Biomedical subjects

E Dabelsteen

Publications and source records attributed to E Dabelsteen.

At least 73 records · Page 4Linked to original sources

PubMed1992

Carbohydrates of the cell surface: molecular aspects of glycosyltransferases and their genes.

With the development of monospecific antibodies to transferase proteins as well as cDNA probes to cloned transferase genes, the study of glycosylation and its regulatory mechanisms holds great promise for the future. Here we provide a brief overview of the present knowledge of glycosyltransferases, their primary structure, cellular topography, regulation, and the basis of the genetic polymorphisms as revealed by blood groups.

Animals↗

PubMed1991

Prognostic value of Rhesus blood groups in oral squamous cell carcinomas.

In the current study of the prognosis of all patients (N equals 70) with squamous cell carcinomas (SCC) of floor of mouth in Norway during the period 1963 to 1972, the authors found that patients with Rhesus (Rh) (D)-negative blood group had significantly poorer prognosis (mean 5-year survival, 8%) than patients with Rh (D)-positive blood group (5-year survival, 30%) (P equals 0.04). This extends the authors' previous observations in another group of oral cancer patients. The authors do not know the explanation for this association. However, the Rh gene locus is located on the short arm of chromosome 1 which reportedly has shown rearrangements in some head and neck SCC and other human neoplasms. The authors therefore speculate that the Rh gene locus may be linked with chromosome 1 changes of importance for the progression of oral SCC.

Analysis of Variance↗

PubMed1991

A multivariate study of the prognosis of oral squamous cell carcinomas. Are blood group and hemoglobin new prognostic factors?

Because blood groups and hemoglobin concentration have been associated with the risk of the development of some cancers, this study evaluated the significance of ABO and Rhesus blood groups and hemoglobin concentration as prognostic factors in oral squamous cell carcinoma (SCC). The authors examined all registered primary SCC of buccal and maxillary alveolar mucosa in the Norwegian population between 1963 and 1972. The biopsy specimens from these patients were reevaluated and borderline cases excluded. The remaining 111 cases were included in the study, and features recorded on first admission were included in the survival analyses. ABO and Rhesus blood groups were found in 99 of these patients. Multivariate survival analysis showed that tumor size, hemoglobin concentration, stage, and Rhesus blood groups were significant prognostic factors, but sex, age, treatment, duration of symptoms, ABO blood groups, and clinical appearance of the tumors were not. The prognostic value of Rhesus blood groups and hemoglobin concentration has not been previously reported for oral SCC.

ABO Blood-Group System↗

PubMed1991

Loss of expression of blood group antigen H is associated with cellular invasion and spread of oral squamous cell carcinomas.

Membrane-bound carbohydrates may influence the metastatic behavior of cancer cells. Forty-two squamous cell carcinomas (SCC) of the buccal and maxillary alveolar mucosa were studied retrospectively using a monoclonal antibody (BE2) that reacts with blood group H (type 2 chain) structure. H-antigen staining within the entire tumor did not correlate with the stage of the tumor, i.e., spread of the tumors. However, loss of staining within the most invasive sites of the tumors correlated significantly with the stage of tumor development and histologic grade of malignancy. These findings support the view that features relating to the cells of deeper parts of the carcinomas are very important for the clinical behavior of the tumors, and that loss of H-antigen expression is related to the stage of tumor and invasion of carcinoma cells.

ABO Blood-Group System↗

PubMed1991

Simple mucin-type carbohydrates in oral stratified squamous and salivary gland epithelia.

Simple mucin-type carbohydrate antigens, T, Tn, and sialosyl-Tn, have been found to be good markers of malignant transformation in several epithelial tissues as a result of incomplete synthesis with precursor accumulation. The T, Tn, and sialosyl-Tn antigens represent the initial, most immature glycosylation of serine and threonine amino acids of proteins. In normal adult cells these structures are generally masked by addition of further saccharides to form more complex structures. We analyzed simple mucin-type carbohydrates in human labial stratified squamous and minor salivary gland epithelia in order to define the glycosylation pattern in normal cells in relation to epithelial differentiation and maturation. A panel of monoclonal antibodies with well-characterized specificity for T, Tn, sialosyl-Tn and the histo-blood group H and A variants hereof were used in immunohistology of sections from 30 individuals with known ABO, Lewis, and secretor status. In stratified epithelium the sialylated T structure was confined to cell membranes of immature basal cells, whereas the H and A variants were observed on cell membranes of more mature parabasal and spinous cell layers. Furthermore, superficial spinous cells produced a fine granular cytoplasmic staining for Tn and sialosyl-Tn antigens. In minor salivary glands mucous cells expressed Tn and sialosyl-Tn as well as the H and A variants in the area of the nucleus, whereas T and the H variant were found in duct cells and unsubstituted T antigen in myoepithelial cells. These results indicate that incomplete synthesis, i.e., deletion of sialyltransferases and/or histo-blood group ABH transferases, may result in accumulation of T, Tn, and sialosyl-Tn antigens in oral epithelia, thus offering a baseline for further studies of changes in premalignant and malignant oral epithelia.

