125,573 research outputs found
Fruits, vegetables, and hMLH1 protein-deficient and -proficient colon cancer: The Netherlands cohort study.
No full textBACKGROUND: Clinical and pathologic differences exist between colon carcinomas deficient and proficient in the mismatch repair protein hMLH1. Animal and in vitro studies suggest that fruits, vegetables, folate, and antioxidants are associated with colonic expression of mismatch repair genes. METHODS: Associations between consumption of fruits and vegetables and hMLH1 protein-deficient and -proficient colon cancer were evaluated in the Netherlands Cohort Study on diet and cancer using a case-cohort approach. A self-administered food frequency questionnaire was completed, in 1986, by 120,852 individuals ages 55 to 69 years. Using immunohistochemistry, hMLH1 protein expression was assessed in colon cancer tissue obtained from 441 patients who were identified over 7.3 years of follow-up excluding the initial 2.3 years. Incidence rate ratios (RR) were estimated for hMLH1 protein-deficient and -proficient colon cancer. RESULTS: hMLH1 protein expression was absent in 54 tumors (12.2%) and present in 387 tumors. Fruit consumption was associated with hMLH1 protein-deficient colon cancer [highest versus lowest tertile, RR, 0.46; 95% confidence interval (95% CI), 0.23-0.90; P(trend) = 0.029] but not with hMLH1 protein-proficient tumors (highest versus lowest tertile, RR, 1.03; 95% CI, 0.78-1.35; P(trend) = 0.81). Total consumption of vegetables was not associated with either type of tumor (hMLH1 protein deficient: RR, 0.86; 95% CI, 0.45-1.65; P(trend) = 0.67; hMLH1 protein proficient: RR, 0.94; 95% CI, 0.72-1.23; P(trend) = 0.72). No associations were observed for folate, fiber, antioxidants, or subgroups of vegetables. CONCLUSION: These analyses indicate that an inverse association between consumption of fruits and colon cancer may be confined to the subgroup of tumors with a deficient mismatch repair system
New Marker of Colon Cancer Risk Associated with Heme Intake: 1,4-Dihydroxynonane Mercapturic Acid
No full textBackground: Red meat consumption is associated with an increased risk of colon cancer. Animal studies show that heme, found in red meat, promotes preneoplastic lesions in the colon, probably due to the oxidative properties of this compound. End products of lipid peroxidation, such as 4-hydroxynonenal metabolites or 8-iso-prostaglandin-F2 (8-iso-PGF2), could reflect this oxidative process and could be used as biomarkers of colon cancer risk associated with heme intake.
Methods: We measured urinary excretion of 8-iso-PGF2 and 1,4-dihydroxynonane mercapturic acid (DHN-MA), the major urinary metabolite of 4-hydroxynonenal, in three studies. In a short-term and a carcinogenesis long-term animal study, we fed rats four different diets (control, chicken, beef, and blood sausage as a high heme diet). In a randomized crossover human study, four different diets were fed (a 60 g/d red meat baseline diet, 120 g/d red meat, baseline diet supplemented with heme iron, and baseline diet supplemented with non-heme iron).
Results: DHN-MA excretion increased dramatically in rats fed high heme diets, and the excretion paralleled the number of preneoplastic lesions in azoxymethane initiated rats (P < 0.0001). In the human study, the heme supplemented diet resulted in a 2-fold increase in DHN-MA (P < 0.001). Urinary 8-iso-PGF2 increased moderately in rats fed a high heme diet (P < 0.0001), but not in humans.
