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)

Vitamin K (VK) congeners (VK1, VK2, and VK3) have been used as antihemorrhagic agents, while VK3 has also been found to inhibit growth in various rodent and human tumor cells. We have compared the antitumor activities of vitamin K1, K2, and K3 against a panel of human cancer cell lines. For each test agent, a dose-response profile was generated by using an MTT (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) and an SRB (sulforhodamine B) assay. Both assays yielded similar results. The respective ID50 values of VK3 in five hepatoma cell lines, HA59T, HA22T, PLC, HepG2, and Hep3B, of increasing differentiation state, were 42, 36, 28, 27, and 20 microM. For nasopharyngeal carcinoma (CG1), leukemia (U937), oral epidermoid carcinoma (KB), and breast carcinoma (BC-M1) cells, the ID50 values of VK3 were 26, 15, 25, and 33 microM, respectively. For all the above cells, the ID50 values of VK1 ranged from 6 to 9 mM, and the ID50 values of VK2 ranged from 1 to 2 mM. Thus, the relative potencies of antitumor activity of VK3 compared to VK2 and to VK1 are about 60- and 300-fold, respectively. These results support the preference for use of VK3 over VK1 and VK2 in cancer therapy.
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PMID:Comparison of antitumor activity of vitamins K1, K2 and K3 on human tumor cells by two (MTT and SRB) cell viability assays. 849 42

1. HL-60 human leukemia cells are a widely employed model system for the analysis of signal transduction processes mediated via regulatory heterotrimeric guanine nucleotide-binding proteins (G-proteins). HL-60 promyelocytes are pluripotent and can be differentiated into neutrophilic or monocytic cells. 2. HL-60 cells express formyl peptide-, complement C5a-, leukotriene B4 (LTB4)- and platelet-activating factor receptors, receptors for purine and pyrimidine nucleotides, histamine H1- and H2-receptors, beta 2-adrenoceptors and prostaglandin receptors. 3. The major G-proteins in HL-60 cells are pertussis toxin (PTX)-sensitive Gi-proteins (Gi2 > Gi3). Gs-proteins and G-proteins of the Gq-family (e.g., G16) are expressed, too. 4. G-protein-regulated effector systems in HL-60 cells are adenylyl cyclase and phospholipase C-beta 2 (PLC-beta 2) and, possibly, phospholipase D (PLD), nonselective cation (NSC) channels and NADPH oxidase. 5. The expression of signal transduction pathways in HL-60 cells strongly depends on the differentiation state of cells. 6. Formyl peptides, via Gi-proteins, mediate activation of PLC, PLD, NSC channels, NADPH oxidase and azurophilic granule release and are referred to as full secretagogues. In dibutyryl cAMP (Bt2cAMP)-differentiated HL-60 cells, C5a and LTB4 are partial and incomplete secretagogues, respectively. There are substantial differences in the Gi-protein activations induced by formyl peptides, C5a and LTB4. 7. In HL-60 promyelocytes, purine and pyrimidine nucleotides mediate activation of PLC and NSC channels largely via PTX-insensitive G-proteins and induce functional differentiation. In Bt2cAMP-differentiated HL-60 cells, they additionally activate PLD, NADPH oxidase and granule release via PTX-sensitive and -insensitive pathways. ATP and UTP are partial secretagogues. Multiple types of receptors (i.e., P2Y- and P2U-receptors and pyrimidinocyeptors) may mediate the effects of nucleotides in HL-60 cells. 8. Bt2cAMP- and 1 alpha,25-dihydroxycholecalciferol-differentiated HL-60 cells express H1-receptors coupled to Gi-proteins and PTX-insensitive G-proteins. In the former cells, histamine mediates activation of PLC and NSC channels, and in the latter, activation of NSC channels. Histamine is an incomplete secretagogue in these cells. 9. HL-60 promyelocytes express H2-receptors coupled to adenylyl cyclase, PLC, and NSC channels. There are substantial differences in the agonist/antagonist profiles of H2-receptor-mediated cAMP formation and rises in cytosolic Ca2+ concentration, indicative of the involvement of different H2-receptor subtypes. H2-receptors mediate functional differentiation of HL-60 cells. 10. Certain cationic-amphiphilic histamine receptor ligands (i.e., 2-substituted histamines, lipophilic guanidines, and a histamine trifluoromethyl-toluidide derivative) show stimulatory effects in HL-60 cells that are attributable to receptor-independent activation of Gi-proteins.
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PMID:G-protein-coupled receptors in HL-60 human leukemia cells. 874 93

