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)

The objective of the present investigation was to screen a series of new N'-oxides of N',N'-dimethylaminoalkylamides of dodecanoic acid for activity in vitro and to investigate the biochemical mode of action. On the basis of primary screening, one of the most active compounds, namely the N'-oxide of 10-(N',N'-dimethylaminodecyl)amide of dodecanoic acid (n = 10) was chosen for detailed biochemical study. This compound inhibited the incorporation of 14C-precursors (adenine, valine, thymidine, uridine) into appropriate macromolecules of P388 murine leukemia and Ehrlich ascites carcinoma cells. The amine oxide also interfered with energy-yielding processes (aerobic glycolysis, endogenous respiration). Cytotoxicity is a consequence of the cytolytic activity of the compounds mentioned above. Membranous effects were demonstrated by the measuring of the release of cytoplasmic materials absorbing at 260 and 280 nm, marker enzyme activities (LDH, MDH), release of protein from the cells into the culture medium, as well as by morphological examination. It is evident that the site of action of the amine oxides investigated was the biological membrane which, after interaction with the amine oxides, showed changes in molecular organization and osmotic and permeability characteristics.
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PMID:Biochemical basis of cytotoxic activity of some new N'-oxides of N',N'-dimethylaminoalkylamides of dodecanoic acid. 142 44

Merocyanine 540 (MC 540) is a photosensitizing dye that is used clinically for the purging of autologous bone marrow grafts and preclinically for the inactivation of enveloped viruses in blood products. Its mechanism of action is not yet well understood. This paper investigates the sites of MC 540-mediated photodamages in L1210 leukemia cells by examining the effects of MC 540-sensitized photoirradiation on several soluble and membrane-bound marker enzymes. When exposed to MC 540 and white light under a standard set of conditions, the activities of Na+/K(+)-ATPase, Mg2(+)-ATPase, and 5'-nucleotidase (three plasma membrane-bound enzymes) were reduced by 54, 49, and 55%, respectively. None of the intracellular enzymes included in this survey was affected by MC 540-sensitized photoirradiation as long as the plasma membrane remained intact. The two soluble enzymes, lactate dehydrogenase and malate dehydrogenase, remained refractory to MC 540-sensitized photoirradiation even after the plasma membrane had been disrupted. By contrast, the activities of the membrane-bound enzymes, NADPH-cytochrome c reductase and succinate dehydrogenase, were reduced in cell lysates by 55 and 81%, respectively. Purified NADPH-cytochrome c reductase was about 3 times less sensitive than the microsomal enzyme, suggesting that the membrane environment facilitated photoinactivation. The MC 540-sensitized photoinactivation of enzymes was accelerated in the presence of deuterium oxide and inhibited if oxygen in the medium was displaced by nitrogen or azide was added to the medium. Taken together, these data support the view that the plasma membrane is a major target of MC 540-mediated photodamages, that the inactivation of membrane-bound enzymes is an oxidative process, and that at least some photodynamic damages are mediated by type II chemistry.
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PMID:Merocyanine 540-sensitized photoinactivation of soluble and membrane-bound enzymes in L1210 leukemia cells. 217 31

Mononuclear cell (MNC) leukemia was identified in 26-month-old F344 rats by splenomegaly, reduced red blood cell counts, and elevated white blood cell counts. Atypical MNC were predominant in spleen and blood with acentric nuclei and red cytoplasmic granules. Pentose shunt, glycolytic, and Krebs cycle enzyme activities were elevated 2- to 11-fold in the enriched MNC fraction (Ficoll-Paque density gradients, 1.077 g/ml) isolated from spleen. A leukemic MNC line was derived from one of the spontaneously leukemic donors and then maintained in vivo by s.c. transfer of 2 X 10(7) spleen cells into 7-8-week-old syngeneic recipients. In these serial transplantation experiments leukemia that was clinically and morphologically indistinguishable from spontaneous leukemia in 104-week-old rats was induced in 22-24-week-old rats. Enhanced enzyme activity in MNC was not essential to maintain the phenotypic expression of Fischer rat leukemia. The pattern of biochemical response in spleen MNC from transplanted cases was the opposite of that previously noted in spontaneously leukemic rats, with 50-70% decreases in the specific activities of pentose shunt enzymes and malate dehydrogenase. Reversal of the expression of these enzymes in MNC may be related to a difference in the growth rate of the tumors or to selective proliferation of the transplanted leukemic cells. In addition acetylcholinesterase activity decreased 35-85% in MNC of spleen and blood. Transplantable MNC from F344 rats provide abundant tumorigenic material with a novel biochemical expression that may be useful in the study of chemotherapeutic intervention.
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PMID:Comparison of the morphology and enzyme activity of mononuclear cells from Fischer 344 rats with either spontaneous or transplanted leukemia. 402 16

Profound changes in the level of certain dehydrogenase enzymes were observed in lymphoid tissues of rats involved by erythroblastic stem cell leukaemia. In lymphoid tissues free of leukaemic involvement, activity of malate dehydrogenase (MDH) always exceeded that of lactate dehydrogenase (LDH). In those which contained substantial infiltrates of leukaemic cells, activity of LDH was increased while MDH activity was reduced. In leukaemic spleen significant changes were observed in the molecular forms of LDH; the proportion of LDH-5 (muscle-type LDH) was greatly increased while the other molecular forms were reduced. The spleen of rats with leukaemia exhibited a marked increase in the normal level of aerobic and anaerobic glycolysis but the rate of respiration was unchanged.The terminal stages of stem cell leukaemia in the rat are characterized by wide-spread leukaemic infiltration of liver and other tissues. Lymph node involvement, however, was found to be selective. Coeliac lymph nodes greatly exceeded other lymph node groups in their incidence of leukaemic involvement. It is considered that the selective nature of lymph node involvement in stem cell leukaemia derives from topographical considerations.
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PMID:Leukaemia evoked with 7,8,12-trimethylbenz(a)anthracene in rat. 3. Changes in lymphoid tissues. 508 76

