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)

Vinblastine-23-oyl amino acid derivatives and the analog deoxy vinblastine derivative were synthesized by linking amino acid carbocyclic esters to the vinca-23-oyl moiety, through an amide linkage. Their experimental chemotherapeutic activities on P388, L1210 leukemias and 6C3HED lymphosarcoma in mice were evaluated in comparison to those of the parent alkaloids vinblastine, vincristine, and the semi-synthetic derivative vindesine. Further, their toxicities and plasmatic clearance are given. We have developed a method for conjugating vinca alkaloid to bovine serum albumin through a covalent and reversible linkage. The chemotherapeutic activity of this conjugate on P388 leukemia was assessed. This conjugate was found stable in blood and serum up to 48 hours. Lysosomal hydrolases liberate about 50 per cent of the tritiated drug after 48 hours.
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PMID:Vinca-23-oyl amino acid derivatives: as new anticancer agents (review). 389 95

Nuclear sugar-binding proteins were detected in membrane-depleted nuclei isolated from hamster BHK cells and mouse L 1210 leukemia cells by means of fluorescein-labelled neoglycoproteins. In fluorescence microscopy, the fluorescence was seen throughout the nucleus but was generally brighter over the nucleoli than over the rest of the nucleus. Flow cytofluorometry analysis demonstrated the presence of nuclear sugar-binding proteins for synthetic glycoproteins associated with different sugar residues. Among the nine neoglycoproteins used, four neoglycoproteins (namely alpha-rhamnosylated, alpha-glucosylated, N-acetyl-beta-glucosaminylated and alpha-mannosylated-6P-serum albumin) strongly labelled nuclei. Various controls strongly argue for the specificity of the nuclear labelling. The possibility that some of the sugar-binding proteins might correspond to endogenous nuclear lectins is considered.
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PMID:Detection of sugar-binding proteins in membrane-depleted nuclei. 397 49

Nutritional status was evaluated on 210 occasions in 90 pediatric oncology inpatients during a 7-month period; 39 had solid tumors and 51 leukemia. Ages ranged from 3 months to 20 yr. Nutritional parameters were defined as normal, "at risk," or "probably malnourished." Fifty-seven and 29% of assessments revealed at least one parameter "at risk" or "probably malnourished," respectively. Prognosis was negatively related to the number of abnormal nutritional parameters. Serum albumin was most frequently abnormal. However, on most occasions, hypoalbuminemia was associated with weight/height, arm muscle area, and triceps skinfold measurements in the normal range. In order to further identify determinants of serum albumin, we analyzed dietary, chemotherapy, and temperature data in 10 prospectively studied leukemia patients, half of whom received parenteral nutrition. In these patients there was little relationship of serum albumin to chemotherapy or dietary intake. In all of these patients, especially those receiving total parenteral nutrition, low serum albumin was highly associated with fever (p less than 0.0005). We concluded that febrile illness is an important determinant of abnormal serum albumin concentrations. In pediatric cancer patients, abnormal serum albumin may more often reflect the acute metabolic response to fever and infection than depletion of body mass.
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PMID:Significance of hypoalbuminemia in pediatric oncology patients--malnutrition or infection? 400 20

In human tumor cells freshly obtained from patients with breast cancer, ovarian cancer, or adenocarcinoma of unknown etiology and in normal human bone marrow cells, the cell-to-medium ratio (intracellular/extracellular concentration) in vitro of 5.42 microM melphalan rose rapidly to levels of 6-17 after 35 min at 37 degrees C in Dulbecco's phosphate-buffered saline containing bovine serum albumin and glucose. Only patient C (breast cancer) had received chemotherapy. In all cells studied, L amino acids (1 mM) such as leucine, glutamine, tyrosine, and methionine reduced the cell-to-medium ratio of melphalan at 3 and 35 min. There was a good correlation between the reduction of melphalan transport at 35 min in the heterogeneous nucleated bone marrow cell population by amino acids and their effect on melphalan cytotoxicity in the CFU-C system. Aminoisobutyric acid (A1B), a specific substrate of the A system of amino acid transport, at a concentration between 1 and 50 mM had no significant effect on melphalan uptake at 3 min in any of the human cells studied except those of patient C. At 35 min A1B (10 or 50 mM) significantly reduced the intracellular melphalan concentration in normal bone marrow cells and tumor cells from patients B and C. At 2 mM, 2-aminobicyclo-(2, 2,1)-heptane-2-carboxylic acid (BCH), a specific substrate of the L system of amino acid transport, reduced the cell-to-medium ratio to 70% of control at 3 and 35 min in human bone marrow cells. In tumor cells from patients A, B, D, and F, 2 mM BCH had no significant effect on melphalan uptake at 3 min; it slightly decreased uptake in tumor cells from patient C. At 35 min, 2 mM BCH significantly reduced melphalan transport in tumor cells from patients C and F only. The lack of a BCH-suppressible component to melphalan uptake into human tumor cells freshly obtained from previously untreated patients contrasts with the presence of this component in murine L1210 leukemia cells, murine P388 leukemia cells, and human tumor cell lines. This suggests that minor differences in melphalan transport may exist amongst species and also between human tumor cells which are freshly obtained and cell lines maintained in culture.
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PMID:Effects of amino acids on the transport and cytotoxicity of melphalan by human bone marrow cells and human tumor cells. 401 61