To improve the efficiency of retroviral transduction into human hepatoma cells, new liposomes were prepared using different cationic and neutral lipids. Their effect on the retroviral transduction was evaluated using PLC/PRF/5 hepatoma cells and Moloney murine leukemia virus-derived retrovirus carrying herpes simplex thymidine kinase gene. Those liposomes consisted of cationic lipids with a long spacer were highly efficient in enhancing retroviral transduction and also less cytotoxic. On the other hand, the length of hydrophobic domains of neutral lipids was not correlated with the efficiency in enhancing the retroviral transduction. These results suggest that liposomes which effectively enhance retrovirus transduction can be developed by using cationic lipids with new spacers.
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PMID:Structural characteristics of cationic liposomes with potent enhancing effect on retroviral transduction into human hepatoma cells. 894 15

Aggregation of the high-affinity receptor for IgE (Fc eta RI) on the surface of intact or permeabilized rodent mast cells results in tyrosine phosphorylation of phospholipase C-gamma 1 (PLC gamma 1) and PLC gamma 2, and translocation of both isozymes to the particulate fraction. We report here that activation of resident tyrosine kinases by the addition of adenosine triphosphate (ATP), orthovanadate, and Mg2+ to rat basophilic leukemia cell (RBL) lysates induces an association of PLC gamma 2 with the Triton-insoluble particulate fraction, with a parallel increase in tyrosine phosphorylation of cellular proteins. Both PLC gamma 2 translocation and tyrosine phosphorylation are supported by millimolar Mg2+ or Mn2+ but not by Ca2+. Both tyrosine phosphorylation and PLC gamma 2 translocation are inhibited by genistein. These data suggest that in vitro activation of tyrosine kinase activity in broken cell preparations induces the formation of association between PLC gamma 2 and ligands with the Triton-insoluble fraction.
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PMID:Translocation of phospholipase C-gamma 2 induced by in vitro activation of protein tyrosine kinase activity in mast cell lysates. 895 50

Two variant sublines of murine L1210 leukemia cells (L1210A and L1210JF) overexpress the cell surface folate receptor (FR). The membrane bound FR in L1210A cells exhibited significantly (up to 17-fold) greater relative affinities for (6S)-N5-methyltetrahydrofolate, (6S)-N5-formyltetrahydrofolate and methotrexate compared to the FR in L1210JF cells. Furthermore, receptor-mediated transport of [3H]-(6S)-N5-methyltetrahydrofolate was much more efficient in L1210A cells compared to L1210JF cells. When solubilized with Triton X-100, the ligand binding characteristics of FR from both sublines resembled those of the receptor associated with L1210 JF cell membranes. N-terminal amino acid sequence analysis as well as RT-PCR analysis of the entire coding region revealed a single species of FR in both cells, identical to murine FR-alpha. The FR in L1210JF cells was sensitive to phosphatidylinositol specific phospholipase C (PI-PLC) indicating the presence of a glycosyl-phosphatidylinositol (GPI) membrane anchor while the FR in L1210A cells was resistant to PI-PLC; however, the FR in L1210A cells was released from plasma membranes by nitrous acid, as expected for GPI and its PI-PLC resistant structural variants. Treatment of L1210A cell membranes with mild base rendered the protein PI-PLC sensitive as expected for GPI anchors acylated in the inositol ring and also decreased the affinities of the membrane associated FR for reduced folates. When the cDNA for murine FR-alpha was expressed in parental L1210 cells the protein was PI-PLC resistant but was sensitive to PI-PLC when the cDNA was expressed in human 293 fibroblasts. In L1210JF, L1210A, and parental L1210 cells, several cell surface proteins, including FR, incorporated [3H]ethanolamine, a component of the GPI membrane anchor; however, the labeled proteins were released by PI-PLC only in L1210JF cells. The above results preclude any peculiarity of the FR polypeptide in either L1210 subline as the basis for the observed differences in PI-PLC sensitivity and membrane-associated functions of FR. Partial deglycosylation of membrane associated FR from either cell with N-glycanase did not influence its ligand binding characteristics. The results of this study lead to the hypothesis that variant GPI structures may modulate the function of a protein by influencing its conformation/topography in the membrane. Such effects may be identified by their disappearance/reduction upon detergent solubilization or mild base treatment of the membrane.
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PMID:Variant GPI structure in relation to membrane-associated functions of a murine folate receptor. 897 5

