Stool Of Colorectal Cancer Patients Research Articles

Analysis of Mutations in DNA Isolated From Plasma and Stool of Colorectal Cancer Patients

Somatic mutations provide uniquely specific markers for the early detection of neoplasia that can be detected in DNA purified from plasma or stool of patients with colorectal cancer. The primary purpose of the present investigation was to determine the parameters that were critical for detecting mutations using a quantitative assay. A secondary purpose was to compare the results of plasma and stool DNA testing using the same technology. We examined DNA purified from the stool of 25 patients with colorectal cancers before surgery. In 16 of these cases, plasma samples also were available. Mutations in stool or plasma were assessed with an improved version of the BEAMing technology. Of the 25 stool DNA samples analyzed, 23 (92%) contained mutations that were present in the corresponding tumors from the same patients. In contrast, only 8 of the 16 (50%) plasma DNA samples analyzed had detectable levels of mutated DNA. We found that the DNA fragments containing mutations in both stool and plasma DNA typically were smaller than 150 bases in size. The sensitivity of the new method was superior to a widely used technique for detecting mutations, using single base extension and sequencing, when assessed on the same samples (92% vs 60%; P = .008, exact McNemar test). When assessed with sufficiently sensitive methods, mutant DNA fragments are detectable in the stool of more than 90% of colorectal cancer patients. DNA purified from stool provides a better template for mutation testing than plasma.

Absorption and lipoprotein transport of sphingomyelin

Dietary sphingomyelin (SM) is hydrolyzed by intestinal alkaline sphingomyelinase and neutral ceramidase to sphingosine, which is absorbed and converted to palmitic acid and acylated into chylomicron triglycerides (TGs). SM digestion is slow and is affected by luminal factors such as bile salt, cholesterol, and other lipids. In the gut, SM and its metabolites may influence TG hydrolysis, cholesterol absorption, lipoprotein formation, and mucosal growth. SM accounts for approximately 20% of the phospholipids in human plasma lipoproteins, of which two-thirds are in LDL and VLDL. It is secreted in chylomicrons and VLDL and transferred into HDL via the ABCA1 transporter. Plasma SM increases after periods of large lipid loads, during suckling, and in type II hypercholesterolemia, cholesterol-fed animals, and apolipoprotein E-deficient mice. SM is thus an important amphiphilic component when plasma lipoprotein pools expand in response to large lipid loads or metabolic abnormalities. It inhibits lipoprotein lipase and LCAT as well as the interaction of lipoproteins with receptors and counteracts LDL oxidation. The turnover of plasma SM is greater than can be accounted for by the turnover of LDL and HDL particles. Some SM must be degraded via receptor-mediated catabolism of chylomicron and VLDL remnants and by scavenger receptor class B type I receptor-mediated transfer into cells.

Decay accelerating factor and colorectal cancer

Objective: To review the significance of decay accelerating factor (DAF) in the colorectal cancer, we searched the data from PubMed and selected the related articles for review. It was found that DAF were expressed in the adenomas and adenocarcinoma of colorectal tissues. The release of DAF in the stool of the patients was also detectable. It increased more significantly in the stool of patients with colorectal cancer than other gastrointestinal cancer. Its detection by ELISA method may render a good test for the noninvasive diagnosis of colorectal cancer. It can be concluded that DAF is expressed extensively in colorectal cancer. And the detection of DAF released in the stool of colorectal cancer patients may be a good noninvasive method for the diagnosis of colorectal cancer.

Difference in Ulex europaeus agglutinin I–binding activity of decay-accelerating factor detected in the stools of patients with colorectal cancer and ulcerative colitis

Expression of decay-accelerating factor (DAF, CD55), a complement-regulatory glycoprotein, is enhanced in colorectal-cancer (CC) cells and colonic epithelium in ulcerative colitis (UC), and stools from these patients contain increased amounts of DAF. Carbohydrate chains of glycoproteins are often altered during malignant transformation or inflammation. In this study, we investigated whether DAF molecules in patients with CC and those with UC differ with respect to oligosaccharide side chains. We analyzed DAF in stools and homogenates of colonic-tissue specimens obtained from patients with CC or UC using solid-phase enzyme-linked assay and Western blotting for reactivity with the lectins Ulex europaeus agglutinin I (UEA-I), wheat-germ agglutinin, peanut agglutinin, and concanavalin A. UEA-I bound to DAF in stools from patients with UC but not in that from the stools of CC patients, as demonstrated on the solid-phase enzyme-linked assay ( P < .05, Mann-Whitney U test) and Western blotting. Binding of UEA-I was specifically inhibited by the addition of fucose. The difference in UEA-I reactivity with DAF was observed also in colonic-tissue homogenates from patients with UC and those with CC. DAF expressed in the mucosa and excreted into the stools of UC patients is different from that expressed in CC with regard to UEA-I reactivity. Future studies should be directed toward determining whether a qualitatively unique isoform of DAF is present, of which sugar chains are specific to CC in UC patients.

Polymorphic expression of decay-accelerating factor in human colorectal cancer.

We have previously shown that expression of decay-accelerating factor (DAF), a complement regulatory protein, is enhanced immunohistochemically on the luminal surface of cancer glands in human colorectal cancer and is detected in stool specimens of patients with colorectal cancer. The amount of DAF present in the stools might be influenced by the stability of DAF on the cell surface which is regulated by biochemical properties such as glycosylation of the protein. In the present study, to help elucidate the mechanism for the release of DAF from human colorectal cancers, we biochemically analyzed DAF expression by western and northern blotting by using surgically resected specimens of colorectal cancers. Surgically resected colorectal cancer tissues were obtained from 10 patients. Expression of DAF was determined by western and northern blotting, and glycosylation of DAF protein was analyzed with glycosidase digestion. Northern blot analysis demonstrated that the expression of DAF mRNA in colorectal cancer was enhanced two- to threefold compared with normal tissues. In western blotting, expression of DAF protein in the cancer tissue was increased, and heterogeneity in the apparent molecular weight of DAF was observed among patients. When o-linked sugars were removed, this heterogeneity of DAF size diminished. The polymorphic expression of DAF in colorectal cancer is likely to reflect variability in the o-glycosylation of the protein. We speculate that this variability could affect the stability of DAF on the surfaces of cancer cells and, in turn, the amount of DAF shed into the stools of colorectal cancer patients.