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 studied the effect of neuraminidase injection in rat's tumor at different doses: 5,10,50,100, 500 U and we concluded that: There was no difference between the rats treated with 5,10,50 U and the controls. The y died 3 weeks after the injection. But the rats treated by 100 at 500 U of NA died quickley, in the week, of long metastases.
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PMID:[Effect of intratumoral injection of bacterial and viral neuraminidase in rats]. 0 91

A transplantable murine osteosarcoma is described. Following transplantation into a syngeneic mouse the tumor grows rapidly and kills the mouse with pulmonary metastases simulating human osteosarcoma. A cell-mediated antibody response is evoked in the host mouse as demonstrated by in vivo and in vitro tests. The number of pulmonary metastases may be decreased with adjunctive immunotherapy following excision of the primary tumor. Immunotherapeutic materials include BCG and isologous cells treated with Vibrio cholerae neuraminidase.
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PMID:Immunological studies in murine osteosarcoma. Immunogenicity, growth kinetics, and immunotherapy. 106 29

Lymphocyte cytotoxicity, serum cytotoxicity, and the ability of the serum to inhibit lymphocyte cytotoxicity (blocking effect) were studied in a melanoma patient treated with six monthly injections of her own (autologous) tumor cells incubated with neuraminidase to increase their antigenicity. The same tumor cells grown in tissue culture were used as target cells for the cytotoxicity test. Large fluctuations of blocking effect in the serum were found, which correlated with the clinical course of tumor removal, recurrence, and regression. After the fifth injection of autologous tumor cells, the blocking effect disappeared from the serum (unblocking). In general, changes in serum cytotoxicity corresponded with changes in the amount of blocking effect produced by the serum. The results suggest that active immunotherapy may play a role in the prevention of metastases and, that when used within the autologous system, the cytotoxicity test is valuable in studying response to this type of therapy.
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PMID:Cytotoxicity reactions during immunotherapy of melanoma with neuraminidase altered autologous tumor cells. 124 39

Cancer-related changes in the serum seromucoid fraction are well known. Last year Woodman published an interesting carbocyanine dye binding method for determination of serum carbohydrate polyanions in sera of normal, traumatized, and tumor-bearing mice. The usefulness of this method for clinical practice has been investigated in this study. Carbocyanine dye-binding polyanion (CPA) and the sialidase-sensitive fraction of this polyanion (SPA) have been determined in sera of 705 human subjects including healthy normal individuals and patients suffering from a broad spectrum of malignant and nonmalignant disease states. Overall, in malignant diseases the CPA and SPA values, in mg pectin equivalents per liter (mean +/-2 S.D.) (292 +/- 111 and 135 +/- 68, respectively) were significantly higher than in the serum from normal controls (166 +/- 33; 74 +/- 18) and patients hospitalized with a variety of nonmalignant disease (195 +/- 56; 92 +/- 36). The highest CPA and SPA values were found in gynecological (331 +/- 117; 149 +/- 69), bronchial (294 +/- 72; 137 +/- 51), and gastrointestinal cancers (316 +/- 111; 154 +/- 69). Elevated CPA values were found in 59.9% and elevated SPA values in 52.8% of patients suffering from malignant diseases. Successfully, radically treated cancer patients with no detectable residues or metastases for at least 1 year had values (186 +/- 39; 76 +/-24) almost within the normal ranges (93 to 250 mg pectin equivalents per liter for CPA and 35 to 120 mg pectin equivalents per liter for SPA).
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PMID:Determination of carbocyanine dye-binding polyanions in malignant and nonmalignant disease states. 127 85

Reliable discriminatory tests to predict metastatic disease would clearly facilitate the management of cancer in the elderly. We have recently identified a 90-110-kilodalton (kDa) cell surface glycoprotein that is differentially expressed in benign and malignant murine adrenal carcinoma cells. In view of the proteins highly glycosylated nature, we have tested its ability to bind to a panel of agarose-bound lectins. Wheat germ agglutinin (WGA), a lectin specific for terminal sialic acid and N-acetylglucosamine (G1cNAc), had a strong affinity for the metastasis-related protein but failed to detect such a glycoprotein in nonmetastatic cells. Treatment of cells with sialidase to remove terminal sialic acids did not affect the affinity of the protein for the lectin, indicating the presence of terminal G1cNAc. We show by in situ that this metastatic binding protein (MBP) is regionally concentrated on the surface of invasive cells but absent in cells unable to invade. We postulate that MBP plays an active role in cell migration through interactions with beta-1,4 galactosytransferase and basement membrane glycoproteines.
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PMID:A murine model for evaluating metastatic potential: characterization of a 90-110-kDa metastasis-binding protein. 142 83

