Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: HUMANGGP:017444 (TNF)
 61,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cells of the monocytic leukemia line, THP-1, mimic several of the functional characteristics of activated monocytes and macrophages following incubation in the tumor promoting agent, mezerein. The current paper explores the nature of the factors in medium conditioned by THP-1 cells which inhibit cell growth and the effects of interferon-gamma (IFN gamma) on their synthesis. Activity inhibiting the growth of the MDA-MB-415 mammary carcinoma line migrated in a pH range of 6.5 to 7.5 and could be resolved into 2 peaks, one corresponding to interleukin-1 beta (IL-1 beta) and the other with an apparent average molecular weight of 43 Kd. Antisera against tumor necrosis factor alpha and beta (TNF alpha and beta) and monocyte colony stimulating factor (M-CSF) had no effect on the 43 Kd inhibitor. IFN gamma enhanced the secretion of IL-1, but decreased the production of the 43 Kd inhibitor. The L-929 cell cytotoxicity assay and an ELISA were used to show that the amount of TNF alpha present was less in medium from IFN gamma treated cells. THP-1 cells also produced an IFN gamma repressed activity separating at pH 4.8 to 6.1 which inhibited the response of T cells to IL-1 in a thymocyte co-mitogenic assay. The inhibitors expressed by THP-1 cells may be comparable to the cytotoxic and cytostatic activities expressed by activated human monocytes and macrophages.
 ...
PMID:Characterization of inhibitory activities secreted by THP-1 leukemia cells and regulation by interferon-gamma. 184 67

The role of IL-6 in the antiproliferative effect of IL-1 for tumor cell lines was investigated using IL-1-sensitive cell lines. Human recombinant IL-1 alpha and IL-6 both inhibited the growth of an IL-1-sensitive cloned human melanoma cell line (A375-C6). However, IL-1 has greater maximum growth inhibitory activity than IL-6. Conditioned medium of the tumor cells that were treated with IL-1 contained IL-6 as determined by ELISA. Northern blot analysis revealed that IL-6 mRNA expression increased in IL-1-treated cells. In addition, antibody against human IL-6 neutralized about 50% of the antiproliferative effect of IL-1. The growth of an IL-1-resistant clone of A375 cells (A375-C5), which cannot be shown to express any detectable IL-1R, was inhibited by IL-6 to the same degree as A375-C6 cells. The A375-C5 cell line did not produce IL-6 or increase IL-6 mRNA after stimulation with IL-1. These results indicate that IL-6 mediates in part the antiproliferative effect of IL-1 on A375-C6 cells by acting as an autocrine antiproliferative factor. IL-1 also inhibited the growth of a malignant human mammary cell line (MDA-MB-415). IL-6 exhibited only slight growth inhibition in this cell line. Neither IL-6 production nor IL-6 mRNA expression was induced in this cell line by IL-1. Antibody against IL-6 did not neutralize the antiproliferative effect of IL-1. Therefore, for MDA-MB-415 cells IL-6 appeared not to be involved in the antiproliferative effect of IL-1. These results indicate that the antiproliferative effect of IL-1 involves at least two pathways, one IL-6 dependent and another IL-6 independent. The contribution of IL-6 to the antiproliferative effect of TNF was also examined. IL-6 appeared not to play a role in the antiproliferative effect of TNF in these cell lines.
 ...
PMID:Contribution of IL-6 to the antiproliferative effect of IL-1 and tumor necrosis factor on tumor cell lines. 258 6

A static adhesion assay employing 6-carboxy-3',6'-diacetylfluorescein (6-CFDA) as a fluorescent marker has been developed to study the interactions of tumour cell lines with endothelial monolayers. This assay allows simple, safe quantification of cell-cell adhesion using living cells. It has been used to demonstrate that the integrin adhesion molecule VLA-4 mediates the attachment of RPMI-7951 melanoma cells to human umbilical vein endothelial cells (HUVEC) which have been activated by TNF alpha. In addition, MDA-MB-231 breast adenocarcinoma cells display greater adhesion to microvessel endothelial cells than to large vessel endothelial cells.
 ...
PMID:A simple fluorometric assay for quantifying the adhesion of tumour cells to endothelial monolayers. 775 Feb 3

