Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the malignant progression changes occur in the composition and content of carbohydrates in the cellular membrane. We studied distribution of lectin receptors SBA, PNA, WGA and HPA in dysplasias and human breast cancer. We established that malignancy is associated with the increase in mosaic staining and shift of lectin receptors from the apical or basal pole of acinar epithelium and ducts to the whole plasmolemma surface, homogeneous staining of cytoplasm and nuclei of tumor cells. It is evident that distribution of lectines in dysplasias and malignant mammary tumors may serve a diagnostic marker and indicator in predicting metastatic potential.
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PMID:[The characteristics of lectin distribution and level in breast dysplasias and cancers]. 969 52

Peanut agglutinin (PNA) lectin-binding site patterns in primary invasive breast ductal not otherwise specified (NOS) carcinomas are related to aggressiveness of the tumor. The present study was designed to compare the expression of PNA-binding sites in the primary tumor and in local lymph node metastases. The expression of lectin-binding sites was studied using the avidin-biotin complex/immunoperoxidase technique and analyzed in relation to age of the patient and size of the breast cancer. Breast cancers and their metastases showed negativity or positivity, the latter being divided into "apical" and "non-apical" (i.e. membrane and/or cytoplasmic) depending on the main localization of staining in tumor cells. No correlation was found between primary tumors and metastases as regards PNA-binding patterns, which confirms the opinion that advanced primary tumors are polyclonal and that selected subclones of malignant cells give rise to metastases. Furthermore, the fact that primary tumors with PNA non-apical expression, a feature related to aggressiveness and poor differentiation, may have lymph node metastases with apical expression, suggests that this pattern, although no longer evident in the primary tumor, is involved in the process of cell metastasis.
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PMID:The lectin-binding sites for peanut agglutinin in invasive breast ductal carcinomas and their metastasis. 979 58

This study documents modifications in the expression and the cellular distribution of binding sites for a 16 kDa chick embryo lectin (CL16-BS) in breast cancer. This lectin binds preferentially to terminal and penultimate N-acetyllactosamine residues (Galbeta1-4GlcNAc). BS density and distribution, studied by lectin binding followed by indirect immunofluorescence, were compared in normal breast tissues and 45 invasive carcinomas (lobular and ductal). Increased number of fluorescent epithelial cells (ETC+) were observed in normal ducts adjacent to lobular carcinomas and in tumors from both types when compared to normal glands. In ductal carcinomas, a significant diminution of ETC+ percentage was observed in the highest anatomopathological SBR grades: 32.7% in grade III, 80.8% in grade II and 66.5% in grade I (p<0.001). For both lobular and ductal carcinomas, ETC+ percentages were also positively correlated with low versus high MSBR grades (p<0.002). The subcellular distribution of CL16-BS varied according to the tumor type and/or the histological grades. It was mostly membrane-associated in low SBR and MSBR grades (p<0.001 and p<0.01, respectively) and cytoplasm-associated in high grades (p<0.02 and p<0.05). Some of these parameters were also correlated with certain other clinicopathological factors, such as tumor size (p<0.02), high S-phase cell fraction (p<0.04 and p<0.03) and low density estrogen receptors (p<0.05). Diminution in CL16-BS density and cytoplasmic versus membrane localization may be considered as indicators of tumor progression but not of metastasis.
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PMID:Association of N-acetyllactosamine with tumor progression in human breast cancer: a study using a 16 kDa chick embryo lectin. 985 96

The aim of the present study was to compare the biological effects of 12 different clinically applied mistletoe preparations (I, II, III and IV) from the host trees "pinus" (P), "malus" (M), "abies" (A) and "quercus" (Q) on human leukocytes. When the preparations I-P, II-P, III-P and IV-A were added to the whole blood cell cultures of 37 cancer patients (breast cancer, n = 22, colorectal cancer, n = 15) and 34 healthy controls, a significant induction of the cytokines IL-1-beta, IL-2, IL-6, IL-10 and TNF-alpha was found with preparation I-P. A significant induction of IL-1-beta and TNF-alpha was obtained with the preparations II-P and III-P as compared to the nonstimulated control cultures. Induction of IFN-gamma was not found with any preparation. Cytokine induction was comparable in the blood cell cultures of the tumor patients and the healthy controls. When the clinical preparations I-P, I-M, I-Q, II-P, II-M, II-A, III-P, III-M, III-A and IV-P, IV-M, IV-A were tested in cultures of peripheral blood mononuclear cells from 5 healthy donors, differences in the induction of cytokine production and apoptosis were seen after addition of the mistletoe preparations from different host trees. Increased levels of IL-1-beta were found after addition of the preparations I-P and I-M, increased levels of TNF-alpha were measured after addition of preparations I-P and III-A. Induction of apoptosis was most evident with the preparations I-M, I-Q, III-M and IV-A. Neither cytokine induction nor apoptosis could be correlated to the amount of lectins found in the preparations. Stimulation of separated CD4(+)-, CD8(+)- and CD14(+)-cells from 5 healthy donors with the above noted preparations revealed an induction of IL-1-beta and TNF-alpha production by the preparations I-P, I-M and I-Q mainly in monocytes and to a minimal extent in lymphocytes. Also apoptosis was seen mainly in CD14(+)-monocytes. From these results it is concluded that both, apoptosis and cytokine production are induced differentially in leukocyte cultures by clinically applied mistletoe preparations. However, there is no correlation between the biological effects and the lectin content of the various preparations and none of them were comparable with respect to the extent of these effects. Therefore, it may be expected that clinical studies with different preparations are not comparable either.
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PMID:Comparison of the effects of various clinically applied mistletoe preparations on peripheral blood leukocytes. 989 35

