UMLS:C0178874 - FACTA Search

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Query: UMLS:C0178874 (tumor progression)
40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver cancer is one of the most frequent and lethal malignancies worldwide. Early detection is hampered by the absence of reliable markers. Mice transgenic for the SV40 large T antigen under the control of a liver-specific promoter spontaneously develop well-differentiated hepatocellular carcinomas between 8 to 10 weeks of age. They are excellent models to investigate the alterations of protein expression in the early stages of tumor development and to follow these changes during tumor progression. In the present study, we analyzed the glycosylation changes occurring during tumor development in transgenic mice expressing the SV40 T antigen under the control of the antithrombin III promoter. The analysis of serum and liver glycoproteins by an ELISA type assay, using the lectin from Sambucus nigra (SNA) as a probe, revealed the presence of increased levels of Neu5Ac alpha2,6Gal beta1,4GlcNAc on N-glycans in the tumor-bearing transgenic mice as compared to controls. On serum glycoproteins the increase in alpha2,6 sialylation followed tumor progression, reaching up to 10 times control levels. However, significantly higher SNA binding (2-fold) could already be observed on serum glycoproteins from mice exhibiting only microscopically small neoplastic foci. On liver membrane glycoproteins, the increase in alpha2,6 sialylation was less pronounced, reaching two to three times control values in 6-month-old mice. Western blotting of serum and liver proteins with radiolabeled SNA showed that all glycoproteins that bind the lectin in controls exhibit larger amounts of Neu5Ac alpha2,6Gal beta1,4GlcNAc on N-glycans in the tumor-bearing mice. This general increase in alpha2,6 sialylation on all glycoproteins is due to the increased activity of the galactoside:alpha2,6 sialyltransferase (ST6Gal I), which specifically transfers Neu5Ac residues in alpha2,6 linkage to Gal beta1,4GlcNAc units on N-glycans. As for the structures synthesized by the enzyme, the increase of ST6Gal I activity in the serum as well as in liver microsomes of the transgenic mice followed tumor progression. Interestingly, the activity of the galactoside:alpha2,3 sialyltransferase (ST3Gal III), which uses the same acceptor substrate (Gal beta1,4GlcNAc), was unchanged in the earlier stages of tumor development but decreased in the serum and in liver microsomes from later stages. Using a rat ST6Gal I cDNA as a probe, Northern blots of total RNA extracted from the livers of control and transgenic mice revealed an increased (4-fold) expression of the ST6Gal I gene. The single transcripts detected in both normal and cancerous liver showed identical size.
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PMID:Increased alpha2,6 sialylation of N-glycans in a transgenic mouse model of hepatocellular carcinoma. 933 Oct 85

Changes in vascular patterns aid in the colposcopic diagnosis of cervical neoplasia. We have studied vessels in 50 cases of normal cervix, cervical intraepithelial neoplasia (CIN I, II, III), and invasive carcinoma by two markers, Von-Willebrand factor (VWF) and ulex europaeus lectin I. With both markers, an increase in microvessel counts parallel to neoplastic progression was seen, with highest counts observed in CIN III. Average counts for ulex lectin and VWF increased from approximately 6 vessels per field in normal cervices to 15 vessels per field in CIN III. For each diagnostic group, comparable numbers of vessels were stained by both markers, with a slight preponderance of VWF in invasive carcinomas and of ulex lectin in noninvasive lesions. No correlation was found between microvessel count and human papilloma virus (HPV) by in situ hybridization. We conclude that enhanced microvessel density occurs in cervical neoplasia. The vessels are mostly blood vessels, not lymphatics. Therefore, the role of enhanced microvessel density in tumor spread remains to be proven.
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PMID:Angiogenesis in uterine cervical intraepithelial neoplasia and squamous cell carcinoma: an immunohistochemical study. 942 Oct 72

The monoclonal antibody UN1 was previously produced in our laboratory on the basis of selective reactivity with human thymocytes and has been classified as unclustered by the 5th and 6th International Workshop and Conference on Human Leukocyte Differentiation Antigens. The antigen recognized by mAb UN1 was found to be expressed on the cell surface of immature human thymocytes, a subpopulation of peripheral T lymphocytes and on several fetal tissues including thymus. The UN1 antigen is purified from children's thymus by ion-exchange and affinity chromatography. Two-dimensional electrophoresis shows that the purified antigen displays microheterogeneity appearing as multiple spots over a pI range 4.4-5.0 at 100-120 kDa. Treatment with neuraminidase results in a retarded migration in SDS-PAGE, an increase in isoelectric point and a reduction in carbohydrate content, indicating a substantial content of sialic acid. Glycosidase digestion and lectin-binding analysis indicate that the carbohydrate residues are essentially O-linked. A preliminary analysis has detected the UN1 antigen in human breast carcinoma tissues but not in normal breast. The biochemical features and the pattern of expression of the UN1 antigen indicate that this molecule may have the characteristics typical of the family of cell-membrane-associated mucin-like glycoproteins; a number of these molecules are thought to have a role in cell-cell interaction, tumor progression and metastasis.
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PMID:Purification and characterization of a human sialoglycoprotein antigen expressed in immature thymocytes and fetal tissues. 967 51

