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  • 1
    Electronic Resource
    Electronic Resource
    Intestinalization of gastric signet ring cell carcinomas with progression (1997)
    Springer
    Virchows Archiv 431 (1997), S. 103-110 
    Details
    ISSN: 1432-2307
    Keywords: Key words Signet ring cell carcinoma ; Stomach ; Cell differentiation ; Histochemistry ; Intestinal metaplasia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recent developments in mucin histochemistry and immunohistochemistry have made reliable determination of the gastric and intestinal phenotypes of gastric carcinoma cells possible. Phenotypic expression changes from gastric epithelial cell type to intestinal epithelial cell type with the growth of gastric tumours in experimental animals. We studied cell differentiation in gastric signet ring cell carcinomas with progression in 203 surgically obtained specimens. The results showed that the proportion of gastric phenotype carcinomas, in which over 90% of the tissue consists of gastric epithelial cell type cells, decreases with the depth of invasion. The proportion of mixed phenotype carcinomas (between 10% and 90% of the tissue made up of gastric and/or intestinal epithelial cell type cells) increases. The intestinal phenotype (over 90% intestinal epithelial cell type carcinoma cells) was found in four carcinomas (about 2%) involving the serosa. No clear relationship was evident between phenotypic expression of carcinoma cells and the degree of intestinal metaplasia of the surrounding mucosa. Progression of gastric signet ring cell carcinomas is associated with a phenotypic shift from gastric to intestinal type expression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050075
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  • 2
    Electronic Resource
    Electronic Resource
    Immunogenicity of synthetic TF-KLH (keyhole limpet hemocyanin) and sTn-KLH conjugates in colorectal carcinoma patients (1995)
    Springer
    Cancer immunology immunotherapy 41 (1995), S. 185-192 
    Details
    ISSN: 1432-0851
    Keywords: Key words Active specific immunotherapy ; Adjuvants ; Thomsen-Friedenreich (TF) ; Sialyl-Tn (sTn) ; Keyhole limpet hemocyanin (KLH) ; Tumor vaccine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Mucins of colorectal carcinomas overexpress the cancer-associated disaccharides Thomsen-Friedenreich antigen (TF) and sialyl-Tn antigen (sTn), making these antigens suitable for active specific immunotherapy. Patients at high risk for recurrent colon cancer, but free from disease after surgical resection, were immunized with synthetic TF and sTn covalently attached by a two-carbon crotyl linker to keyhole limpet hemocyanin (KLH). Four groups of patients were treated with TF-KLH without adjuvant, TF-KLH plus the immunological adjuvant Detox, sTn-KLH plus Detox, or sTn-KLH plus the immunological adjuvant QS-21, and the serological response was monitored. Enzyme-linked immunosorbent assay (ELISA), dot-blot immunostains, and inhibition assays were used to identify antibody responses against synthetic TF and sTn epitopes and against natural antigens, including asialoglycophorin expressing TF antigen, and ovine submaxillary mucin and the human colon cancer line LS-C expressing sTn antigen. Our results demonstrate that vaccines containing TF or sTn-KLH conjugates plus immunological adjuvants Detox and especially QS-21 induced high IgM and IgG antibody titers against the respective synthetic disaccharide epitopes. However, when tested against natural antigens expressing these disaccharide epitopes, IgM antibodies showed weak to moderate reactivity, while IgG antibodies were almost totally unreactive. On the basis of these results we are continuing to test modifications of synthetic TF and sTn epitopes to identify those that induce IgM and IgG antibodies that are more reactive with these antigens as they are expressed on tumor mucins.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01521345
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  • 3
    Electronic Resource
    Electronic Resource
    Immunogenicity of synthetic TF-KLH (keyhole limpet hemocyanin) and sTn-KLH conjugates in colorectal carcinoma patients (1995)
    Springer
    Cancer immunology immunotherapy 41 (1995), S. 185-192 
    Details
    ISSN: 1432-0851
    Keywords: Active specific immunotherapy ; Adjuvants ; Thomsen-Friedenreich (TF) ; Sialyl-Tn (sTn) ; Keyhole limpet hemocyanin (KLH) ; Tumor vaccine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mucins of colorectal carcinomas overexpress the cancer-associated disaccharides Thomsen-Friedenreich antigen (TF) and sialyl-Tn antigen (sTn), making these antigens suitable for active specific immunotherapy. Patients at high risk for recurrent colon cancer, but free from disease after surgical resection, were immunized with synthetic TF and sTn covalently attached by a two-carbon crotyl linker to keyhole limpet hemocyanin (KLH). Four groups of patients were treated with TF-KLH without adjuvant, TF-KLH plus the immunological adjuvant Detox, sTn-KLH plus Detox, or sTn-KLH plus the immunological adjuvant QS-21, and the serological response was monitored. Enzyme-linked immunosorbent assay (ELISA), do-blot immunostains, and inhibition assays were used to identify antibody responses against synthetic TF and sTn epitopes and against natural antigens, including asialoglycophorin expressing TF antigen, and ovine submaxillary mucin and the human colon cancer line LS-C expressing sTn antigen. Our results demonstrate that vaccines containing TF or sTn-KLH conjugates plus immunological adjuvants Detox and especially QS-21 induced high IgM and IgG antibody titers against the respective synthetic disaccharide epitopes. However, when tested against natural antigens expressing these disaccharide epitopes, IgM antibodies showed weak to moderate reactivity, while IgG antibodies were almost totally unreactive. On the basis of these results we are continuing to test modifications of synthetic TF and sTn epitopes to identify those that induce IgM and IgG antibodies that are more reactive with these antigens as they are expressed on tumor mucins.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01521345
