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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of hormones and growth factors in the pathogenesis and therapy of colon cancer is biologically intricate and medically important. The effects of the previously described hormones and growth factors on normal and neoplastic colonic growth and development suggest the mechanisms by which hormonal alteration might either enhance or suppress the cancer process. The high degree of association between the specific endocrine-related processes (breast cancer, acromegaly, hyperparathyroidism, gastrin sensitivity of colon cancer, and cancer cell lines) suggests a significant role for hormones in colonic carcinogenesis. The relationship between the specific hormones and cancers is often unclear. This is the result of many factors: the variable presence of specific hormone receptors on the surface of the tumor or cell line; the inconsistent response to exogeneous hormone administration in vivo and in vitro; and the occasional failure of specific hormone-blocking agents to affect cell proliferation. The relationship between growth factors and cancers is also unclear. The following questions must be resolved in order to understand the significance of growth factors and the neoplastic process: (1) Is a growth factor significant in either an autocrine or a paracrine capacity? (2) Are combinations of growth factors rather than individual growth factors more biologically significant? (3) Do structural alterations of the immunologically similar, but functionally different growth factors modify their effect on the neoplastic tissue? The potential for manipulation of hormones and growth factors in the prevention and treatment of colon cancer is evidence to date suggesting that such efforts are indeed justified.
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PMID:Relationship of hormones and growth factors to colon cancer. 306 40

Deaths from colon cancer number over 60,000 each year in the United States. Because early detection results in a high cure rate, development of noninvasive techniques for detection of colon cancer has received much interest. The ability to detect early changes in colonocyte genes and gene expression would provide valuable information. We have shown previously that alterations in protein kinase C (PKC) isoform expression are associated with changes in colonic cell proliferation, a key intermediate marker for the prediction of tumorigenesis. Here, we describe a method for the quantitative detection of mRNAs for select PKC isoforms isolated from rat feces containing exfoliated colonocytes. After total RNA extraction from fresh fecal material, polyadenylated RNA was selectively purified and quantitated with slot blotting and hybridization to oligodeoxythymidylic acid. Fecal polyadenylated RNA was used for semiquantitative (mimic) RT-PCR to quantitate PKC isoform mRNA expression. We detected mRNA for PKC-alpha, PKC-delta, PKC-epsilon, and PKC-sigma, but not for PKC-beta or PKC-gamma, which is consistent with the profile of isoforms detected previously in scraped colonic mucosa using immunoblot analysis. This noninvasive method, utilizing feces containing exfoliated colonocytes, is a sensitive noninvasive technique for quantitating luminal mRNAs. This provides a means to monitor gene expression of colonic epithelial cells, which may have predictive value in monitoring the neoplastic process.
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PMID:Noninvasive detection of putative biomarkers for colon cancer using fecal messenger RNA. 854 31

Evidence of a role for steroid hormones and reproduction in colon neoplasia remains tantalizing but unclear. Hormone replacement therapy (HRT) has been reported in a number of recent studies to be associated with a reduced risk of colon cancer. A case-control study was undertaken to establish whether HRT is associated with lower risk of adenomatous polyps. This case-control study was undertaken as a project of the Minnesota Cancer Prevention Research Unit. Cases (n = 219) were women, ages 30-74 years with colonoscopy-proven, pathology-confirmed, adenomatous polyps of colon and rectum recruited at Digestive Healthcare PA (Minneapolis, MN). Two control groups were selected: women without polyps at colonoscopy (n = 438) at Digestive Healthcare and age- and zip code-matched women selected from the general community (n = 247). Response rates were 68% among those colonoscoped and 65% among community controls. Parity, age at first live birth, and oral contraceptive use did not distinguish cases from either control group. Multivariate adjusted odds ratios and 95% confidence limits for use of HRT for less than 5 years (compared with never use) among postmenopausal women were 0.52 (0.32-0.85) versus colonoscopy-negative controls and 0.74 (0.44-1.26) versus community controls. For 5 years of use or greater, the corresponding figures were 0.39 (0.23-0.67) and 0.61 (0.34-1.07). These results were not materially different when stratified on body mass index, oophorectomy, hysterectomy, aspirin use, or family history. There is no marked increase in risk even 5 years after cessation of HRT use. HRT appears to lower risk of colorectal adenomatous polyps, suggesting that it acts quite early in the neoplastic process. Mechanisms remain unclear. Reduction of risk of colorectal neoplasia is an additional benefit of postmenopausal HRT.
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PMID:Hormone replacement therapy is associated with lower risk of adenomatous polyps of the large bowel: the Minnesota Cancer Prevention Research Unit Case-Control Study. 889 88

