1,721,178 research outputs found
EARLY EVENTS IN HUMAN COLORECTAL CARCINOGENESIS - ABERRANT CRYPTS AND MICROADENOMA
No full textExperimental studies have allowed the identification of foci of aberrant crypts on the fixed methylene-blue-stained mucosal surface of rodent colons after colon carcinogens administration. Similar lesions can also be observed and quantified on the mucosal surface of the human colon, using the same technique. Several foci showed dysplasia at histological examination, thus allowing the identification of microadenomas. Microadenoma may thus be a precursor lesion of adenomas and colorectal cancer. The identification of aberrant crypt foci and microadenomas in vivo could provide a new end-point for studies on the effect of enviromental and genetic factors in the early stages of cancer of the large intestine. Further studies are needed to define the natural history of these lesions. Moreover, a critical evaluation of current colon cancer prevention strategies should be considered
Prevention of colorectal cancer: How many tools do we have in our basket?
No full textPrevention is the main strategy in order to reduce colorectal cancer incidence and mortality. It can be accomplished through primary prevention, using measures affecting factors known to confer higher risk of colorectal cancer, or through secondary prevention, aimed at early diagnosis of cancer or preneoplastic lesions in groups of subjects at increased risk of cancer. Although primary prevention should be the goal for future years, because it acts on the probable causes of colorectal cancer, at present it seems that secondary prevention is more effective on colorectal cancer survival, and the approaches which have yielded the most satisfying results, in terms of reduced mortality for cancer, are those aimed at detecting preneoplastic lesions, or cancer at an early stage in selected groups of subjects at average or increased risk of colorectal cancer. These groups are subjects aged 50 years or older, affected individuals (gene carriers) or family members of hereditary colorectal cancer syndromes (i.e., Lynch syndrome and familial adenomatous polyposis), and patients with inflammatory bowel diseases. The most effective procedures used, though with some drawbacks, are fecal occult blood tests and colonoscopy. Future research should be addressed to find new approaches that will render preventive strategies more acceptable for the population, and more cost-effective
Chemerin/chemR23 axis in inflammation onset and resolution
No full textChemerin is an adipokine secreted by adipocytes and associated with obesity, insulin resistance and metabolic syndrome. Different chemerin fragments with pro- or anti-inflammatory action can be produced, depending on the class of proteases predominating in the microenvironment. Chemerin binds to three receptors, especially to chemR23, expressed on various cells, as dendritic cells, macrophages and natural killer cells, regulating chemotaxis towards the site of inflammation and activation status. Recently, the chemerin/chemR23 axis has attracted particular attention for the multiple roles related to the control of inflammation, metabolism and cancerogenesis in different organs and systems as lung (allergy and cancer), skin (psoriasis, lupus, cancer, wound repair), cardiovascular system (lipid profile and atherosclerosis), reproductive apparatus (polycystic ovary syndrome, follicular homoeostasis), and digestive tract (inflammatory bowel diseases and cancer). This pathway may regulate immune responses by contributing both to the pathogenesis of inflammatory diseases and to the resolution of acute inflammation. Thus, chemerin-derived peptides or other substances that may affect the chemerin/chemR23 axis could be used in the future for the treatment of many diseases, including cancer at different sites
The cause of colorectal cancer
No full textColorectal cancer continues to represent one of the major causes of cancer-related morbidity in all western countries. A review has been made of the main aetiological factors which have been related to colorectal cancer development with particular attention being focused on: a) new advancements in molecular biology, and b) the interaction between genetic predisposition and environmental factors. Worldwide, approximately 900,000 cases of colorectal malignancies have been diagnosed in 1996 and this accounts for 8.5% of all new Gases of cancer. Crude incidence rates range from 0.6-5.0 cases/100,000/year in Senegal and India to 50-70 cases in developed countries. Environmental factors, such as meat, saturated fat, low physical activity, obesity, smoking, alcoholic beverages, and inflammatory bowel diseases seem to increase the risk of colorectal cancer. in contrast, fruit, vegetables, fibre, antioxidant vitamins, calcium, folate, physical exercise and non-steroidal anti-inflammatory drugs seem to show a protective effect. For some of these factors, the molecular basis of their mechanism of action begins to be elucidated. Colorectal cancer develops from benign precursors, the adenomatous polyps; there is extensive evidence that polyps transform into cancer in a stepwise manner, and that several molecular abnormalities (mutations of oncogenes, inactivation of tumour suppressor genes and microsatellite instability) accompany and, somehow, determine colorectal tumourigenesis. Two major Hereditary Colorectal Cancer syndromes - Familial Adenomatous Polyposis and Hereditary Non-polyposis Colorectal Cancer - have been described and characterized st molecular levels; it is estimated that these inherited conditions might account for up to 5% of all large bowel malignancies. Familial colorectal cancer remains undefined and is presumably due to multifactorial inheritance. Recently, identified germline mutations (such as /1307K in the APC gene) might account for a fraction of these familial cases, at least in some populations. At variance with many other tumours, the aetiology and pathogenesis of colorectal cancer have been partially clarified, so that we are now in the position to take preventive measures and to design surveillance programmes which might lead to a certain reduction in incidence and mortality. However, since many of the aetiological factors are strictly related to modern customs and lifestyle, they will be difficult to eradicate; this awareness should stimulate further investigations in this exciting field of research
Classification of aberrant crypt foci and microadenomas in human colon
No full textAberrant crypt foci (ACF) can be observed and quantified on the mucosal surface of formalin-fixed human colon resections after staining with methylene blue. To determine whether these ACF could be identified in fresh tissue, 10 colon resections were collected after surgery for colorectal cancer. Unfixed and fixed flat normal colonic mucosa from each colon were scored for ACF under a dissecting microscope after methylene blue staining. The number of ACF per cm2 and the average number of crypts per foci correlated highly in unfixed and fixed mucosa (r = 0.93 and 0.78, respectively). A significantly higher frequency of lesions was found in left-sided compared to right-sided colon resections. To determine whether the topographic features of the ACF gave an indication of the histological appearance, 68 specimens containing ACF or normal mucosa were examined histologically. The presence of slit-like lumen in the crypts of ACF on the mucosal surface correlated with the presence of dysplasia at histology, thus identifying microadenomas. These two observations suggest that the topographic classification of ACF in vivo could be used to distinguish microadenomas, a putative precursor lesion of colon cancer
Inflammatory pathways in the early steps of colorectal cancer development
Full text linkColorectal cancer is a major cause of cancer-related death in many countries. Colorectal carcinogenesis is a stepwise process which, from normal mucosa leads to malignancy. Many factors have been shown to influence this process, however, at present, several points remain obscure. In recent years some hypotheses have been considered on the mechanisms involved in cancer development, expecially in its early stages. Tissue injury resulting from infectious, mechanical, or chemical agents may elicit a chronic immune response resulting in cellular proliferation and regeneration. Chronic inflammation of the large bowel (as in inflammatory bowel diseases), has been associated with the subsequent development of colorectal cancer. In this review we examine the inflammatory pathways involved in the early steps of carcinogenesis, with particular emphasis on colorectal. Firstly, we describe cells and proteins recently suggested as central in the mechanism leading to tumor development. Macrophages and neutrophils are among the cells mostly involved in these processes and proteins, as cyclooxygenases and resolvins, are crucial in these inflammatory pathways. Indeed, the activation of these pathways establishes an oxidative and anaerobic microenvironment with DNA damage to epithelial cells, and shifting from an aerobic to an anaerobic metabolism. Many cellular mechanisms, such as proliferation, apoptosis, and autophagy are altered causing failure to control normal mucosa repair and renewal
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