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

Mediation of cell adhesion by defined molecules can be studied by their immobilization onto a nitrocellulose matrix and incubation with cells. In order to infer the capacity of deliberately selected protein-carbohydrate interactions to establish sugar-inhibitable cell adhesion, a panel of immobilized neoglycoproteins was employed for the murine lymphosarcoma lines RAW-117 with low (P) and high (H10) metastatic capacity, a human mammary carcinoma line (DU4475) and three human colon carcinoma lines (C205, SW480, SW620). Exhibiting an otherwise rather similar behavior relative to the line with low metastatic potential, the murine line RAW117-H10 bound strongly to the matrix with carboxyl group-bearing N-acetylneuraminic acid and glucuronic acid as well as rhamnose. Whereas the analysis of carbohydrate-mediated adhesion yielded comparable results for the three colon carcinoma lines, a markedly reduced number of adherent cells was counted for matrix-attached alpha- and beta-galactosyl, alpha-mannosyl and alpha-glucosyl moieties in the case of the mammary carcinoma line, raising evidence for cell lineage-dependent alterations of this property. From the carbohydrate-binding proteins, the plant lectin, concanavalin A and Viscum album agglutinin almost invariably served well as cell adhesion molecules. Appropriate cell surface sugar receptors, probed with neoglycoproteins, and glycoconjugates, probed with lectins, thus can contribute to adhesion in this model system. The immobilized human beta-galactoside-binding lectin (Mr 14kDa) caused adhesion of the murine lines and one colon carcinoma line (SW480). Neither C-reactive protein under conditions that induce its activity as lectin nor serum amyloid P component nor a lactose-binding immunoglobulin G fraction from human serum were reactive. However, cell adhesion to the alpha-galactoside-binding immunoglobulin G fraction of human serum was seen with the murine line of low metastatic capacity and the mammary carcinoma line. Cells of this line adhered also to the mannan-binding protein from human serum, supporting the view for its potential role in host defence against aberrantly glycosylated tumor cells.
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PMID:Are matrix-immobilized neoglycoproteins, plant and human lectins and carbohydrate--binding antibodies from human serum mediators of adhesion in vitro for carcinoma and lymphosarcoma cells? 773 29

Embryonal carcinoma (EC) cells represent an important model for studying the regulation of cellular differentiation during embryonic development and tumor formation. The differentiation of EC cells is associated with changes in the expression of a number of cellular genes, some of which have been implicated directly in the regulation of differentiation. To facilitate further studies of the possible roles of cellular gene products during the differentiation of EC cells, we have used transient transfection assays to compare the function of three promoter systems that direct the conditional expression of recombinant gene constructs. One system employs the mouse mammary tumor virus (MMTV) promoter, which is induced by glucocorticoid hormones. The other two systems are based on chimeric transactivator proteins consisting of the bacterial lac repressor or tet repressor, respectively, fused with a viral transactivation domain. The chimeric proteins function in mammalian cells as sequence-specific activators of transcription that are regulated by either lactose analogs or tetracycline. Transient transfections of mouse F9 EC cells and their differentiated cells with an MMTV promoter-reporter gene construct and a second plasmid encoding the rat glucocorticoid receptor resulted in a dramatic induction of reporter gene expression by glucocorticoid hormone of approximately 200-fold. The conditional expression system based on the tetracycline-responsive transactivator exhibited a similar range of reporter gene expression in response to tetracycline. In contrast, the system based on the lac repressor exhibited a much more limited range of conditional reporter gene expression in our studies. These findings and others discussed in this report suggest that the tetracycline-responsive promoter system may be useful for the conditional expression of recombinant gene constructs in F9 EC cells. Furthermore, data are presented indicating that the human beta-actin promoter should be suitable for stable expression of conditional transactivators, such as the tetracycline-responsive transactivator, in F9 cells before and after differentiation.
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PMID:The function of inducible promoter systems in F9 embryonal carcinoma cells. 773 54

