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)

CEA is a beta1-glycoprotein (mol. w. approx. 200 000) which in embryonic life is usually found as a cell membrane associated antigen in the gastrointestinal (GI) tract and pancreas. Furthermore, it is secreted into body fluids. In healthy adults a very low serum concentration may be found. The clinical significance of CEA lies in its increased formation in primary and secondary adenocarcinomas of colon and rectum and pancreatic carcinoma, where values of 20 ng/ml and more are observed. However, other gastrointestinal (e.g. oesophagus, stomach, gall-bladder) and extragastrointestinal tumors (e.g. lung, breast, urogenital, prostatic, ovarial carcinomas) as well as non-malignant diseases mainly of the GI tract (e.g. hepatitis, cirrhosis, pancreatitis, colitis, diverticulitis) may provoke less frequent and lower increases in the CEA level. Healthy smokers also tend to show a slight increase in CEA concentration. A certain relationship exists between the CEA level and the size and extent of the tumor so that a decrease following operation may account for complete tumor removal, whereas a persistent or recurring increase in the CEA level is highly suspicious of metastases and/or recurrent tumor. Difficulties in proving and purifying CEA are mainly caused by multiple cross-reactions of CEA with other substances, e.g. blood group substances (A, B, Lea, Leb) and normal or other antigens (NGP, NCA, CEX, CCEA 2, NCA 2, CCA-III, FSA, BCGP). The radioimmunoassay is the most suitable method to determine CEA levels in body fluids. The 3 procedures used differ in the precipitation of the specific immune complex by ammonium sulphate (AS), Z-gel (ZG) or a second antibody (SA). Depending on the method, the upper normal limit in serum or plasma corresponds to approximately 2.5 (AS, ZG) or 12.5 (SA) nanogramme/milliliter. CEA determination in the urine is of interest in patients suffering from bladder carcinoma.
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PMID:[Carcinofetal antigens. II. Carcinoembryonic antigen (CEA). (author's transl)]. 108 Feb 18

Cell free extracts from metastases of human melanoma contain a highly active ribonucleoside diphosphate reductase (RR) which uses guanosine diphosphate (GDP) as substrate and deoxythymidine triphosphate (dTTP) as effector. No activity could be detected in these extracts when cytidine diphosphate (CDP) was used as the substrate with adenosine triphosphate (ATP) as effector. The activity of this RR required the presence of either magnesium or calcium: there was a time lag before cell extracts from melanotic melanoma metastases showed full activities, but extracts from amelanotic tumors showed normal kinetics in the presence of these divalent cations. By contrast to other RRs, the activities in cell-free extracts could not be inhibited by hydroxyurea (10(-2) M). Even though an activity related free radical could be detected by electron paramagnetic resonance spectroscopy at 77 degrees K, the signal could not be quenched by 10(-2) M of this free radical trap. However, after ammonium sulphate fractionation, enzyme activity from melanotic melanoma was inhibited by 66% in 1 h. In the presence of substrates, effector and cofactors, the radical signal at g = 2.009 was also quenched by 60%; in the absence of substrate, effectors and cofactors, this signal was unaffected. These results indicate that two different free radicals must be present on melanoma RR. One is present in the resting enzyme, and the other is used during catalytic activity. The thiolate-active site of RR from melanoma was inhibited by the new nitrosourea anti-tumour drug fotemustine (IC50 = 10(-4) M as determined from a dose-response study).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ribonucleotide diphosphate reductase from human metastatic melanoma. 133

