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 have previously reported that abdominal irradiation of mice inhibited lung metastases of a weakly immunogenic fibrosarcoma, and that transmigration after the irradiation of Enterobacter cloacae into mesenteric lymph nodes coincided with this phenomenon. In this paper, we show that Escherichia coli as well as E. cloacae reduce the number of metastatic lung colonies when these bacteria were intravenously injected into mice prior to the tumour cell challenge. The inhibition was caused not only by the administration of living bacteria but also by that of killed bacteria. Bacterial lipopolysaccharide (LPS), a component of membrane, replaced at least in part the effect of whole bacteria. Transfer of spleen cells from LPS-treated mice into intact recipients prominently inhibited metastatic development in the recipient mice. 'Cross transfer' between LPS high responders and LPS low responders suggested an indirect activity of transferred spleen cells. The antimetastatic activity of LPS depended on the tumour cell type; metastasis of fibrosarcomas was extensively inhibited by LPS irrespective of tumour immunogenicity while that of adenocarcinomas was only slightly inhibited. These results suggest that non-immunological mechanisms are involved in the antimetastatic activity of LPS.
 ...
PMID:Active components of intestinal bacteria for abdominal irradiation-induced inhibition of lung metastases. 175 83

Murine macrophages from different anatomical sites were compared for their ability to become tumoricidal and to secrete interleukin-1 (IL-1) and tumor necrosis factor (TNF) following stimulation in vitro by several biological response modifiers (BRM). Peritoneal macrophages (PM), alveolar macrophages (AM), and tumor-infiltrating-macrophages (TIM), isolated from B16F10 melanoma colonies in the lung, were incubated overnight with BRM [recombinant murine interferon gamma (rMulFN-gamma), lipopolysaccharide (LPS), muramyl dipeptide (MDP)], either alone or in combination. PM exhibited an increased cytotoxic response following incubation with LPS or rMuIFN-gamma but not with MDP. Both AM and TIM were induced to become tumoricidal following incubation with rMuIFN-gamma plus LPS or rMuIFN-gamma plus MDP but not after stimulation with any BRM alone; the level of cytotoxicity obtained with TIM incubated with rMuIFN-gamma plus LPS was slightly lower than that observed with PM or AM, while with rMuIFN-gamma plus MDP both AM and TIM had lower cytotoxicity than PM. Secretion of IL-I and TNF was observed in PM stimulated with LPS or MDP but not with rMuIFN-gamma. Likewise, secretion of IL-I by AM or TIM was also induced with LPS, although less than that obtained with PM. AM stimulated with LPS secreted larger amounts of TNF than PM while TIM secreted very low amounts of TNF. However, this result may be a consequence of the enzymatic isolation procedure used to obtain TIM since TNF secretion was also impaired in LPS-stimulated normal lung macrophages isolated by a similar enzymatic procedure, or enzyme-treated PM. Our results suggest that TIM obtained from lung metastases share certain functional characteristics with normal AM and respond to BRM in like manner with respect to induction of tumoricidal activity and cytokine secretion.
 ...
PMID:Tumoricidal activity and cytokine secretion by tumor-infiltrating macrophages. 190 30

Interleukin-1 (IL-1) release by alveolar macrophages (AMs) from 29 patients with primary bronchogenic carcinoma, lung metastases, acute pneumonitis, and chronic infection was evaluated in response to a standard stimulus, lipopolysaccharide (LPS). The results were compared to those of AMs from normal smokers or nonsmokers (volunteers). AMs derived from healthy smokers secreted significantly more IL-1 than AMs from nonsmokers. In contrast, AMs from smokers affected with primary lung cancer have lost their capacity of secreting high levels of IL-1, whereas IL-1 secretion was high in nonsmokers with hematogenous metastases. AMs release high IL-1 levels in patients with acute bacterial infections. A significant correlation exists between numbers of AMs and IL-1 levels in normal individuals, a relationship which disappears in patients. These observations suggest that AMs in inflammatory lung disease, even discrete, have an increased capacity to secrete IL-1 on stimulation with LPS. They also suggest that an intrinsic dysfunction of AMs may accompany primary bronchogenic carcinoma. The influence of tobacco in modifying the functions of AMs is stressed.
 ...
PMID:Interleukin-1 secretion by lipopolysaccharide-stimulated alveolar macrophages. Relationships to cell numbers--influence of smoking habits. 281 73

