Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We found that recombinant and natural lymphotoxin differ from TNF in that they only marginally induce differentiation of human myeloblastic leukemia ML-1 cells. Even at 1,000-fold concentrations, lymphotoxin was significantly less potent than TNF. Lymphotoxin competitively, but not completely, inhibited TNF-induced differentiation. Based on studies of the two types of TNF receptors (55 kDa and 75 kDa) using monoclonal antibodies, the binding activity of lymphotoxin to the receptors was less than 1/3 that of TNF, but lymphotoxin could bind to both TNF receptors. Both receptors were involved in induction of differentiation by TNF. However, lymphotoxin, differed from TNF; it seemed to be weak in sending signals for differentiation through the 75 kDa receptor.
 ...
PMID:Lymphotoxin and TNF differ greatly in capacity to induce differentiation of human myeloblastic leukemia ML-1 cells. 806 28

1. Using the RT/PCR method, we examined mRNA expression of several inflammatory factors in mouse embryos during mid-late embryonal development. mRNAs of tumor necrosis factor (TNF)-alpha, TNF-beta, their receptors (TNF-RI, TNF-RII), transforming growth factor (TGF)-beta, were expressed constitutively in most of the embryonic tissues. 2. While mRNAs of other factors, interleukin (IL)-1 alpha, IL-1 beta, IL-3, IL-6, granurocyte-colony stimulating factor (G-CSF), leukaemia inhibitory factor (LIF), and interferon (IFN)-gamma were only limitedly expressed. 3. The mRNAs of several complement components (C2, C3, C4, C5) and receptors (CR1, CR2) were also detected. Among them, the expression of C3 and CR1 were prominent. These results strongly support our idea that inflammation-like system play an important role to regulate embryogenesis.
 ...
PMID:Constitutive expression of TNF-alpha and -beta genes in mouse embryo: roles of cytokines as regulator and effector on development. 813 38

The production of interleukin-2 (IL-2) by phytohemagglutinin (PHA)-stimulated human leukemia T cell lines was significantly increased by 6 different cytokines. The most effective cytokines were interleukin-1 alpha (IL-1 alpha) and IL-1 beta; less effective were interferon-alpha (IFN-alpha), tumor necrosis factor-alpha (TNF-alpha), IFN-beta and TNF-beta. The combinations of two cytokines had synergistic or additive effects and increased IL-2 production to a greater extent than either cytokine alone. Other cytokines tested, such as IL-3, IL-4, IL-6, IL-7, IL-8 and IFN-gamma, had no effect on IL-2 production. However, a remarkable heterogeneity in sensitivity to the enhancing effects of the active cytokines was found among the IL-2-producing T cell lines studied. While IL-2 production in the most sensitive cell line, MOLT-16, was increased by all 6 active cytokines, other cell lines responded by increasing IL-2 production to stimulation with only some of the cytokines tested. The production of IL-2 in T cell line H9 was not enhanced by any of the cytokines used. These results show that several cytokines can increase IL-2 production by having a direct effect on the activated IL-2-producing T cells, but also that the outcome of the regulatory effects of individual cytokines depends considerably upon the individual IL-2-producing T cell clone.
 ...
PMID:Enhancement of interleukin-2 (IL-2) production by 6 different cytokines: heterogeneity among IL-2 producing T cell clones. 834 81

