Early Detection Of Colon Cancer Research Articles

Identification of calreticulin as a nuclear matrix protein associated with human colon cancer.

Colon cancer is one of the most common malignancies among populations in the United States and Western Europe, and one of the leading causes of worldwide morbidity and mortality due to cancer. The early detection of colon cancer is central to the effective treatment of this disease and early detection markers are needed. We have demonstrated that high-resolution two-dimensional gel analysis of nuclear matrix proteins (NMPs) demonstrated a specific oncological fingerprint of colon cancer. Utilizing this approach, four proteins specific for colon cancer was identified. Additionally, one protein was expressed much more strongly in colon cancer compared to adjacent and normal donor tissue. The amino acid composition of this protein revealed sequence similarity with calreticulin. The multi-functional protein, calreticulin, is normally found in the lumen of the endoplasmic reticulum although some reports have described a nuclear localization of the protein. The aim of this study was to confirm the identity of the protein as calreticulin as well as to evaluate the localization of calreticulin in the nuclear matrix of colon cancer tissue.

Quantification of human intestinal gene expression profiles using exfoliated colonocytes: a pilot study

Early detection of colon cancer can result in a high cure rate; therefore, an accurate screening method is imperative. Adoption of non-invasive testing designed to reduce anxiety over colorectal cancer screening and improve early detection is highly desirable. Therefore, we have developed a novel non-invasive methodology utilizing exfoliated colonocytes in order to quantify colonic messenger RNAs (mRNAs). Previously we have demonstrated in the rat that intact eukaryotic mRNA can be isolated due to the presence of exfoliated colonocytes in the faecal stream. To assess use of this methodology in humans, this pilot study evaluated exfoliated colonocyte mRNA expression of 11 putative biomarkers using real-time reverse transcription-polymerase chain reaction (RT-PCR) in seven normal subjects, four subjects with inflammation, and 10 tumour-bearing subjects presenting for colonoscopy. Expression of the biomarkers was evaluated following normalization to TATA box binding protein mRNA levels. Tumour-bearing subjects diagnosed with adenoma had elevated levels of cyclin Dl (p = 0.041). In addition, subjects displaying inflammation of the colon exhibited higher mRNA levels of cyclooxygenase-2 (p = 0.007). These data suggest that mRNA isolated from exfoliated colonocytes could be used to detect early stages of colon cancer, and possibly chronic inflammation. To broaden the utility of non-invasive marker analysis, additional studies are needed to generate a multi-target assay panel of diagnostic markers. This will allow for the development of robust classifiers that can determine critical gene sets for the diagnosis and prediction of colon cancer in animal models and humans.

Adjuvant chemotherapy for colon cancer.

Colon cancer remains the third most common cancer, and cause of cancer-related death in the United States. Greater public awareness and acceptance of screening programs have contributed significantly to increasingly earlier detection of colon cancer and decreased mortality. Advances made in the understanding of this disease, both in terms of its clinical behavior and molecular pathogenesis, have translated into major improvements in its therapy. Several large randomized trials during the last two decades have helped the oncology community forge a successful multi-modality treatment strategy against colon cancer. These studies have defined the role of adjuvant therapy for colon cancer after curative surgery. Despite all the advances, a large number of patients continue to succumb to this disease, and the search for better therapies is still necessary. In this article, we discuss the evolution and the current state of adjuvant chemotherapy in colon cancer and briefly review new developments.

Monoclonal antibody recognizing a determinant on type 2 chain blood group A and B oligosaccharides detects oncodevelopmental changes in azoxymethane‐induced rat colon tumors and human colon cancer cell lines

Altered expression of ABH blood group substances is a common feature of human colorectal carcinoma, yet it remains unclear how these structural changes influence the biological properties of tumor cells. Azoxymethane-induced rat colon tumors display many features of the human disease, thereby providing a potentially useful model to study the role of blood group substances in colon cancer progression. We have prepared monoclonal antibodies to a microsomal fraction isolated from an azoxymethane-induced rat colon tumor and selected an antibody that detects cancer-associated changes. Monoclonal antibody (mAb) 3A7 recognizes a determinant on type 2 chain blood group A (GalNAc alpha 1-3[Fuc alpha 1-2]Gal beta 1-4GlcNAc-R) and B (Gal alpha 1-3[Fuc alpha 1-2]Gal beta 1-4GlcNAc-R) oligosaccharides. Expression of the epitope detected by this antibody was developmentally regulated in rat colon, with maximal expression from day 4-21 after birth. Immunohistochemical staining and Western blotting analyses of azoxymethane-induced colon tumors revealed increased expression of the epitope in all of the 21 colonic tumors examined, including preneoplastic glands within transitional mucosa. Conventional and signet-ring adenocarcinomas that had invaded through the muscularis propria (Duke's B2) consistently showed the most intense staining with mAb 3A7, including regions depicting angioinvasion. Some of the lymph node metastases (Duke's C2) stained poorly with the antibody. The epitope was also expressed in blood group A positive human colon carcinoma cell lines, including HT29 and SW480 but not by SW620, a cell line derived from a lymph node metastasis isolated in vivo from the SW480 primary tumor, or in the blood group B cell line SW1417. The glycoproteins detected by mAb 3A7 in rat colon tumors and HT29 cells ranged in size between 50 and 200 kd, including a major species of 140 kd. Affinity chromatography of detergent lysates of normal rat colon on the blood group A specific lectin Dolichos biflorus (DBA)-agarose resulted in nearly quantitative binding of glycoprotein species detected by the antibody. By contrast, immunoreactive glycoproteins from rat colon tumors or HT29 cells bound poorly to DBA-agarose but were retained by another blood group A-binding lectin, Helix-pomatia (HPA)-agarose. These results indicate that colon carcinogenesis results in quantitative as well as qualitative changes in oligosaccharides detected by mAb 3A7 and suggest that the combined use of mAb 3A7 and blood group A-specific lectins may provide a useful tool for early detection of colon cancer.

