Glycobiomarkers by glycoproteomics and glycan profiling (glycomics): emergence of functionality

2011 ◽  
Vol 39 (1) ◽  
pp. 399-405 ◽  
Author(s):  
Hans-Joachim Gabius
Keyword(s):  
Growth Regulation ◽  
Structural Complexity ◽  
Cancer Growth ◽  
Glycan Structure ◽  
Promising Candidate ◽  
Functional Consequences ◽  
Glycan Profiling ◽  
Specific Receptors ◽  
Analytical Processing ◽  
New Biomarkers

Glycans stand out from all classes of biomolecules because of their unsurpassed structural complexity. This is generated by variability in anomeric status of the glycosidic bond and its linkage points, ring size, potential for branching and introduction of diverse site-specific substitutions. What poses an enormous challenge for analytical processing is, at the same time, the basis for the fingerprint-like glycomic profiles of glycoconjugates and cells. What's more, the glycosylation machinery is sensitive to disease manifestations, earning glycan assembly a reputation as a promising candidate to identify new biomarkers. Backing this claim for a perspective in clinical practice are recent discoveries that even seemingly subtle changes in the glycan structure of glycoproteins, such as a N-glycan core substitution by a single sugar moiety, have far-reaching functional consequences. They are brought about by altering the interplay between the glycan and (i) its carrier protein and (ii) specific receptors (lectins). Glycan attachment thus endows the protein with a molecular switch and new recognition sites. Co-ordinated regulation of glycan display and presentation of the cognate lectin, e.g. in cancer growth regulation exerted by a tumour suppressor, further exemplifies the broad functional dimension inherent to the non-random shifts in glycosylation. Thus studies on glycobiomarkers converge with research on how distinct carbohydrate determinants are turned into bioactive signals.

scholarly journals Targeting extracellular and juxtamembrane FGFR2 mutations in chemotherapy-refractory cholangiocarcinoma

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Michael Bitzer ◽  
Stephan Spahn ◽  
Sepideh Babaei ◽  
Marius Horger ◽  
Stephan Singer ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Response To Treatment ◽  
Gene Fusions ◽  
Potential Treatment ◽  
Promising Candidate ◽  
Recommended Treatment ◽  
Tumor Boards ◽  
Functional Consequences ◽  
Selection For ◽  
A Current

AbstractIntrahepatic cholangiocarcinoma (iCCA) has emerged as a promising candidate for precision medicine, especially in the case of activating FGFR2 gene fusions. In addition to fusions, a considerable fraction of iCCA patients reveals FGFR2 mutations, which might lead to uncontrolled activation of the FGFR2 pathway but are mostly of unknown functional significance. A current challenge for molecular tumor boards (MTB) is to predict the functional consequences of such FGFR2 alterations to guide potential treatment decisions. We report two iCCA patients with extracellular and juxtamembrane FGFR2 mutations. After in silico investigation of the alterations and identification of activated FGFR2 downstream targets in tumor specimens by immunohistochemistry and transcriptome analysis, the MTB recommended treatment with an FGFR-inhibiting tyrosine kinase inhibitor. Both patients developed a rapidly detectable and prolonged partial response to treatment. These two cases suggest an approach to characterize further detected FGFR2 mutations in iCCA to enable patients´ selection for a successful application of the FGFR -inhibiting drugs.

scholarly journals Identification and assessment of new biomarkers for colorectal cancer with serum N-glycan profiling

Cancer ◽  
2011 ◽  
Vol 118 (3) ◽  
pp. 639-650 ◽  
Author(s):  
Yun-Peng Zhao ◽  
Can-Ping Ruan ◽  
Hao Wang ◽  
Zhi-Qian Hu ◽  
Meng Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Glycan Profiling ◽  
New Biomarkers

The sugar code: letters and vocabulary, writers, editors and readers and biosignificance of functional glycan–lectin pairing

2019 ◽  
Vol 476 (18) ◽  
pp. 2623-2655 ◽  
Author(s):  
Herbert Kaltner ◽  
José Abad-Rodríguez ◽  
Anthony P. Corfield ◽  
Jürgen Kopitz ◽  
Hans-Joachim Gabius
Keyword(s):  
Information Transfer ◽  
Structural Complexity ◽  
Structural Variations ◽  
Carbohydrate Recognition Domains ◽  
Random Assortment ◽  
Specific Receptors ◽  
Spatial Presentation ◽  
Biochemical Signals ◽  
Enzymatic Machinery ◽  
Lectin Recognition