Natural killer (NK) cells lyse autologous and allogeneic target cells even in the absence of major histocompatibility complex (MHC) class I antigens on the target cells. Recently, however, human allospecific NK cell clones have been generated that recognize at least five distinct specificities inherited recessively and controlled by genes linked to the MHC. Because the genetic specificity of these alloreactive NK cells in vitro appears analogous to that of in vivo NK cell-mediated murine hybrid resistance, i.e., the rejection of parental bone marrow in irradiated F1 animals, we tested the ability of human alloreactive NK clones to recognize allogeneic hematopoietic progenitor cells. NK cells from two specificity 1 alloreactive NK clones, ES9 and ES10, significantly and often completely suppressed colony formation by purified peripheral blood hematopoietic progenitor cells from specificity 1-susceptible donors, but had no significant effect on the cells of specificity 1-resistant donors. Activated polyclonal NK cells were less efficient than the NK clones in inhibiting colony formation and had a similar effect on cells from both specificity 1-susceptible and -resistant donors. The alloreactive NK clones produced cytokines with a suppressive effect on in vitro hematopoiesis, such as interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha), when exposed to phytohemagglutinin blasts from specificity 1-susceptible, but not -resistant donors. However, the mechanism by which alloreactive NK cells inhibit colony formation is more consistent with a direct cytotoxic effect than with the production of inhibitory cytokines because antibodies (anti-IFN-gamma, alpha-TNF-alpha, and -lymphotoxin) that completely blocked the inhibition by polyclonal NK cells had only a minimal effect on the inhibition by the alloreactive clones. Moreover, the alloreactive clones were directly cytolytic in a 51Cr release assay against enriched preparations of peripheral blood progenitor cells from specificity 1-susceptible donors. These data indicate that the alloreactive NK cells are likely the human counterpart of the cells mediating murine hybrid resistance and that these cells might play clinically important roles in rejection or in graft-versus-leukemia reactions after allogeneic bone marrow transplantation.
 ...
PMID:Regulation of hematopoiesis in vitro by alloreactive natural killer cell clones. 845 6

The relationship between cytokine production patterns and immunophenotype marker profiles was studied in a panel of 18 T cell lines originating from various types of hematological malignancies and from human T cell lymphotropic virus-I (HTLV-I)-transformed cells. The production of 11 different cytokines by both unstimulated and phytohemagglutinin (PHA)-stimulated cells was tested. The production of interleukin-1 alpha (IL-1 alpha), IL-2, IL-3/granulocyte-macrophage colony stimulating factor (GM-CSF), IL-4, IL-5, IL-6, tumor necrosis factor-alpha (TNF-alpha), TNF-beta and interferon-gamma (IFN-gamma) by some of the cell lines was detected, and no cell line produced IL-1 beta or IFN-alpha. All 4 cell lines producing IL-1 alpha also produced other inflammatory cytokines, namely, IL-6, TNF-alpha and TNF-beta, but they did not produce IL-2. The IL-1 alpha-producing cell lines had the phenotype of mature, activated T cells, regardless of leukemia or transformant origin (TdT-, CD4+, CD8-, IL-2R+, HLA-DR+) and all were HTLV-1+. However, the production of other cytokines followed a random distribution, and no relationship emerged between cytokine production patterns and alpha/beta or gamma/delta type of T cell receptor (TcR) expression, immunophenotypic marker profiles, or the clinical origin of the cells. These results thus show that human leukemia and HTLV-I-transformed T cell lines can produce a large number of biologically active cytokines and that, except for the association of inflammatory cytokine production with mature activated cells, random patterns of cytokine production reflect the individuality of leukemia cell lines.
 ...
PMID:Multiple and heterogeneous patterns of cytokine production in 18 leukemia and in vitro transformed mature T cell lines reflect the individuality of human leukemias. 849 92

