Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the endogenous production of a serum cytotoxic factor when recombinant interferon-gamma (rIFN-gamma) is combined with synthetic lipid A subunit analogs of low toxicity (GLA compounds). The cytotoxic activity of the serum was measured by the crystal violet staining method with L929 cells as a target. Intravenous administration of rIFN-gamma followed by intravenous administration of lipopolysaccharide induced the endogenous production of a cytotoxic factor in the serum. The priming effect of rIFN-gamma appeared immediately and persisted for approximately 20 h after the injection. Administration of lipopolysaccharide as a trigger enhanced the production of the cytotoxic factor in the serum maximally 2 h after the injection. The cytotoxic activity in the serum was completely inhibited by anti-(mouse tumor necrosis factor) (TNF) antibody. A synthetic lipid A subunit analog (GLA-60), which is much less toxic in its endotoxin activities than lipopolysaccharide or synthetic lipid A (compound 506), induced the endogenous production of serum TNF in rIFN-gamma-primed mice. GLA-60 entrapped within liposomes induced the production of serum TNF in rIFN-gamma-primed mice more effectively than GLA-60 solubilized in phosphate-buffered saline. Intravenous or intranasal administrations of rIFN-gamma followed by intranasal administration of GLA-60 produced TNF in the lung washing fluid but not in the serum, indicating that TNF production can be induced locally rather than systemically by the alteration of the administration route of the primer and trigger. These results indicate that GLA-60, a lipid A subunit analog of low toxicity, is a beneficial triggering agent in the production of endogenous TNF, as well as having other immunopharmacological properties, and may provide a basis for cancer (metastases) treatment as a result of its ability to induce endogenous TNF.
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PMID:Induction of an endogenous tumor necrosis factor in mice by murine recombinant interferon-gamma combined with a lipid A subunit analog (GLA-60) of low toxicity. 249 79

We have investigated the effect of endogenous production of tumor necrosis factor (TNF) induced by the combination of recombinant interferon gamma (rIFN gamma) as a primer followed by GLA-60 as a trigger (rIFN gamma/GLA-60) on murine lung metastases caused by B16-BL6 melanoma. In order to examine the therapeutic effect of endogenous TNF on tumor metastasis, the ability of multiple administrations of rIFN gamma/GLA-60 to induce TNF production was also tested. The multiple administrations of rIFN gamma/GLA-60 at intervals of 2 days were effective for the induction of endogenous TNF in mice but continuous multiple administrations of them for 2-4 days were not. In tumor-bearing mice, the production of endogenous TNF by rIFN gamma/GLA-60 was less than that of normal mice, but treatment 3 days after the surgical excision of primary tumors showed the endogenous TNF production to be similar to that in normal mice. In the experimental lung metastasis model, intravenous administration of rIFN gamma followed by intravenous or intranasal administration of GLA-60 showed potent inhibition of lung metastases of B16-BL6 melanoma, whereas the reverse sequence of administration (GLA-60/rIFN gamma) or administration of a mixture of rIFN gamma and GLA-60, which cannot induce the production of TNF, caused no inhibition of lung metastases. These results indicated that the regression of tumor metastases by rIFN gamma/GLA-60 was mediated by the production of endogenous TNF in addition to the direct effects of both immunostimulants. Furthermore, the administration of rIFN gamma and GLA-60 significantly inhibited the tumor metastases in spontaneous lung metastasis model. These results may provide a promising approach for the treatment of cancer metastasis as a result of its ability to induce endogenous TNF.
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PMID:Antimetastatic effect of endogenous tumor necrosis factor induced by the treatment of recombinant interferon gamma followed by an analogue (GLA-60) to synthetic lipid A subunit. 251 13

