by enveloped viruses. 630 90

Changes in mean corpuscular volume (MCV) were studied in cancer patients. Vitamin B12 or erythrocyte folate deficiencies were observed in only 9% of macrocytic patients (MCV greater than or equal to 100 fl). Bone marrow study in seven macrocytic patients with normal hemograms and normal levels of vitamin B12 and folic acid, on per os daily cyclophosphamide single agent therapy, showed myelodysplastic features. The highest MCV and MCV increases during therapy among 203 patients were observed in those cancers and cytotoxic therapies most commonly followed by secondary leukemia: Hodgkin's disease treated with MOPP and radiotherapy, and multiple myeloma and ovarian cancer treated with Melphalan. 21 patients who developed secondary leukemia had a higher MCV and a greater MCV increment than the control patients. Differences were significant in Hodgkin's disease. This preliminary report strongly supports monitoring MCV changes during cytotoxic therapy to attempt identification of patients at high risk of secondary leukemia.
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PMID:[Changes in the mean corpuscular volume during the cytotoxic treatment of cancer and risk of secondary leukemia. Preliminary results]. 632 84

Nitrous oxide (N2O) inactivates the vitamin B12-dependent enzyme methionine synthetase with subsequent impairment of folate metabolism and a reduction of cellular proliferation. Indications exist that this effect is antagonized by S-adenosylmethionine (SAM), and it was investigated whether combination with an inhibitor of SAM synthesis, cycloleucine, would result in increased inhibition of growth in rat leukaemia model (BNML). Leukaemic growth was compared in untreated rats, in rats treated with either nitrous oxide/oxygen (1:1) or cycloleucine (50 mg kg-1 i.p.), and in rats receiving both agents. Combined treatment resulted in the strongest reduction of leukaemic infiltration in spleen and liver, and this reduction often was more than the added effects of single treatments. Peripheral leukocyte counts were also lowest after combined treatment. The deoxyuridine suppression test, measuring folate-dependent de novo synthesis of thymidine, was more severely disturbed with combined treatment. Levels of vitamin B12 in plasma were reduced in rats receiving N2O, but an increase in plasma folate occurred in all treated rats. These results indicate that a reduction of SAM synthesis by cycloleucine can increase the disturbance of folate metabolism that is caused by nitrous oxide, with a potentiation of the effects on leukaemic growth.
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PMID:Synergistic growth inhibiting effect of nitrous oxide and cycloleucine in experimental rat leukaemia. 649 76

Leucocyte B12 and B12-binding capacity were measured by Simultrac radioassay in eosinophilic granulocytes, neutrophilic granulocytes and leucocytes obtained from patients with chronic granulocytic and lymphocytic leukaemia. It is shown that (a) eosinophils are a possible source of B12-binding protein similar to neutrophils and (b) granulocytes in myeloproliferative disorders and normal neutrophils have similar B12 and B12-binding capacity indicating that increased B12 and B12-binding capacity in myeloproliferative disorders arise from an increase in myeloid cell turnover.
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PMID:Eosinophilic granulocytes as a possible source of vitamin B12-binding protein. 658 Jul 20


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