To ascertain whether the tumor cells can regulate the host immune systems through the production of the cytokines or their receptors, we examined the expressions of tumor necrosis factor alpha (TNF alpha), tumor necrosis factor beta (TNF beta), interleukin 2 (IL-2) and interleukin 2 receptor alpha chain (IL-2R alpha) on the human cancer cell lines by Northern blot analysis. We used K562 (leukemia cell line), MCF-7 (breast cancer cell line), LS180, HT29 (colon cancer cell lines), SH101 (gastric cancer cell line) and PH101 (pancreas cancer cell line). Expressions of TNF alpha, TNF beta and IL-2 mRNA were not detected in any of the tumor cell lines. However, 1.4 and 3.5 kilobases of the IL-2R alpha mRNA were expressed in the PH101 cells, but not in the other five cell lines. Furthermore, IL-2R alpha was detected on the cell surface of the PH101 cells by the flow-cytometric analysis with an anti-IL-2R alpha monoclonal antibody. Interestingly, the soluble IL-2R alpha (sIL-2R alpha) was found in the conditioned media obtained from the PH101 cell culture with a sandwich enzyme immunoassay. Moreover, the sIL-2R alpha secreted from the PH101 cells blocked the IL-2 dependent lymphocyte proliferation. These results indicate that the expression of IL-2R alpha on PH101 might suppress the IL-2 induced lymphocyte proliferation.
 ...
PMID:The expression and biological activity of IL-2 receptor on a human pancreas cancer cell line. 850 43

Prostate tumor cells preferentially metastasize to bony sites and lymph nodes at a frequency in excess of that which would be predicted by random tumor cell dissemination. In order to determine whether chemoattractants in these organs promote organ-specific metastasis, we utilized human cell lines derived from and/or related to these organs as sources of potential chemoattractants. Secretory proteins derived from the cell lines MG-63 (osteosarcoma), SK-ES-1 (Ewing's sarcoma), and KG-1 (leukemia) stimulated chemomigration of the TSU-pr1 prostate tumor cells in a dose-dependent manner in Boyden chambers. In addition, secretory proteins from a human prostatic stromal cell line (hPS) and from the TSU-Pr1 prostate tumor cell line were also able to stimulate chemomigration of the TSU-pr1 cells through Boyden chambers. Since lymph nodes and bony sites represent organs of hematopoietic/lymphoid proliferation and activation, we undertook identification of specific cytokines present at these sites which may promote the chemomigration of prostate tumor cells. In this context, the cytokines interleukin-1 alpha, interleukin-2, interleukin-6, tumor necrosis factor-beta, transforming growth factor-beta, interferon alpha 2-a, and granulocyte-macrophage colony-stimulating factor did not stimulate chemomigration of the TSU-pr1 prostate tumor cell line. In contrast, the cytokine epidermal growth factor (EGF) stimulated chemomigration of the TSU-pr1 prostate tumor cells through the Boyden chambers in a dose-dependent manner. Western blot analysis of secretory proteins from the cell lines KG-1, SK-ES-1, MG-63, hPS, and TSU-pr1 identified EGF-immunoreactive proteins in all cases. In addition, EGF immunoreactivity was localized to the stroma of the human prostate, the osteogenic stroma of pelvic medullary bone, and the stroma within the capsule and trabeculae of pelvic lymph nodes. Hence, these results demonstrate that the cytokine EGF promotes the chemomigration of the TSU-pr1 prostate tumor cell line, and that EGF within the stroma of pelvic lymph nodes and medullary bone may act as a chemoattractant for prostate tumor cells, thereby facilitating the preferential formation of metastatic foci within these organs.
 ...
PMID:Epidermal growth factor (EGF) promotes chemomigration of a human prostate tumor cell line, and EGF immunoreactive proteins are present at sites of metastasis in the stroma of lymph nodes and medullary bone. 854 75

We have examined the effects of tumor necrosis factor alpha (TNF) and lymphotoxin (LT) on gelatinase (72 kDa and 92 kDa) and tissue inhibitor of metalloprotease 1 (TIMP1) secretion by human myeloblastic leukemia cells (ML-1) in vitro. TNF (0.1-30 ng/ml) significantly stimulated 92 kDa gelatinase secretion in a dose-dependent manner, but did not significantly stimulate 72 kDa gelatinase secretion. LT also significantly stimulated 92 kDa gelatinase secretion, but the stimulation was less effective compared to TNF. TNF, but not LT, concentrations at 30 ng/ml slightly stimulated TIMP1 secretion. Because 92 kDa gelatinase is thought to play a pivotal role in tumor invasion, we examined the effect of TNF or LT on ML-1 cell invasion through a reconstituted basement membrane (Matrigel). Exposure of ML-1 cells to TNF (3, 10, and 30 ng/ml) or LT (3, 10, and 30 ng/ml) stimulated ML-1 cell invasion through Matrigel in a dose-dependent manner in vitro. The data suggest that TNF- and LT-stimulated 92 kDa gelatinase secretion could play an important role in TNF- or LT-stimulated ML-1 cell invasion.
 ...
PMID:Tumor necrosis factor alpha and lymphotoxin stimulate human myeloblastic leukemia cell (ML-1) invasion through a reconstituted basement membrane (Matrigel) with concomitant induction of 92 kDa gelatinase secretion. 855 14

