Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied tissue transglutaminase (TGase) expression in human myelomonocytic leukemia cells treated by combinations of all-trans retinoic acid (RA) and 1,25 dihydroxyvitamin D3 (VD). We found that in U937 cells, as in HL-60 and THP-1 cells, RA alone caused an early induction of enzyme activity, correlated with increased mRNA expression. VD alone also induced rapid TGase mRNA expression but in this case TGase enzymatic activity was not measurable until 96 h following onset of treatment. Combinations of both agents had no additional effects over those of RA alone on HL-60 cells, THP-1, and U937 cells during the first 48 h. However, following further incubation, U937 cells expressed increased levels of TGase when treated by both agents. By many criteria, including their sensitivity to various inducers of oxidative burst, lipopolysaccharide-induced production of monokines and in the present work, lysozyme secretion and TGase expression, U937 cells exposed to combinations of RA and VD exhibit a behavior different from those of HL-60 and THP-1 cells. They represent a type of leukemia cell amenable by this treatment to a stage close to that of a terminally differentiated macrophage.
Leukemia 1995 Oct
PMID:Differentiation of U937 myelomonocytic cell line by all-trans retinoic acid and 1,25-dihydroxyvitamin D3: synergistic effects on tissue transglutaminase. 756 22

Apoptosis, or programmed cell death, was studied in B-1 (CD5+ B) cells from NZB mice and their hybrids. NZB mice, as they age, develop clones of B-1 cells with the majority of the clones possessing extra chromosomes (hyperdiploid). These clones differ in growth characteristics, varying from a slow-growing non-invasive clonal expansion of B-1 cells, similar to chronic lymphocytic leukemias (CLL), to an aggressive fast-growing invasive malignancy, similar to Richter's syndrome. Apoptosis was induced in cultures of B-1 cells purified from peritoneal wash-out cells with either anti-immunoglobulin (anti-IgM) or lipopolysaccharide (LPS). The malignant hyperdiploid B-1 cells had increased apoptosis in response to these stimuli as determined by the presence of fragmented DNA. The amount of apoptosis was directly related to the aggressive nature of the B-1 cells. The increased apoptosis observed in malignant B-1 cells was also correlated with the state of activation of the cells. Malignant B-1 cells undergoing high levels of apoptosis had high spontaneous activation and IgM production. The supernatant levels of IgM in unstimulated cultures of aggressive malignant B-1 cells were the same as that stimulated with LPS, indicating that the malignant B-1 clones were maximally activated in vivo. In conclusion, hyperdiploid B-1 cells appear to have altered responses to stimuli that normally activate mature B cells. A signal for apoptosis rather than stimulation may result when malignant B-1 clones have their antigen receptors engaged. The increased apoptosis capability of malignant B-1 cells may be exploited as a therapeutic tool.
Leukemia 1993 Jun
PMID:Apoptosis induction in CD5+(Ly1+) malignant B cells. 768 96