Injections of thymic extract (TE), TE primed lymphocytes or normal lymph node cells were effective in bringing about total remission of the Dunning leukaemia in inbred Fisher CD rats. Survival greater than 365 days occurred in 10-80% of the various treated groups whereas untreated leukaemic rats, or leukaemic rats treated with spleen "mock thymus extract" or bovine serum albumin, died within an average of 10-17 days. Administration of antilymphocyte serum into leukaemic rats enhanced their death rate. Stimulation of cell mediated immunity via the production of functional thymus stimulated lymphocytes is postulated as the mechanism by which tumour rejection occurred.
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PMID:Immunotherapy of the Dunning leukaemia with thymic extracts. 475 37

Monoclonal DNP-specific IgG (lambda 2 epsilon 2), IgM (kappa 2 mu2) and IgG [kappa 2 (gamma 1)2] were isolated fom the culture supernatant of hybridomas by affinity chromatography with 2,4-dinitrophenol bovine serum albumin (DNP-BSA) sepharose and characterized by biochemical and biological methods. The molecular weights were 84,200 for the epsilon chain, 55,400 for the gamma chain and 77,500 for the mu chain as determined by sodium dodecylsulphate polyacrylamide del electrophoresis (SDS-PAGE). The association constants for [3H]-DNP-lysine determined by equilibrium dialysis were 0 . 87 X 10(7) l/mol for IgE and 1 . 91 X 10(8) 1/mol for IgG1. The isoelectric focusing of the purified monoclonal antibodies revealed for IgG1 seven bands at a pH range of 6 . 3 - 7 . 2 and for IgE sixteen bands at a pH range of 4 . 5 to 6 . 8. the binding of 125I-anti-IgE to rat basophilic leukaemia (RBL) and rat mast cells which had been preincubated with various amounts of monoclonal IgE was studied. At saturation conditions of IgE, about 2 . 14 X 10(5) molecules of anti-IgE were bound per rat mast cell. Rat mast cells coated with monoclonal anti-DNP IgE were triggered for the release of histamine in the presence of either the antigen or guinea-pig anti-mouse IgE. A mutual inhibition of the passive cutaneous anaphylaxis (PCA) reaction in the rat by either mixing mouse reaginic serum directed against ovalbumin or rat reaginic serum directed against Nippostrongylus brasiliensis with monoclonal mouse anti-DNP IgE was demonstrated.
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PMID:Generation of monoclonal murine anti-DNP-IgE, IgM and IgG1 antibodies: biochemical and biological characterization. 618 Sep 75

We evaluated chemotactic properties of four sublines of rat basophilic leukemia cells using blindwell Boyden chamber assays. After sensitization with a mouse monoclonal IgE directed against dinitrophenyl (DNP), cells from sublines 2H3-C and 926a underwent chemotaxis toward DNP-bovine serum albumin (BSA) and sublines RBL-1 and 4A did not. Chemotactic responses required specific IgE and were determined by the IgE antigen specificity used for sensitization. The threshold for chemotaxis was on the order of 10(-10) M DNP-BSA. Release of incorporated [3H]-serotonin did not always parallel chemotactic responses, which suggests that chemotaxis and secretion may be two unlinked processes that occur during basophil activation. Our results predict a possible in vivo mechanism whereby specific chemotactic responses of basophils and other FcR epsilon-bearing cells are mediated via specific IgE bound to membrane FcR epsilon.
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PMID:IgE-mediated chemotaxis of rat basophilic leukemia cells towards specific antigen. 618 56