An early sign of erythroblastic leukemia in rat was nodule formation in the spleen. Hyperplastic foci of stem cells, indistinguishable histologically from leukemic stem cells, were found in the red pulp whereas the malpighian corpuscles were uninvolved. Anemia is a normal phenomenon in immature rats and the spleen of the prepubertal rat possesses considerable hemopoietic potential. Pulse-doses of 7, 8, 12-trimethylbenz(a)anthracene prevented the physiologic hematological development of maturing rats and was associated with subsequent development of leukemic stem cells in the red pulp of the spleen. Significant enzyme changes were observed in leukemic spleens. Compared with the spleens of normal littermates, the concentration of lactate dehydrogenase rose while that of malate dehydrogenase fell; the content of alkaline phosphatase rose whereas acid phosphatase fell. Increased alkaline phosphatase activity in leukemic spleen was attributed to nonleukemic foci of myelopoiesis.
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PMID:Leukemia evoked with 7,8,12-trimethylbenz(a)anthracene in rat. I. Changes in spleen and thymus. 528 70

Adriamycin is used for the treatment of leukemia and other neoplastic processes. Unfortunately the drug has a toxic effect on some tissues. Cardiotoxicity in particular limits the use of the drug. Several hypotheses have been given to explain adriamycin heart toxicity. The authors have studied the effect of the drug on the enzymes isocitrate dehydrogenase-NADP, malic enzyme, 6-P-gluconate dehydrogenase, malic dehydrogenase-NAD+, hexokinase, and phosphofructokinase. They observed that adriamycin inhibits the NADP-dependent enzymes, and that the sulfhydryl group of the enzymes may be involved in the inhibitory action of adriamycin.
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PMID:[Study of the inhibition produced by adriamycin against specific enzymes in the rat heart]. 610 Apr 65

Circulating non-T lymphocytes had higher activities of 5'nucleotidase (plasma membrane), neutral alpha-glucosidase (endoplasmic reticulum) and basal leucine amino-peptidase than did T lymphocytes. Activities of catalase (peroxisomes), malate dehydrogenase (mitochondria), lactate dehydrogenase (cytosol) and N-acetyl-beta-glucosaminidase, beta-glucuronidase and acid phosphatase (lysosomes), were similar in the lymphocyte subfractions. Lymphocyte 5'nucleotidase (plasma membrane) in patients with common variable hypogammaglobulinaemia is much lower than normal. However, the decrease is less marked in X-linked hypogammaglobulinaemia, chronic lymphatic leukaemia or protein loosing enteropathy or in lymphocytes isolated from cord blood. Cells from patients with nephrotic syndrome had normal levels of 5'nucleotidase. Other plasma membrane marker enzymes (gamma-glutamyl transferase, leucine amino-peptidase) were normal in lymphocytes from patients with common variable hypogammaglobulinaemia. There is a selective reduction of mitochondrial (malate dehydrogenase) and cytosolic (lactate dehydrogenase) enzymes, with normal activities of lysosomal, peroxisomal and endoplasmic reticulum enzymes, in patients with common variable hypogammaglobulinaemia. The lymphocyte subcellular organelles in normal subjects and patients with common variable hypogammaglobulinaemia have similar properties on sucrose density gradient centrifugation. It is suggested that lymphocytes from patients with common variable hypogammaglobulinaemia show a specific enzymopathy and that this is not simply a reflection of cellular immaturity.
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PMID:Lymphocyte enzyme activities in immunodeficiency syndromes with particular reference to common variable hypogammaglobulinaemia. 630 45

The response to initial glucocorticoid therapy in childhood acute lymphoblastic leukaemia (ALL) reliably predicts the response to multiagent chemotherapy. Patients resistant to glucocorticoids (prednisone poor responders (PPR)) have a poorer event-free survival compared to glucocorticoid-sensitive patients (prednisone good responders (PGR)). A case-control study was performed to investigate differential protein expression in leukaemic blasts from PGR and PPR childhood ALL patients. Two-dimensional gel electrophoresis (2-DE) was used for an unsupervised screening and surface enhanced laser desorption/ionisation-time of flight mass spectrometry (SELDI-TOF MS) for the characterisation of protein spots. In difference maps of average gels for the proteomes of each responder group, differentially expressed proteins were identified after tryptic digestion and spotting onto H4-SELDI-TOF-MS chips. Proteins overexpressed in PPR were Catalase, RING finger protein 22 alpha, Valosin-containing protein (VCP) and a G-protein-coupled receptor. Proteins overexpressed in PGR were protein kinase C and malate dehydrogenase. Valosin-containing protein was chosen for validation and quantification by Western blot analysis in a second case-control group of ALL patients. In this second independent cohort, median VCP expression (P25-P75) was 0.15 (0.11-0.28) in PGR and 0.34 (0.14-0.99) in PPR patients (P = 0.04). We conclude that high VCP expression is associated with poor prednisone response in childhood ALL patients.
Leukemia 2006 May
PMID:Unsupervised proteome analysis of human leukaemia cells identifies the Valosin-containing protein as a putative marker for glucocorticoid resistance. 1654 Nov 42