Carboxylic esterases are widely distributed in hematopoietic cells. Monocytes express the esterase isoenzyme (termed 'monocyte-specific esterase', MSE) that can be inhibited by NaF in the alpha-naphthyl acetate cytochemical staining. We examined the expression of MSE in normal cells and primary and cultured leukemia-lymphoma cells. The MSE protein was demonstrated by isoelectric focusing (IEF); MSE mRNA expression was investigated by Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). The following samples were positive for MSE protein and Northern mRNA expression: 20/24 monocytic, 4/32 myeloid, and 1/20 erythroid-megakaryocytic leukemia cell lines, but none of the 112 lymphoid leukemia or lymphoma cell lines; of the normal purified cell populations only the monocytes were positive whereas, T, B cells, and granulocytes were negative; of primary acute (myelo) monocytic leukemia cells (CD14-positive, FAB M4/M5 morphology) 14/20 were Northern mRNA and 11/14 IEF protein positive. RT-PCR revealed MSE expression in 29/49 Northern-negative lymphoid leukemia-lymphoma cell lines. The RT-PCR signals in monocytic cell lines were on average 50-fold stronger than the mostly weak trace expression in lymphoid specimens. On treatment with various biomodulators, only all-trans retinoic acid significantly upregulated MSE message and protein levels but could not induce new MSE expression in several leukemia cell lines; lipopolysaccharide and interferon-gamma increased MSE expression in normal monocytes. Analysis of DNA methylation with sensitive restriction enzymes showed no apparent regulation of gene expression by differential methylation; the MSE gene is evolutionarily conserved among mammalian species; the half-life of the human MSE transcripts was about 5-6 h. The extent of MSE expression varied greatly among different monocytic leukemia samples. However, the MSE overexpression in a significant number of specimens was not associated with gene amplification, gross structural rearrangements or point mutations within the cDNA region. Taken together, the results suggest that MSE expression is not absolutely specific for, but strongly associated with cells of the monocytic lineage; MSE is either not expressed at all or expressed at much lower levels in cells from other lineages. The biological significance, if any, of rare MSE messages in lymphoid cells detectable only by the hypersensitive RT-PCR remains unclear. Further studies on the regulation of this gene and on the physiological function of the enzyme will no doubt be informative with respect to its striking overexpression in some malignant cells and to a possible role in the pathobiology of monocytic leukemias.
Leukemia 1994 Sep
PMID:Characterization of the monocyte-specific esterase (MSE) gene. 809 31

Cytokine treatment in patients with myelodysplastic syndrome (MDS) aims to overcome the maturation defects of myeloid lineage cells associated with cytopenia and cellular dysfunction of mature cells. Since phagocytes play a major role in host defense against microbial infection, we investigated cytokine secretion and oxygen radical release (ORR) from peripheral blood monocytes (PBMC) in a total of 16 MDS patients, 12 patients with refractory anemia (RA) and four patients with RA and excess of blasts (RAEB). Interleukin (IL-6), tumour necrosis factor alpha (TNF alpha), IL-1 beta, and IL-8 secretion from monocytes in response to lipopolysaccharide (LPS) was significantly reduced in the 12 patients with RA compared to 12 healthy controls, whereas no difference was seen in ORR. We further assessed cytokine secretion from monocytes of 10 MDS patients before and after therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, or a combination therapy with GM-CSF and cytosine arabinoside (AraC). In all 10 patients, secretion of IL-1 beta, IL-6, and TNF alpha from PBMC increased after cytokine therapy, whereas IL-8 secretion increased only in five patients with GM-CSF or IL-3 therapy receiving a dosage > or = 250 micrograms/m2 per day but decreased in all other patients. ORR increased in all patients on either GM-CSF or IL-3 therapy. These data indicate that the ability of monocytes to secrete secondary cytokines is impaired in MDS patients but can be restored by in vivo administration of GM-CSF and IL-3.
Leukemia 1993 Nov
PMID:Restoration of impaired cytokine secretion from monocytes of patients with myelodysplastic syndromes after in vivo treatment with GM-CSF or IL-3. 823 Dec 42