Conclusion: Urinary DHN-MA is a useful noninvasive biomarker for determining the risk of preneoplastic lesions associated with heme iron consumption and should be further investigated as a potential biomarker of colon cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2274–9
Diabetes alone should not be a reason for withholding adjuvant chemotherapy for stage III colon cancer
No full textBackground: With increasing prevalence of diabetes mellitus and colon cancer, the number of patients suffering from both diseases is growing, and physicians are being faced with complicated treatment decisions. Objective: To investigate the association between diabetes and treatment/course of stage III colon cancer and the association between colon cancer and course of diabetes. Materials and Methods: Additional information was collected from the medical records of all patients with both stage III colon cancer and diabetes (n=201) and a random sample of stage III colon cancer patients without diabetes (n=206) in the area of the population-based Eindhoven Cancer Registry (1998–2007). Results: Colon cancer patients without diabetes were more likely to receive adjuvant chemotherapy compared with diabetic colon cancer patients (OR 1.8; 95% CI 1.2–2.7). After adjustment for age, this difference was borderline significant (OR 1.6; 95% CI 1.0–2.6). Diabetic patients did not have: significantly more side-effects from surgery or adjuvant chemotherapy; more recurrence from colon cancer; significantly shorter time interval until recurrence; or a poorer disease-free survival or overall survival. Age and withholding of adjuvant chemotherapy were most predictive of all-cause mortality. After colon cancer diagnosis, the dose of antiglycaemic medications was increased in 22% of diabetic patients, resulting in significantly lower glycaemic indexes than before colon cancer diagnosis. Conclusions: Since diabetic patients did not have more side-effects of adjuvant chemotherapy, and adjuvant chemotherapy had a positive effect on survival for both patients with and without diabetes, diabetes alone should not be a reason for withholding adjuvant chemotherapy.Journal of Comorbidity 2011;1(1):19–2
Calcium Carbonate Suppresses Haem Toxicity Markers without Calcium Phosphate Side Effect on Colon Carcinogenesis
No full textRed meat intake is associated with increased risk of colorectal cancer. We have previously shown that haemin, haemoglobin and red meat promote carcinogen-induced preneoplastic lesions, aberrant crypt foci, in the colon of rats. We have also shown that dietary calcium phosphate inhibits haemin-induced promotion, and normalizes faecal lipoperoxides and cytotoxicity. Unexpectedly, high-calcium phosphate control diet-fed rats had more preneoplastic lesions in the colon than low-calcium control diet-fed rats. The present study was designed to find a calcium supplementation with no adverse effect, by testing several doses and types of calcium salts. One in vitro study and two short-term studies in rats identified calcium carbonate as the most effective calcium salt to bind haem in vitro and to decrease faecal biomarkers previously associated with increased carcinogenesis: faecal water cytotoxicity, thiobarbituric acid reactive substances. A long term carcinogenesis study in dimethylhydrazine-injected rats demonstrated that a diet containing 100 µmol/g calcium carbonate did not promote aberrant crypt foci, in contrast with previously tested calcium phosphate diet. The results suggest that calcium carbonate, and not calcium phosphate, should be used to reduce haem-associated colorectal cancer risk in meat-eaters. They support the concept that the nature of the associated anion to a protective metal ion is important for chemoprevention
Hyperspectral texture analysis for colon tissue biopsy classification
No full textDiagnosis and cure of colon cancer can be improved by performing automated histopathological analysis of colon biopsy samples. Due to significant observational variation between pathologists in several histological features, there is a need for the development of automated, quantitative analysis techniques. This paper presents a promising automative technique for the classification of hyperspectral colon tissue biopsy images. The application of hyperspectral imaging techniques in medical image analysis is a new domain for researchers. The main advantage of using hyperspectral imaging is the increased spectral resolution and detailed subpixel information. The proposed classification algorithm is based on the subspace projection techniques particularly Support Vector Machines (SVM) with Gaussian Kernel. Dimensionality reduction and tissue segmentation is achieved by Independent Component Analysis (ICA) and k-means clustering. Morphological features, which describe the shape, orientation and other geometrical attributes, are extracted in first set of experiments. Grey level cooccurrence matrices are computed for the second set of experiments. The SVM with appropriate choice of parameters for its Gaussian kernel efficiently exploits the non linear boundary between the benign and malignant classes of the colon tissue biopsies