Human lung adenocarcinoma sub-cell lines HAL-8, HAL-24 and HAL-33, showing different lung colonization potential (LCP), were established from human lung adenocarcinoma cell line KUM-LK-2 using repeated cloning with limiting dilution technique. Cell lines HAL-8 and -33 were characterized by high and low LCP, respectively, while HAL-24 did not give rise to lung colonies. The cell surface protein and carbohydrate profiles were determined by cell surface labeling (with lactoperoxidase-dependent 125I-iodination and galactose oxidase-NaB3H4, respectively) followed by SDS-gel electrophoresis. Various carbohydrate epitopes expressed at the cell surface were analysed by cytofluorometry using various monoclonal antibodies (MAbs) directed to Le(x), sialosyl-Le(x), sialosyl dimeric Le(x), T, Tn and sialosyl-Tn structures, which are often reported as being highly expressed in a variety of human cancers, particularly adenocarcinoma. Expression of sialosyl dimeric Le(x) (defined by MAb FH6) was high on HAL-8, moderate on HAL-33, and relatively low on HAL-24. In contrast, each of the three lines showed essentially equal expression (as determined by MAb reactivity) of sialosyl-Tn (defined by MAb TKH2), Le(x) (defined by MAb SH1), and Tn (defined by MAb 1E3). The cell lines showed extremely weak expression of T (defined by MAb HH8). LCP of HAL-8 and -33 was completely inhibited by sialidase treatment of cells. It is suggested that higher expression of sialosyl dimeric Le(x) (defined by MAb FH6) in HAL-8 cells may play an important role in higher potential of blood-borne lung colonization.
Clin Exp Metastasis
PMID:Human lung adenocarcinoma cell lines with different lung colonization potential (LCP), and a correlation between expression of sialosyl dimeric Le(x) (defined by MAb FH6) and LCP. 167 53

Colorectal primary carcinomas and metastases from 20 Dukes' stage C or D patients were examined for the immunohistochemical localization and contents of various fucosylated N-acetyl-lactosamine oligomers by specific monoclonal antibodies (MAbs). MAbs used were SH1, specific for Lewis X antigen; FH4, specific for dimeric Lewis X antigen; FH6, specific for sialyl-dimeric Lewis X antigen; and KH1, specific for Lewis Y-Lewis X antigen. The distribution of the carbohydrate antigens identified by these MAbs was heterogeneous within the primary tumor as well as within the metastatic lesion. Examinations of serial sections indicated that areas within an individual tumor which were stained with one MAb were not always reactive with the other MAbs, although these four MAbs identify closely related structures. The degree of MAb reactivity with carcinoma sections was classified by percentage positive carcinoma cells, and primary tumors and metastases from the same patients were compared. An equivalent or higher proportion of carcinoma cells in the metastatic lesions were reactive with MAb FH6 than in the primary colon carcinomas, but each correlation was not seen with the other MAbs. Electrophoretic separation of tumor tissue extracts followed by staining with these MAbs revealed that a component having an approximate molecular weight of 1,000,000 is the major site for the binding of MAbs, FH6, FH4, and KH1. The electrophoretic mobility of the antigenic molecule on polyacrylamide gels as shown by direct MAb bindings was slightly different from that of a major sialomucin revealed by wheat germ agglutinin in the same tissues. MAb FH6 binding to a high molecular weight component was eliminated by prior treatment of the glycoprotein with mild acid or sialidase to remove sialic acid. Simultaneously, binding of MAb SH2, specific for dimeric Lex antigen, to this component increased. An extract was prepared from a liver metastasis, and high molecular weight components were isolated by gel filtration and then fractionated by DEAE-cellulose ion exchange chromatography. A fraction eluted from DEAE-cellulose between 0.10-0.25 M sodium chloride contained most of the MAb FH6 reactivity, as shown by antibody affinity chromatography. These results support a hypothesis that high molecular weight glycoproteins produced by colorectal carcinoma tissues are heterogeneous with regard to their carbohydrate chains and their antigenic structures may change during tumor progression.
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PMID:Sialyl-dimeric Lewis-X antigen expressed on mucin-like glycoproteins in colorectal cancer metastases. 197 61