A panel of fluorescein-conjugated lectins was used to investigate the cell surface carbohydrates of cell lines isolated from a mouse mammary adenocarcinoma which differ markedly in their morphological and metastatic properties. The lectin-binding profiles of the cells showed them to express generally similar cell surface characteristics; however, two minor differences were evident. Galactose moieties recognized by peanut lectin were expressed on all highly metastatic fusiform cell types examined, but only on 50-60 per cent of the polygonal cells of limited metastatic capacity. Similarly, N-acetylgalactosamine moieties were demonstrated on fusiform cell types by soya bean lectin binding but were not expressed on intact polygonal cells. In both cases pretreatment of polygonal cells with neuraminidase allowed lectin binding comparable with that of fusiform cells suggesting that Gal and GalNAc sugars were abundantly present but masked by sialic acid residues. Using a novel technique in which tumour cells were incubated on cryostat sections of normal tissues, it was found that the cell lines exhibited different adhesion patterns which to some extent reflected their preferential sites for spontaneous metastasis and organ colonization in vivo. Thus the adherence of fusiform cells to liver was five times as great as that of polygonal cells, whereas the latter bound preferentially to lung tissue. Prior treatment of polygonal cells with neuraminidase doubled their frequency of attachment to liver sections, but had no effect on their binding to other tissues. Also, the presence of 100 mM N-acetylgalactosamine during incubation specifically inhibited the adherence of fusiform cells to liver tissues, but did not significantly influence other cell-tissue interactions. The data suggest that the expression of galactosyl or N-acetylated galactosyl groups on the fusiform cells facilitates their attachment to lectin-like receptors on liver cells and contributes to their superior capacity, compared with polygonal cells, for growth and metastasis in this organ.
Clin Exp Metastasis
PMID:Studies of mammary carcinoma metastasis in a mouse model system. II: Lectin binding properties of cells in relation to the incidence and organ distribution of metastases. 654 7

The small cell lung cancer cell lines GLC-2 and DMS 456 were genetically labeled with the lacZ gene and examined for invasive and metastatic potential in META/Bom nude mice. The lacZ gene encodes the enzyme beta-D- galactosidase, and cells expressing this enzyme were identified by staining with the chromogenic substrate X-gal. lacZ expressing cells were investigated after subcutaneous (s.c.) inoculation and intravenous (i.v.) injection. The X-gal detection of beta-D-galactosidase activity proved to be a rapid and easy means for specific and highly sensitive identification of metastases. All primary s.c. tumors stained by X-gal. The primary tumors of GLC-2 regularly demonstrated local invasive growth and produced multiple metastases in several organs. In contrast, primary DMS 456 tumors only occasionally demonstrated local invasion and very rarely generated secondary foci. No experimental metastases were found after i.v. injection of the examined tumor lines. The results indicate an intratumoral heterogeneity among individual SCLC tumors in the capacity for invasion and metastatic spread. The different metastatic pattern of GLC-2 after s.c. and i.v. inoculation supports the hypothesis that initial steps of the metastatic cascade occurring in the primary tumor are necessary for the subsequent production of growing metastases.
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PMID:Dissemination in athymic nude mice of lacZ transfected small cell lung cancer cells identified by X-gal staining. 757 76

Bone metabolism marker evaluation is expected to play an auxiliary role in the diagnosis and follow-up of bone metastases in patients affected by different types of neoplasms. In this study we have evaluated osteoblastic and osteoclastic markers in 18 patients with bone metastases from breast cancer at diagnosis and for 1 year of follow-up during treatment with the aromatase inhibitor formestane. Osteoblastic markers include the carboxy-terminal propeptide of type I procollagen, the bone-specific alkaline phosphatase and the bone GLA protein. The carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) was evaluated as a marker of osteoclastic activity. The patients were classified into three groups according to clinical response. A good correlation between marker level modifications and clinical evolution of skeletal metastases was observed for all the examined markers. Patients with progressive disease showed increasing levels of all markers, whereas patients in regression showed a reduction compared to the basal levels; patients with stable disease fell in between these two categories. We also found that basal ICTP values have prognostic significance: in the stable and progressive disease group they were higher than in the partial response group.
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PMID:Serum markers of bone metastases in postmenopausal breast cancer patients treated with formestane. 921 4

