Cancer Biomarkers - Volume 14, issue 1

Authors: Marino, Pamela

Article Type: Editorial

DOI: 10.3233/CBM-2014-14101

Citation: Cancer Biomarkers, vol. 14, no. 1, pp. 1-1, 2014

Authors: Krasnewich, Donna

Article Type: Research Article

Abstract: Over the past 20 years, clinical disorders of glycosylation have expanded to include over 50 recognized defects in the network of glycobiologic pathways. In parallel, more cases have been recognized by astute clinicians increasing both the number of known affected individuals as well as the breadth of clinical features attributed to these disorders. The descriptions of affected individuals may include a functional adult with cognitive impairments, a developmentally normal child with significant gastrointestinal symptoms, a severely ill infant or a fetus with hydrops fetalis. These clinical cases have led to the recognition of gene mutations affecting different enzymes and transporters …active in the interconnected synthetic pathways of the myriad of oligosaccharides with essential roles in human development and biology. Show more

Keywords: Glycosylation, glycobiology, congenital disorders of glycosylation

DOI: 10.3233/CBM-130374

Citation: Cancer Biomarkers, vol. 14, no. 1, pp. 3-16, 2014

Authors: Albrecht, Simone | Unwin, Louise | Muniyappa, Mohankumar | Rudd, Pauline M.

Article Type: Research Article

Abstract: Changes in serum protein glycosylation play an important role in inflammatory arthritis. Altered galactosylation of immunoglobulin G (IgG) in rheumatoid arthritis attracts special attention due to the devastating nature of the disease. Studying glycosylation changes of serum proteins has been recognized as a potential strategy to provide added value regarding diagnostics, aetiopathology and therapy of inflammatory arthritic diseases. Key questions, which are approached in these fields of research, are whether or not glycosylation can be used as a complementary pre-clinical and clinical marker for disease differentiation, diagnosis, the prediction of disease course and severity as well as for the evaluation …of disease therapies. These studies mainly focus on TNF antagonists, which present a new and promising way of treating inflammatory arthritis. The recent availability of new high-throughput glycoanalytical tools enables a more profound and efficient investigation in large patient cohorts and helps to gain new insights in the complex mechanism of the underlying disease pathways. Show more

Keywords: Inflammatory arthritis, serum protein glycosylation, diagnostics, aetiopathology, therapy

DOI: 10.3233/CBM-130373

Citation: Cancer Biomarkers, vol. 14, no. 1, pp. 17-28, 2014

Authors: Muthana, Saddam M. | Gildersleeve, Jeffrey C.

Article Type: Research Article

Abstract: Over the last 10 years, glycan microarray technology has emerged as a powerful high-throughput tool for studying the interactions of carbohydrates with a variety of biomolecules. The array format allows one to screen thousands of binding interactions in a single experiment using minimal amounts of scarce materials. More recently, this technology has been applied to the discovery of biomarkers for diagnosis, prognosis, risk prediction, and monitoring immune responses. Biomarker discovery using glycan arrays has primarily focused on monitoring changes to the anti-glycan antibody repertoires in serum, since the populations of antibodies can change significantly with the onset of disease, exposure …to pathogens, or vaccination. Herein, we review efforts to use glycan arrays to identify new biomarkers for cancer, infections, autoimmune diseases, and immune responses. Show more

Keywords: Carbohydrate, biomarker, antibodies, glycomics, glycan microarray

DOI: 10.3233/CBM-130383

Citation: Cancer Biomarkers, vol. 14, no. 1, pp. 29-41, 2014

Authors: Gulati, Shelly | Lasanajak, Yi | Smith, David F. | Cummings, Richard D. | Air, Gillian M.

Article Type: Research Article

Abstract: Influenza viruses initiate infection by attaching to sialic acid receptors on the surface of host cells. It has been recognized for some time that avian influenza viruses usually bind to terminal sialic acid that is linked in the α2-3 configuration to the next sugar while human viruses show preference for α2-6 linked sialic acid. With developments in synthetic chemistry and chemo-enzymatic methods of synthesizing quite complex glycans, it has become clear that the binding specificity extends beyond the sialic acid, and this has led to considerable interest in developing glycan reagents that could be used either as a diagnostic tool …for particular influenza viruses, or to identify cells that are susceptible to infection by certain influenza viruses. Here we describe the use of the Consortium for Functional Glycomics Glycan Array to investigate binding specificity of influenza hemagglutinin and cleavage by neuraminidase, using seasonal and pandemic H1N1 influenza viruses as examples, and compare the results with published data using other array methods. Show more

Keywords: Influenza virus, hemagglutinin, neuraminidase, Glycan array, Consortium for Functional Glycomics

DOI: 10.3233/CBM-130376

Citation: Cancer Biomarkers, vol. 14, no. 1, pp. 43-53, 2014

Authors: Dolezal, Samuel | Hester, Shanterian | Kirby, Pamela S. | Nairn, Allison | Pierce, Michael | Abbott, Karen L.