Increase of beta1,6-branched oligosaccharides is possibly associated with tumor progression and lymph node metastasis. The aim of this study was to determine the prognostic value of beta1,6 branches in human colorectal carcinoma. Expression of beta1,6 branches was histochemically evaluated using the leukoagglutinating Phaseolus vulgaris lectin, PHA-L, in 92 clinically documented colorectal carcinomas, of which 31 had formed lymph node metastases. The follow-up time ranged between 4 and 14 years (median, 10.3 years). A PHA-L staining index (SI), taking into account staining intensity and its percentage of tumor cut surface area, was established. The carcinoma SI was highly associated with the disease-free survival (P = 0.004) and overall survival (P = 0.005). Patients with a carcinoma SI of >1, as compared to those with a SI of < or =1, were at significantly higher risk for tumor recurrence, with a shorter disease-free survival (hazard ratio = 2.59, P = 0.005) and significant higher risk of death with shorter overall survival (hazard ratio = 2.51, P = 0.007). The carcinoma SI was also associated with the presence of lymph node metastases. We conclude that PHA-L staining in human colorectal carcinoma sections provides an independent prognostic indicator for tumor recurrence and patient survival and is associated with the presence of lymph node metastases.
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PMID:Prognostic value of beta1,6-branched oligosaccharides in human colorectal carcinoma. 985 94

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

Galectin-3 is a beta-galactoside-specific lectin that binds to laminin sugar-sites and is involved in tumor malignancy. Galectin-3 expression in relation to primary tumor and liver metastasis of colorectal cancer was examined to determined its involvement in cancer progression and metastasis. Immunohistochemical staining of galectin-3 was performed on 117 primary lesions and 15 liver metastases of colorectal cancer using TIB166 monoclonal antibody. The expression of galectin-3 was evaluated by grading the intensity of the staining as either negative, weakly positive, or strongly positive. Normal mucosa of all patients were strongly positive for galectin-3, but the staining in these tissues was still significantly less than in the primary lesions of the cancer (31.6%). Galectin-3 expression in the primary lesions was significantly increased, correlating with the progression of clinical stage (p=0. 0224), liver metastasis (p<0.0001), venous invasion (p=0.0048), and lymph node metastasis (p=0.0289). Liver metastatic lesions also showed up-regulated levels of galectin-3 compared to the primary lesions (p=0.0030). The group showing strongly positive galectin-3 had a significantly poorer prognosis than the negative/weakly positive group in terms of disease-free survival (p=0.0224). The strong expression of galectin-3 in colorectal cancer correlates with cancer progression, liver metastasis, and poor prognosis for patients.
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PMID:Involvement of galectin-3 expression in colorectal cancer progression and metastasis. 1037 7

The expression of carbohydrate antigens has been shown by retrospective immunohistochemical analysis to correlate to the progression and metastases of human cancers. However, the mechanisms of these changes of carbohydrate expression and the role of carbohydrates in the malignant behavior of tumor cells are not well known. In this article, we introduce methods to experimentally modify carbohydrate expression in tumor cells and to assess the involvement of these carbohydrate antigens in the malignant behavior of tumor cells. Modifications of the biosynthesis of O- and N-linked carbohydrates, and glycolipids are achieved by treating cultured tumor cells with culture media containing Benzyl-alpha-GalNAc, swainsonine, or D-PDMP, respectively. Enzymatic digestion of cell surface carbohydrates with sialidase, endo-beta-galactosidase or other glycosidases can also be performed. These cells can be used for short term experiments such as adhesion assays. However, modified carbohydrates may be recovered during in vitro and in vivo assays. By transfection of glycosyltransferase cDNA, or selection of tumor cells by binding lectins or antibodies, stable carbohydrate variant cells can be obtained which are suitable for long term experiments such as the experimental formation of metastases in vivo. The biological function of tumor cell surface carbohydrates may be diverse. These molecules are thought to influence adhesion interaction between tumor cells and the endothelial cells of target organs. However, carbohydrate recognition molecules, or lectins, are expressed on a variety of cells in the vascular system and in the immune system. Therefore, it is essential to design appropriate experimental models to study the biological significance of carbohydrate-lectin interactions in cancer progression and metastatic dissemination. Adhesion assays of tumor cells to selectin-transfected CHO cells were performed. Taking molecules other than selectins into consideration, adhesion assays using frozen tissue sections were also performed.
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PMID:[Tumor metastases and adhesion molecules carbohydrates and lectins]. 1041 Jan 58