It is widely known that dietary lipids can modify the ability of different cancers to grow up and metastasize, especially mammary gland tumors. However, it is still unclear whether n-6 fatty acids behave as tumor promoters in this gland cell population. The effect of different nutritional polyunsaturated fatty acids (PUFAs) on tumor growth parameters of two transplantable murine mammary gland adenocarcinomas of low and high metastatic ability was tested on hosts fed diets with corn oil (CO) rich in 18:2n-6, evening primrose oil (EPO) containing 18:3n-6 (GLA) and a third formula supplemented with olein (O) 18:1n-9, which induces an essential fatty acid deficiency (EFAD). Tumor growth parameters were not adversely affected in the corn oil group with respect to stock-fed controls. Furthermore, metastatic spreading diminished in this group. EPO showed a moderate antitumor activity whereas the n-9-enriched diet showed no clear-cut effects. In both mammary gland tumors, n-6 fatty acid-rich lipids formulae, containing GLA and linoleic acid, were not tumor promoters. On the contrary, both exhibited anticancer activity.
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PMID:Differential modulation by dietary n-6 or n-9 unsaturated fatty acids on the development of two murine mammary gland tumors having different metastatic capabilities. 958 60

Lung cancer is one of the most common malignant tumors in humans. Metastasis is the basic biological feature of malignant tumors, which is the main cause of death. Molecular mechanism of metastasis is still unclear, although lots of studies have been done in tumor metastasis. To study and explore the molecular basis of metastasis in lung cancer, and isolate tumor metastasis-related genes, two human lung adenocarcinoma cell lines AGZY 83-a and Anip 973 were chosen as research materials. The Anip973 was derived from AGZY83-a, but manifested much higher metastasis potential than the parent line. Using mRNA differential display technique, an unknown cDNA fragment, OPB7-1, which is over-expressive in Anip973 cell line, was obtained. It was used as a template to isolate its corresponding cDNA through dbEST searching and PCR. To search and clone lung adenocarcinoma metastasis-related candidate gene, and to explore the molecular basis of development of lung carcinoma, differential expression of OPB7-1 cDNA fragment among 9 human lung adenocarcinoma cell lines and 12 normal human tissues were detected using cell culture, cDNA clone, Northern blot analysis and bioinformation technology. Results showed that there were significant differences in OPB7-1 expression among 9 human lung adenocarcinoma cell lines. High expression tendency was observed in Anip973 cell line with high metastasis potential, TKB-18 cell line with high invasion potential and GLC-82 cell line with low differentiation potential. Besides, a bigger fragment can be found in Anip973 cell line on the Northern blot hybridization. The 3.0 kb transcriptions were found in various tissues. Over-expression in heart and skeletal muscle could be observed, whereas expression in spleen, liver, kidney, placental and lung could be found except colon, thyroid gland and small intestine. These manifests indicate that OPB7-1 gene has a wide-rage expression in human multiple tissues. A 1.0 kb cDNA fragment was acquired by linking up EST fragments homologous match 5' end and PCR. BLAST analysis revealed that OPB7-1 gene has extremely low sequence identity with any known genes from GenBank and any sequences from EST database. The chromosomal localization of it was determined by RH location method. The OPB7-1 fragment was localized to chromosome 1p31-34. That OPB7-1 gene has an extensive expression pattern, may be a novel tumor gene related to lung carcinoma. Further research needs to be done to obtain the full-length cDNA of OPB7-1 gene. It will be helpful to investigate the expression in lung cancer cases and other tumor tissues for further determining the function of OPB7-1 gene in development of tumor.
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PMID:[Mapping and expression analysis of a different expression cDNA fragment from lung adenocarcinoma cell line]. 1209 22

