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 use of sonicated phospholipid vesicles (liposomes) as carriers of methyl [5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl] carbamate (Nocodazole), a water insoluble antimitotic compound active on mouse L1210 leukemia was investigated. Nocodazole was incorporated in dipalmitoyl-phosphatidylcholine: cholesterol: stearylamine (4:3:1) liposomes that were stable at room temperature for at least 48 hr. No drug leakage nor lipid exchange occurred after a 4 hr incubation at 37 degrees C with RPMI 1640 medium supplemented with 10% fetal calf serum. L1210 cells preincubated (2 x 10(6) cells/ml) at 37 degrees C for 3 hr with various concentrations of micronized Nocodazole or liposome-entrapped Nocodazole were injected i.p. into normal CDF1 mice (10(5) cells/mouse). Longest mean survival times and long-time survivors were observed in the group inoculated with L1210 cells preincubated with liposomes containing Nocodazole. CDF1 mice bearing i.p. or i.v. L1210 leukemia were treated i.p. on days 1, 5 and 9 with micronized or liposome-entrapped Nocodazole. Administration of this latter preparation induced a 50% increase in animal life span at the dosage (25 mg/kg/day) half the one required with the free compound (50 mg/kg/day). The present data indicate that enclosing Nocodazole, a water insoluble antimitotic compound, in liposomes results in an enhanced therapeutic activity against L1210 murine leukemia.
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PMID:Chemotherapeutic efficacy of Nocodazole encapsulated in liposomes on L1210 murine leukemia. 619 Feb 3

The Fc receptor for IgE (Fc epsilon R) on murine B lymphocytes was studied by using BALB/c mice infected 12 to 18 days previously with Nippostrongylus brasiliensis. B cells were enriched in the Sephadex G-10-passed lymphocytes by treating with anti-Thy-1.2 and complement (C). After stripping any cytophilic Ig with low pH, the B cells were 125I surface labeled; subsequently the membranes were solubilized with nonionic detergent, and putative Fc epsilon R components were allowed to bind to IgE-coated adsorbents. Bound radiolabel was eluted with low pH, and when examined by SDS-PAGE, was found to consist primarily of a relatively broad band centered at 49,000 m.w. (49K). Fluid-phase IgE could prevent the binding of the 49K component to the IgE solid-phase adsorbents. Rebinding studies further indicated that the 49K component exhibited a specificity for IgE, thus confirming that the 49K component was the murine B lymphocyte Fc receptor for IgE (Fc epsilon R). Some rebinding to rabbit IgG was observed, and by using 2.4G2, the monoclonal anti-Fc gamma 2b receptor (Fc gamma 2bR) antibody to isolate the IgG2b receptor, a clear distinction between the FC gamma 2bR and the 49K IgE receptor was demonstrated by SDS-PAGE analysis. Rabbit IgG was thus found to interact with both the 49K Fc epsilon R and the 59K FC gamma 2bR. The murine B lymphocyte Fc epsilon R was compared with the human B cell Fc epsilon R from the RPMI 8866 cell line and with the high affinity Fc epsilon R on rat basophilic leukemia cells by one- and two-dimensional gel analyses. The lymphocyte Fc epsilon R from mouse and human was found to be quite similar with respect to m.w. (45 to 50K) and isoelectric point (pI 4.5 to 5.0), whereas the basophil Fc epsilon R differed in both aspects.
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PMID:The murine lymphocyte receptor for IgE. I. Isolation and characterization of the murine B cell Fc epsilon receptor and comparison with Fc epsilon receptors from rat and human. 622 1

Both human lymphoblastoid (RPMI 6410) and murine leukemia (L1210) cells were found to have a component of uridine transport which is insensitive to the nucleoside transport inhibitor nitrobenzylthioinosine (NBMPR). In both cell lines NBMPR-insensitive uridine transport is inhibited by other nucleosides and by the sulfhydryl reagent p-chloromercuribenzenesulfonate. In RPMI 6410 cells NBMPR-insensitive transport accounts for only 2% of the initial rate of uridine transport. In contrast, 20% of the initial rate of transport of L1210 cells is insensitive to NBMPR, and uridine uptake over longer periods (10 min) is completely insensitive to NBMPR.
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PMID:Nitrobenzylthioinosine-insensitive uridine transport in human lymphoblastoid and murine leukemia cells. 630 52