We have previously shown that, unlike monomeric IgE, chemically derived dimers, trimers, and heavier oligomers of IgE were internalized efficiently. This finding suggested that endocytosis, like mediator release, is triggered by cross-linking of the cell surface receptors for IgE. In the present study, we analyzed the temporal and functional relationships between the two events. We used rat basophilic leukemia cells (RBL-HR+-2H3) and rat peritoneal mast cells, which were allowed to bind monomeric 125I mouse IgE hybridoma anti-dinitrophenyl (HI-DNP-E-26-82), and the polyvalent antigen 131I-dinitrophenylated human serum albumin (DNP15-HSA). We found that at 37 degrees C, 50% of the cell surface-bound immune complexes were internalized rapidly (t1/2 3 to 5 min) by RBL-HR+-2H3 cells with only minimal reduction (1/3) in the extent of internalization when very few of the receptors (approximately 5%) were saturated with IgE. Normal mast cells internalized cell surface-bound immune complexes at a similar rate (t1/2 4 to 5 min). Unlike serotonin release, internalization was independent of extracellular calcium and continued to increase as the ratio of DNP15-HSA to IgE increased 10- to 100-fold over the ratio required for optimal histamine release. In the RBL cells, internalization preceded serotonin release, reaching a peak at about 10 min, while the release (t1/2 13 to 19 min) continued for up to 60 min. Presumably, some of the cross-linked IgE internalized less effectively and continued to trigger serotonin release. The reverse relationship between the rates of internalization and release (t1/2 less than 1 min) was found in normal rat mast cells. We conclude that although cross-linking of two or more receptors triggered both endocytosis and exocytosis, the two events are not necessarily sequential.
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PMID:The fate of IgE bound to rat basophilic leukemia cells. III. Relationship between antigen-induced endocytosis and serotonin release. 620 83

The presence and the sugar specificity of membrane lectins on the cell surface of mouse L1210 leukemia cells were demonstrated by using various neoglycoproteins (glycosylated serum albumin) substituted with fluorescein or methotrexate. Neoglycoproteins were prepared by reaction of glycosidophenylisothiocyanates with bovine serum albumin. The binding of neoglycoproteins to L1210 cells depends on the nature of the carried sugar and on the number of bound sugar residues per neoglycoprotein molecule. The best results were obtained with fucosylated serum albumin containing 25 +/- 5 residues of fucose. The amount of cell-associated fluorescein-labeled neoglycoproteins was several fold higher at 37 degrees C than at 4 degrees C suggesting a specific endocytotic process. The membrane lectin-mediated endocytosis was further demonstrated by showing that the cell-associated fluorescence upon cell incubation in the presence of fluorescein-labeled neoglycoproteins at 37 degrees C increased several fold after addition of monensin, a proton/sodium ionophore known to raise the pH of endosomes and lysosomes. The analysis of fluorescein-labeled neoglycoproteins association to the L1210 cells were achieved by quantitative flow cytofluorometry after standardization with calibrated polystyrene sulfonate beads carrying various amounts of 1-(fluoresceinylthioureido)-4,8-diazalicosane. In addition, the cytotoxicity of neoglycoprotein-bound methotrexate was shown to be related to the presence and to the nature of the carried sugar: fucosylated serum albumin was shown to be the most efficient neoglycoprotein carrier, and to have a cytotoxicity close to that of anti L1210 cell IgM monoclonal antibody carrying methotrexate.
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PMID:Uptake of neoglycoproteins via membrane lectin(s) of L1210 cells evidenced by quantitative flow cytofluorometry and drug targeting. 624 Mar 1

The murine bone marrow population mainly responsible for the unique competing activity of this lymphoid organ in the competition radioimmunoassay (cRIA) for AKR murine leukaemia viruses gp71 has been partially purified and characterized. That population could be distinguished by the following properties: (i)gp71+ cells (cell population expressing the AKR MuLV gp71 antigen) are mainly medium density cells, according to their distribution in the layers of a discontinuous bovine serum albumin (BSA) gradient; (ii) The gp71 positive cells are not mature lymphocytes; (iii) This cell population is found both in the FcR+ and FcR- compartments and is not included in the complement (C') receptor-positive population; and finally, (iv) the gp71+ cells are phagocytic cells and an adherent cell population according to its capacity to adhere to plastic surfaces, nylon wool and Sephadex G-10.
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PMID:Characterization of the bone marrow cell population expressing an AKR murine leukaemia-virus gp71-like antigen. 627 66


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