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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GnT-V generated, beta1,6-branched polylactosamines are a common feature shared by normal granulocytes, monocytes, and a variety of malignant cells. Furthermore, activation of GnT-V in oncogenic transformation induces invasiveness and metastatic potential in mice as well as in humans. In view of the common expression of lymphocytic/monocytic trait, motility, and GnT-V by metastatic cancer cells, macrophage fusion hybrids were generated in vitro with Cloudman S91 mouse melanoma cells to test whether the parental traits are co-expressed in hybrids and how those are related to altered phenotypes in relation to metastasis. In fact, the fusion hybrids are highly metastatic in vivo, motile in vitro, and express macrophage-associated traits of increased GnT-V activity, beta1,6 branching, and polylactosamine content. A Spontaneously formed lung melanoma metastases have been identified and characterized as host x tumor hybrid containing higher DNA content than parental cells and increased GnT-V activity. The results, taken together, could reflect prior fusion of tumor-associated macrophages with cells of the primary tumor, and therefore establish a possible common link between elevated expression of GnT-V and malignant transformation, a well-known report. Moreover, the fusion hybrids with metastatic potential ranging from high to low offer a genetically matched model system, for identification and characterization of differentially expressed genes in association with metastasis, since the fusion partners are derived from the same species of mouse (DBA/2J).
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PMID:GnT-V, macrophage and cancer metastasis: a common link. 1285 24

We showed expression of the tryptophan hydroxylase gene and of tryptophan hydroxylase protein immunoreactivity in mouse skin and skin cells. Extracts from skin and melanocyte samples acetylated serotonin to N-acetylserotonin and tryptamine to N-acetyltryptamine. A different enzyme from arylalkylamine N-acetyltransferase mediated this reaction, as this gene was defective in the C57BL6 mouse, coding predominantly for a protein without enzymatic activity. Serotonin (but not tryptamine) acetylation varied according to hair cycle phase and anatomic location. Serotonin was also metabolized to 5-hydroxytryptophol and 5-hydroxyindole acetic acid, probably through stepwise transformation catalyzed by monoamine oxidase, aldehyde dehydrogenase and aldehyde reductase. Activity of the melatonin-forming enzyme hydroxyindole-O-methyltransferase was notably below detectable levels in all samples of mouse corporal skin, although it was detectable at low levels in the ears and in Cloudman melanoma (derived from the DBA/2 J mouse strain). In conclusion, mouse skin has the molecular and biochemical apparatus necessary to produce and metabolize serotonin and N-acetylserotonin, and its activity is determined by topography, physiological status of the skin, cell type and mouse strain.
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PMID:Characterization of the serotoninergic system in the C57BL/6 mouse skin. 1289 90

Psychological stress modulates the immune system through the hypothalamic-pituitary-adrenal axis, the sympatho-adrenomedullary axis and the opioid system. According to literature data, restraint stress increases the immune cell apoptosis, decreases the spleen and thymus cell content, the natural killer (NK) activity in the spleen, and it compromises the anti-tumor immune response in mice. We immobilized mice in two consecutive nights, and then determined the cell number, apoptosis, NK cell content, NK activity and the level of cytokine mRNAs (TNF-beta, TNF-alpha, IL-4, IL-5, IL-1alpha, IFN-gamma, IL-2, IL-6, IL-1beta and IL-3) in the thymus and spleen. No consistent changes were detected in any of the immune parameters either in C57Bl/6 or in DBA/2 mice. Stressed or control B6 mice were injected with B16 melanoma cells immediately after the immobilization or one week later. No significant differences were found in the growth of primary tumors and lung metastases in stressed and control animals. Taken together, our mice, kept in a general-purpose non-SPF animal house, seemed to be refractory to the stress-induced immunomodulation. Our interpretation is that stress-induced immunomodulation can occur only in mice isolated from any background stressors, or rather natural stimuli, throughout their life.
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PMID:Restraint stress and anti-tumor immune response in mice. 1453 22