5'-Nucleotidase activity of normal human embryonic lung fibroblasts (IMR-90) was found to be inhibited by the homogenates of seven different cell lines originated from patients with different kinds of leukemia and of fresh lymphocytes from a patient with Sezary syndrome (circulating T-cell lymphoma). About 97% of the inhibiting activity was found in the soluble fraction of RPMI 8402 cells, a cell line originated from the lymphocytes of a patient with acute lymphocytic leukemia. This inhibiting activity was not destroyed by dialysis, heating at 56 degrees C for 30 min, nor digestion with RNAase or DNAase. About 85% of the inhibiting activity was destroyed by digestion with papain at 37 degrees C for 1 h and it was destroyed completely by heating at 100 degrees C for 30 min. When the heated (56 degrees C for 30 min) soluble fraction of RPMI 8402 cells was mixed with the homogenate of IMR-90 cells, it had no effect on the activities of alkaline, neutral or acid phosphatases, nor of N-acetyl-beta-D-glucosaminidase or cytochrome c oxidase of IMR-90 cells. Preincubating the mixed samples for 1, 20 and 45 min, respectively, before adding the substrate, the heated soluble fraction of RPMI 8402 cells did not increase the percentage of inhibition for 5'-nucleotidase of the homogenate of IMR-90 cells. No inhibition of other enzyme activities was observed under similar conditions. These data suggest that the inhibiting activity is due to a protein(s) that is not a protease. The inhibiting activity was found in a single peak after the soluble fraction was fractionated by Sephadex G-100 chromatography and sedimentation centrifugation. The molecular weight of the inhibitor was found to be approx. 35,000 by comparing its retention volume and sedimentation rate with those of proteins of known molecular weight. The present study suggest that the previously reported undetectability of 5'-nucleotidase in permanent cell lines could be due to the presence of a protein inhibitor for 5'-nucleotidase in these human leukemic cell lines. It also supports the hypothesis that the increased 5'-nucleotidase activity in normal senescent cells in vitro may be a control in cellular aging that is missing from leukemic cells in vitro.
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PMID:Implications of a 5'-nucleotidase inhibitor in human leukemic cells for cellular aging and cancer. 630 89

The characteristics of nucleoside transport were examined in L1210 murine leukemia cells and five other cultured neoplastic cells. The initial rates of uridine, adenosine, and thymidine transport in L1210 cells were only partially inhibited by 1 microM nitrobenzylthioinosine (NBMPR), a potent inhibitor of nucleoside transport in other cells. The IC50 for NBMPR inhibition of uridine transport was 5 nM, but 20% of the activity remained insensitive to concentrations as high as 3 microM. Uridine uptake in the presence of 1 microM NBMPR was saturable and was inhibited by other nucleosides, suggesting the participation of an NBMPR-insensitive transport mechanism. There appeared to be little difference in the specificity of NBMPR-sensitive and -insensitive transport for the physiological nucleosides. Uridine, adenosine, and thymidine were all substrates for both mechanisms, and the Km values for total and NBMPR-insensitive uridine transport were the same (250 microM). Furthermore, little difference was found in the ability of several other nucleosides to inhibit total or NBMPR-insensitive uridine transport. In both cases, adenosine was the most effective inhibitor while cytidine and deoxycytidine were the least effective. The two transport processes did, however, differ from each other in their sensitivity to p-mercuribenzenesulfonate (pMBS). NBMPR-insensitive uridine transport was inhibited by pMBS with an IC50 less than 25 microM, while the IC50 for NBMPR-sensitive transport was greater than 400 microM. Cloning of the parent L1210 cell line indicated that both NBMPR-sensitive and -insensitive transport occurred in the same cell. Both types of uridine transport activity were also observed in three other cell lines (RPMI 6410, L5178Y, and P388), while two lines, S49 and Walker 256, exhibited only NBMPR-sensitive and -insensitive transport, respectively. The level of NBMPR-insensitive transport was an important determinant in the ability of NBMPR to inhibit uridine uptake over prolonged periods (10 min), with as little as 20% NBMPR-insensitive transport sufficient to render uptake over 10 min virtually insensitive to NBMPR. The existence of these two types of nucleoside transport activity in mammalian cells may have important implications in the chemotherapeutic use of transport inhibitors in combination with cytotoxic nucleosides or with inhibitors of pyrimidine and purine biosynthesis.
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PMID:Heterogeneity of nucleoside transport in mammalian cells. Two types of transport activity in L1210 and other cultured neoplastic cells. 631 17