This study focused on the differential expression levels of proteins that may exist between bone-derived and marrow-derived vascular endothelial cells (BVEC and MVEC). The vascular cells were isolated from trabecular bone regions and central marrow cavity regions of mouse long bones. Cells were cultured for 1 week to expand the population then separated from non-vascular cells using biotinylated isolectin B4, streptavidin-coated metallic microbeads, and a magnetic column. After an additional week of culture time, RNA was isolated from both cell types and compared using microarray analysis. RT-PCR was used to confirm and relatively quantitate the RNA messages. The bone-derived cells expressed more aldehyde dehydrogenase 3A1 (ALDH3A1), Secreted Modular Calcium-2 (SMOC-2), CCAAT enhancer binding protein (C/EBP-beta), matrix metalloproteinase 13 (MMP-13), and annexin 8 (ANX8) than the marrow-derived cells. Spalpha and matrix GLA-protein (MGP) were produced in greater abundance by the marrow-derived cells. This study reveals that there are profound and unique differences between the vasculature of the metaphysis as compared to that of the central marrow cavity. The unique array of proteins expressed by the bone-derived endothelial cells may support growth of tumors from cancer cells that frequently metastasize and lodge in the trabecular bone regions.
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PMID:Evaluation of bone-derived and marrow-derived vascular endothelial cells by microarray analysis. 1737 35

Antigen tumor markers employed in monitoring therapeutical approaches are limited by their specificity (Sp) and sensitivity (Se). The aim of this study was to investigate the suitability of a lipid tumor marker derived from ether-linked phospholipids and to compare it with others usually assayed in clinical practice. Complex lipids from normal and pathological breast, lung, and prostate tissue were isolated and analyzed by TLC and c-GLC methods. Results were compared as pooled samples, or by means of the averaged percent changes with respect to the composition observed in the normal tissue of the same patient. Sp, Se, negative-predictive (NPV) and positive- predictive values (PPV) were established for conventional markers and for the proposed lipid-derived marker. Results demonstrated that the content of monoenoic fatty acyl chains was significantly increased in total lipids, phosphatidylethanolamine, and especially in ethanolamine-containing ether lipids of neoplastic tissues with respect to their corresponding normal ones. Major changes were observed in the plasmalogen sub-fraction where the ratio monoenoic/saturated fatty acids can distinguish with high Se normal tissues from either benign or neoplastic tissues from breast, lung, or prostate lesions. Analyses of fatty acyl chains from ethanolamine-containing plasmalogens provided a reliable tumor marker that correlated with high Se and linearity with metastases spreading. This fact may be useful in prognosis of the most frequently observed human cancers.
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PMID:A reliable biomarker derived from plasmalogens to evaluate malignancy and metastatic capacity of human cancers. 1804 93

The differentially expressed in adenocarcinoma of the lung-1 (DAL-1) protein is a member of the membrane-associated cytoskeleton protein 4.1 family. This protein was previously found to be downregulated or lost in more than half of primary non-small cell lung cancers (NSCLC). In this study, the relationship between DAL-1 expression and NSCLC metastasis was examined. DAL-1 mRNA and protein levels were measured in NSCLC cell lines and in tumor cells isolated from the pleural fluid of NSCLC patients clinically diagnosed with distant metastases to the bone or brain. The results revealed that DAL-1 expression was observed in two (GLC-82 and NCI-H460) out of seven metastatic NSCLC cell lines examined. DAL-1 expression was not observed in the cells isolated from the pleural fluid in nine out of ten patients. Overexpression of DAL-1 in A549 cells, a cell line lacking endogenous DAL-1, inhibited cell migration and invasion by approximately 38 and 48 %, respectively. In contrast, DAL-1 knockdown in NCI-H460 cells enhanced the migration and invasion potential of this cell line 4.6- and 3-fold, respectively. Furthermore, DAL-1 promoter methylation was observed in six of nine pleural fluid NSCLC cell isolates and in two cell lines (A549 and H1299), as evidenced by a lack of endogenous DAL-1. Demethylation in A549 cells successfully restored DAL-1 mRNA and protein expression levels, resulting in a parallel remarkable inhibition of migration and invasion. These results indicated that DAL-1 was pivotal in triggering NSCLC migration and invasion and that loss of DAL-1 expression was due to the epigenetic methylation.
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PMID:Loss of expression of the differentially expressed in adenocarcinoma of the lung (DAL-1) protein is associated with metastasis of non-small cell lung carcinoma cells. 2278 4


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