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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinoids, including retinoic acid (RA), are naturally occurring and synthetic analogs of vitamin A that inhibit cell growth and induce cell differentiation in many experimental tumor models. Differentiation of the human myelogenous leukemia cell line HL-60 by RA led to the finding that cells from patients with acute promyelocytic leukemia (APL) are terminally differentiated by RA. One mechanism for the activity of RA in a variety of cell types involves the RA nuclear receptors (RA receptors [RARs] and retinoid X receptors), which have specific high-affinity binding sites for RA and some of its metabolites. Other mechanisms may also be involved in RA-induced differentiation. Recent studies suggest that RA acylation (retinoylation) may be involved in the RA induction of differentiation in leukemia cells. Combinations of RA with cyclic adenosine monophosphate (cAMP)-elevating agents led to synergistically induced differentiation of HL-60 cells. The lower doses of RA needed in combination therapy are unlikely to lead to RA resistance, a major limitation of RA therapy in APL. In vitro studies suggest that combinations of RA with either PGE or the butyric acid (BA) prodrug tributyrin (TB) may be useful in differentiation therapy for APL and other malignancies. This is a US government work. There are no restrictions on its use.
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PMID:Potential applications of cytodifferentiation therapy in hematologic malignancies. 783 81

This report demonstrates the ability of the anti-cancer drug suramin to interfere with the binding of interleukin (IL)-1 to its receptor and to inhibit IL-1-induced biological activities. In a radioreceptor cell based assay, suramin inhibits the binding of IL-1 alpha to several murine cell lines expressing predominantly type I and type II IL-1 receptors. Affinity cross-linking experiments using IL-1 alpha and EL-4.6.1 cells confirms that suramin inhibits the binding of the ligand to the 80 kDa IL-1 type I receptor. In contrast, suramin fails to displace significantly prebound IL-1. In a cell-free system, suramin prevents the binding of IL-1 alpha and IL-1 beta to murine and human recombinant soluble type I IL-1 receptors. For example, the IC50 for suramin inhibiting IL-1 alpha and IL-1 beta binding to soluble human IL-1 receptor were 204 microM and 186 microM, respectively. The suramin analogues, NF-058 and NF-103 (which bear the same number of sulfate groups as suramin), are between three- and ten-fold less active than suramin in inhibiting IL-1 binding to EL-4.6.1 cells, and to recombinant soluble IL-1 receptor. Furthermore, in a dose-dependent manner suramin prevents several IL-1 mediated biological responses, including thymocyte proliferation, PGE-2 synthesis and IL-6 production. The inhibitory effect of the drug can be significantly reversed by the addition of excess cytokine. Taken together, the results indicate that suramin is a competitive IL-1 receptor antagonist. Because IL-1 participates in a broad range of immunological and inflammatory functions, the data suggest that suramin administration may influence important activities beyond those associated strictly with tumor inhibition.
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PMID:Suramin blocks the binding of interleukin-1 to its receptor and neutralizes IL-1 biological activities. 786 98

Incubation of rat liver macrophages in vitro with free or liposome-encapsulated muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine; MDP) resulted in a rapid but transient release of tumor necrosis factor-alpha (TNF-alpha), followed by a slow, steady release of nitric oxide (NO) and prostaglandin (PG) E. The secretion pattern induced in situ was determined by isolating the liver macrophages at 2, 12, 24, 48, and 72 h after injection of liposomal MDP and measuring the amounts of products secreted in a 24-h period following isolation. TNF-alpha secretion was detected only in macrophages isolated as early as 2 h after injection of liposomal MDP and not at later time points. Considerable heterogeneity was observed among macrophages of different size: For example, the large-sized cells were far more potent in TNF secretion than the smaller cells. Nitric oxide secretion, on the other hand, was maintained over a full 24-h period following MDP administration and was virtually independent of macrophage size. With regard to PGE release, similar to TNF-alpha secretion, considerable differences in secretory activity between cells of different size were observed. Also in this case the large cells were several times more active than the small cells. In contrast to TNF, however, PGE secretion could be detected up to 24 h after injection of liposomal MDP. These findings support the notion that the development and maintenance of the activated state of liver macrophages, induced by immunomodulators such as liposomal MDP, are under the control of a complex network of regulatory functions and that multiple secretory products play a role in the observed macrophage-mediated cytotoxicity.
J Immunother Emphasis Tumor Immunol 1994 May
PMID:Secretion pattern of the rat liver macrophage population following activation with liposomal muramyl dipeptide in vivo and in vitro. 806 99