Previously it was established that L1210 mouse leukemia and a variety of other tumor cell types produced a soluble factor(s), designated tumor-derived recognition factor (TDRF), which synergized with interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) or lipopolysaccharide (LPS) to promote increased tumor necrosis factor-alpha (TNF-alpha) and nitric oxide synthase (NOS) mRNA synthesis by murine macrophages (M phi). Other work revealed that pretreatment of L1210 tumor targets with IFN-gamma rendered them more susceptible to NO-mediated killing by LPS-activated M phi. Now we have combined these observations to determine if pretreatment of L1210 or P815 tumor targets with IFN-gamma and/or IL-2 would augment production of TDRF to enhance M phi activation. Results confirmed that pretreatment of either L1210 or P815 targets with 200 u/ml of IFN-gamma or 1,000 u/ml of IL-2 significantly increased their susceptibility to M phi-mediated cytotoxicity owing to increased NO production. Similar pretreatment of L1210 targets with suboptimal concentrations of IFN-gamma and IL-2 in combination resulted in additive rather than synergistic augmentation of NO-mediated cytotoxicity by cytotoxic M phi. Pretreatment of L1210 targets with IFN-gamma or IL-2 alone or in combination increased the production of TDRF above constitutive levels as demonstrated by increased production of NO and induction of NOS mRNA expression by cytotoxic M phi. Thus IFN-gamma and/or IL-2 promoted increased TDRF production by tumor targets which in turn promoted M phi generation of tumor cytotoxic NO. It appears that M phi activating cytokines have a dual role in acting on certain tumor targets to augment the process of M phi activation through the increased elicitation of immunopotentiating tumor-derived soluble factor(s).
 ...
PMID:Interferon-gamma and interleukin-2 stimulate production of a soluble factor by L1210 and P815 tumor targets to promote macrophage activation. 885 3

We intend to use a gene complementation approach to clone a tumor suppressor gene on mouse chromosome 2, the loss of which contributes to myeloid leukemia. An in vitro model system has been generated using a clonal cell line, in which tumorigenic chromosomal lesions have been selected along with myeloid differentiation. Among these lesions are deletions of chromosome 2. Comparison of subclones with deleted vs intact chromosomes 2 has allowed the identification of a growth related phenotypic pattern which correlates with the deletion, viz the retention of a marker of immature cells, resistance to inhibition by lipopolysaccharide (LPS), even in the presence of markers of mature myeloid cells, such as resistance to killing by apoptosis-inducing agents. The phenotype is shared by chromosome 2-deleted cell lines derived from conventional tumors. We have begun to investigate the mechanism of the phenotype. The LPS resistance does not correlate with lack of mRNA for CD14, a known cell surface receptor for this agent, or with failure to induce TNF alpha or nitric oxide synthase in response to its binding. The system should allow cloning of the gene using complementation of this phenotype in transfected cell lines.
Leukemia 1998 Dec
PMID:Phenotypic effect correlating with loss of a novel tumor suppressor gene: towards cloning by complementation. 984 23

Zoledronic acid (ZA) is a nitrogen-containing bisphosphonate with antitumor activity used to treat patients with malignant diseases. ZA treatment induces, as a side effect, inflammatory responses, which are accompanied by expansion of gammadelta T cells. In our study, we analyzed the function and differentiation of monocyte-derived immature and lipopolysaccharide (LPS)-stimulated dendritic cells (moDCs) treated with different ZA concentrations, which are achieved in patients. We found that moDC activation with TLR4 ligand LPS is modulated by ZA. The expression of maturation markers was diminished with increasing ZA levels upon LPS activation. The migratory capacity, interleukin-12 secretion and generation of cytotoxic- T-cell responses were reduced at higher ZA levels. Increasing ZA concentrations downregulated nuclear factor-kappaB family members and interferon-regulatory factor (IRF)-3. Surprisingly, in immature moDCs, low ZA concentrations caused upregulation of RelB, c-Rel, IRF-3 and IRF-8. We conclude that ZA concentrations used to treat patients have inhibitory effects on DC activation. This might lead to immunosuppression or result in infectious complications.
Leukemia 2007 Apr
PMID:Zoledronic acid inhibits the function of Toll-like receptor 4 ligand activated monocyte-derived dendritic cells. 1730 19