Article Type: Research Article

Abstract: The glycosylphosphatidylinositol (GPI) anchor is a glycan and lipid posttranslational modification added to proteins in the endoplasmic reticulum. Certain enzymes within the GPI biosynthetic pathway, particularly the subunits of the GPI transamidase, are elevated in various human cancers. Specific GPI anchored proteins, such as carcinoembryonic antigen and mesothelin, have been described as potential biomarkers for certain cancers; however, the overall levels of GPI anchored proteins present in plasma from cases of human cancers have not been evaluated. We have developed the use of a bacterial toxin known as alpha toxin from Clostridium septicum to detect GPI anchored proteins in vitro. …In this study, we use alpha toxin to detect GPI anchored proteins present in plasma from cases of several types of human cancers. Our data indicate that human cancers with previously documented elevations of GPI transamidase subunits show increased alpha toxin binding to plasma from patients with these cancers, indicating increased levels of GPI anchored proteins. Furthermore, our results reveal very low levels of alpha toxin binding to plasma from patients with no malignant disease indicating few GPI anchored proteins are present. These data suggest that GPI anchored proteins present in plasma from these cancers represent biomarkers with potential use for cancer detection. Show more

Keywords: Cancer, plasma, GPI-anchored proteins, GPIT, alpha toxin, human

DOI: 10.3233/CBM-130377

Citation: Cancer Biomarkers, vol. 14, no. 1, pp. 55-62, 2014

Authors: Ju, Tongzhong | Aryal, Rajindra P. | Kudelka, Matthew R. | Wang, Yingchun | Cummings, Richard D.

Article Type: Research Article

Abstract: The Tn antigen is a tumor-associated carbohydrate antigen that is not normally expressed in peripheral tissues or blood cells. Expression of this antigen, which is found in a majority of human carcinomas of all types, arises from a blockage in the normal O-glycosylation pathway in which glycans are extended from the common precursor GalNAcα1-O-Ser/Thr (Tn antigen). This precursor is generated in the Golgi apparatus on newly synthesized glycoproteins by a family of polypeptide α-N-acetylgalactosaminyltransferases (ppGalNAcTs) and then extended to the common core 1 O-glycan Galβ1-3GalNAcα1-O-Ser/Thr (T antigen) by a single enzyme termed the T-synthase (core 1 β3-galactosyltransferase or C1GalT). Formation …of the active form of the T-synthase requires a unique molecular chaperone termed Cosmc, encoded by Cosmc on the X-chromosome (Xq24 in humans, Xc3 in mice). Cosmc resides in the endoplasmic reticulum (ER) and prevents misfolding, aggregation, and proteasome-dependent degradation of newly synthesized T-synthase. Loss of expression of active T-synthase or Cosmc can lead to expression of the Tn antigen, along with its sialylated version Sialyl Tn antigen as observed in several cancers. Both genetic and epigenetic pathways, in addition to potential metabolic regulation, can result in abnormal expression of the Tn antigen. Engineered expression of the Tn antigen by disruption of either C1GalT (T-syn) or Cosmc in mice is associated with a tremendous range of pathologies and engineered expression of the Tn antigen in mouse embryos leads to embryonic death. Studies indicate that many membrane glycoproteins expressing the Tn antigen and/or truncated O-glycans may be dysfunctional, due to degradation and/or misfolding. Thus, expression of normal O-glycans is associated with health and homeostasis whereas truncation of O-glycans, e.g. the Tn and/or Sialyl Tn antigens is associated with cancer and other pathologies. Show more

Keywords: Cosmc, T-synthase, Tn antigen, cancer

DOI: 10.3233/CBM-130375

Citation: Cancer Biomarkers, vol. 14, no. 1, pp. 63-81, 2014