Chimeric BR96-doxorubicin conjugate (BR96-DOX) is an immunoconjugate designed to specifically target and kill certain tumor cells. The linker between the chimeric BR96 antibody and DOX is an acid-labile hydrazone group which was designed to undergo lysosomal hydrolysis to release DOX in vivo. Stability studies indicated that acid-catalyzed hydrazone hydrolysis was the major degradation route in vitro. Even under optimal conditions of pH and temperature, the stability of BR96-DOX in solution was not acceptable for long-term storage. Lyophilization of BR96-DOX in the presence of added sugars, such as lactose or sucrose, and subsequent storage of the lyophile under refrigeration significantly improved the stability. Therefore lyophilization appears to be a viable approach for achieving long-term stabilization of BR96-DOX.
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PMID:Stabilization of chimeric BR96-doxorubicin immunoconjugate. 778 36

Feeding lactose or other slowly digestible carbohydrates to adult mammals may induce a variety of effects including hyperplasia and neoplasia. The most fundamental effect probably is the increased production in the large intestine of short-chain fatty acids (SCFA) resulting from increased fermentation of carbohydrate residues. To find out whether the increased production of these acidic compounds is involved in the induction of certain alterations caused by low-digestibility carbohydrates, the modifying effects of an acidifying (NH4Cl) or an alkalizing (KHCO3) diet supplement on lactose-induced changes in rats were studied. Three groups of 50 rats per sex were fed a 20% lactose diet unsupplemented or supplemented with 1% NH4Cl or 2% KHCO3, for at most 2.5 yr. One control group was fed the basal diet which contained wheat starch instead of lactose. Feeding lactose resulted in wet faecal pellets, reduced pH of the faeces, higher intake of food and water, lower body weights, increased caecal weights and fewer deaths. These effects were not significantly modified by NH4Cl or KHCO3. Feeding lactose increased urinary calcium levels, the effect being enhanced by NH4Cl and reduced by KHCO3. Lactose also tended to increase blood values of alkaline phosphatase and to decrease those for bicarbonate and base excess. These tendencies were generally more marked with NH4Cl, and less marked or absent with KHCO3. In addition, rats fed lactose showed decreased severity of nephrosis, increased mineralization and hyperplasia of the renal pelvic epithelium, and relatively high incidences of Leydig cell hyperplasia and neoplasia. NH4Cl supplementation was associated with a relatively small number of single and multiple tumours, with decreased incidences of hyperplasia and mineralization of the renal pelvis epithelium and with a markedly reduced incidence of proliferative changes in the adrenal medulla. With the KHCO3 supplement the incidences of Leydig cell proliferation and of bladder tumours were relatively high. These findings, in particular the differences between the diet groups in urinary calcium levels and possibly also the variations in blood levels of alkaline phosphatase, bicarbonate and base excess, suggest that the acidic end products of carbohydrate fermentation (SCFA) act as an acid load on the body.
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PMID:Effects of a dietary load of acid or base on changes induced by lactose in rats. 782 70

Two carbohydrate-binding proteins with subunit molecular weight of about 17,500 and 16,500, respectively, were isolated from Triton X-100 extracts of rat kidney using a lactose affinity column. They did not require Ca2+ for the carbohydrate-binding nor reducing agents for maintaining their activity. The partial amino acid sequence of the 17.5-kDa protein (rkCBP-17.5), the main component, revealed that this protein is a novel member of a superfamily of beta-galactoside-binding animal lectins. The N-terminal amino acid sequence of the 16.5 kDa component (rkCBP-16.5) indicated that it is a fragment derived from the IgE-binding protein (IgEBP). Monoclonal antibodies to rkCBP-17.5 were prepared and used to examine the distribution of the lectin in various organs of adult rats. Immunoreactive protein with the same molecular weight was found in lung, spleen and liver, in lesser amounts in heart, and in trace amounts in brain and skeletal muscle. rkCBP-17.5 exhibits binding activity to various saccharides with the following order of affinity: N-acetyllactosamine > lactose > D-galactose > methyl alpha-D-galactopyranoside > N-acetyl-D-galactosamine > methyl beta-D-galactopyranoside. It binds to Engelbreth-Holm-Swarm(EHS) tumor laminin and rat plasma fibronectin, but does not bind to human plasma fibronectin.
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PMID:A novel beta-galactoside-binding lectin in adult rat kidney. 785 73