Abstract Ubiquitous occurrence in Nature, abundant presence at strategically important places such as the cell surface and dynamic shifts in their profile by diverse molecular switches qualifies the glycans to serve as versatile biochemical signals. However, their exceptional structural complexity often prevents one noting how simple the rules of objective-driven assembly of glycan-encoded messages are. This review is intended to provide a tutorial for a broad readership. The principles of why carbohydrates meet all demands to be the coding section of an information transfer system, and this at unsurpassed high density, are explained. Despite appearing to be a random assortment of sugars and their substitutions, seemingly subtle structural variations in glycan chains by a sophisticated enzymatic machinery have emerged to account for their specific biological meaning. Acting as ‘readers’ of glycan-encoded information, carbohydrate-specific receptors (lectins) are a means to turn the glycans’ potential to serve as signals into a multitude of (patho)physiologically relevant responses. Once the far-reaching significance of this type of functional pairing has become clear, the various modes of spatial presentation of glycans and of carbohydrate recognition domains in lectins can be explored and rationalized. These discoveries are continuously revealing the intricacies of mutually adaptable routes to achieve essential selectivity and specificity. Equipped with these insights, readers will gain a fundamental understanding why carbohydrates form the third alphabet of life, joining the ranks of nucleotides and amino acids, and will also become aware of the importance of cellular communication via glycan–lectin recognition.

scholarly journals Specific Receptors for the Chemokines CXCR2 and CXCR4 in Pancreatic Cancer

2020 ◽  
Vol 21 (17) ◽  
pp. 6193
Author(s):  
Ala Litman-Zawadzka ◽  
Marta Łukaszewicz-Zając ◽  
Mariusz Gryko ◽  
Agnieszka Kulczyńska-Przybik ◽  
Bogusław Kędra ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Marker ◽  
Immunological Methods ◽  
Healthy Controls ◽  
Serum Concentrations ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Diagnosis And Prognosis ◽  
Specific Receptors ◽  
New Biomarkers

Background: The mortality rate of pancreatic cancer (PC) is equal to its incidence and the majority of PC patients die within a few months of diagnosis. Therefore, a search for new biomarkers useful in the diagnosis and prognosis of PC is ongoing. Objectives: The aim of our study was to compare the utility of CXCR2 and CXCR4 in the diagnosis and prediction of PC with classical tumor marker (carcinoembryonic antigen, CEA) and marker of inflammation–C-reactive protein (CRP). Patients and Methods: The study comprised 64 subjects — 32 PC patients and 32 healthy volunteers. Serum concentrations of tested proteins were analysed using immunological methods. Results: Serum CXCR2 and CXCR4 concentrations, similarly to those of CEA and CRP, were significantly elevated in PC patients compared to healthy controls. Moreover, concentrations of CXCR4 were significantly correlated with CXCR2 and CRP levels, while CRP concentrations were correlated with CXCR2 and CEA levels. The diagnostic sensitivity and the predictive value for negative (PV−ve) results for CXCR4 were similar to those of CEA and higher than those of CXCR2 and CRP, while the area under the ROC curve (AUC) for CXCR4 was the highest among all tested proteins (CXCR2, CEA, CRP). Moreover, serum CXCR2 was found to be a significant predictor of PC risk. Conclusions: CXCR4 is a better candidate for a tumor marker than CXCR2 in the diagnosis of PC, while serum CXCR2 is a significant predictor of PC risk.

Hyperthermia in cancer growth regulation

Biotherapy ◽  
1992 ◽  
Vol 4 (4) ◽  
pp. 307-315 ◽  
Author(s):  
Clare Vernon
Keyword(s):  
Growth Regulation ◽  
Cancer Growth

Cancer growth regulation by 4-hydroxynonenal

2017 ◽  
Vol 111 ◽  
pp. 226-234 ◽  
Author(s):  
Ana Cipak Gasparovic ◽  
Lidija Milkovic ◽  
Suzana Borovic Sunjic ◽  
Neven Zarkovic
Keyword(s):  
Growth Regulation ◽  
Cancer Growth

scholarly journals The complex nature of oestrogen signalling in breast cancer: enemy or ally?

