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 cell adhesion molecules, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, are important mediators of immune interactions within the central nervous system (CNS). A wide variety of pro-inflammatory insults to the brain, including viral infection, result in upregulation of these molecules on brain endothelial cells, astrocytes, and microglia. This study investigated the expression of ICAM-1 and VCAM-1 in chronic encephalitis induced by infection with a temperature sensitive (ts-1) strain of Moloney murine leukaemia virus (MoMuLV), an ecotropic murine retrovirus. During the late stages of disease, viral antigen was present in both endothelial cells and microglia, but not astrocytes, in regions of spongiform change and gliosis. In these areas, ICAM-1 staining was detected on activated microglia, but not on endothelial cells or astrocytes. In contrast, no cells showed increased VCAM-1 expression in the CNS. These findings demonstrate that there is cell-specific, differential expression of these adhesion molecules in ts-1 retroviral encephalitis. The lack of endothelial cell expression correlates with the characteristic lack of lymphocytic infiltrate in this chronic retroviral encephalitis and suggests that increased microglial ICAM-1 expression may play a role in the pathogenesis of MoMuLV (ts-1)-mediated neurodegeneration.
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PMID:Differential expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in chronic murine retroviral encephalitis. 1093 66

Human T-cell leukaemia/lymphotropic virus type 1 (HTLV-1), aetiologically linked to lymphoproliferative as well as inflammatory diseases, infects and activates CD4(+) helper T-cells and thus alters immunoregulatory pathways. The viral regulatory Tax protein has been shown previously to induce the expression of vascular cell adhesion molecule-1 (VCAM-1) by T-cells. To determine the functional role of this adhesion molecule, Jurkat T-cells stably expressing either Tax or both Tax and Rex (another viral regulatory protein) were used in binding and coculture assays performed with either control Jurkat cells or primary human T-lymphocytes. Evidence was provided that VCAM-1 acting in synergy with leucocyte function-associated antigen-3 promotes T-cell-T-cell interactions and increases T-cell proliferation. Interestingly, Rex was found to modulate these events. These data establish that VCAM-1 induced by Tax on T-cells thus contributes to the immunopathological process triggered by HTLV-1 infection.
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PMID:Vascular cell adhesion molecule-1 induced by human T-cell leukaemia virus type 1 Tax protein in T-cells stimulates proliferation of human T-lymphocytes. 1125 88

We have previously shown that erythroleukemia cells (K562) transfected with vascular adhesion molecule 1 (VCAM-1) are susceptible to human T-cell leukemia virus type 1 (HTLV-1)-induced syncytium formation. Since expression of VCAM-1 alone is not sufficient to render cells susceptible to HTLV-1 fusion, K562 cells appear to express a second molecule critical for HTLV-induced syncytium formation. By immunizing mice with K562 cells, we have isolated four monoclonal antibodies (MAbs), K5.M1, K5.M2, K5.M3, and K5.M4, that inhibit HTLV-induced syncytium formation between infected MT2 cells and susceptible K562/VCAM1 cells. These MAbs recognize distinct proteins on the surface of cells as determined by cell phenotyping, immunoprecipitation, and Western blot analysis. Since three of the proteins recognized by the MAbs appear to be GPI linked, we isolated lipid rafts and determined by immunoblot analysis that all four MAbs recognize proteins that sort entirely or in large part to lipid rafts. Dispersion of lipid rafts on the cells by cholesterol depletion with beta-cyclodextrin resulted in inhibition of syncytium formation, and this effect was not seen when the beta-cyclodextrin was preloaded with cholesterol before treating the cells. The results of these studies suggest that lipid rafts may play an important role in HTLV-1 syncytium formation.
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PMID:Characterization of new syncytium-inhibiting monoclonal antibodies implicates lipid rafts in human T-cell leukemia virus type 1 syncytium formation. 1146 7

Cell adhesion molecules are involved in a number of biological functions, such as cell survival, cell differentiation, tissue repair, and development. A novel molecule, POEM (preosteoblast epidermal growth factor-like repeat protein with meprin, A5 protein, and receptor protein-tyrosine phosphatase mu domain), was isolated by reverse transcription-polymerase chain reaction using a set of degenerate primers designed after other known epidermal growth factor (EGF)-like motifs. From its structure, POEM was suggested to be a novel adhesion molecule with five EGF-like domains, an Arg-Gly-Asp (RGD) cell binding motif, and a meprin, A5 protein, and receptor protein-tyrosine phosphatase mu (MAM) domain. By in situ hybridization using embryonic day 16.5 (E16.5) mouse embryos, strong expression of POEM mRNA was observed in developing kidney renal tubules, parathyroid and thyroid glands, developing bone, tooth germ, and endocrine organs of the brain. The inner ear, skeletal muscle, smooth muscle (except for the vascular system), and skin were also positive for POEM expression. Bacterial recombinant POEM protein containing the RGD sequence and MAM domain showed strong cell adhesion, spreading, and survival-promoting activities. By mutating the RGD sequence to RGE, the cell spreading and survival activities were significantly decreased, but the MAM domain was shown to contribute only to cell adhesion and not to cell spreading and survival-promoting activities. The distribution of POEM in several tissues was close to that of alpha(8)beta(1) integrin. Therefore, we conducted cell adhesion assays using KA8 cells, a K562 leukemia clone stably expressing alpha(8) integrin. Parental K562 cells, which expressed alpha(5)beta(1) integrin, bound to fibronectin but not to POEM. On the other hand, KA8 cells showed strong binding and spreading on both fibronectin and POEM. These results suggest that POEM is a novel ligand for alpha(8)beta(1) integrin and that POEM may be involved in the development and function of various tissues, such as kidney, bone, muscles, and endocrine organs.
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PMID:Molecular cloning of POEM: a novel adhesion molecule that interacts with alpha8beta1 integrin. 1154 98