Growth and metastasis to the lung of the human breast cancer cell line MDA-MB-435 in nude mice fed a high-fat (20% wt/wt) high-linoleic acid (LA; 12% wt/wt) diet were significantly reduced by the addition of the cyclooxygenase inhibitor indomethacin to the drinking water at a dose of 10 micrograms/ml (approximately 1 mg/kg body wt). No toxicity was observed in these mice; at 20 micrograms/ml indomethacin, gastric ulcerations occurred. After necropsy, tumor eicosanoids were measured by radioimmunoassay in the control and 10 micrograms/ml indomethacin treatment groups. Levels of the cyclooxygenase products prostaglandin (PG) E (PGE), 6-keto-PGF1 alpha, and thromboxane B2 (TxB2) were significantly reduced in indomethacin-treated mice compared with controls; however, the 6-keto-PGF1 alpha-to-TxB2 ratio was significantly increased. Two lipoxygenase products, 5-hydroxyeicosatetraenoic acid (5-HETE) and 15-HETE, were unaffected, but the 12-HETE levels were increased compared with the untreated high-LA-fed group. Metastases to the lungs in mice fed a high-fat low-LA (2% wt/wt) diet were also reduced compared with those in the high-LA-fed control mice, but whereas tumor cyclooxygenase and lipoxygenase product levels were reduced, no change in the 6-keto-PGF1 alpha-to-TxB2 ratio was observed. The use of selective cyclooxygenase inhibitors may prevent LA-mediated progression of breast cancer at several levels of the metastatic cascade, among which may be interference with tumor cell-vascular endothelial cell interaction and with angiogenesis.
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PMID:Dietary linoleic acid-stimulated human breast cancer cell growth and metastasis in nude mice and their suppression by indomethacin, a cyclooxygenase inhibitor. 877 66

Pectin is a partially methoxylated polymer of galacturonic acid obtained from fruits. Among pectin, apple pectin exerts stronger bacteriostatical action on Staphylococcus aureus, Streptococcus faecalis, Pseudomonas aeruginosa and Escherichia coli in comparison with citrus pectin. In this study, we used water-soluble methoxylated pectin from apple. The diet, supplemented by 20% apple pectin, significantly decreased the number of tumors and the incidence of colon tumor. PGE2 level in distal colonic mucosa in 20% apple pectin fed rats were lower than those in basal diet fed rats. Fecal beta-glucuronidase activities in the apple pectin fed group, which has been considered a key enzyme for the final activation of Dimethylhydrazine metabolism to carcinogens in the colonic lumen, were signifieantly lower than those in control group at initiation stage of carcinogenesis. In the case the concentrations of beta-glueosidase and azoreductase were also decreased. The effect of apple pectin on the colon carcinogenesis may partially depend on PGE, concentration decrease in colonic mucosa and on the type of pectin, also related to fecal enzyme activities.
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PMID:Anticarcinogenic action of apple pectin on fecal enzyme activities and mucosal or portal prostaglandin E2 levels in experimental rat colon carcinogenesis. 914 58

The present study was undertaken to investigate a mechanism of the inhibitory effect of vitamin E in urethane-induced lung tumorigenesis in mice. We assayed ornithine decarboxylase (ODC) activity and the prostaglandin E2 (PGE2) level in lung at 8 weeks after urethane injection (promotion phase). Excessive vitamin E feeding or indomethacin treatment suppressed the urethane-induced increase in ODC activity, while exogenous PGE2 overcame the effect of vitamin E on ODC activity. Furthermore, the amount of PGE, and the level of ODC activity were well correlated. These results indicate that the vitamin E-induced decrease in PGE2 level probably contributes to the inhibition of ODC induction and the prevention of tumor development in the lung.
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PMID:The modulation effect of vitamin E on prostaglandin E2 level and ornithine decarboxylase activity at the promotion phase of lung tumorigenesis in mice. 926 30