Galactoside-binding lectins (galectins) with molecular masses of about 14.5 kilodaltons (galectin-1) and 31 kilodaltons (galectin-3) have been found in a variety of normal and malignant cells and have been implicated in the regulation of cell growth, cell adhesion, and metastasis. The KM12 human colon carcinoma cell line was found to express only galectin-3. Because the levels of both galectins are developmentally regulated and can be modulated during the differentiation of several cultured tumor cell lines, we studied the ability of 11 differentiation-inducing agents to induce galectin-1 expression in the KM12 cells. Treatment of these cells with sodium butyrate, an established differentiation-inducing agent for colon carcinoma cells, resulted in the induction of galectin-1, which was detected by immunoblotting as well as by affinity chromatography. This effect was not seen with any of the 10 other differentiating agents: hexamethylene bisacetamide, dimethyl sulfoxide, dimethyl formamide, herbimycin A, mycophenolic acid, retinoic acid, difluoromethyl ornithine, dibutyryl cAMP, 8-chloro cAMP, and transforming growth factor beta 1. Galectin-1 induction by butyrate was observed in seven other human colon carcinoma cell lines. Further studies with the KM12 cells revealed that butyrate caused cell flattening, suppressed cell proliferation and colony formation in agarose, and increased the level of carcinoembryonic antigen, a marker of human colon carcinoma cell differentiation, within 48 h of treatment. The increase in galectin-1 level was dependent linearly on butyrate concentration (range, 1-4 mM). Galectin-1 mRNA expression was detected by Northern blotting as early as 6 h, and the protein was detected after 24 h of treatment initiation. The level of the constitutively expressed galectin-3 was also increased by butyrate but to a lesser extent than the level of galectin-1. Butyrate-induced galectin-1 was detected on the cell surface by immunoprecipitation from radioiodinated cell surface proteins as well as by indirect immunofluorescence labeling. Affinity-purified human galectin-1 was found to bind to purified polylactosamine-containing glycoproteins and to detergent-solubilized cellular proteins electroblotted onto nitrocellulose membranes. Affinity chromatography of [3H]glucosamine-labeled KM12 cell extracts on immobilized galectin-1 followed by immunoprecipitation from the lactose-eluted material demonstrated that lysosome-associated membrane glycoprotein-1, carcinoembryonic antigen, and nonspecific cross-reacting antigen are the major galectin-1-binding proteins in these cells. These results indicate that galectin-1 expression may be associated with the differentiation of KM12 cells and that several glycoproteins shown to be important in colon carcinoma adhesion and metastasis are capable of functioning as its endogenous ligands.
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PMID:Concomitant increases in galectin-1 and its glycoconjugate ligands (carcinoembryonic antigen, lamp-1, and lamp-2) in cultured human colon carcinoma cells by sodium butyrate. 795 33

The endogenous human tumor-associated galectin-3 (hL-31) is a functional molecule which acts as a receptor for ligands containing poly-N-acetyllactosamine sequences. However, little is known about its native ligand(s). In order to identify the ligand(s), the human melanoma cell line A375 was metabolically labeled with [3H]glucosamine, and total cell extracts and serum-free conditioned medium of the labeled cells were affinity-purified on immobilized recombinant hL-31 followed by elution with lactose, the specific sugar inhibitor of the lectin. Cellular ligands for hL-31 were found to be composed of the two lysosome-associated membrane proteins, LAMP-1 and LAMP-2, while secreted ligands consisted of two glycoproteins of 98 and 70 kDa. N-terminal protein microsequencing revealed that the 98 kDa and 70 kDa species share the same N-terminal sequence. The functional relevance of these secreted ligands was demonstrated by their ability to inhibit lectin-mediated hemagglutination in a manner similar to the specific sugar inhibitor lactose. Computer-assisted sequence library searches have identified the 98 kDa human melanoma secreted ligand to be the Mac-2-binding protein (Mac-2-BP), also known as the human lung tumor L3 antigen.
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PMID:Identification of human melanoma cellular and secreted ligands for galectin-3. 802 81