A new monoclonal antibody specific for human B cell differentiation antigen (HLB-1) is produced by a hybridoma established by fusion of splenocytes of mice immunized with the Epstein-Barr virus (EBV)-transformed peripheral B cell line, RPMI-8057. This monoclonal, antibody designated anti-HLB-1 monoclonal antibody (anti-HLB-1), reacted with surface immunoglobulin (sIg)-positive B cells of normal peripheral blood and lymphoid tissues and sIg-positive leukemic cells. The cells of T cell leukemia, non-T non-B acute lymphoblastic leukemia (ALL) and nonlymphoid leukemia were HLB-1 negative. These data were further confirmed by studying a panel of cultured human hematopoietic cell lines. Anti-HLB-1 reacted with B cell lines derived from pre-B, Burkitt's lymphoma, B cell type ALL and EBV-transformed peripheral B cells. Anti-HLB-1 was reactive with only one of three human myeloma cell lines, and with none of the T cell, myeloid and non-T non-B ALL cell lines. This newly defined HLB-1 antigen is different from other conventional human B cell markers such as sIg, Ia antigens, and receptors for the Fc portion of Ig and complement C3.
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PMID:A monoclonal antibody defining human B cell differentiation antigen (HLB-1 antigen). 640 55

We have generated and characterized a hybridoma monoclonal antibody, termed SN1, that defines a unique human T-cell leukemia antigen. This antibody was generated by using a human leukemia antigen preparation isolated from cell membranes of MOLT-4, a leukemia T-cell line derived from a patient with T-cell-type acute lymphoblastic leukemia (T-ALL). SN1 was characterized by a sensitive microscale radioimmunoassay using a variety of cultured and uncultured human cells. In selected cases, the cell specimens were further tested by immunoperoxidase staining and an immunofluorescence staining test. The results of the radioimmunoassay were in agreement with those of the two other tests. Among the various cultured malignant and nonmalignant cell lines, SN1 reacted only with leukemia T-cell lines derived from patients with T-ALL; it reacted with all six T-ALL cell lines tested-i.e., JM, CCRF-CEM, CCRF-H-SB2, RPMI 8402, PEER, and MOLT-4. In the case of uncultured cell specimens derived from cancer patients, SN1 reacted with four of four cases of T-ALL but did not react with specimens derived from 41 patients with other types of cancer. SN1 did not react with any normal human cell specimens tested, both cultured and uncultured. These specimens include normal lymphoblastoid cell lines, thymocytes, bone marrow cells, spleen cells, lymph node cells, peripheral blood mononuclear cells, lymphocytes containing B and T cells, purified T cells, monocytes, granulocytes, erythrocytes, and platelets. Furthermore, SN1 did not react with phytohemagglutinin-activated T cells nor with concanavalin A-activated T cells. The results show that monoclonal antibody SN1 defines a type of human leukemia antigen that is expressed on the cell surface of T-cell-type ALL cells. The results further show the usefulness of SN1 in the diagnosis of cancer patients and suggest its therapeutic potential. We designate this antigen TALLA, a T-cell ALL antigen.
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PMID:Monoclonal antibody that defines a unique human T-cell leukemia antigen. 660 Aug 41