The aspartyl protease cathepsin D (EC 3.4.23.5) appears to be found in increased amounts and/or abnormally secreted in breast cancer cells, and may contribute to the metastatic spread of malignancy. In the present study, cathepsin D was purified 4800-fold in 20% yield from malignant human breast tissue using affinity chromatography on pepstatin-agarose and DEAE-Sephadex chromatography. Slab gel SDS-PAGE of the purified cathepsin D indicated the presence of three major protein bands (31, 13, 12, kDa) and two minor protein bands (47, 29 kDa). Western blotting indicated that the 31 kDa band was the major immunoreactive species. Isoelectric focusing indicated that the purified cathepsin D consisted of three major isoforms at approximate pIs of 7.4, 7.0 and 6.6, and a possible isoform of lower activity centered around pI 3.2. The pH curve of purified cathepsin D indicated a broad optimum centered around pH 3.4. Lectin blotting suggested the presence of mannose residues but no evidence was found for lectin-available sialic acid, fucose, N-acetylglucosamine and galactose residues. The investigated properties of purified cathepsin D from malignant breast tissue are very similar, if not identical, to the properties of cathepsin D previously purified from normal human breast tissue. Our findings suggest that the elevated activity and antigenic levels of cathepsin D in malignant breast tissue are due to increased amounts of apparently normal enzyme.
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PMID:Characterization of purified cathepsin D from malignant human breast tissue. 991 8

In sporadic breast cancer, no mutations of the BRCA1 gene have been reported so far, whereas BRCA1 mRNA is markedly decreased in invasive breast cancer. To elucidate the contribution of the BRCA1 gene in sporadic breast cancer, we quantified the BRCA1 protein, using [125I] labeling of whole-cell proteins, lentil-lectin affinity chromatography, immunoprecipitation by anti-BRCA1 antibodies (C-20, D-20, I-20 and K-18), purification of the immune complex by protein A affinity chromatography and chromato-focusing. As loss of 1 allele may lead to a decreased expression of the gene, 10 tumors were previously checked for loss of heterozygosity (LOH) of the BRCA1 gene, using 3 intragenic microsatellite markers. Our results indicated that the BRCA1 gene product was decreased in the 4 tumors with LOH compared with matched normal breast tissues. Reduced amounts of BRCA1 protein were also detected in 3 of 6 tumors without LOH. Our quantitative method allowed us to demonstrate that the BRCA1 protein level was decreased in sporadic invasive breast carcinomas with or without LOH of the BRCA1 gene, implying multiple mechanisms of BRCA1 expression down-regulation in these tumors. Our data suggest that the amount of BRCA1 protein present may play an important role in human sporadic breast carcinoma.
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PMID:Quantification of BRCA1 protein in sporadic breast carcinoma with or without loss of heterozygosity of the BRCA1 gene. 1007 13

This study examines the Helix pomatia lectin (HPA) binding characteristics of metastases arising from primary breast cancer, and compares HPA binding patterns with binding of Dolichos biflorus lectin (DBA), Limax flavus lectin (LFA), and a monoclonal antibody against the Tn epitope. Of 81 blocks of metastases in a range of tissues, taken at autopsy from 46 individuals, 79% were HPA positive. No site specificity with regard to HPA binding was observed. Both HPA-positive and -negative tumour deposits were seen within a single individual. HPA-positive tumours were commonly negative for binding of sialic acid specific lectin LFA (86% were negative). Binding patterns of alpha-GalNAc specific HPA and DBA, and a monoclonal antibody against Tn epitope (GalNAc-O-Ser/Thr) were markedly different.
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PMID:Expression of N-acetyl galactosaminylated and sialylated glycans by metastases arising from primary breast cancer. 1047 24

