Glycotope structures and intramolecular affinity factors of plant lectins for Tn/T antigens

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Carbohydrate antigens in nipple aspirate fluid predict the presence of atypia and cancer in women requiring diagnostic breast biopsy

<p>Abstract</p> <p>Background</p> <p>The goal of this prospective study was to determine (a) concentrations of the carbohydrate biomarkers Thomsen Friedenreich (TF) antigen and its precursor, Tn antigen, in nipple discharge (ND) collected from women requiring biopsy because of a suspicious breast lesion; and (b) if concentration levels predicted pathologic diagnosis.</p> <p>Methods</p> <p>Adult women requiring biopsy to exclude breast cancer were enrolled and ND obtained. The samples from 124 women were analyzed using an anti-TF and anti-Tn monoclonal antibodies in direct immunoassay.</p> <p>Results</p> <p>The highest median concentration in ND for TF and Tn was in women with ductal carcinoma <it>in situ </it>(DCIS). TF was higher in women with 1) cancer (DCIS or invasive) vs. either no cancer (atypia or benign pathology, p = .048), or benign pathology (p = .018); and 2) abnormal (atypia or cancer) versus benign pathology (p = .016); and was more predictive of atypia or cancer in post- compared to premenopausal women. Tn was not predictive of disease. High TF concentration and age were independent predictors of disease, correctly classifying either cancer or abnormal vs. benign pathology 83% of the time in postmenopausal women.</p> <p>Conclusions</p> <p>TF concentrations in ND were higher in women with precancer and cancer compared to women with benign disease, and TF was an independent predictor of breast atypia and cancer. TF may prove useful in early breast cancer detection.</p

Tumour-associated carbohydrate antigens in breast cancer

Glycosylation changes that occur in cancer often lead to the expression of tumour-associated carbohydrate antigens. In breast cancer, these antigens are usually associated with a poor prognosis and a reduced overall survival. Cellular models have shown the implication of these antigens in cell adhesion, migration, proliferation and tumour growth. The present review summarizes our current knowledge of glycosylation changes (structures, biosynthesis and occurrence) in breast cancer cell lines and primary tumours, and the consequences on disease progression and aggressiveness. The therapeutic strategies attempted to target tumour-associated carbohydrate antigens in breast cancer are also discussed

Cognitive testing of physical activity and acculturation questions in recent and long-term Latino immigrants

<p>Abstract</p> <p>Background</p> <p>We ascertained the degree to which language (English versus Spanish), and residence time in the US influence responses to survey questions concerning two topics: self-reported acculturation status, and recent physical activity (PA). This topic is likely to be of general interest because of growing numbers of immigrants in countries worldwide.</p> <p>Methods</p> <p>We carried out qualitative (cognitive) interviews of survey items on acculturation and physical activity on 27 Latino subjects from three groups: (a) In Spanish, of those of low residence time (less than five years living in the U.S.) (n = 9); (b) In Spanish, of those of high residence time (15 or more years in the U.S) (n = 9); and (c) in English, of those of high residence time (n = 9).</p> <p>Results</p> <p>There were very few language translation problems; general question design defects and socio-cultural challenges to survey responses were more common. Problems were found for both acculturation and PA questions, with distinct problem types for the two question areas. Residence time/language group was weakly associated with overall frequency of problems observed: low residence time/Spanish (86%), high residence time/Spanish (67%), and English speaking groups (62%).</p> <p>Conclusions</p> <p>Standardized survey questions related to acculturation and physical activity present somewhat different cognitive challenges. For PA related questions, problems with such questions were similar regardless of subject residence time or language preference. For acculturation related questions, residence time/language or education level influenced responses to such questions. These observations should help in the interpretation of survey results for culturally diverse populations.</p

Structural Basis for Distinct Binding Properties of the Human Galectins to Thomsen-Friedenreich Antigen

The Thomsen-Friedenreich (TF or T) antigen, Galβ1-3GalNAcα1-O-Ser/Thr, is the core 1 structure of O-linked mucin type glycans appearing in tumor-associated glycosylation. The TF antigen occurs in about 90% of human cancer cells and is a potential ligand for the human endogenous galectins. It has been reported that human galectin-1 (Gal-1) and galectin-3 (Gal-3) can perform their cancer-related functions via specifically recognizing TF antigen. However, the detailed binding properties have not been clarified and structurally characterized. In this work, first we identified the distinct TF-binding abilities of Gal-1 and Gal-3. The affinity to TF antigen for Gal-3 is two orders of magnitude higher than that for Gal-1. The structures of Gal-3 carbohydrate recognition domain (CRD) complexed with TF antigen and derivatives, TFN and GM1, were then determined. These structures show a unique Glu-water-Arg-water motif-based mode as previously observed in the mushroom galectin AAL. The observation demonstrates that this recognition mode is commonly adopted by TF-binding galectins, either as endogenous or exogenous ones. The detailed structural comparisons between Gal-1 and Gal-3 CRD and mutagenesis experiments reveal that a pentad residue motif (51AHGDA55) at the loop (g1-L4) connecting β-strands 4 and 5 of Gal-1 produces a serious steric hindrance for TF binding. This motif is the main structural basis for Gal-1 with the low affinity to TF antigen. These findings provide the intrinsic structural elements for regulating the TF-binding activity of Gal-1 in some special conditions and also show certain target and approach for mediating some tumor-related bioactivities of human galectins

Accelerated FoxP2 Evolution in Echolocating Bats

FOXP2 is a transcription factor implicated in the development and neural control of orofacial coordination, particularly with respect to vocalisation. Observations that orthologues show almost no variation across vertebrates yet differ by two amino acids between humans and chimpanzees have led to speculation that recent evolutionary changes might relate to the emergence of language. Echolocating bats face especially challenging sensorimotor demands, using vocal signals for orientation and often for prey capture. To determine whether mutations in the FoxP2 gene could be associated with echolocation, we sequenced FoxP2 from echolocating and non-echolocating bats as well as a range of other mammal species. We found that contrary to previous reports, FoxP2 is not highly conserved across all nonhuman mammals but is extremely diverse in echolocating bats. We detected divergent selection (a change in selective pressure) at FoxP2 between bats with contrasting sonar systems, suggesting the intriguing possibility of a role for FoxP2 in the evolution and development of echolocation. We speculate that observed accelerated evolution of FoxP2 in bats supports a previously proposed function in sensorimotor coordination