Prostaglandins (PGs) have been implicated in tumor promotion. In this study, we investigated the effect of the hepatic tumor promoters lindane and phenobarbital (PB) on the PG metabolism of Kupffer cells in vitro and in vivo, in particular on the expression of cyclooxygenase (COX), the leading enzyme in prostanoid synthesis. Exposure of primary cultures of Kupffer cells to lindane for 1 h stimulated the production of the PGs PGE(2) and PGD(2) markedly (up to 50-fold) and that of PGF(2alpha) by >3-fold. This effect was accompanied by an increase in the COX-2 protein, as demonstrated by western blotting. Similarly, PB, which shares several effects with lindane in rat liver, also clearly induced COX-2. Lindane and PB affected the PG synthesis in vitro and in vivo in Kupffer cells of rats that had been treated with the two compounds for 56 days. Kupffer cells, which were isolated at days 2, 5 and 56 of the treatment, showed a significant increase in the levels of COX-2 mRNA and protein. Total COX activity was increased approximately 2-fold and 3- to 5-fold in Kupffer cell homogenates of PB- and lindane-treated animals, respectively, compared with the untreated controls. These results suggest that paracrine mechanisms may contribute to the tumor-promoting activity of lindane and PB, stimulating the production of PGs by Kupffer cells.
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PMID:Effect of lindane and phenobarbital on cyclooxygenase-2 expression and prostanoid synthesis by Kupffer cells. 1042 85

A novel model of mammary carcinogenesis is proposed involving sequential induction and upregulation of cyclooxygenase and aromatase genes by essential fatty acids prominent in the US diet. The basic carcinogenic processes are: (1) constitutive prostaglandin biosynthesis and formation of mutagenic oxygen and nitrogen free radicals responsible for tumor initiation; (2) PGE-2-induced expression of aromatase and constitutive estrogen biosynthesis which sustains mitogenesis and tumor promotion; and (3) PGE-2-induced expression of vascular endothelial growth factor which stimulates angiogenesis and tumor metastasis.
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PMID:Genetic induction and upregulation of cyclooxygenase (COX) and aromatase (CYP19): an extension of the dietary fat hypothesis of breast cancer. 1046 64

As shown earlier, the cells transformed in vitro by several different oncogenes, or spontaneously, during in vivo growth in normal hosts would be gradually replaced by the highly-tumorigenic descendants co-expressing high H2O2-catabolizing and PGE2-releasing activities. Acquisition of (H2O2(CA) + PGE(S)) phenotype provides the cells with local defense mechanisms against the host innate immunity effectors. However, it remained unknown, whether the expression of (H2O2(CA) + PGE(S)) phenotype is implicated in susceptibility of tumor cells expressing tumor-specific transplantation antigens to rejection in immune animals. Here, with the use of SV40 in vitro transformed parental cells, negative in expression (H2O2(CA) + PGE(S)) phenotype, and their in vivo selected descendant tumor cell lines expressing this phenotype, we show that: (1) the rates of in vivo selection of the parental SV40 tumor cells expressing (H2O2(CA) + PGE(S)) phenotype are the same in normal and SV40-immune animals; (2) in vivo selected SV40 tumor cells expressing (H2O2(CA) + PGE(S)) phenotype, although they retain specific immunosensitivity, are 100 times less effectively rejected in SV40-immunized animals, as compared with their in vitro SV40-transformed parental cells. Thus, in vivo acquired immunologically non-specific local mechanisms of tumor cells defense against the host innate immunity effectors, significantly decreases the effectiveness of their specific immunorejection.
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PMID:In vivo acquired mechanisms of tumor cells local defense against the host innate immunity effectors: implication in specific antitumor immunity. 1054 Oct 50

Tumor cells may influence the host's immune reactivity by the production of immunosuppressive factors (ISFs). In this study, the effects of ISFs derived from nine polyclonal colorectal carcinoma (CRC) cell lines on PHA-induced lymphocyte proliferation and cytokine secretion was investigated. We found that most of the culture supernatants (8/9) from CRC cell lines contained ISFs, which inhibited T cell proliferation to a variable degree in a dose-dependent manner. Comparison of T cell proliferation in the presence or absence of monocytes showed that monocytes can modulate the effects of tumor-derived ISFs on lymphocyte function. In addition, exposure of activated PBMC to the tumor cell supernatants resulted in an altered secretion of cytokines by these cells, i.e. the secretion of IFN-gamma was generally reduced while the secretion of IL-1beta, IL-2 and TNF-alpha was little affected. We further investigated the supernatants' inhibitory effects on PBMC in respect to the production of prostaglandin E(2) (PGE(2)). It was found that PGE(2) was secreted by all tumor cell cultures. Therefore this substance is probably involved in the immunosuppression in vivo. However, the secreted PGE(2) was shown not to be solely responsible for the observed suppression of lymphocyte proliferation in vitro. Our results suggest that the secretion of ISF is a common property of CRCs as demonstrated with newly established CRC cell cultures, and therefore this may also be an important immune escape mechanism of colonic carcinomas in vivo.
Tumour Biol
PMID:Comparison of the effects of immunosuppressive factors from newly established colon carcinoma cell cultures on human lymphocyte proliferation and cytokine secretion. 1060 37


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