Antibodies, Monoclonal↗

PubMed1991

Lewis blood group antigens in salivary glands and stratified epithelium: lack of regulation of Lewis antigen expression in ductal and buccal mucosal lining epithelia.

The expression of Lewis antigens is thought to be controlled by the Secretor and Lewis genes. While secretor status is known to regulate the expression of ABH antigens in many tissues, few studies have attempted to correlate Lewis antigen expression on erythrocytes and saliva with that of epithelial tissues. We examined the expression of Lewis a and b and related antigens in human epithelium of minor salivary glands and labial nonkeratinized oral mucosae from 16 individuals by immunohistology using monoclonal antibodies. The expression of these antigens, as detected by monoclonal antibodies (MAbs) used, was correlated with erythrocyte phenotype and saliva secretor status. In acinar cells of glands, Leb antigen was expressed only in secretors, and Lea only in nonsecretors. However, in gland ducts and oral mucosae, Leb was found in both secretors and nonsecretors, as well as in 2 cases of Lea-b-, secretors. Thus, antigen expression in acinar cells of minor salivary glands was correlated with the predicted genotypes, whereas inappropriate expression of Leb antigen was found in epithelial cells of gland ducts and oral mucosae. The present data indicate that the Lewis blood group phenotype is regulated differently in duct cells and stratified epithelium than in saliva and erythrocytes.

Carbohydrate Sequence↗

PubMed1991

Expression of mucin type carbohydrates may supplement histologic diagnosis in oral premalignant lesions.

Recent studies have shown that changes within membrane bound carbohydrates may be essential for cellular differentiation and malignant transformation. We have therefore, by means of immunohistochemistry, studied the expression of T/Tn related (Thomsen-Friedenrich) carbohydrates in 13 oral lesions with squamous cell dysplasia. The epithelial grade of dysplasia was graded as mild, moderate or severe. The following carbohydrate structures were studied: Tn, T, mucintype 3 chain H, and the sialylated derivates, sialosyl-Tn and sialosyl-T. In general, short structures were detected on the basal cells and longer structures on the more mature spinous cells. In many cases, this sequential expression was more disturbed with increasing grade of epithelial dysplasia. However, our results also showed that some lesions with the same grade of epithelial dysplasia showed different carbohydrate expression. These findings indicate that expression of carbohydrates may supplement histologic diagnosis in the evaluation of the prognosis of premalignant lesions.

Antigens, Surface↗

PubMed1991

Aberrant glycosylation in oral malignant and premalignant lesions.

Cell surface carbohydrates serve as differentiation and developmental markers characteristic of different cell and tissue types. The expression of these carbohydrate antigens is often significantly altered in tumors, particularly in those arising from epithelial tissues. Analysis of cell surface carbohydrates in oral epithelium have shown that in normal epithelium they are expressed in a way that shorter carbohydrates are found on basal cells and that these carbohydrate structures are elongated parallel to terminal differentiation. The carbohydrate expression is altered in oral carcinomas and in some oral premalignant lesions. The change in carbohydrate expression can at present be explained by the lack of synthesis of specific glycosyltransferases. We have found mosaicism in the expression of carbohydrate antigens in all tumors and have found that the expression of a specific carbohydrate in the deep invasive parts of the tumor correlates with tumor prognosis.

Carbohydrate Metabolism↗

PubMed1991

Reproducibility of two malignancy grading systems with reportedly prognostic value for oral cancer patients.

Supplementary prognostic factors should be added to the TNM classification for oral squamous cell carcinomas in order to optimize its clinical value. We have recently published two prognostically valuable malignancy grading systems based on histopathology and immunohistology of the most invasive cells in oral squamous cell carcinomas (OSCCs). However, a major problem with classifications based on histologic features is frequent lack of interobserver agreement which limits the clinical value of subjective histologic classifications. Thirty-eight file cases of OSCCs were therefore graded by three pathologists according to criteria of the histologic malignancy grading system which includes 5 morphologic features, each graded from 1 to 4. Agreement was calculated by kappa statistics, which showed that interobserver agreement was not optimal, but significantly better than by chance alone. We also studied the reproducibility of grading of immunohistologic membrane expression of a tumor-associated marker (blood group antigen H), and found a similar level of agreement. We conclude that the clinical value of our grading systems will increase by improving reproducibility.

Carcinoma, Squamous Cell↗

PubMed1991

Expression of blood group-related carbohydrate antigens in normal human pancreatic tissue.