The abnormal expression of macrophage colony stimulating factor (M-CSF) isoforms, i.e. membrane bound M-CSF (m-M-CSF) and intracellular M-CSF (c-M-CSF), and their receptor were reported in some leukemia and tumor cells. Furthermore, the nuclear localization of them may be related to poor prognosis and metastasis, while the mechanism is uncertain. We previously reported that m-M-CSF and its receptor played auto-juxtacrine and adhesion molecule role in human leukemia cell line J6-1. In this paper, we show that HL-60 cells highly express M-CSF and its receptor. The localization of positive reactions was mainly in cytoplasma and nuclear in HL-60 cells. In cytoplasma and nuclear, three isoforms of M-CSF were found with molecular weight (MW) of 20, 16 and 14 kDa, while one type of m-CSF receptor (M-CSFR) was discovered with MW of 120 kDa. Immunoprecipitation assay showed that these ligands could exist separately or binding with their receptor. Monoclonal antibody (McAb) against M-CSF and anti-sense oligodeoxynucleotides (ASON) blocking M-CSF expression inhibited the proliferation of HL-60 cells. McAb and ASON regulated the expression of cyclin D1/E, CDK2/4 and p16. Simultaneous administration of both McAb and ASON inhibited the proliferation of HL-60 cells and modulate the expression of cyclins at greater degrees. Our results suggested an autocrine and possible an intracrine loop of M-CSF/M-CSFR in HL-60 cells.
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PMID:Autocrine and possible intracrine regulation of HL-60 cell proliferation by macrophage colony-stimulating factor. 1168 85

It has previously been found that the anti-leukaemia agent Arsenic Trioxide (ATO) causes vascular shutdown in solid tumours and markedly sensitizes tumours to hyperthermia. The present study was designed to evaluate the mechanism of action and dose-dependence of ATO-induced thermosensitization in FSaII and SCK murine tumours. The role of oxidative stress was studied by observing ATO-induced vascular shutdown in vivo and ATO-induced endothelial cell adhesion molecule expression in vitro in the presence or absence of an anti-oxidant. It was found that a dose as low as 2 mg/kg ATO impaired vascular function, as estimated by 86Rb uptake, in the tumour. The degree of tumour growth delay induced by 1 h of hyperthermia at 42.5 degrees C, applied 2 h after ATO injection, was proportional to the dose of ATO administered. In addition, it was found that ATO can directly thermosensitize tumour cells in vitro. The development of massive tissue necrosis in the tumour was observed in the days after treatment, especially with the combination of ATO and heating. ATO-induced adhesion molecule expression in vitro was abolished when the anti-oxidant n-acetyl-cysteine (NAC) was introduced prior to exposure, while the addition of NAC in vivo partially blocked ATO-induced vascular shutdown. These results suggest that the expression of adhesion molecules by the vasculature due to oxidative stress contribute to the ATO-induced selective tumour vascular effects observed and that the clinical use of ATO to increase tumour thermosensitivity via direct cellular and vascular effects appears feasible.
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PMID:Arsenic trioxide induces selective tumour vascular damage via oxidative stress and increases thermosensitivity of tumours. 1475 49

To date, immunoreceptor tyrosine-based inhibition motifs (ITIMs) have been shown to mediate inhibitory properties. We report a novel triggering receptor expressed on myeloid cells (TREM) family member, TREM-like transcript-1 (TLT1), which differs from the activating members because its cytoplasmic tail contains two ITIMs at Y245 and Y281. A TLT1 splice variant (TLT1sp) encodes a different cytoplasmic tail lacking ITIMs. Both isoforms are expressed in resting platelet alpha-granules, which are up-regulated to the cell surface following activation. TLT1 recruited Src homology 2 domain-containing tyrosine phosphatase (SHP)-2 to the "classical" ITIM (Y281) but not the "nonclassical" ITIM (Y245). In contrast to previously characterized ITIM receptors, TLT1 enhanced, rather than inhibited, FcepsilonRI-mediated calcium signaling in rat basophilic leukemia cells, a property dependent on the SHP-2 recruiting classical Y281 ITIM. Therefore, TLT1 represents a new costimulatory ITIM immunoreceptor and is the second ITIM-bearing receptor to be identified in platelets after platelet endothelial cell adhesion molecule-1.
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PMID:Cutting edge: TREM-like transcript-1, a platelet immunoreceptor tyrosine-based inhibition motif encoding costimulatory immunoreceptor that enhances, rather than inhibits, calcium signaling via SHP-2. 1512 62