We generated a monoclonal antibody, termed SN2, which defines a human T cell leukemia-associated cell surface glycoprotein, GP37, with an approximate m.w. of 37,000. This antibody was generated by using a human leukemia antigen preparation. The reactivity and specificity of SN2 were characterized by a sensitive radioimmunoassay against a variety of cultured and uncultured human cells. In selected cases, the cell specimens were tested further by indirect immunofluorescence staining. Among the various cultured malignant and nonmalignant human cell lines tested, SN2 reacted only with leukemic T cell lines, with one exception. It reacted with 10 of 11 leukemic T cell lines tested; the 10 reactive cell lines are PEER, JM, MOLT-4, CCRF-CEM, CCRF-H-SB2, RPMI 8402, DND-41, HPB-ALL, SKW-3, and HPB-MLT; the unreactive line was HUT 78. The reactive cell lines were derived from patients either with T cell-type acute lymphoblastic leukemia (the first eight cell lines), with T cell chronic lymphocytic leukemia (SKW-3), or with Japanese adult T cell leukemia-lymphoma (HPB-MLT). The unreactive cell line, HUT 78, was from a patient with Sezary syndrome. Results consistent with the above were obtained from studies in which uncultured malignant cell specimens from different cancer patients were tested against SN2; SN2 reacted only with T leukemia cells. Among various uncultured normal cell specimens tested, SN2 did not react with thymocytes, bone marrow cells, peripheral blood lymphocytes containing B and T cells, purified T cells, monocytes, granulocytes, or erythrocytes. It did, however, react with platelets.
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PMID:Monoclonal antibody SN2 defining a human T cell leukemia-associated cell surface glycoprotein. 660 54

Plasma and medium composition significantly affect cellular association of the lipid-soluble antifolate 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine (DDMP). This was demonstrated by measuring association of labeled drug with cells and by assaying the antimetabolic effect of DDMP on incorporation of deoxyuridine into DNA. Uptake of both aqueous and lipid-soluble antifolates was substantially reduced in the human lymphoblastoid cell line WIL-2 when Eagle's minimum essential medium (EMEM) was substituted for a basal salts solution containing glucose [DDMP approximatley 50%, methotrexate (MTX) approximately 30%]. Uptake of DDMP, however, was inhibited by the amino acid fraction of EMEM or glutamine alone, whereas MTX uptake was unaffected by amino acids. Further studies with human leukemia cells showed that DDMP was only about 25% as effective an inhibitor of deoxyuridine incorporation in autologous human plasma when compared to its inhibitory effect in RPMI-1640 medium MTX inhibition of deoxyuridine incorporation in these cells was essentially unaffected by substitution of autologous human plasma for RPMI-1640 medium. Replacing EMEM with pooled human plasma resulted in a 60-70% decrease in DDMP uptake but had only a marginal effect upon MTX uptake. Thus the choice of medium is important in studies of lipid-soluble antifolates such as DDMP that have a high affinity for cellular and medium lipoprotein components.
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PMID:Human plasma and amino acids as moderators of uptake and metabolic consequences of antifolates in WIL-2 and human leukemia cells. 693 1

The leukocyte migration inhibition assay has been widely used as an in vitro test cell mediated immunity to various substances. Using a leukemic cell line (RPMI 8402) as the source of antigen, we assayed leukocyte migration inhibition in seven children with acute lymphocytic leukemic (ALL), their family members (14 patients and 13 siblings), and 17 healthy adult controls. In six families, the patients showed stronger inhibition than their family members or controls. The patients differed significantly from their family members (P = 0.003) and all other persons without leukemia (P = 0.02). These results suggest that patients with ALL have developed a specific cellular immune reactivity to an antigen or antigens on leukemic cells, while their family members have not.
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PMID:Leukocyte migration inhibition of leukemia-associated antigen in children with acute leukemia and their family members. 696 64


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