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Different modes of sialyl-Tn expression during malignant transformation of human colonic mucosa (1998)
    Springer
    Glycoconjugate journal 15 (1998), S. 29-35 
    Details
    ISSN: 1573-4986
    Keywords: mucin ; sialyl-Tn ; STn ; cluster STn ; monomeric STn ; O-acetylation ; colon cancer ; immunohistochemistry ; ELISA ; ovine submaxillary mucin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Monoclonal antibodies TKH2 and B72.3, which react with the mucin-associated sialyl-Tn(STn) antigen, preferentially bind to cancerous but not normal colonic tissues. If O-acetyl groups are removed by saponification of tissues, MAb TKH2 will react with normal colonocytes, whereas MAb B72.3 remains non-reactive. To explain this difference in binding specificity, we tested both MAbs against synthetic constructs of single (monomeric) or clustered (trimeric) STn epitopes by enzyme immunoassay. Both MAb TKH2 and MAb B72.3 reacted with trimeric STn, but MAb TKH2 demonstrated greater binding than MAb B72.3 to monomeric STn. This suggests that normal colonic mucosa expresses monomeric STn epitopes, but that with transformation to malignancy, clustered STn epitopes appear. The appearance of clustered STn epitopes during colonic carcinogenesis represents a novel pattern of carbohydrate antigen expression and implicates alterations at the level of apomucins and/or glycosyltransferases responsible for cluster epitope formation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006935331756
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  • 5
    Electronic Resource
    Electronic Resource
    Enzymatic basis for sialyl-Tn expression in human colon cancer cells (1998)
    Springer
    Glycoconjugate journal 15 (1998), S. 595-603 
    Details
    ISSN: 1573-4986
    Keywords: sialyl-Tn ; core 1 β3-Gal-transferase ; colon cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Sialyl-Tn antigen (SAα2-6 GalNAcα-Ser/Thr) is expressed as a cancer-associated antigen on the surface of cancer cells and its expression correlates with a poor prognosis in patients with colorectal and other adenocarcinomas. To understand the enzymatic basis of sialyl-Tn (STn) antigen expression, we used two clonal cell lines, LSB and LSC, derived from LS174T human colonic cancer cells. LSC cells express only the truncated carbohydrate antigen Tn (GalNAcα-Ser/Thr) and sialyl-Tn on their mucin molecules, whereas LSB cells express elongated oligosaccharide chains. Both cell lines demonstrated similar activities of glycosyltransferases involved in the biosynthesis of elongated and terminal structures of complex O-glycans. However, LSC cells were unable to synthesize core 1 (Galβ1-3GalNAc-) because the ubiquitous enzyme activity of UDP-Gal:GalNAc-R β3-Gal-transferase (core 1 β3-Gal-transferase) was lacking. Core 1 β3-Gal-transferase could not be reactivated in LSC cells by treatment with sodium butyrate or by in vivo growth of LSC cells in nude mice. In contrast, LSB cells were able to synthesize and process core 1 and core 2 (GlcNAcβ1-6 (Galβ1-3) GalNAc-). LSC cells represent the first example of a non-hematopoietic cell line which lacks core 1 β3-Gal-transferase activity. The lack of core 1 β3-Gal-transferase in LSC cells explains why they are incapable of forming the common mucin O-glycan core structures and are committed to synthesizing the short Tn and STn oligosaccharides. These findings suggest that the activity of core 1 β3-Gal-transferase is an important determinant of the STn phenotype of colon cancer cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006967910803
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  • 6
    Electronic Resource
    Electronic Resource
    Blood group-related carbohydrate antigen expression in malignant and premalignant colonic neoplasms (1992)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 50 (1992), S. 97-101 
    Details
    ISSN: 0730-2312
    Keywords: adenomatouspolyps ; blood group antigens ; carbohydrate antigens ; chemoprevention ; colorectal cancers ; glycosylation ; intermediate biomarker ; Lex antigen, Ley antigen ; sialosyl-Tn (STn) antign ; T antigen ; Tn antigen ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Cell surface glycoconjugates of colonic epithelial cells carry certain carbohydrate antigens related to blood group substances. During the progression to malignancy, these oligosaccharide immunodeterminants undergo specific type of alterations. In colon cancers, the blood group antigens A, B, H and Leb, which are normally expressed only in the proximal colon, can be re-expressed in distal colon cancers or deleted in proximal colon cancers. Also, an antigen which is incompatible with the individual's blood type can be expressed. Similar alterations occur in adenomatous polyps, but with reduced frequency. The simple form of blood group-related Lex and Ley antigens found in normal mucosa can undergo modification by oligosaccharide elongation, internal fucosylation, and sialylation into novel structures found in carcinomas as well as in adenomas with greatest malignant potential. Finally, antigens representing the first steps of glycosylation, Tn, T, sialosyl-Tn (STn), whiich are normally cryptic in the colon, can be unmasked due to incomplete glycosylation in adenomatous polyps and cancers. Several of these antigens, such as extended Lex, extended Ley, T, and sialosyl-Tn, are quite cancer-specific in that they are rarely expressed in normal mucosa or hyperplastic polyps, but preferentially occur in adenomas of greatest malignant potential. As such, these antigens might be useful as candidate intermidate endpoint biomarkers. © 1992 Wiley-Liss, Inc.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240501118
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