Following immunologic activation, pulmonary macrophages may prevent or cause regression of lung metastases by mechanisms which remain largely unknown. The studies described here were designed to determine if enhanced oxygen metabolite release was related to postactivation tumoricidal activity. We have shown that in vitro activation of Fischer 344 rat pulmonary macrophages by either free or liposome-encapsulated muramyl dipeptide leads to both enhanced release of superoxide anions and marked tumoricidal activity against syngenic (Fischer 13762), allogeneic (Schmidt-Ruppin RR 1022) and xenogeneic (Fibrosarcoma MCA-F) 125I-deoxyuridine-labeled target cells. This immune modulator did not, however, metabolically activate pulmonary macrophages as effectively as liposome-encapsulated lipopolysaccharide. A 24-h in vitro incubation with either 150 U or 300 U of interferon-gamma (3 X 10(6) U/mg) or 30 U, 150 U or 300 U of interferon-alpha (6 X 10(5) U/mg) caused a significant elevation in superoxide release above controls, whereas short-term exposure (2 or 4 h) had little or no effect. Free or encapsulated 6-O-stearoyl muramyl dipeptide, on the other hand, did increase superoxide levels at all 3 time periods. When either interferon-gamma or free or encapsulated muramyl dipeptide derivative were administered to intact rats by either i.v. injection, intratracheal instillation or osmotic minipump infusion, pulmonary macrophage tumoricidal activity was observed 96 h after cell harvesting. Zymosan-stimulated superoxide release, however, was not consistently elevated above control or empty liposome treatment following this course of in vivo activation. The data collectively suggest that in vivo pulmonary macrophage activation to a tumoricidal state and metabolic activation resulting in enhanced superoxide may be separable events.
 ...
PMID:Modulation of pulmonary macrophage superoxide release and tumoricidal activity following activation by biological response modifiers. 302 50

It has been reported that treatment with cimetidine, a histamine H2-receptor antagonist, increased survival and decreased the number of lung metastases in mice bearing the Lewis Lung carcinoma [29]. It was suggested that this effect was due to the ability of cimetidine to block histamine activation of suppressor lymphocytes and hence allow host defence mechanisms to inhibit tumour growth. In the present studies, C3H/He mice were implanted with a C3H mouse mammary adenocarcinoma on Day 0. This tumour metastasizes to the lungs in 30-50 days. Primary tumours were ablated with X-rays when they had grown to about 0.2 g and animals were given drinking water with or without cimetidine (10 mg ml-1) until the end of the experiment. Cimetidine reduced the number of mice dying from metastatic disease from 7/15 (controls) to 3/13. Cimetidine treatment also prolonged survival of mice that did succumb to metastatic disease by about 12 days. The response of spleen lymphocytes to the mitogens phytohaemagglutinin and lipopolysaccharide was assessed in vitro by uptake of 3H-thymidine 0, 16, 45 and 58 days after tumour implantation. Lymphocyte responsiveness was depressed by tumour burden. The influence of cimetidine treatment was equivocal being dependent upon time after tumour implantation and dose of mitogen. In this mouse-tumour system, the mechanism of the antimetastic effect of cimetidine is different from that previously suggested [29].
 ...
PMID:Antimetastatic effect of cimetidine on mice bearing a C3H mouse mammary adenocarcinoma: survival and lymphocyte function studies. 654 88

The purpose of these studies was to determine whether the induction of NO synthase activity in murine K-1735 melanoma cells correlated with their metastatic potential. Nonmetastatic, metastatic, and somatic cell hybrids (produced by fusion of nonmetastatic and metastatic cells) were injected i.v. into syngeneic C3H/HeN mice. Metastatic cells survived to produce experimental lung metastases, whereas nonmetastatic cells did not. The various clones and somatic cell hybrids were incubated in vitro with combinations of tumor necrosis factor, interleukin 1, gamma-interferon, and lipopolysaccharide. Nonmetastatic cells exhibited high levels of inducible NO synthase activity and NO, whereas metastatic cells did not. Both the cytotoxic effects of the cytokines and NO production were inhibited by the addition of NG-monomethyl-L-arginine, a specific inhibitor of NO synthase. These data demonstrate an inverse correlation between production of endogenous NO and the ability of K-1735 cells to survive in syngeneic mice to produce lung metastases.
 ...
PMID:Inverse correlation between expression of inducible nitric oxide synthase activity and production of metastasis in K-1735 murine melanoma cells. 750 36

The purpose of this study was to determine whether the expression of the JE/MCP-1 gene encoding for the monocyte chemottractant protein, MCP-1 (also known as monocyte chemotactic and activating factor MCAF, TDCF, and SMC-CF) can influence the metastatic properties of tumor cells. The highly metastatic murine colon carcinoma CT-26 cells, syngeneic to BALB/c mice that do not produce endogenous JE/MCP-1 protein, were transfected with a BCMGS-Neo expression vector (control) or a vector containing full-length JE cDNA. CT-26 parental cells, CT-26 Neo, and CT-26 JE/MCP-1-positive cells were injected into syngeneic or nude mice. The CT-26 JE/MCP-1-positive cells produced significantly fewer lung metastases. The decrease in incidence of metastasis was not due to the inability of the transfected cells to arrest in the lung vasculature or to differences in cell cycle time. CT-26 cells producing JE/MCP-1 were highly susceptible to lysis by syngeneic macrophages treated with subthreshold concentrations of lipopolysaccharide. In addition, culture supernatants of JE/MCP-1-expressing cells plus lipopolysaccharide synergistically activated tumoricidal properties in syngeneic macrophages. This activity was blocked by anti-JE/MCP-1 antibodies, indicating the involvement of the JE/MCP-1 molecule in this process. Moreover, purified JE/MCP-1 added to lipopolysaccharide-containing medium resulted in significant activation of macrophages against parental CT-26 cells. These data suggest that, in addition to its chemotactic properties, JE/MCP-1 can synergize with bacterial endotoxins to activate macrophages to become tumoricidal and, hence, could suppress metastasis.
 ...
PMID:Expression of the JE/MCP-1 gene suppresses metastatic potential in murine colon carcinoma cells. 795 25