The effects of dexamethasone on protein synthesis were studied in human fibrosarcoma (HT-1080) cells. Dexamethasone induced a new protein of 46 kD which was rapidly secreted into the medium, while neither progesterone nor estradiol would induce the synthesis of this protein and only a small increase in its amount could be seen in the presence of testosterone. The 46 kD protein was partially purified by ammonium sulfate precipitation and gel filtration and mouse monoclonal antibodies to it were produced in mouse hybrid cells. Altogether 13 positive clones were found, of which six reacted only with native and seven reacted with the unreduced 46 kD protein in Western blotting. It was possible by using polyclonal antibodies to plasminogen activator inhibitor type I (PAI-1) and purified plasminogen activator inhibitor type I to confirm that the 46 kD protein purified and characterized here was PAI-1. In addition, the 46 kD protein clearly inhibited plasminogen activation, thus further confirming that protein isolated was an inhibitor of plasminogen activator. Since the induction of PAI-1 by dexamethasone was very extensive, it is possible that glucocorticoids regulate proteolysis and fibrinolysis in vivo by increasing the amount of the inhibitor of plasminogen activator and thus preventing the activation of plasminogen to plasmin. The reduction of activation of plasminogen to plasmin by glucocorticoid-induced inhibitor could be of great importance, e.g., in various blistering diseases, in metastases from malignant cells, and in the migration of inflammatory cells.
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PMID:Dexamethasone-induced plasminogen activator inhibitor: characterization, purification, and preparation of monoclonal antibodies. 214 2

The goal of this study has been to identify and characterize metalloproteinases from a highly metastatic human small cell lung cancer cell line. The cytosol isolated from NCI-H82 lung cancer cells propagated as solid tumors in nude mice contained a gelatinolytic enzyme that was subjected to ammonium sulfate precipitation, zinc chelate Sepharose column chromatography, anion exchange chromatography and gel permeation chromatography. This purification scheme resulted in a 280-fold enrichment of an active gelatin and type IV collagen-degrading enzyme. On gelatin zymography two bands of gelatinolytic activity were detected, corresponding to Mr of 75,000 and 63,000. Gelatinolytic activity was inhibited by metal chelators, tetracyclines, and serum. On immunoblotting using an affinity-purified polyclonal rabbit antibody to a peptide region of type IV collagenase, the tumor enzyme was identified as type IV collagenase. A second tumor metalloproteinase of Mr = 29,000, which degraded proteoglycan substrates, was also isolated.
Invasion Metastasis 1989
PMID:Gelatin-degrading type IV collagenase isolated from human small cell lung cancer. 254 76

In this report we describe the isolation and characterization of a neutral metalloproteinase, from human small cell lung cancer cells, which degrades a wide range of connective tissue proteins. Treatment of tumor cytosol by ammonium sulphate precipitation followed by zinc chelated column chromatography, anion exchange chromatography, and gel filtration chromatography yielded a single enzymatically active protein, which on SDS-PAGE appeared as a diffuse band of 65,000-70,000 daltons. The tumor metalloproteinase, which was inhibited by metal chelators and serum, was able to digest gelatin, type I collagen, type IV collagen, laminin, and fibronectin. We propose that the capacity of this proteinase to degrade both components of blood vessel basement membranes and other connective tissue matrices facilitates the dissemination of human lung cancer cells during the multistep process of metastasis.
Clin Exp Metastasis
PMID:Characterization of a connective tissue degrading metalloproteinase from human small cell lung cancer cells. 283 54

Electron spin resonance spectroscopy has been used to measure the reduction of nitroxide radicals on a spin-labeled quaternary ammonium substrate by plasma membrane-associated thioredoxin reductase (EC 1.6.4.5) at the surface of cutaneous and subcutaneous melanoma metastases from one patient (B.M.). Enzyme activity in these metastases was shown to be hyperactive compared to normal skin and was subject to inhibition by calcium. From the remainder of the tissue (50.6 g), plasma membrane-associated thioredoxin reductase has been isolated and its molecular properties were compared with the same enzyme purified from the cytosol of rat liver and Escherichia coli. The enzyme from melanoma possessed an identical molecular weight to that from rat liver as determined by SDS-polyacrylamide gel electrophoresis (Mr 58,000). Upon fluorescence spectroscopic examination, the enzyme from melanoma was shown to contain flavin adenine dinucleotide as previously shown in the enzymes from E. coli and rat liver. The increased activities in plasma membrane-associated thioredoxin reductase in metastases of malignant melanotic melanoma are discussed in terms of the cellular functions of this important enzyme.
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PMID:The activity and purification of membrane-associated thioredoxin reductase from human metastatic melanotic melanoma. 284 80