Bortezomib is a potent drug for the treatment of multiple myeloma. Its anti-tumor activity is mediated by proteasome inhibition leading to decreased cell proliferation and induction of apoptosis. However, an unimpaired proteasomal function plays a crucial role for the induction of anti-tumor immunity by dendritic cells (DCs), which are currently used for therapeutic vaccination against various tumors including myeloma. In the present study, we investigated the impact of bortezomib on the immunostimulatory capacity of 6-sulfo LacNAc (slan) DCs, which represent a major subset of human blood DCs. We demonstrated that this proteasome inhibitor efficiently impairs the spontaneous in vitro maturation of slanDCs and the release of tumor necrosis factor (TNF)-alpha as well as interleukin (IL)-12 upon lipopolysaccharide (LPS) stimulation. Functional data revealed that bortezomib profoundly inhibits slanDC-induced proliferation and differentiation of CD4(+) T cells. In addition, the capacity of slanDCs to promote interferon-gamma secretion and tumor-directed cytotoxicity of natural killer (NK) cells is markedly impaired by bortezomib. These results provide evidence that bortezomib significantly reduces the ability of native human blood DCs to regulate innate and adaptive anti-tumor immunity and may have implications for the design of therapeutic strategies combining DC vaccination and bortezomib treatment.
Leukemia 2007 Jul
PMID:Bortezomib significantly impairs the immunostimulatory capacity of human myeloid blood dendritic cells. 1749 70

To determine whether primary plasma cell leukemia (PPCL) remains a high-risk multiple myeloma feature in the context of contemporary therapy and gene-expression profiling (GEP), we reviewed records of 1474 patients with myeloma, who were enrolled in Total Therapy protocols or treated identically off protocol. A total of 27 patients (1.8%) were classified as having PPCL. As a group, these patients more often had low hemoglobin, high beta-2-microglobulin, high lactate dehydrogenase, low albumin and cytogenetic abnormalities. Among 866 patients with GEP results, the PPCL group more often had disease that was classified as high risk, and in CD-1 and MF molecular subgroups. Regardless of the therapeutic protocol, patients with PPCL had shorter median overall survival (OS; 1.8 years), progression-free survival (PFS; 0.8 years) and complete response duration (CRD; 1.3 years) than the remainder, whose clinical outcomes had improved markedly with successive protocols. Multivariate analyses of pretreatment parameters showed that PPCL was a highly significant independent adverse feature linked to OS, PFS and CRD. In GEP analyses, 203 gene probes distinguished PPCL from non-PPCL; the identified genes were involved in the LXR/RXR activation, inositol metabolism, hepatic fibrosis/hepatic stellate-cell activation and lipopolysaccharide/interleukin-1-mediated inhibition of RXR function pathways. Different treatment approaches building on these genomic differences may improve the grave outcome of patients with PPCL.
Leukemia 2012 Nov
PMID:Primary plasma cell leukemia: clinical and laboratory presentation, gene-expression profiling and clinical outcome with Total Therapy protocols. 2250 8

Chronic lymphocytic leukemia (CLL) can be immunosuppressive in humans and mice, and CLL cells share multiple phenotypic markers with regulatory B cells that are competent to produce interleukin (IL)-10 (B10 cells). To identify functional links between CLL cells and regulatory B10 cells, the phenotypes and abilities of leukemia cells from 93 patients with overt CLL to express IL-10 were assessed. CD5(+) CLL cells purified from 90% of the patients were IL-10-competent and secreted IL-10 following appropriate ex vivo stimulation. Serum IL-10 levels were also significantly elevated in CLL patients. IL-10-competent cell frequencies were higher among CLLs with IgV(H) mutations, and correlated positively with TCL1 expression. In the TCL1-transgenic (TCL1-Tg) mouse model of CLL, IL-10-competent B cells with the cell surface phenotype of B10 cells expanded significantly with age, preceding the development of overt, CLL-like leukemia. Malignant CLL cells in TCL1-Tg mice also shared immunoregulatory functions with mouse and human B10 cells. Serum IL-10 levels varied in TCL1-Tg mice, but in vivo low-dose lipopolysaccharide treatment induced IL-10 expression in CLL cells and high levels of serum IL-10. Thus, malignant IL-10-competent CLL cells exhibit regulatory functions comparable to normal B10 cells that may contribute to the immunosuppression observed in patients and TCL1-Tg mice.
Leukemia 2013 Jan
PMID:Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function. 2271 48


<< Previous 1 2 3 Next >>