Synthesis and expression of CDw75 antigen in human colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Increased ST6Gal I activity has been associated with the α(2,6)sialylation enhancement of membrane glycoconjugates observed in metastatic colorectal carcinomas (CRC). Siaα(2,6)Galβ(1,4)GlcNAc sequence, known as CDw75, is a sialylated carbohydrate determinant generated by the ST6Gal I. This epitope has been reported to be associated with the progression of gastric and colorectal tumours, hence there are only a few conclusive studies to date.</p> <p>Methods</p> <p>By radioisotopic techniques we evaluated the ST6Gal I activity in healthy, transitional and tumour tissues from 43 patients with CRC. By immunohistochemistry we assessed the CDw75 expression in 25 colorectal adenomas, 43 tumours, 13 transitional and 28 healthy tissues of CRC patients.</p> <p>Results</p> <p>ST6Gal I activity was likewise found to be statistically higher in tumour tissue respect to healthy tissue from CRC patients. CDw75 expression was positive in 20% of colorectal adenomas. Furthermore, 70% of tumour specimens and 8.3% of transitional specimens were positive for CDw75 expression, whereas none of the healthy ones showed the presence of the epitope.</p> <p>Conclusion</p> <p>The major contribution of this study is the inclusion of data from transitional tissue and the analysis of CDw75 antigen expression in CRC and in colorectal adenomas, little known so far. ST6Gal I activity and CDw75 antigen expression were increased in CRC. Although their comparison did not reach the statistical significance, a great extent of patients showed both, an enhanced tumour ST6Gal I activity and an increased CDw75 expression in the tumour tissue. So, these two variables may play a role in malignant transformation. The expression of CDw75 in colorectal adenomas suggests that this antigen may be a tumour marker in CRC.</p

Identification of α(1,6)fucosylated proteins differentially expressed in human colorectal cancer

<p>Summary</p> <p>Background</p> <p>A universal hallmark of cancer cells is the change in their glycosylation phenotype. One of the most frequent alterations in the normal glycosylation pattern observed during carcinogenesis is the enhancement of α(1,6)linked fucose residues of glycoproteins, due to the up-regulation of the α(1,6)fucosyltransferase activity. Our previous results demonstrated the specific alteration of this enzyme activity and expression in colorectal cancer, suggesting its implication in tumour development and progression.</p> <p>Methods</p> <p>In the current work we combined a LCA-affinity chromatography with SDS-PAGE and mass spectrometry in order to identify α(1,6)fucosylated proteins differentially expressed in colorectal cancer. This strategy allowed the identification of a group of α(1,6)fucosylated proteins candidates to be involved in CRC malignancy.</p> <p>Results</p> <p>The majority of the identified proteins take part in cell signaling and interaction processes as well as in modulation of the immunological response. Likewise, we confirmed the increased expression of GRP94 in colorectal cancer tissue and the significant down-regulation of the IgGFcBP expression in tumour cells.</p> <p>Conclusion</p> <p>All these results validate the importance of <it>core-</it>fucosylated proteins profile analysis to understand the mechanisms which promote cancer onset and progression and to discover new tumour markers or therapeutic targets.</p

sLea and sLex expression in colorectal cancer: implications for tumourigenesis and disease prognosis

The glycoconjugates expressed by cancer cells frequently contain sialylated oligosaccharide chains. Among these oligosaccharides the sialyl Lewis a (sLea) and sialyl Lewis x (sLex) antigens are found to be overexpressed in tumours of different origin. The current study assesses sLea and sLex expression in different colorectal specimens in order to establish the correlation of these biomarkers with both malignant transformation of colorectal mucosa and the progression of colorectal cancer (CRC). Healthy disease-free and inflammatory mucosa specimens showed no presence of the antigens. sLea was expressed in 6.7% of the healthy tissue from CRC patients, in 20.8% of the adenomas, and in 33.3% and 42.6% of the transitional tissue and tumour tissue, respectively. sLex expression was observed in 6.7% of the healthy tissue from CRC patients, in 27.0% of the adenomas, and in 25.6% and 74.8% of the transitional and the tumour tissue, respectively. The expression of the sLea and sLex antigens was correlated in adenomas, as well as in healthy and tumour tissue from CRC. Moreover, the high expression of sLex in adenomas was correlated with a high degree of dysplasia (p=0.042). Finally, the survival analysis suggested that sLea expression may be a prognostic factor for predicting disease-free survival in colorectal cancer (p=0.012)

Prevalence of reduced lung diffusing capacity and CT scan findings in smokers without airflow limitation: a population-based study

Background Population distribution of reduced diffusing capacity of the lungs for carbon monoxide (DLCO) in smokers and main consequences are not properly recognised. The objectives of this study were to describe the prevalence of reduced DLCO in a population-based sample of current and former smoker subjects without airflow limitation and to describe its morphological, functional and clinical implications.Methods A sample of 405 subjects aged 40 years or older with postbronchodilator forced expiratory volume in 1 s/forced vital capacity (FVC) &gt;0.70 was obtained from a random population-based sample of 9092 subjects evaluated in the EPISCAN II study. Baseline evaluation included clinical questionnaires, exhaled carbon monoxide (CO) measurement, spirometry, DLCO determination, 6 min walk test, routine blood analysis and low-dose CT scan with evaluation of lung density and airway wall thickness.Results In never, former and current smokers, prevalence of reduced DLCO was 6.7%, 14.4% and 26.7%, respectively. Current and former smokers with reduced DLCO without airflow limitation were younger than the subjects with normal DLCO, and they had greater levels of dyspnoea and exhaled CO, greater pulmonary artery diameter and lower spirometric parameters, 6 min walk distance, daily physical activity and plasma albumin levels (all p&lt;0.05), with no significant differences in other chronic respiratory symptoms or CT findings. FVC and exhaled CO were identified as independent risk factors for low DLCO.Conclusion Reduced DLCO is a frequent disorder among smokers without airflow limitation, associated with decreased exercise capacity and with CT findings suggesting that it may be a marker of smoking-induced early vascular damage.Trial registration number NCT03028207