Recently we reported an antimetastatic activity of bacterial lipopolysaccharide (LPS) on a NK-cell-resistant murine fibrosarcoma (NFSa). Here we investigate and report the mechanistic significance of platelets in this activity. The number of circulating platelets was reduced to 63% of the control 3 days after an i.v. injection of 1.0 micrograms LPS, and then recovered to the level of control at day 10. Aggregation efficiency of platelets was impaired by LPS. The number of metastatic lung colonies after an i.v. injection of tumor cells was maximally reduced to 2.2% of the control at day 3 and increased in proportion to the recovery of platelet number. Neuraminidase (Ndase), which caused a non-immunological thrombocytopenia, also inhibited lung metastasis when injected prior to an i.v. tumor cell challenge. LPS and Ndase showed an identical pattern against five other syngeneic tumors; these agents inhibited lung metastases of the FSa fibrosarcoma and the SCC VII squamous cell carcinoma but failed to inhibit those of the NR-S1 squamous cell carcinoma, the MMCa#4 mammary adenocarcinoma and the NR-PG parotid gland tumor. All the three cells which were not responsive to any agents possessed a high aggregating activity of platelets while the other three tumors responsive to both agents did not show a detectable level of this activity. Platelet transfusion failed to modify the antimetastatic activity of LPS. These results suggest that platelets play an important role in the antimetastatic activity of LPS, though whether the role is principal or assistant remains to be seen.
 ...
PMID:Significance of platelets in an antimetastatic activity of bacterial lipopolysaccharide. 847 98

We studied the relationship between tumour necrosis factor (TNF) and interleukin 6 (IL-6) levels, and the metastatic process in C57BL/6 mice after intravenous inoculation of B16-BL6 melanoma cells. Bioactive TNF was not detectable in the sera of inoculated mice, but these animals did show higher TNF levels following intraperitoneal challenge with lipopolysaccharide (LPS) compared to control animals. Serum IL-6 levels were increased in inoculated animals. Injection of a hybrid molecule (p55-sf2) composed of the human p55 TNF receptor extracellular domain coupled to a human constant region backbone, decreased serum TNF (after LPS challenge) and IL-6 levels in inoculated animals. Lung metastases at 7-14 days were reduced, compared to human IgG-injected control animals, but this effect was lost at day 21 postinoculation. The results suggest that the reduction in the number of metastases may be related to the effect of blocking TNF activity.
 ...
PMID:Effect of blocking TNF on IL-6 levels and metastasis in a B16-BL6 melanoma/mouse model. 921 89

Surgical removal of a primary tumour is often followed by rapid growth of previously dormant metastases. Endotoxin or lipopolysaccharide, a cell wall constituent of Gram-negative bacteria, is ubiquitously present in air and may be introduced during surgery. BALB/c mice received a tail vein injection of 10(5) 4T1 mouse mammary carcinoma cells. Two weeks later, animals were subjected to surgical trauma or an intraperitoneal injection of endotoxin (10 microg per animal). Five days later, animals which underwent open surgery, laparoscopy with air sufflation or received an endotoxin injection displayed increased lung metastasis compared to anaesthetic controls. These increases in metastatic tumour growth were reflected in increased tumour cell proliferation and decreased apoptosis within lung metastases. Circulating levels of the angiogenic cytokine, vascular endothelial growth factor (VEGF), were also elevated in these groups and correlated with increased plasma levels of endotoxin. Endotoxin treatment for 18 h (>10 ng ml(-1)) directly up-regulated VEGF production by the 4T1 tumour cells in vitro. Metastatic tumour growth in mice undergoing carbon dioxide laparoscopy, where air is excluded, was similar to anaesthetic controls. These data indicate that endotoxin introduced during surgery is associated with the enhanced growth of metastases following surgical trauma, by altering the critical balances governing cellular growth and angiogenesis.
 ...
PMID:The role of endotoxin/lipopolysaccharide in surgically induced tumour growth in a murine model of metastatic disease. 1060 27


1 2 Next >>