ELISA assay for colon cancer

AbstractThe high mortality rate for patients with colon cancer results largely from the inability to diagnose the condition in its early stages. The assay described in this report may be useful in early detection of colon cancer. In the study we use the cotton‐top tamarin, Saguinus oedipus, as an animal model for studying human colon cancer. This New World monkey develops a high incidence of colitis and colon cancer. Antibodies that recognize adenocarcinoma cells and antigens from these cells can be detected in the sera of tamarins with colon cancer. The antibodies are not found in sera of healthy animals. In one procedure, tamarin adenocarcinoma cells are used to coat the wells of a microtiter plate. In an alternate procedure, a glycoprotein adenocarcinoma antigen is used. The antigen is extracted from a cultured tamarin colon cancer line by detergent solubilization followed by affinity chromatography. Test sera are examined by adding biotinylated immunoglobulin serum fractions to the coated wells. The wells are washed and an avidin‐enzyme conjugate is added. Positive sera are identified by the addition of the substrate. The presence of the autoantibodies in the sera may be taken as evidence that the animal has colon cancer.

Transmural electrical potential difference as an early marker in colon cancer.

It has been suggested that relative depolarization of the cell membrane occurs during carcinogenesis. A study was undertaken to determine the effect on the colonic transmural potential difference in CF1 mice following the administration of a carcinogen, a cytotoxic agent, and bile acids. Depolarization of the distal colonic mucosa was seen in mice treated with the carcinogen but not with the cytotoxic agent, and bile acids caused further depolarization of the mucosa. These experiments support the hypothesis that epithelial depolarization is a putative mechanism in carcinogenesis, which could have important implications for the early detection of colon cancer.

Early Histopathologic Events to Evolution of Colon Cancer in C57BL/6 and CF1 Mice Treated With 1,2-Dimethylhydrazine<xref ref-type="fn" rid="FN2">2</xref>

After administration of the intestinal carcinogen 1,2-dimethylhydrazine (DMH), C57BL/6J and CF1 mice were observed for early precursor lesions to large bowel cancer. Among the initial events seen following DMH treatment, an abrupt reduction in colonic DNA synthesis was the earliest lesion detectable. The frequency of aberrant colonic nuclei rose shortly after DMH treatment, reaching a maximum value 24 hours later and remaining elevated for 3 days following the exposure. Mucin changes, detected histochemically, and cell kinetic alterations in crypt proliferation rates were observed much later and were a constant feature for both strains following 4 weekly treatments with DMH, while carcinomas appeared in all animals 32 weeks after the start of DMH treatment. The quantitative comparison of these histopathologic observations for the early detection of colon cancer suggests that the induction of colonic nuclear aberrations in the mucosa of the large bowel might provide a sensitive and rapid indication of genotoxicity to this organ and thus might provide the basis for a screening methodology for colon carcinogens.

II. Screening for Colo-Rectal Cancer

Recently, according to the change of our environmental factors such as diet and habits and the improvement of colon diagnostics, colo-rectal cancer has been increasing in Japanese as in American and European. Therefore, the screening system as gastric mass survey regime should be established as quickly as possible. Though it was possible to distinguish an advanced cancer from normal subjects by analyses of questionaire responses and fecal occult blood testing, this was ineffective in the diagnosis of early cancer.Therefore, endoscopic screening for the lower part of the colon using a flexible sig-moidofiberscope (TCF-ls, CF-ITS) were performed during the last four years. Screeing for colon cancer was easily and effectively performed with minimal bowel preparation, and not only cancer but also several colon diseases were detected. It is emphasized that for the early detection of colon cancer, the screening examination using a sigmoidofiberscope should be performed regardless to their complaints or age.

Modern approaches to early identification of large-bowel cancer. Prospects for newer methodologies.

Prospects for future improvement in survival from colon cancer may depend on advances in our knowledge of biochemical and immunological alterations that occur in malignancy. However, even when these tests indicate an abnormality, all current methods would have to be used to localize a lesion to obtain a tissue diagnosis. At present we must work primarily with all of our investigative tools in order to make a diagnosis in the symptomatic patient. However, intensive, periodic, selective investigation of high-risk patients such as those with familial polyposis, previous polyps or cancer, or ulcerative colitis are sure to be rewarding. An additional high-risk population could be identified by testing the stools of the asymptomatic patient for occult blood. These patients could then be studied with an aggressive diagnostic approach including sigmoidoscopy, colonoscopy, blood CEA, and newer techniques such as pulsatile lavage for CEA in the washings, for cytology, fluorescent cytology, enzymes, and for isotopic labeling. It is clear that if we are to salvage larger numbers of patients, very early diagnosis, or diagnosis in the incipient stage of disease, is vitally needed. Indications are that findings from some of the studies discussed may in the foreseeable future lead to useful clinical application which will meet this need for the early detection of colon cancer.