Increased expression of the bisecting GlcNAc has been correlated with tumor progression in several experimental tumor models. Its expression and function in brain tumors are, however, not yet known. In this study, we investigated expression of the bisecting GlcNAc structure in a series of pediatric brain tumors and its relationship to tumor response to vinblastine. A plant lectin (E-PHA) that recognizes the bisecting GlcNAc structure was used for detection of this molecule in a total of 90 pediatric brain tumors and normal brain tissue specimens. Our results showed that, whereas E-PHA staining was undetectable in the normal brain tissue, pediatric brain tumor specimens exhibited different levels of reactivity. Lectin staining was particularly prominent in high-grade astrocytomas (73%) and ependymomas (72%). In astrocytomas, there was a positive correlation with the tumor grade, which suggests that the bisecting GlcNAc may be of particular interest as a tumor marker for diagnosis and/or prognosis. By using a human glioma cell culture model, we have found that treatment of these cells with E-PHA lectin enhances their sensitivity to vinblastine. E-PHA interacted directly with the drug transporter P-glycoprotein and inhibited its drug efflux function. In a drug-resistant glioma cell line transfected with the mdr1 gene, drug resistance was reversed by E-PHA. Our findings indicate that: (a) expression of the bisecting GlcNAc in pediatric brain tumors may have a potential relevance as a tumor marker; and (b) glioma response to chemotherapy may be modulated through the bisecting GlcNAc.
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PMID:Expression of bisecting GlcNAc in pediatric brain tumors and its association with tumor cell response to vinblastine. 1058 84

The metastatic potential of tumor cells has been shown to be correlated with the expression of tri- and tetra-antennary beta1,6-N-acetylglucosamine (beta1,6-GlcNAc)-bearing N-glycans, which are recognized by Phaseolus vulgaris leukoagglutinating lectin (L-PHA). The expression of beta1,6-GlcNAc-bearing N-glycans also has been used as a marker of tumor progression in human breast and colon cancers. In this report, the role of N-glycan branching in regulating glioma migration and invasion was examined. The expression of beta1,6-GlcNAc-bearing N-glycans was found in human glioma specimens, whereas astrocytes from normal adult brain were negative. The expression of N-acetylglucosaminyltransferase V (GnT-V) mRNA, which is responsible for the biosynthesis of beta1,6-GlcNAc-bearing N-glycans, was high in glioma cell lines with robust ets-1 expression. To study the molecular mechanism of GnT-V expression in human glioma cells, an inducible ets-1 gene was stably transfected into SNB-19 cells using a tetracycline repressor system. GnT-V mRNA expression was increased by the induction of c-ets-1, suggesting that the Ets-1 transcription factor directly regulates the transcription of GnT-V. Stable transfection of GnT-V into human glioma U-373 MG cells resulted in changes in cell morphology and focal adhesions and a marked increase in glioma invasivity in vitro. L-PHA has little effect on cell migration. On the contrary, Phaseolus vulgaris erythroagglutinating lectin (E-PHA), which recognizes bisecting beta1,4-GlcNAc-bearing N-glycans, strongly inhibits cell migration (haptotaxis) on a fibronectin substrate in U-373 MG transfectants and other glioma cell lines tested. These results suggest that the increased beta1,6-GlcNAc-bearing N-glycan expression found in malignant gliomas is modulated by GnT-V through the Ets-1 transcription factor, and that the branching of complex type N-glycans plays a major role in glioma invasivity.
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PMID:Beta1,6-N-acetylglucosamine-bearing N-glycans in human gliomas: implications for a role in regulating invasivity. 1064 65

The accurate determination of levels of differentiation is of prognostic value in human head and neck squamous cell carcinomas (HNSCCs). Because the deliberate selection of biochemical determinants accompanying certain stages of differentiation can refine the predictive power of histochemical assessments, the application of the quantitative evaluation of staining distribution and intensity by computer-assisted microscopy is one prerequisite to potential improvements. We used 2 innovative approaches with peanut agglutinin based on encouraging results with respect to common lectin-histochemistry. First, we used a custom-made neoglycoprotein to monitor the presence of Thomsen-Friedenreich (T) antigen-binding sites. Second, we measured the presence of 2 galectins immunohistochemically and, at the same time, measured lectin-histochemically the presence of accessible ligands for the endogenous lectins. We also monitored the presence of calcyclin, a protein with relevance to cell cycle progression or exocytosis. With 61 cases of HNSCC as their basis, including 31 oral, 20 laryngeal, and 10 hypopharyngeal lesions, the data show that the main modifications observed in connection with a loss of differentiation are related to a modification in the levels of both galectin-3/galectin-3-binding site and T-antigen/T-antigen-binding site expressions. The data obtained also suggest that galectin-3 could act as an acceptor site for the T antigen. Because the level of differentiation is known to be indicative of the recurrence rate in HNSCCs and our data clearly indicate that galectin-3 and the T antigen (and their respective binding sites) are involved in dedifferentiation processes, further investigation is warranted into the roles of galectins in HNSCC tumor progression and recurrence analysis.
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PMID:Correlation of galectin-3/galectin-3-binding sites with low differentiation status in head and neck squamous cell carcinomas. 1082 95

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