We have developed a non-invasive method utilizing feces, containing sloughed colonocytes, as a sensitive technique for detecting diagnostic colonic biomarkers. In this study, we used the rat colon carcinogenesis model to determine if changes in fecal protein kinase C (PKC) expression have predictive value in monitoring the neoplastic process. Weanling rats were injected with saline or azoxymethane (AOM) and 36 weeks later fecal samples and mucosa were collected, poly A+ RNA isolated, and quantitative RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and zeta mRNA levels were altered by the presence of a tumor, with tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII expression as compared with animals without tumors. In addition, AOM-injection increased mucosal PKC betaII mRNA expression compared with saline controls. No effect of tumor incidence on mucosal PKC betaII expression was observed. In contrast, fecal PKC zeta expression was 2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus saline. Since tumor incidence exerts a reciprocal effect on fecal PKC betaII and zeta mRNA expression, data were also expressed as the ratio between PKC betaII and zeta. The isozyme ratio was strongly related to tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25, animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that the expression of fecal PKC betaII and zeta may serve as a noninvasive marker for development of colon tumors. A sensitive technique for the detection of colon cancer is of importance since early diagnosis can substantially reduce mortality.
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PMID:Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer. 949 73

A significantly high GABA level and GAD activity was found in human colon cancer tissue as compared with normal macroscopically unchanged human colon wall taken from the same patients. Similarly in athymic nu/nu mice transplanted with human colon adenocarcinoma cells established in in vitro culture (line CX-2) the high level of GABA accompanied by high GAD activity was found in subcutaneously growing tumors as compared with the unchanged colon wall and unchanged skin tissue from the same tumor bearing mice. Interestingly, the level of GAD activity in the macroscopically unchanged colon tissue of mice transplanted with tumor cells were increased in comparison with normal colon of healthy control mice. For the skin, only GAD activity was higher in the material coming from tumor bearing mice than in the material from normal control mice, whereas GABA level was even lower in the skin of tumor inoculated mice compared with control group. An increase in GABA level and in GAD activity can perhaps reflect a local immune response to the neoplastic process. The observed direction of GABA metabolism in tumor of the colon indicates a possibility to interfere in this process using the agonists of the GABA-ergic system.
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PMID:GABA content and GAD activity in colon tumors taken from patients with colon cancer or from xenografted human colon cancer cells growing as s.c. tumors in athymic nu/nu mice. 967 Jan 13

Colorectal cancer is one of the most common malignancies in the United States. Although both genetic and environmental factors play a role in colorectal tumorigenesis, recent advances in genetics have more clearly defined the impact of inheritance in the multistep process of the disease. Researchers have identified single genes that confer a susceptibility to familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). Because these genes are inherited in an autosomal dominant fashion, offspring of carriers have a 50% chance of inheriting the gene mutation and its associated risk. The FAP gene, when mutated, initiates the neoplastic process. HNPCC gene mutations disrupt mismatch repair, thus inducing progression of tumor formation. Discovery of these genes has helped our understanding of sporadic colon cancer as well. Genetic testing for the FAP and HNPCC genes is now available, and results of this testing have implications for surveillance and management. In addition, testing raises complex psychosocial and ethical issues. At present, genetic testing is primarily conducted in the research setting, but it will soon be available in the clinical arena. To prepare for the challenges that these new advances will present, nurses must begin now to enhance their knowledge of genetics and its application to oncology.
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PMID:Inherited predisposition to colon cancer. 984 95