Thrombopoietin (TPO) is the major regulator of the proliferation and differentiation of megakaryocyte precursors through interaction with its receptor encoded by the c-mpl protooncogene. We established the human TPO-dependent leukemia cell line, UT-7/TPO (Blood 87, 4552, 1996). In these cells, TPO activated protein kinase C (PKC) in a time dependent manner. Subsequently, the c-myc gene was transiently induced to a maximal level 60-90 minutes after TPO exposure. In addition, we found that stimulating UT-7/TPO cells with TPO rapidly induces the significant accumulation of inositol 1, 4, 5-trisphosphate (Ins-P3), leading to the mobilization of calcium from intracellular stores. Taken together, the activation of PKC and subsequent c-myc gene induction are involved in the TPO-induced cellular response(s), presumably through the activation of PLC.
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PMID:Protein kinase C and c-myc gene activation pathways in thrombopoietin signal transduction. 907 Feb 65

CD8+ T-cells recognize antigenic peptides presented by major histocompatibility complex (MHC) class I molecules. These peptides bind to MHC class I molecules in the endoplasmic reticulum (ER) lumen. Antigenic peptides are translocated from the cytosol to the lumen of ER by transporter associated with antigen presentation (TAP) proteins. In this study, it is shown that TAP1 polymorphism influences the peptide substrate specificity in human B-lymphoblastoid and tumor cell lines. TAP1A and 1C alleles specifically enhance translocation of model peptides containing basic C-terminal amino acid residue. However, TAP1B allele does not show specificity for the peptide C-terminus. Human basophilic leukemia (Ku812), and hepatocellular carcinoma (PLC/PRF/5) cells express TAP1 molecules and exhibit TAP-mediated allele-specific peptide uptake after gamma-interferon (gamma-IFN) treatment. Ku812 cells express TAP1A and preferentially take up antigenic peptides with a basic C-terminus, however, PLC/PRF/5 cells with the TAP1B allele take up low but equivalent levels of peptides regardless of basic, acidic, or hydrophobic C-termini. Moreover, TAP2 polymorphisms have no influence on the peptide translocation in normal or tumor cell lines. In addition, Daudi, a beta2-microglobulin (beta2m) deficient human Burkitt lymphoma, cell line also showed TAP-dependent peptide uptake. Taken together, these results suggest that human TAP1 but not TAP2 polymorphisms influence the antigenic peptide transport and that this transport is independent of beta2m in this system.
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PMID:Peptide transport in human lymphoblastoid and tumor cells: effect of transporter associated with antigen presentation (TAP) polymorphism. 956 72