Serine proteases, such as alpha-chymotrypsin or elastase, caused an aggregation of rat ascites tumour cell lines, AH-130, AH-109A and YS, in a protein free medium which preserved the cell viability. This aggregation, which was monitored spectrophotometrically, was dependent upon the protease activities and was resistant to treatment with either a calcium chelating reagent (EDTA) or neuraminidase. However, the tumour cell aggregates were redispersed by treatment with deoxyribonuclease I (DNase I). This dispersal effect was dependent upon the DNase activity. A possible relationship between the tumour cell aggregation and development of blood-borne metastasis was studied. An intravenous inoculation in rats of tumour cell aggregates performed by the alpha-chymotrypsin treatment resulted in significantly higher numbers of lung metastatic foci than an injection of single cells. When the re-separated single cells, prepared in vitro by treatment with DNase I following alpha-chymotrypsin treatment, were injected instead of the aggregates, the enhancement of metastasis was reversed. These enhancement and reversal effects were mimicked in vivo by intravenous injections of protease and nuclease following inoculation of a single cell suspension. That is, the number of metastatic foci caused by single cell inoculation followed by an intravenous alpha-chymotrypsin injection, was higher than that in a control group receiving PBS instead of alpha-chymotrypsin. Again, this augmentation was reversed by an injection of DNase I following alpha-chymotrypsin injection. Furthermore, an injection of DNase I alone itself reduced the starting number of metastases resulting from injection of the single tumour cell suspension. These data suggest that the metastatic behaviour of tumour cells may be increased by protease inducible DNA dependent cell aggregation should it occur in the blood stream.
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PMID:Serine protease-induced enhancement of blood-borne metastasis of rat ascites tumour cells and its prevention with deoxyribonuclease. 212 Dec 20

A syngeneic model system for the study of metastases is described. The system consisted of 2 lymphoma clones (A/63-I and A/63-2) derived from a single thymoma (A/63) induced by a wild-type Abelson-Moloney viral complex. Phenotype and genotype analyses revealed that both clones were derived from transformation of early T-cell precursors. An in vivo study of the colonizing potential following intravenous (i.v.) injection of clones showed that only the A/63-I cell clone colonized the liver. This observation was confirmed by quantitative analysis of organ distribution of both cell clones consecutive to i.v. injection of 125IUdR-labelled cells. In the same way, an in vitro study of the invasive potential of both clones was performed on frozen liver sections and showed that only the A/63-I cell clone had the ability to attach to liver. This specific adhesion was inhibited by L-fucose, D-galactose, N-acetyl-D-galactosamine (D-GalNAc) and with D-galactose- and L-fucose-containing neoglycoproteins. Differences in cell surface carbohydrates of the 2 cell clones were detected using various lectins: peanut agglutinin (PNA), Dolichos biflorus (DBA), Aleuria aurantia (AAA) and Galactia tenuiflora agglutinins (GTA). A/63-I was found to react strongly with PNA, DBA and GTA, and the removal of sialic acid by neuraminidase treatment increased DBA and PNA receptor sites of A/63-2 as compared to A/63-I. The present data suggest that cell-surface GalNAc, galactosyl and fucosyl residues are responsible for the ability of the A/63-I cell clone to recognize liver tissue probably through binding to a Kupffer-cell-associated lectin.
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PMID:Fucose and galactose receptor and liver recognition by lymphoma cells. 215 78

A33 is a mouse immunoglobulin G2a (IgG2a) monoclonal antibody (mAb) that detects a heat-stable, protease- and neuraminidase-resistant epitope. The antigen is homogeneously expressed by virtually all colon cancers and in the colon mucosa but not other epithelial tissues. The biodistribution and imaging characteristics of iodine-131 (131I)-mAbA33 were studied in colorectal carcinoma patients with hepatic metastases. Antibody labeled with 2 to 5 mCi of 131I was administered intravenously (IV) 7 to 8 days before surgery at five dose levels, ranging from 0.2 mg to 50 mg, with three or more patients entered at each dose level. In addition, three patients received 2 mg 131I-mAbTA99 (an isotype-matched control mAb) together with 125I-mAbA33. Evaluation included whole-body imaging with a gamma camera, technetium-99 (99mTc)-human serum albumin blood pool scans, liver/spleen scans, abdominal computed tomographic (CT) scans, hepatic arteriograms, antibody pharmacokinetics, and assessment of antibody distribution in biopsied malignant and normal tissues. Selective mAbA33 localization to tumor tissue was demonstrated in 19 of 20 patients, and external imaging correlated with surgical inspection, pathologic examination, and tissue radioactivity. One week after antibody administration, tumor:liver ratios ranged from 6.9:1 to 100:1 and tumor:serum ratios from 4.1:1 to 25.2:1. 99mTc-albumin blood pool studies showed that liver metastases were hypovascular, emphasizing the selective localization of mAbA33 despite poor tumor-blood flow. Control mAbTA99 studies showed mAbA33 localization was antigen-specific; tumor:liver ratios were 2.3- to 45-fold higher for specific antibody. In metastatic lesions, radioisotope was localized primarily in the viable periphery; however, even the necrotic tumor core concentrated specific antibody. External imaging showed isotope visualization in some patients' large bowel; whether this represents specific antibody uptake or gastric iodine secretion is unclear.
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PMID:Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33. 223 Aug 77


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