The expression of type 1, 2 and 3 chain carbohydrate structures in 15 normal pancreata was investigated by immunohistochemical methods using well-defined monoclonal antibodies. Surgical biopsies of pancreata were obtained from kidney donors while the organs were still perfused. Type 1 chain structures were abundantly expressed including monosialylated(ms)- and disialylated(ds)-Le(a) antigens, which have previously been associated with cancer. Type 2 chain structures were represented by H and Le(y) antigens and to a lesser extent by the precursor structure N-acetyllactosamine, whereas Le(x), dimeric Le(x), and ms-Le(x) were only sporadically observed, in contrast to fetal pancreatic tissue, in which Le(x) has been found to be abundantly expressed. H chain 3 antigen was found in nearly all specimens, whereas precursor structures Tn, sial-Tn and T antigens were absent. Desialylation unmasked the T antigen in all specimens. Absence/masking of Tn, T and related antigens is of special interest, since these antigens are associated with tumor development in other tissues, and may be of importance in pancreatic cancer diagnostics in the future.

Adolescent↗

PubMed1991

Grading of nuclear pleomorphism in oral carcinomas. Higher prognostic value than stereological assessment of nuclear volume.

A more objective and reproducible grading system is needed in order to give better prognostic indicators and thereby offer improved treatment to oral cancer patients. Recently, simple objective stereological techniques for cellular estimates have emerged, of which the estimate of mean nuclear volume has shown a correlation with prognosis for various cancers. We have therefore measured the mean nuclear volume in 44 invasive buccal mucosal squamous cell carcinomas and related it to the survival of patients. The mean nuclear volume did not correlate with prognosis for these patients (p = 0.25). However, the nuclear polymorphism, which is subjective even though it is based on well-described criteria in a histopathological grading system, correlated significantly with prognosis (p = 0.03). These findings indicate that the traditional histopathological evaluation of nuclear polymorphism includes valuable prognostic information.

Carcinoma, Squamous Cell↗

PubMed1991

Histo-blood group antigens as differentiation markers in testicular germ cell tumours.

The distribution of histo-blood group antigens in a series of eleven human non-seminomatous testicular germ cell tumours is described and the variable expression of these antigens is related to the patterns of differentiation that are reflected morphologically within these tumours. The results suggest that histo-blood group antigens of type 2 chain carbohydrate structures may be used as markers of differentiation. All the tumours contained binary 2-3 sialosyllactosamine structures. N-acetyllactosamine and Le(y)-negative tumors were the least differentiated morphologically, while N-acetyllactosamine and Le(y)-positive tumours exhibited more differentiated tumour patterns. Whether the occurrence of the latter antigens in poorly differentiated forms of germ cell tumours reflects a biological potential for differentiation remains to be proven in a larger material.

Antibodies, Monoclonal↗

PubMed1991

Cell surface carbohydrates are markers of differentiation in human oral epithelium.

Carbohydrates of the epithelial cell membrane are involved in cell-cell and cell-substrate interaction, and changes are seen in relationship to cell differentiation and neoplastic transformation. The terminal part of carbohydrate structures carried on oral epithelial cells often expresses antigens of the ABO and Lewis blood group systems. The expression of these antigens are in oral mucosa genetically regulated by the A, B, H, Lewis, and secretor genes with subsequent correspondence between the blood group antigens expressed on erythrocytes and on oral epithelial cells. Variation in expression of carbohydrates is also seen in relationship to terminal differentiation in that blood group antigens and their immediate precursor structures are sequentially expressed on cells during their pathway through the epithelium. Various organs and tissues differ in their expression of cell surface carbohydrates. In oral mucosa, a close relationship is seen between the type of tissue differentiation and expression of blood group antigen; keratinized, nonkeratinized, and junctional epithelium all show different patterns of carbohydrate expression.

Antigens, Surface↗

PubMed1991

Cell adhesion molecules in oral mucosa.

The way in which cells communicate with each other is fundamentally important for developing and maintaining normal tissue structure and function. In order to get a better understanding of cell adhesion, researchers have long been trying to identify and characterize chemical structures at the cell surface that might participate in, or mediate, cell-cell and cell-matrix adhesion. During the last decade, this has led to the identification of a number of cell-surface adhesion proteins and their ligands, which may be either proteins or carbohydrates. The LEC cell-adhesion molecule family is a group of cell-adhesion molecules with a lectinlike domain. They bind to carbohydrate structures, some of which have been identified on dendritic cells in oral epithelium. LEC cell-adhesion molecules are found on endothelial cells during inflammation and may, in such situations, be involved in the recruiting of dendritic and other inflammatory cells, thereby playing a role in the regulation of inflammatory reactions in the oral mucosa. The integrin family is another group of cell-surface adhesion molecules recently identified in oral mucosa that participate in cell-matrix and cell-cell adhesion in many important processes including wound healing, immunodefense mechanisms, and oncogenic transformation. Knowledge of the distribution of cell-adhesion molecules and their ligands and of the mechanism that controls their expression is, therefore, of great importance in understanding of the development of disease in the oral mucosa.