2016 ◽  
Vol 36 (3) ◽  
Author(s):  
Yulia Lipovka ◽  
John P. Konhilas
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Potential Outcomes ◽  
Cancer Growth ◽  
Complex Nature ◽  
Dual Effect ◽  
Unique Role ◽  
Specific Receptors ◽  
Potential Impact ◽  
Oestrogen Signalling

The pleiotropic nature of oestradiol, the main oestrogen found in women, has been well described in the literature. Oestradiol is positioned to play a unique role since it can respond to environmental, genetic and non-genetic cues to affect genetic expression and cellular signalling. In breast cancer, oestradiol signalling has a dual effect, promoting or inhibiting cancer growth. The potential impact of oestradiol on tumorigenesis depends on the molecular and cellular characteristics of the breast cancer cell. In this review, we provide a broad survey discussing the cellular and molecular consequences of oestrogen signalling in breast cancer. First, we review the structure of the classical oestrogen receptors and resultant transcriptional (genomic) and non-transcriptional (non-genomic) signalling. We then discuss the nature of oestradiol signalling in breast cancer including the specific receptors that initiate these signalling cascades as well as potential outcomes, such as cancer growth, proliferation and angiogenesis. Finally, we examine cellular and molecular mechanisms underlying the dimorphic effect of oestrogen signalling in breast cancer.

Proteolysis of platelet receptors in humans and other species

2010 ◽  
Vol 391 (8) ◽  
Author(s):  
Jian L. Qiao ◽  
Yang Shen ◽  
Elizabeth E. Gardiner ◽  
Robert K. Andrews
Keyword(s):  
Molecular Mechanisms ◽  
Surface Expression ◽  
Altered Expression ◽  
Platelet Receptors ◽  
Published Evidence ◽  
Functional Consequences ◽  
Specific Receptors ◽  
Thrombotic Diseases ◽  
Von Willebrand

AbstractIn the past 5 years, metalloproteinase-mediated ectodomain shedding of platelet receptors has emerged as a new mechanism for modulating platelet function. By regulating surface expression of the platelet-specific receptors, glycoprotein (GP)VI that binds collagen, and GPIbα (the major ligand-binding subunit of the GPIb-IX-V complex) that binds von Willebrand factor (VWF) and other procoagulant and proinflammatory ligands, shedding not only irreversibly downregulates GPVI/GPIbα function, but generates proteolytic fragments that might be unique biomarkers or modulators in plasma. This is potentially significant because GPVI and GPIbα are involved in initiating thrombotic diseases such as heart attack and stroke, as well as autoimmune diseases where anti-platelet antibodies result in thrombocytopenia. Altered expression levels of GPIbα/GPVI are associated with both thrombotic propensity and platelet aging, suggesting an additional role in platelet clearance. Although emerging data are elucidating molecular mechanisms underlying GPIbα/GPVI shedding, evidence for the functional consequences of sheddingin vivo, either clinically or in animal models, is far more limited. Here we consider recent published evidence for GPVI or GPIbα shedding in humans, nonhuman primates and mice, and whether conservation of sheddase cleavage sites across species points to a functional role for metalloproteolytic sheddingin vivo.

scholarly journals Serum CXCL8 and Its Specific Receptor (CXCR2) in Gastric Cancer

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5186
Author(s):  
Elżbieta Pawluczuk ◽  
Marta Łukaszewicz-Zając ◽  
Mariusz Gryko ◽  
Agnieszka Kulczyńska-Przybik ◽  
Barbara Mroczko
Keyword(s):  
Gastric Cancer ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Promising Candidate ◽  
Diagnosis And Prognosis ◽  
Established Tumor ◽  
Novel Biomarkers ◽  
Specific Receptors

Gastric cancer (GC) is the second leading cause of cancer-related deaths worldwide. This malignancy is usually diagnosed at an advanced stage. Therefore, novel biomarkers useful in the early detection of GC are sorely needed. Some authors suggest the role of chemokines and their specific receptors in GC pathogenesis. The aim of the study was to investigate whether serum CXCL8 and its receptor (CXCR2) might be considered as potential candidates for biomarkers in the diagnosis and prognosis of GC. The study included 98 subjects: 64 GC patients and 34 healthy volunteers. CXCL8 and CXCR2 concentrations were assessed by the enzyme-linked immunosorbent assay (ELISA) method. Serum CXCL8 and CXCR2 concentrations were significantly higher in GC patients than in healthy controls, similar to the well-established tumor marker (CA19-9) and marker of inflammation (CRP). Diagnostic sensitivity of CXCL8 was the highest among all proteins tested and increased for the combined assessment with CA19-9. The area under the ROC curve for CXCL8 was higher than those for CXCR2 and classical tumor markers. Serum CXCL8 levels were indicated as a significant risk factor of GC occurrence. Our findings suggest that serum CXCL8 is a promising candidate for a biomarker in GC diagnosis and might be used as a significant predictor of GC risk.

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