In vitro fusion of weakly metastatic Cloudman S91 melanoma cells with macrophages from DBA/2J mice (syngeneic with Cloudman S91 melanoma) produced hybrids with metastatic potentials ranging from low to high, with more than half showing enhanced metastasis over the parental melanoma [Clin. Exp. Metastasis 16 (1998) 299]. These hybrids, derived from the same parental fusion partners, represent a unique genetically matched model for analyzing differential gene expression regulating the metastatic phenotype. We have examined the differences in gene expression in metastatic fusion hybrid compared to its parental partners, non-/poorly metastatic melanoma cells and normal macrophages. An approach by selective polymerase chain reaction (PCR) amplification and display of 3' end restriction fragments of double-stranded cDNAs was used [Methods Enzymol. 303 (1999) 272]. Gene expression analyses showed an extensive set of transcripts that were up- or down-regulated in the most metastatic hybrid, H95-1, compared to the parental macrophages or melanoma cells. Sequence analyses of more than 60 of these differentially expressed cDNAs revealed significant up- or down-regulation of a number of genes known to be associated with metastasis of melanoma and other solid tumors. Some genes are found to express exclusively either in normal macrophages or in melanoma. Thirteen fragment sequences were found with no matches with GenBank search. Comparison of these gene expression patterns should be of great value in understanding the coordinate programs regulating metastasis. Further, the increased expression of gene(s) common in macrophage and fusion hybrids may be of importance in identifying the regulatory factor(s) related to macrophage-like trait, motility, a critical step of metastatic processes, in hybrids.
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PMID:Differential gene expression in genetically matched mouse melanoma cells with different metastatic potential. 1455 76

The constantly produced small amounts of reactive oxygen species (ROS) are reduced by anti-oxidant enzymes and cellular scavengers. The oxidative stress developed by defect in ROS clearance can result in cell injury and may lead to carcinogenesis. Pentoxifylline is a methylxanthine derivative with rheologic and membrane modifier property. We have examined whether Pentoxifylline (PTX) ameliorates oxidative stress produced in subcutaneously injected mice with B16F10 melanoma cells. Treatment of mice with PTX significantly reduced oxidative stress and attenuated the altered changes of reduced glutathione and lipid peroxides. Our findings provide an experimental basis for using PTX to attenuate oxidative stress induced by B16F10 melanoma cells in liver and lung of DBA/2 mice.
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PMID:Amelioration of B16F10 melanoma cells induced oxidative stress in DBA/2 mice by pentoxifylline. 1458 99

TNF is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory diseases, but also in metastasis in certain types of cancer. In terms of therapy, TNF is targeted by anti-TNF neutralising monoclonal antibodies or soluble TNF receptors. Recently, a novel strategy based on the generation of self anti-TNF antibodies (TNF autovaccination) has been developed. We have previously shown that TNF autovaccination successfully generates high anti-TNF antibody titres, blocks TNF and ameliorates collagen-induced arthritis in DBA/1 mice. In this study, we examined the ability of TNF autovaccination to generate anti-TNF antibody titres and block metastasis in the murine B16F10 melanoma model. We found that immunisation of C57BL/6 mice with TNF autovaccine produces a 100-fold antibody response to TNF compared to immunisation with phosphate-buffered saline vehicle control and significantly reduces both the number (P<0.01) and size of metastases (P<0.01) of B16F10 melanoma cells. This effect is also observed when an anti-TNF neutralising monoclonal antibody is administered, confirming the essential role TNF plays in metastasis in this model. This study suggests that TNF autovaccination is a cheaper and highly efficient alternative that can block TNF and reduce metastasis in vivo and trials with TNF autovaccination are already underway in patients with metastatic cancer.
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PMID:TNF autovaccination induces self anti-TNF antibodies and inhibits metastasis in a murine melanoma model. 1502 13