We investigated the role of the LFA-1/ICAM, VLA-4/VCAM-1 and CD2/LFA-3 adhesion pathways in the cytolysis of tumor cells mediated by an anti-EGF-R/anti-CD3 bispecific monoclonal antibody (biMAb). The biMAb induced efficient lysis of EGF-R+ tumor cells (A431, HT-29, IGROV-1 and MDA-MB468) by cytotoxic T lymphocytes (CTL) cultured in IL-2. Pretreatment of effector cells by anti-LFA-1 alpha (CD11a) and anti-LFA-1 beta (CD18) MAbs significantly inhibited cytolysis of all types of EGF-R+ tumor cells, while anti-CD2 and anti-VLA-4 MAbs were virtually ineffective. We investigated the expression of adhesion-molecule counter-receptors on tumor target cells by indirect immunofluorescence. HT-29, A431 and MDA-MB 468 tumor cells expressed an ICAM-1+2-3- VCAM-1- LFA-3+ phenotype, while IGROV-1 was ICAM-1-2+3- VCAM-1- LFA-3+. Pre-treatment of A431, HT-29 and MDA-MB468 with anti-ICAM-1 MAb inhibited cytolysis, further supporting the functional involvement of the LFA-1/ICAM adhesion pathway in biMAb-targeted tumor-cell lysis. In addition, treatment of target cells with TNF alpha or IFN gamma for 24 hr increased the expression of ICAM-1 in HT-29, A431 and MDA-MB468 (ICAM-2 was induced on IGROV-1) and also enhanced the sensitivity of these target cells to biMAb-targeted cytotoxicity. These data suggest that up-regulation of ICAM-molecule expression by inflammatory cytokines may increase susceptibility of tumor cells to biMAb-targeted lysis. Anti-LFA-1 MAbs did not significantly inhibit the formation of conjugates between biMAb-coated T lymphocytes and tumor cells. Co-aggregation of LFA-1 molecules with biMAb-bound CD3 molecules resulted in a more sustained and prolonged increase in the intracellular concentration of free Ca++ in CD8+ cultured CTL lines. These findings indicate that in T cells targeted by anti-CD3/anti-TAA biMAb LFA-1 may act as a co-receptor molecule which enhances signal transduction through the CD3/TCR complex.
 ...
PMID:The LFA-1/ICAM cell adhesion pathway is involved in tumor-cell lysis mediated by bispecific monoclonal-antibody-targeted T lymphocytes. 790 79

Synthesis of the biologically active oestrogen, oestradiol, within breast tumours makes an important contribution to the high concentrations of oestrogens which are present in malignant breast tissues. In breast tumours, oestrone is preferentially converted to oestradiol by the Type I oestradiol 17 beta-hydroxysteroid dehydrogenase (E2DH). Several growth factors, such as insulin-like growth factor Type I, and cytokines, such as Tumour Necrosis Factor alpha (TNF alpha), have been shown to stimulate E2DH activity in MCF-7 breast cancer cells. As little is known about the regulation of Type I E2DH expression and activity in other breast cancer cell lines, the expression and activity of this enzyme was examined in other oestrogen receptor positive and also oestrogen receptor negative breast cancer cell lines. As it is possible that E2DH activity may be limited by co-factor availability, the effects of exogenous co-factors on enzyme activity in these cell lines was also investigated. For T47D and BT20 breast cancer cells, the addition of exogenous co-factors was found to enhance enzyme activity. TNF alpha, in addition to stimulating E2DH activity in MCF-7 cells, also increased activity in T47D and MDA-MB-231 cells, although to a lesser extent than in MCF-7 cells. An investigation of signalling pathways involved in the regulation of E2DH activity revealed that stimulation of both the protein kinase C (PKC) and PKA pathways may be involved in regulation of E2DH activity. As several growth factors and cytokines have now been found to be involved in regulating E2DH activity, the role that macrophages and lymphocytes have in supplying these factors and the mechanism by which these factors may stimulate tumour growth, is also reviewed.
 ...
PMID:The role and proposed mechanism by which oestradiol 17 beta-hydroxysteroid dehydrogenase regulates breast tumour oestrogen concentrations. 854 83

The vascular endothelium plays a critical role in cancer metastasis by directing circulating cancer cells into extravascular tissues and by expressing cell adhesion molecules. The authors investigated the interaction between breast cancer cells and vascular endothelial cells in the expression of E-selectin, and the effect of corticosteroids or medroxyprogesterone acetate (MPA) on such interaction. An MDA-MB-231 cell line, derived from human breast cancer induced E-selectin on the cell surface of human umbilical vascular endothelial cells. This induction was enhanced with a supplement of mononuclear cells of peripheral blood added to the culture medium. Corticosteroids and MPA blocked the induction of E-selectin proportional to concentration. Anti-IL-1 beta, but not anti-IL1 alpha or- TNF a, antibodies blocked induction. These findings suggest that MDA-MB-231 cells induce expression of E-selectin on vascular endothelium by releasing IL-1 beta directly or indirectly, but this induction is blocked by corticosteroids and MPA. Corticosteroids and MPA may inhibit cancer metastasis by blocking E-selectin expression on the vascular endothelium.
 ...
PMID:Corticosteroids and medroxyprogesterone acetate inhibit the induction of E-selectin on the vascular endothelium by MDA-MB-231 breast cancer cells. 866 17