Oncogene activation and loss of tumor suppressor genes are known to play a role in tumor initiation as well as its progression. The potential roles of these genes in perturbation of genome stability has become a major interest. To better understand the relationship between expression of an oncogene and genetic instability, we have studied a cell line expressing an activated human Ha-ras under the control of bacterial lactose operon regulatory elements for changes in methotrexate resistance and dihydrofolate reductase (dhfr) gene amplification following mutant Ha-ras induction. In these cells mutant Ha-ras is directed by an inducible SV40 promoter containing a bacterial lac operator sequence which is repressed due to constitutive expression of bacterial lac repressor gene. The expression of this Ha-ras is specifically induced by the addition of isopropyl-1-thio-beta-D-galactopyranoside (IPTG), a lactose analogue, to the culture medium. During single-step methotrexate selection, these cells showed an increased frequency of methotrexate resistance in the presence of IPTG. More than 60% of the methotrexate-resistant colonies showed a 2-6-fold amplification of the dhfr gene. One clone with rearranged dhfr had about 100-fold amplification of the gene. The increased capacity to amplify DNA in response to mutant Ha-ras induction was not locus specific since cells also displayed an increased frequency of resistance to N-(phosphonacetyl)-L-aspartic acid in the presence of ITPG. Four of the methotrexate-resistant clones with amplified dhfr gene were cultured further in the presence or absence of IPTG and subsequently compared for their ability to grow in soft agar as a measure of transformation. In medium containing methotrexate but no IPTG, the clones were unable to grow in soft agar, indicating that methotrexate resistance due to gene amplification is separable from transformation.
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PMID:Increased methotrexate resistance and dhfr gene amplification as a consequence of induced Ha-ras expression in NIH 3T3 cells. 816

Many human tumors contain an activating mutation in one of the ras protooncogenes. Additionally, these tumor cells are often heteroploid and characterized by chromosome breaks and rearrangements that are consequences of the genomic instability that is thought to contribute to tumor progression. The concurrence of ras mutations and genomic instability in tumors prompted us to ask whether selective induction of an activated Ha-ras gene could render a genome unstable. The NIH 3T3 cells used in this study contained mutant p53 genes and carried a selectively inducible activated (EJ) Ha-ras transgene under the control of bacterial lactose regulatory elements. When stably transfected cells were induced to express activated Ha-ras by isopropyl beta-D-thiogalactoside administration, there was a marked increase in the number of gross chromosomal aberrations including acentric fragments, multicentric chromosomes, and double minutes, which occurred within the time frame of a single cell cycle from the time of induction. To confirm that these aberrations occurred within the first cell cycle after mutant Ha-ras induction, the cells were arrested in G1 phase by serum depletion and, subsequently, released by administration of isopropyl beta-D-thiogalactoside or serum. The mitoses from cells released with isopropyl beta-D-thiogalactoside contained a 3-fold elevation in the fraction of chromosomes containing aberrations compared to mitoses from parallel cell cultures that were released with serum. Thus, the induction of activated Ha-ras gene expression in these cells results in genomic instability that can be detected as aberrant chromosomes at the next mitosis.
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PMID:The human Ha-ras oncogene induces genomic instability in murine fibroblasts within one cell cycle. 819 95

Fetal bovine ligamentum nuchae fibroblasts express a 67-kDa, lactose-sensitive receptor that binds to VGVAPG, a repeated hexapeptide, of bovine and human tropoelastin. Recently, studies utilizing recombinant tropoelastin deletion proteins in conjunction with synthetic peptides identified a second fibroblast receptor binding site, PGAIPG. To evaluate whether PGAIPG is a ligand for elastin receptors of other cells, the chemotactic response of neutrophils and Lewis lung carcinoma tumor cells (M27) was studied. PGAIPG was chemotactic for both of these cells. The maximal response was seen at 10(-9) M. VGVAPG desensitized neutrophils to migration induced by PGAIPG confirming that PGAIPG was binding to the 67-kDa receptor. GAIPG, a chemokinetic peptide for fibroblasts, did not induce neutrophil migration. This corroborates the conclusion that GAIPG's mechanism of action in fibroblasts was independent of the 67-kDa receptor. Unlike fibroblasts and neutrophils, GAIPG was chemotactic for M27 tumor cells.
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PMID:PGAIPG, a repeated hexapeptide of bovine and human tropoelastin, is chemotactic for neutrophils and Lewis lung carcinoma cells. 839 88


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