DNA vaccines can induce impressive specific cellular immune response (IR) when taking advantage of their recognition as pathogen-associated molecular patterns (PAMP) through Toll-like receptors (TLR) expressed on/in cells of the innate immune system. Among the many types of PAMP, immunostimulatory DNA, so-called CpG motifs, was shown to interact specifically with TLR9, which is expressed in plasmacytoid dendritic cells (pDC), a key regulatory cell for the activation of innate and adaptive IR. We now report that CpG motifs, when introduced into the backbone, are a useful adjuvant for plasmid-based DNA (pDNA) vaccines to induce melanoma antigen-specific protective T cell responses in the Cloudman M3/DBA/2 model. The CpG-enriched pDNA vaccine induced protection against subsequent challenge with melanoma cells at significantly higher levels than its parental unmodified vector. Preferential induction of an antigen-specific, protective T cell response could be demonstrated by (i) induction of antigen-dependent tumor cell protection, (ii) complete loss of protection by in vivo CD4+/CD8+T cell- but not NK cell-depletion, and (iii) the detection of antigen-specific T cell responses but not of relevant NK cell activity in vitro. These results demonstrate that employing PAMP in pDNA vaccines improves the induction of protective, antigen-specific, T cell-mediated IR.
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PMID:CpG motifs are efficient adjuvants for DNA cancer vaccines. 1524 38

Spin trapping/electron paramagnetic resonance (EPR) spectroscopy allows specific detection of nitric oxide (NO) generation, in vivo. However, in order to detect an EPR signal in living organism, usually a stimulation of immune system with LPS is used to achieve higher than physiological NO levels. Here, we report non-invasive spin trapping of NO in tumors of non-treated, living animals. EPR spectroscopy was performed at S-band to detect NO in Cloudman S91 melanoma tumors growing in the tail of living, syngeneic hosts-DBA/2 mice. Iron (II) N-(dithiocarboxy)sarcosine Fe2+(DTCS)(2) was used as the spin trap. The results were confirmed by X-band ex vivo study. A characteristic three-line spectrum of NO-Fe(DTCS)(2) (A(N)=13 G) was observed (n=4, out of total n=6) in non-treated tumors and in tumors of animals treated with l-arginine. Substrate availability did not limit the detection of NO by spin trapping. Half-life time of the NO-Fe(DTCS)(2) in tumor tissue was about 60 min. The feasibility of non-invasive spin trapping/EPR spectroscopic detection of NO generated in tumor tissue in living animals, without additional activation of the immune system, was demonstrated for the first time.
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PMID:In vivo spin trapping of nitric oxide from animal tumors. 1711 95

This unit presents an experimental tumor model which has led to pivotal advances in tumor immunology culminating in the preclinical development of human cancer vaccines for melanoma. The model employs the use of the P815 mastocytoma cell line. Although the P815 cell line belongs to the mast cell lineage, it offers several advantages for in vivo experimentation of the tumor-host relationship. It grows progressively in the majority of syngeneic DBA/2 mice and can be implanted either intraperitoneally or subcutaneously. Moreover, immunogeneic variants have been created yielding tumors that are spontaneously rejected BB a behavior that has provided a context in which to study the immunologically relevant molecules and cells that dictate a successful anti-tumor response.
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PMID:The p815 mastocytoma tumor model. 1843 77

Experiments on male C57Bl/6 mice with intraperitoneally transplanted Ehrlich carcinoma and DBA/2 mice with subcutaneously transplanted S-91 melanoma showed that preliminary injection of mononuclear leukocytes obtained from animals 6-8 h after tumor resection induce resistance to transplantation of malignant transformed cells. Our results suggest that not only humoral factors, but also immunocompetent cells are involved in the regulation of tumor growth. The resistance to tumor transplantation was not induced by mononuclear leukocytes isolated over the first hours and 10-12 h after removal of the primary tumor node, which excludes the direct cytotoxic effect of these cells and suggests that this phenomenon is not associated with activation of the effector mechanisms for innate and adoptive immunity.
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PMID:Mononuclear leukocytes from mice with resected tumor induce resistance to transplantation of tumor cells to animals. 1990 5


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