Soluble kit receptor in human serum

c-kit encodes the transmembrane receptor tyrosine kinase (Kit) for the recently described ligand stem cell factor (SCF). We have developed an enzyme-linked immunosorbent assay for measuring soluble human Kit and we have used the assay to show high levels of soluble Kit in human serum. The distribution of soluble Kit levels was investigated among 112 normal human serum donors. The mean serum level (+/- SD) was found to be 324 +/- 105 ng/mL with the values falling between 163 ng/mL and 788 ng/mL. No correlation between soluble Kit levels and the sexes or ages of the donors was found. Partial purification using immunoaffinity chromatography allowed us to characterize the soluble Kit from pooled human serum. Antibodies generated to a 497-amino acid recombinant human soluble Kit corresponding to the N-terminal extracellular domain of the receptor recognized the serum-derived soluble Kit by immunoblotting. We found that the serum-derived soluble Kit is glycosylated, with mostly N- linked but also O-linked carbohydrate, and with terminal sialic acid residues. When compared with the recombinant human soluble Kit, the serum-derived material was similar both in size and glycosylation pattern. CNBr cleavage of the isolated serum-derived material followed by amino terminal sequencing confirmed the presence of five peptides expected for the extracellular portion of the Kit molecule. The immunoaffinity purified serum-derived soluble Kit inhibited binding of [125I]SCF to membrane-bound receptor in an in vitro assay. These results indicate that soluble Kit could modulate the activity and functions of SCF in vivo.     

Endoscopic innovations to increase the adenoma detection rate during colonoscopy

Up to a quarter of polyps and adenomas are missed during colonoscopy due to poor visualization behind folds and the inner curves of flexures, and the presence of flat lesions that are difficult to detect. These numbers may however be conservative because they mainly come from back-to-back studies performed with standard colonoscopes, which are unable to visualize the entire mucosal surface. In the past several years, new endoscopic techniques have been introduced to improve the detection of polyps and adenomas. The introduction of high definition colonoscopes and visual image enhancement technologies have been suggested to lead to better recognition of flat and small lesions, but the absolute increase in diagnostic yield seems limited. Cap assisted colonoscopy and water-exchange colonoscopy are methods to facilitate cecal intubation and increase patients comfort, but show only a marginal or no benefit on polyp and adenoma detection. Retroflexion is routinely used in the rectum for the inspection of the dentate line, but withdrawal in retroflexion in the colon is in general not recommended due to the risk of perforation. In contrast, colonoscopy with the Third-Eye Retroscope^® may result in considerable lower miss rates compared to standard colonoscopy, but this technique is not practical in case of polypectomy and is more time consuming. The recently introduced Full Spectrum Endoscopy™ colonoscopes maintains the technical capabilities of standard colonoscopes and provides a much wider view of 330 degrees compared to the 170 degrees with standard colonoscopes. Remarkable lower adenoma miss rates with this new technique were recently demonstrated in the first randomized study. Nonetheless, more studies are required to determine the exact additional diagnostic yield in clinical practice. Optimizing the efficacy of colorectal cancer screening and surveillance requires high definition colonoscopes with improved virtual chromoendoscopy technology that visualize the whole colon mucosa while maintaining optimal washing, suction and therapeutic capabilities, and keeping the procedural time as low and patient discomfort as optimal as possible.