Protein (lectin)-carbohydrate (cellular glycoconjugate) recognition is operative in biochemical information transfer. Galectins constitute a family of endogenous galactoside-binding lectins with conserved features in the binding site. The members of this lectin category are assumed to be involved in cell adhesion and growth regulation. To assess to what extent the different modes of binding-site presentation and/or carbohydrate fine-specificities will affect aspects of galectin behavior, homodimeric cross-linking galectin-1 and monomeric chimeric galectin-3, with its collagenase-sensitive stalk linked to the carbohydrate-recognition domain, were investigated. Cell-surface expression of the two galectins and accessible galectin-binding sites on various tumor cell lines was ascertained by FACScan analysis. In particular, ligand accessibility for the two galectins differed for the tested cell line types. Binding of tumor cells to laminin and plasma or placental fibronectin was generally reduced by treatment of cells or matrix with galectins. Galectin-3 was more efficient than galectin 1 at impairing laminin's potency as matrix. Cell binding of galectin-1, on the other hand, proved on average more effective for blocking cell association to fibronectins after its preincubation with cell suspensions. Differences were also apparent in the biodistribution of the galectins, where an avian homolog of galectin- served as the control to distinguish effects of spatial and sugar-binding features. Histopathological analysis of lymph-node-negative and -positive breast and colorectal carcinomas (n = 180 including 60 metastatic lesions) indicated a correlation of either increased galectin-1 binding and reduced galectin-3 expression or reduced binding of both galectins with the occurrence of lymph node lesions. Together with data on the heparin-binding lectin, revealing reduced expression to be associated with a positive lymph-node status in the breast cancer group, these results can be interpreted to reflect cell-type-dependent requirements of galectin ligand presentation during the metastatic cascade. By introducing mammalian lectins to lectin-histochemical studies, the detection of quantitative differences in glycosylation brings an understanding of its cell biological significance one step closer.
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PMID:Galectins-1 and -3 and their ligands in tumor biology. Non-uniform properties in cell-surface presentation and modulation of adhesion to matrix glycoproteins for various tumor cell lines, in biodistribution of free and liposome-bound galectins and in their expression by breast and colorectal carcinomas with/without metastatic propensity. 1048 Mar 38

The lectin from Helix pomatia, the Roman snail (HPA), recognises terminal alpha N-acetylgalactosamine residues. A large number of lectin histochemical studies have demonstrated that expression of HPA-binding glycoproteins by cancer cells to be a marker of metastatic competence and poor prognosis in a range of common human adenocarcinomas, including those of breast, stomach, ovary, oesophagus, colorectum, thyroid and prostate. Around 80% of metastases arising from primary breast cancer are predictably HPA positive, but, intriguingly, around 20% do not express HPA binding glycoproteins reflecting the complexity of metastatic mechanisms and the further disruptions in cellular glycosylation that attend tumour progression. HPA binding is not an independent prognostic factor, but is strongly associated with the presence of metastases in local lymph nodes. It does appear to be independent of other clinical features of prognostic importance such as tumour size, histological grade, S-phase fraction, ploidy, and there is little convincing evidence of any association with oncogene expression or hormone receptor positivity. The precise nature of the metastasis-associated HPA binding partner(s) is a question of some interest, but thus far remains unclear. HPA will recognise, for example, the Tn epitope and blood group A antigen, but its prognostic significance appears to be through recognition of a much broader and heterogeneous array of N-galactosaminylated glycoproteins. Their synthesis appears to be mediated through alteration in expression or activity of one or more of the enzymes of glycosylation. The most likely putative roles of HPA-binding ligands in the metastatic cascade may be enhancement of invasive capacity, or interaction with an as yet unidentified lectin-like receptor facilitating adhesion processes. The prognostic information provided by HPA lectin histochemistry may be used clinically to inform the physician and aid treatment decisions; far more interesting is the challenge of further understanding the precise nature of the HPA-binding ligands, and defining their role in the complex mechanisms of metastasis.
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PMID:The involvement of Helix pomatia lectin (HPA) binding N-acetylgalactosamine glycans in cancer progression. 1066 5

The overexpression of lectins by malignant cells compared with normal ones can be used for the targeting of drug-loaded liposomes to tumours with the help of specific carbohydrate ligands (vectors). Recently we have shown that liposomes bearing specific lipid-anchored glycoconjugates on a polymeric matrix bind in vitro to human malignant cells more effectively and, being loaded with a lipophilic prodrug of merphalan, reveal higher cytotoxic activity compared with unvectored liposomes. In this study, carbohydrate-equipped cytotoxic liposomes were tested in vivo in a mouse breast cancer model, BLRB-Rb (8.17)1Iem strain with a high incidence of spontaneous mammary adenocarcinoma (SMA). Firstly, a cell line of the SMA was established which was then used to determine the specificity of the tumour cell lectins. After screening of the lectin specificity of a number of fluorescent carbohydrate probes, SiaLe(X) was shown to be the ligand with the most affinity, and a lipophilic vector bearing this saccharide was synthesised. Then different liposomal formulations of the synthetic merphalan lipid derivative and SiaLe(X) vector were prepared and applied in the treatment of mice with grafted adenocarcinomas. The results of the tumorigenesis data show that the therapeutic efficacy of merphalan increases sharply after its insertion as a lipophilic prodrug into the membrane of SiaLe(X)-vectored liposomes.
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PMID:Antitumour activity of cytotoxic liposomes equipped with selectin ligand SiaLe(X), in a mouse mammary adenocarcinoma model. 1078 1


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