In the past year, several papers have been published which implicate a link between alterations in chromatin structure and the development of cancer. Both histone hyperacetylation and hypoacetylation appear to be important in the neoplastic process, depending on the target gene involved. In the case of colon cancer, induction of the p21 gene by histone hyperacetylation may be a mechanism by which dietary fiber prevents carcinogenesis.
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PMID:Histone acetylation and cancer. 1032 42

A new era involving the evaluation of recombinant vaccines for colon cancer has begun with the concurrent emergence of insights and technologies in the fields of molecular biology and immunology. These advances include (I) the identification and cloning of an array of genes associated with the neoplastic process, such as oncogenes, suppressor genes, genes encoding oncofetal antigens, and tissue lineage determinants; (2) the development of a variety of viral and bacterial vectors to deliver and present gene products; (3) the identification of numerous T-cell costimulatory molecules and the knowledge of their mode of action; (4) the cloning and analysis of the modes of action of an array of cytokines and other immunomodulatory molecules; and (5) a more sophisticated knowledge of the mode(s) of antigen presentation and T-cell activation.
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PMID:Strategies in the development of recombinant vaccines for colon cancer. 1060 60

Although exposure to asbestos fibers is associated with the development of lung cancer, the underlying mechanism(s) remains unclear. Using human papillomavirus-immortalized human bronchial epithelial (BEP2D) cells, we previously showed that UICC chrysotiles can malignantly transform these cells in a stepwise fashion before they become tumorigenic in nude mice. In the present study we used cDNA expression arrays to screen differentially expressed genes among the tumorigenic cells. A total of 15 genes were identified, 11 of which were further confirmed by northern blot. Expression levels of these genes were then determined among transformed BEP2D cells at different stages of the neoplastic process, including non-tumorigenic cells that were resistant to serum-induced terminal differentiation, early and late passage transformed BEP2D cells, five representative tumor cell lines and fused tumorigenic-control cell lines which were no longer tumorigenic. A consistent 2- to 3-fold down-regulation of the DCC (deleted in colon cancer), Ku70 and heat shock protein 27 genes were detected in all the independently generated tumor cell lines while expression levels in early transformants as well as in the fusion cell lines remained normal. In contrast, all the tumor cell lines examined demonstrated 2- to 4-fold overexpression of the insulin receptor and its signal transduction genes. Differential expression of these genes was completely restored in the fusion cell lines examined. No alteration in c-jun or EGF receptor expression was found in any of the cell lines. Our data suggest that activation of the insulin receptor pathway and inactivation of DCC and Ku70 may cooperate in malignant transformation of BEP2D cells induced by asbestos.
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PMID:Differentially expressed genes in asbestos-induced tumorigenic human bronchial epithelial cells: implication for mechanism. 1106 61

In order to diagnose colon cancer at an earlier, more localized stage, there is a need to develop diagnostic markers (genes) which can detect early patterns of gene expression in exfoliated colonocytes shed in the stool during routine screening for this disease. An RNA-based detection is more pertinent than either a DNA-based or a protein-based method as a screening procedure, but it has not been widely used as a cancer screen because of the difficulty of handling and stabilizing the RNA molecule. We describe a method that permits extraction of intact nondegraded total RNA from human colonocytes in stool and from normal and malignant colon tissues (which were employed for comparison with stool). Because it utilizes commercially available kits, this method is simpler than other published methods and does not require isolation of messenger (m)RNA, thereby reducing the chances of contaminating the preparations with degrading nucleases, and even a small amount of isolated total RNA can be adequately reverse transcribed, making high-quality copy (c) DNA. This is followed by PCR (either qualitative end point or semiquantitative real-time) using colon cancer-specific gene primers. By routinely and systematically being able to perform quantitative gene expression measurements on noninvasive samples, the goal of this pilot work is to lay the groundwork for conducting a large clinical study to identify groups of selected genes whose expression is consistently altered at an early stage in the neoplastic process. Such work will permit noninvasive monitoring of at-risk patients through the analysis of their stool samples. Correct diagnosis will allow for surgical and/or other interventions before the tumor is well established and, thus, should decrease mortality from this preventable disease.
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PMID:Improved methods for extracting RNA from exfoliated human colonocytes in stool and RT-PCR analysis. 1562 22


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