Antibody-mediated cross-linking of Thy-1 glycoprotein on the surface of rat mast cells and rat basophilic leukemia (RBL) cells initiates biochemical events which culminate in secretion of allergy mediators. Thy-1, like some other glycosylphosphatidylinositol (GPI)-anchored proteins, forms detergent-insoluble complexes containing protein tyrosine kinases (PTK) and some other molecules which are implicated in the signaling pathway. On the surface of a rat mast cell there are more than 10(6) Thy-1 molecules; however, it is not known which fraction of them is involved in transmembrane signaling, and what exactly is the heterogeneity of Thy-1 complexes. Using sucrose density gradient ultracentrifugation of detergent-lysed RBL cells we found that the density of Thy-1 complexes depended on the detergent used and the lysis conditions employed. Sepharose 4B gel chromatography fractionation followed by density gradient ultracentrifugation revealed both size and density heterogeneity of Thy-1 and Lyn PTK complexes. Cross-linking of surface Thy-1 caused significant changes in the density of these complexes, and an increase in Lyn kinase activity in low/medium-density fractions. Thy-1 in low-density fractions was relatively resistant to cleavage with phosphatidylinositol-specific phospholipase C (PI-PLC). Interestingly, removal of only a small fraction of surface Thy-1 by PI-PLC abolished the cell activation as determined by tyrosine phosphorylation of certain proteins. When Triton X-100 lysates were fractionated at 12000 x g, about 50 % of Thy-1 remained associated with the nuclear/cytoskeleton pellet; this fraction of Thy-1 exhibited an increased sensitivity to PI-PLC. Confocal laser scanning microscopy on fixed cells revealed that the total Thy-1 was relatively homogeneously distributed over the plasma membrane, whereas the PI-PLC-resistant Thy-1 was found mostly in small clusters. The combined data suggest that specialized membrane microdomains enriched in Thy-1 with increased sensitivity to PI-PLC are directly involved in coupling Thy-1 aggregation to transmembrane signaling.
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PMID:Functional heterogeneity of Thy-1 membrane microdomains in rat basophilic leukemia cells. 964 66

It has been postulated that tumor cells expressing Fas ligand (FasL) can evade immune surveillance by inducing apoptosis in T cells expressing Fas. In this study, we investigated FasL expression in 13 human hepatoma cell lines. Strong FasL expression was detected by reverse transcription-polymerase chain reaction or immunofluorescence in Hep G2.2.15, in which the hepatitis-B-virus (HBV) genome was transfected, and in SNU-354, which showed HBx transcripts. To determine the biological activity of FasL, Hep G2.2. 15 was co-cultured with MOLT-4, T-cell-leukemia cells. Hep G2.2.15 induced apoptosis in MOLT-4 and this was inhibited by the antagonistic anti-Fas antibody, ZB4. For further analysis of the role of HBx in the induction of FasL, PLC/PRF/5 cells were transfected transiently with the HBV genome, or HBx, or the frameshift mutant of HBx. In PLC/PRF/5 cells transfected with the HBV genome or HBx but not in cells transfected with the frameshift mutant of HBx, FasL expression was detected. Our data suggest that HBx plays a role in the induction of FasL in hepatoma cells and in the escape from immune surveillance.
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PMID:Expression of fas ligand in human hepatoma cell lines: role of hepatitis-B virus X (HBX) in induction of Fas ligand. 1040 75

Aggregation of the high affinity receptor for IgE (FceRI) on mast cells results in the rapid phosphorylation of tyrosines on the beta and gamma chains of the receptor by the Src family kinase Lyn, which initiates the signaling cascades leading to secretion of inflammatory mediators. The detergent-resistant membranes (DRMs) have been implicated in FcepsilonRI signaling because aggregated receptors emigrate to DRMs that are enriched in certain signaling components. We evaluated the role of DRMs in FcepsilonRI signaling by disruption of DRMs using a cholesterol-binding agent, methyl-beta-cyclodextrin (MBCD). While treatment of rat basophilic leukemia cells with MBCD inhibits degranulation and Ca(2+) mobilization upon aggregation of FcepsilonRI, MBCD hardly affects the aggregation-induced tyrosine phosphorylation of FcepsilonRI as well as other signaling molecules such as phospholipase C-gamma1 (PLC-gamma1). MBCD delocalizes phosphatidylinositol 4,5-bisphosphate from DRMs, which may prevent MBCD-treated cells from producing inositol 1,4,5-trisphosphate by means of activated PLC-gamma1. These data suggest an indispensable role for DRMs in the Ca(2+) response rather than tyrosine phosphorylation, and support a model of receptor phosphorylation in which aggregated FcepsilonRI is tyrosine phosphorylated outside DRMs by constitutively associated Src family kinase Lyn via a transphosphorylation mechanism.
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PMID:Detergent-resistant membrane domains are required for mast cell activation but dispensable for tyrosine phosphorylation upon aggregation of the high affinity receptor for IgE. 1138 99


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