Eleven acute rejections were found in 9 patients with liver transplantation due to end-stage liver cirrhosis. The rejections were diagnosed with fine-needle aspiration biopsy (FNAB) giving the cellular picture of immunoactivation in the liver graft when compared to a simultaneous sample of peripheral blood. s-Alkaline phosphatase and s-bilirubin increased within 1 week after onset of rejection in 7 and 10 cases, respectively. s-Alanine amino-transferase and b-ammonium were of no value in the diagnosis of acute rejection. A core biopsy was obtained only in a case of severe liver damage, mainly to estimate the need for retransplantation. One year after grafting, 6 out of 7 cirrhotic patients are well, all with normal liver function. Two have died of sepsis. One patient died from pulmonary metastases of occult liver carcinoma 6 months after the transplantation. FNAB seems helpful in detecting early acute rejection and also excluding such an event in the liver graft.
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PMID:Diagnosis of acute rejection in liver transplantation. 304 94

Antisera were raised in rabbits against nonmetastasizing (NML) and metastasizing (ML) forms of hamster lymphosarcoma and were purified against normal hamster tissues. Immunoglobulins from the purified antisera were precipitated with 1.6 M ammonium sulfate, radioiodinated and IgG separated by Sephadex G-200 gel filtration. 125I-IgG preparations were analyzed by a direct cell binding assay and by a complement-dependent cytotoxicity test, employing single cell suspensions from primary lymphosarcoma. In some experiments, 125I-IgG was also tested against ML cells obtained from primary tumor (1 degree) and its liver metastasis (2 degrees). NML induced greater anti-tumor antibody production than ML, suggesting greater antigenicity of the non-metastasizing tumor. The two lymphosarcomas appeared to share some common tumor-associated antigens since antibody to one tumor type was either completely or partially absorbed by tumor cells of the other type. Anti-ML 125I-IgG proved up to 2-5 times more cytotoxic for ML 1 degree than 2 degrees cells. Although both tumors were highly tumorigenic in hamsters, only ML gave rise to distant metastases, predominantly in the liver.
Invasion Metastasis 1985
PMID:Antigenic heterogeneity of metastasizing and nonmetastasizing forms of hamster lymphosarcoma: comparison of primary tumor and spontaneous liver metastases. 316 45

A long-term invasion assay using fibrous connective tissue matrices was developed. The matrices were prepared by treating murine skin or human dura mater with 25 mM ammonium hydroxide containing proteinase inhibitors at 4 degrees C for 7 days. They could be maintained almost indefinitely without the degeneration and necrosis. Electron micrographs of them revealed the preservation of native collagen fibers, and sequential enzyme digestion showed the presence of glycoprotein in the matrices. Local dissolution of extracellular matrix by cultured human rectal adenocarcinoma cell line, RCM-1, was observed morphologically and confirmed by a quantitative assay using radiolabeled matrices. The destruction of extracellular matrix occurred associated with membrane vesicle-shedding from the cells. Both the advantages and disadvantages of this assay were discussed.
Invasion Metastasis 1988
PMID:A new long-term in vitro invasion assay using fibrous connective tissue matrices maintaining architectural characteristics of connective tissue. 319 27

We developed a model to assess the therapeutic effects of the 45-2D9-ricin A-chain immunotoxin (RTA) on pulmonary metastases. The 45-2D9 mouse monoclonal antibody recognizes a Mr 74,000 glycoprotein highly expressed by rat fibroblasts transformed with the Kirsten sarcoma virus (transformed rat fibroblasts). These cells metastasize spontaneously and form lung colonies in nu/nu and irradiated BALB/c mice. Injection i.v. of 45-2D9-RTA specifically reduced formation of spontaneous pulmonary metastases and lung colonies originating from freshly disaggregated tumor cells or cultured cells. Antibody alone or mixed with unconjugated ricin A chain and an immunotoxin that recognizes a melanoma-associated antigen were ineffective. Unconjugated 45-2D9 antibody specifically blocked the 45-2D9-RTA activity in vivo. Administration of the lysosomotrophic agents ammonium chloride and chloroquine in vivo did not potentiate immunotoxin-mediated reduction in lung colonies although they were effective in vitro. Monensin potentiated 45-2D9-RTA activity in vitro and in vivo.
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PMID:Mediation of reduction of spontaneous and experimental pulmonary metastases by ricin A-chain immunotoxin 45-2D9-RTA with potentiation by systemic monensin in mice. 325 69


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