Antigens, Differentiation↗

PubMed1991

Distribution of histo-blood group antigens in cervical and uterine endometrium.

Cell surface carbohydrates serve as differentiation and developmental markers characteristic of different cell and tissue types. Expression of these carbohydrate antigens is often significantly altered in tumors particularly in those arising from epithelial tissues. Analysis of the expression of cell surface carbohydrates in normal endometrium has shown that this glycosylation is hormonally influenced. Change in expression of carbohydrates in malignant tissue should therefore be evaluated against this normal fluctuation. In normal cervical uterine epithelium the result shows that the glycosylation of metaplastic squamous cells is different from that of original squamous cells indicating that the regulation and differentiation of the epithelium in the transformation zone is different from that of the original squamous epithelium. This variation in expression of carbohydrates seen in the metaplastic epithelium may be of importance for the development of carcinomas in this area.

Antigens, Surface↗

PubMed1991

[Oral cancer. Prognostic aspects].

The present knowledge regarding growth and progression of intraoral squamous cell carcinoma is still fragmentary. The 5-year survival for these patients is poor. In order to improve the prognosis in this highly lethal cancer, it is important to gain more knowledge about its biological behaviour. In the present paper we suggest that certain cells at the invasive margins of the tumors are most important for prognostic evaluation of the cancer. We have studied the expression of a group of cell membrane bound carbohydrates (blood group antigens) on these deep, invasive cells and found an association between loss of expression of one of these structures and invasion and spread of the cancer cells. Furthermore, we have found a hitherto not reported prognostic value of Rhesus blood groups. We suggest that chromosome instability reported to occur on chromosome 1 in some oral squamous cell carcinomas in some way involve the Rhesus gene that is located in the same area of chromosome 1.

Carcinoma, Squamous Cell↗

PubMed1990

Loss of expression of blood group antigen H is associated with cellular invasion and spread of oral squamous cell carcinomas.

Membrane-bound carbohydrates may influence the metastatic behavior of cancer cells. Forty-two squamous cell carcinomas (SCC) of the buccal and maxillary alveolar mucosa were studied retrospectively using a monoclonal antibody (BE2) that reacts with blood group H (type 2 chain) structure and an immunoperoxidase (avidin-biotin peroxidase complex) staining technique. H-antigen staining within the entire tumor did not correlate with the stage of the tumor, i.e., tumor spread. However, loss of staining within the most invasive sites of the tumors correlated significantly with the stage of tumor development and histologic grade of malignancy. These findings support the view that features regarding the cells of deeper parts of the carcinomas are very important for the clinical behavior of the tumors and that loss of H-antigen expression is related to the stage of the tumor and invasion of carcinoma cells.

ABO Blood-Group System↗

PubMed1990

Murine monoclonal antibodies directed to the human histo-blood group A transferase (UDP-GalNAc:Fuc alpha 1----2Gal alpha 1----3-N-acetylgalactosaminyltransferase) and the presence therein of N-linked histo-blood group A determinant.

Mouse MAbs (WKH-1 through -3) to the human histo-blood group A glycosyltransferase (Fuc alpha 1----2Gal alpha 1----3 galactosaminyltransferase) were established by immunization with the purified native A transferase protein. Hybridomas were selected on the basis of solid-phase reactivity with the purified native A transferase, cell immunofluorescence and immunoprecipitation of transferase activity, and absence of reactivity with blood group ABH carbohydrate determinants. Three MAbs, thus selected, were found most likely to react with the protein epitopes unrelated to carbohydrate epitopes of purified A transferase. The MAbs reacted with cells having high A transferase activity and immunoprecipitated the A transferase activity as well as the 40,000 MW iodinated transferase protein. The antibodies were shown, however, to immunoprecipitate and partially inhibit not only A1 and A2 but also B transferase activity from plasma and A transferase from human lung, and to react with B cells expressing B transferase, thus indicating a cross-reactivity with B transferase. In contrast, they showed no reactivity with various cells having the O phenotype and did not immunoprecipitate the A transferase from porcine submaxillary glands or the alpha 1----2fucosyltransferase from Colo205 cells. The purified A glycosyltransferase was found to carry blood group A carbohydrate determinants by immunochemical detection with a panel of anti-carbohydrate MAbs. These determinants are believed to be N-linked, since treatment of the purified A transferase with N-glycanase removed activity. Immunohistological studies of three epithelial tissues showed that the antibodies stained the Golgi area of cells in epithelia from A and B, but not O, individuals.

ABO Blood-Group System↗