An experimental model was used to determine the changes in TNF, MDA and SOD in granulation tissues during natural wound healing after skin excision on rats. Our results indicated that the changes in TNF and SOD exhibited a curve of V. The levels of TNF and SOD were lower on day 7 than day 3. The levels of MDA rose gradually, especially on day 7. A positive correlation was shown between TNF and MDA (at days 3, 5, 7), also between TNF and SOD (at day 3, 7). When the concentration of TNF was lower than 90 Pg/mg protein, the process of wound healing was best, while wound healing was hindered when the levels of SOD were low. The results suggest that in the process of wound repair there are influential changes in the contents of TNF, MDA and SOD. Lower levels of TNF and higher levels of SOD are apparently beneficial to wound healing after trauma.
 ...
PMID:[Relationship between wound healing and TNF, MDA and SOD contents in granulation tissues of rats in the first week]. 875 29

Since experimental studies have shown that tumour necrosis factor-alpha (TNF-alpha) has potent anti-tumour activity that can be potentiated with cytokines, we tested the efficacy of TNF-alpha with interferon-gamma (IFN-gamma) on different human breast cancer cell lines, particularly comparing hormone-dependent and -independent phenotypes. TNF-alpha inhibited the growth of hormone-dependent human MCF-7, ZR-75-1 and T47-D breast cancer cells with a half maximal concentration of 0.25 nM. In contrast, the growth of hormone-independent cells MDA-MB-231 and HS578T was not affected by TNF-alpha alone, but a synergistic inhibition was observed when using IFN-gamma and TNF-alpha together. The mRNA for the proto-oncogene C-MYC, as an intracellular indicator of cell activation, was significantly increased in MCF-7 cells in the presence of TNF-alpha. In MDA-MB-231 cells this mRNA was increased only in the presence of both TNF-alpha and IFN-gamma, without a change in the number of surface TNF receptors. These findings indicate that TNF-alpha treatment in combination with IFN-gamma may provide a successful approach to overcome the cellular heterogeneity of advanced breast tumours.
 ...
PMID:Tumour necrosis factor and interferon are selectively cytostatic in vitro for hormone-dependent and hormone-independent human breast cancer cells. 903 15

These serial clinical and experimental studies were designed to clarify the pathogenesis of postburn MODS. Both animal and clinical studies were performed. In animal experiments, 46 male cross-bred dogs were cannulated with Swan-Ganz catheters and 39 of them were inflicted with 50% TBSA third degree burns (7 were used as controls). The burned dogs were randomly divided into 4 groups: immediate infusion, delayed infusion, delayed fast infusion and delayed fast infusion combined with ginsenosides. All dogs were kept under constant barbiturate sedation during the whole study period. Hemodynamics, visceral MDA, mitochondrial respiratory control rate (RCR) and ADP/O ratio, ATP, succinic dehydrogenase (SDH), organ water content as well as light and electron microscopy of visceral tissues were determined. In the clinical study, 61 patients with extensive deep burns were chosen, of which 16 sustained MODS. Plasma TXB2/6-keto-PGF1alpha ratio, TNF, SOD, MDA, circulatory platelet aggregate ratio (CPAR), PGE2, interleukin-1, total organ water content and pathological observations of visceral tissues from patients who died of MODS were carried out. Results demonstrated that ischemic-reperfusion damage due to severe shock, sepsis and inhalation injury are three main causes of postburn death. All inflammatory mediators increased markedly in both animals and patients who sustained organ damage or MODS. SDH, RCR, ADP/O and ATP decreased significantly. These findings suggested that ischemic damage and systemic inflammatory response syndrome (SIRS) initiated by mediators or cytokines might be important in the pathogenesis of postburn MODS.
 ...
PMID:Serial experimental and clinical studies on the pathogenesis of multiple organ dysfunction syndrome (MODS) in severe burns. 991 70

In order to investigate the effects of early enteral feeding on the gut after burn, 21 cases (mean burn area 45%) were randomly divided into early feeding group (EF group) and delayed feeding group (DF group). The results showed that the levels of plasma endotoxin and MDA in EF group were much lower on PBD 4, 8, 14 than those of DF group (P < 0.05-0.01), and plasma SOD was much lower in DF group on PBD 4, 8 (P < 0.01). The contents of serum gastrin and plasma motilin were obviously increased, and TNF IL-8 much lower in EF group at most time points (P < 0.05-0.01). Therefore, it seems that the early enteral feeding can decrease the level of plasma endotoxin in blood, reduce reperfusion injury of the gut, and blunt the chain reaction of "endotoxin-inflammatory mediator-gut mucosa injury."
 ...
PMID:[A clinical study of early enteral feeding to protect the gut function in burned patients]. 1045 11


1 2 3 4 5 6 7 8 9 10 Next >>