The organization of cellular niches is known to have a key role in regulating normal stem cell differentiation and regeneration, but relatively little is known about the architecture of microenvironments that support malignant metastasis. Using dynamic in vivo confocal imaging, here we show that murine bone marrow contains unique anatomic regions defined by specialized endothelium. This vasculature expresses the adhesion molecule E-selectin and the chemoattractant stromal-cell-derived factor 1 (SDF-1) in discrete, discontinuous areas that influence the homing of a variety of tumour cell lines. Disruption of the interactions between SDF-1 and its receptor CXCR4 inhibits the homing of Nalm-6 cells (an acute lymphoblastic leukaemia cell line) to these vessels. Further studies revealed that circulating leukaemic cells can engraft around these vessels, suggesting that this molecularly distinct vasculature demarcates a microenvironment for early metastatic tumour spread in bone marrow. Finally, purified haematopoietic stem/progenitor cells and lymphocytes also localize to the same microdomains, indicating that this vasculature might also function in benign states to demarcate specific portals for the entry of cells into the marrow space. Specialized vascular structures therefore appear to delineate a microenvironment with unique physiology that can be exploited by circulating malignant cells.
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PMID:In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. 1595 17

Paclitaxel is a microtubule-stabilizing and apoptosis-inducing drug that is commonly used to treat metastatic breast cancer, although the mechanism of paclitaxel-induced apoptosis remains incompletely understood. Furthermore, adhesion molecule expression is attenuated on mouse mastocytoma and human leukemia cells that survive short-term culture in the presence of paclitaxel. In the present study we show that MDA-MB-435 human breast carcinoma cells that survived culture for 72 h in the presence of submaximal cytotoxic concentrations of paclitaxel (0.02 and 0.01 microg/ml) showed decreased expression of the adhesion molecule ICAM-1. Paclitaxel treatment of MDA-MB-435 cells was associated with the generation of reactive oxygen species (ROS), dissipation of mitochondrial transmembrane potential, and the activation of caspase-3. The antioxidant glutathione protected MDA-MB-435 cells from paclitaxel-induced cytotoxicity and reduced ICAM-1 expression. In addition, a selective inhibitor of caspase-3 (Z-DEVD-FMK), as well as a pan-caspase inhibitor (Z-VAD-FMK), partially prevented the decrease in ICAM-1 expression observed following paclitaxel treatment, but did not protect against paclitaxel-induced cytotoxicity. We conclude that the paclitaxel-induced reduction in ICAM-1 expression by MDA-MB-435 breast carcinoma cells is both ROS- and caspase-dependent, whereas paclitaxel-induced cytotoxicity is ROS-dependent and does not involve caspases. Decreased ICAM-1 expression by breast carcinoma cells that survive paclitaxel treatment may negatively impact on cytotoxic lymphocyte-mediated destruction of paclitaxel-resistant breast cancer cells in the context of chemo-immunotherapy or chemo-adoptive immunotherapy.
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PMID:Contribution of reactive oxygen species and caspase-3 to apoptosis and attenuated ICAM-1 expression by paclitaxel-treated MDA-MB-435 breast carcinoma cells. 1627 28

C-phycocyanin (C-PC), a water-soluble protein pigment, isolated from Spirulina platensis, is of great importance because of its various medical and pharmacological properties. In the present study, we first investigated the effect of highly purified C-PC on growth and proliferation of HeLa cells in vitro. The results indicated that there was a significant decrease in the number of cells that survived for HeLa cells treated with C-PC compared with control cells untreated with C-PC. Further electron-microscopic studies revealed that C-PC could induce characteristic apoptotic features, including cell shrinkage, membrane blebbing, microvilli loss, chromatin margination and condensation into dense granules or blocks. Agarose electrophoresis of genomic DNA of HeLa cells treated with C-PC showed fragmentation pattern (DNA ladder of oligomers of 180-200 bp) typical for apoptotic cells. Flow-cytometric analysis of HeLa cells treated with different concentrations of C-PC demonstrated an increasing percentage of cells in sub-G0/G1 phase. In addition, we found that C-PC could promote the expression of Fas and ICAM-1 (intercellular cell-adhesion molecule 1) protein, while it held back the Bcl-2 (B-cell lymphocytic-leukaemia proto-oncogene 2) protein expression. This suggested that C-PC could induce the activation of pro-apoptotic gene and downregulation of anti-apoptotic gene expression and then facilitate the transduction of tumoural apoptosis signals that resulted in the apoptosis of HeLa cells in vitro. Caspases 2, 3, 4, 6, 8, 9, and 10 were activated in C-PC-treated HeLa cells, which suggested that C-PC-induced apoptosis was caspase-dependent. C-PC treatment of HeLa cells also resulted in release of cytochrome c from the mitochondria into the cytosol that was related to apoptosis of C-PC-treated HeLa cells.
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PMID:Molecular immune mechanism of C-phycocyanin from Spirulina platensis induces apoptosis in HeLa cells in vitro. 1631 16


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