Epstein-Barr virus (EBV) and human immunodeficiency virus type 1 (HIV-1), as well as human T-cell leukemia-lymphoma virus type I (HTLV-I), may interact in the pathogenesis of human retroviral infections. The placental syncytiotrophoblast layer represents a barrier protecting the fetal compartment from exposure to retroviruses. We studied the interactions of EBV with HIV-1 and HTLV-I in human term syncytiotrophoblast cells to investigate the significance of double infections in transplacental transmission of human retroviruses. We found that syncytiotrophoblast cells could be productively infected with EBV. Dual infection of the cells with EBV and HTLV-I resulted in full replication cycle of otherwise latent HTLV-I. In contrast, the restricted permissiveness of syncytiotrophoblasts for HIV-1 was not influenced by coinfection of the cells with EBV. Infection of syncytiotrophoblast cells with EBV, but not HTLV-I, induced interleukin-2 and interleukin-6 secretion, and augmented secretion occurred on coinfection with both viruses. Coinfection of syncytiotrophoblast cells with EBV and HTLV-I induced tumor necrosis factor-beta and transforming growth factor-beta 1 secretion, but infection with either virus alone did not lead to secretion of these cytokines. Permissive replication cycle of HTLV-I was induced by the EBV immediate-early gene product Zta. Pseudotype formation between EBV and HTLV-I in coinfected syncytiotrophoblast cells was not found. Our data suggest that activation of HTLV-I gene expression by EBV in coinfected syncytiotrophoblast cells may be a mechanism for transplacental transmission of HTLV-I.
 ...
PMID:Epstein-Barr virus permissively infects human syncytiotrophoblasts in vitro and induces replication of human T cell leukemia-lymphoma virus type I in dually infected cells. 912 52

The Tax protein of Human T-cell leukemia virus type 1 (HTLV-1) is important for the T-cell immortalizing properties of this virus in vitro and is considered to be responsible for the early stages of leukemogenesis in infected hosts. Tax can upregulate expression of TNF-alpha and TNF-beta, as well as potentiate apoptosis in activated T-cells and in serum starved murine fibroblasts. To examine the role of CD95 (APO-1/Fas) and ICE-proteases in Tax-mediated active T-cell death, Jurkat T cells expressing (APO(S)) or lacking (APO(R)) cell surface expression of CD95 (APO-1/Fas) were genetically modified to express hormone-inducible HTLV-1 Tax constructs. Hormone-inducible action of Tax alone was sufficient to promote programmed cell death in CD95-expressing Jurkat T-cell clones. In contrast, clones lacking CD95 surface expression were resistant to the antiproliferative action of Tax. Both APO(S) and APO(R) clones exhibited Tax-dependent upregulation of CD95 ligand and TNF-alpha. Blocking experiments suggested that while the apoptotic action of Tax critically required ICE-protease function it was largely independent of cell surface interaction of CD95 ligand or TNF-alpha with their corresponding receptors. These observations strongly implicate ICE-proteases in Tax-induced T-cell death, and suggest a possible involvement of CD95 in this process.
 ...
PMID:ICE-proteases mediate HTLV-I Tax-induced apoptotic T-cell death. 917 2


<< Previous 1 2 3 4 5 6 7 Next >>