Co-occurrence and morphological analysis for colon tissue biopsy classification
No full textDiagnosis and cure of colon cancer can be improved by efficiently classifying the colon tissue cells from biopsy slides into normal and malignant classes. This paper presents the classification of hyperspectral colon tissue cells using morphology of gland nuclei of cells. The application of hyperspectral imaging techniques in medical image analysis is a new domain for researchers. The main advantage of using hyperspectral imaging is the increased spectral resolution and detailed subpixel information. The proposed classification algorithm is based on the subspace projection techniques. Support vector machine, with 3rd degree polynomial kernel, is employed in final set of experiments. Dimensionality reduction and tissue segmentation is achieved by Independent Component Analysis (ICA) and k-means clustering. Morphological features, which describe the shape, orientation and other geometrical attributes, are extracted in one set of experiments. Grey level co-occurrence matrices are also computed for the second set of experiments. For classification, kernel discriminant analysis (LDA) with co-occurrence features gives comparable classification accuracy to SVM using a gaussian kernel. The algorithm is tested on a limited set of samples containing ten biopsy slides and its applicability is demonstrated with the help of measures such as classification accuracy rate and the area under the convex hull of ROC curves
Dehydroalanine and Lysinoalanine in Thermolyzed Casein do not Promote Colon Cancer in the Rat
No full textThermolysis of proteins produces xenobiotic amino-acids such as the potentially toxic lysinoalanine, and the alkylating agent, dehydro¬alanine, which have been considered possible health hazards. We observed that thermolysed casein promoted aberrant crypt foci (ACF) and colon cancer growth in rats initiated with azoxymethane and speculated that promotion might be due to the formation of these compounds. To test this notion we first measured the concentration of the modified amino acids as a function of thermolysis time. The concentration of dehydroalanine in the casein paralleled the degree of promotion, that of lysinoalanine did not. We then tested diets containing foods with high levels of dehydroalanine (thermolysed sodium-caseinate, cooked Swiss cheese) for their effect on ACF promotion. They decreased the number and/or size of ACF significantly, indicating that dehydroalanine did not promote, but protected rats against colon carcinogenesis. These results do not support the notion that lysinoalanine or dehydroalanine are a hazard with respect to colon carcinogenicity
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Heme-Induced Biomarkers Associated with Red Meat Promotion of colon Cancer Are Not Modulated by the Intake of Nitrite
No full textRed and processed meat consumption is associated with the
risk of colorectal cancer. Three hypotheses are proposed to explain this association, via heme-induced oxidation of fat, heterocyclic amines, or N-nitroso compounds. Rats have often been used to study these hypotheses, but the lack of enterosalivary cycle of nitrate in rats casts doubt on the relevance of this animal model to predict nitroso- and heme-associated human colon carcinogenesis.
The present study was thus designed to clarify whether a nitrite intake that mimics the enterosalivary cycle can modulate hemeinduced nitrosation and fat peroxidation. This study shows that, in contrast with the starting hypothesis, drinking water added with nitrite to mimic the salivary nitrite content did not change the effect of hemoglobin on biochemicalmarkers linked to colon carcinogenesis, notably lipid peroxidation and cytotoxic activity in the colon
of rat. However, ingested sodium nitrite increased fecal nitrosocompounds level, but their fecal concentration and their nature (iron-nitrosyl) would probably not be associated with an increased risk of cancer.We thus suggest that the rat model could be relevant for study the effect of red meat on colon carcinogenesis, in spite of the lack of nitrite in the saliva of rats
Colonic Protein Fermentation and Promotion of Colon Carcinogenesis by Thermolyzed Casein
No full textThermolyzed casein is known to promote the growth of aberrant crypt foci (ACF) and colon cancer when it is fed to rats that have been initiated with azoxymethane. We speculated that the promotion was a consequence of increased colonic protein fermentation (i.e., that the thermolysis of the casein decreases its digestibility, increases the amount of protein reaching the colon, and increases colonic protein fermentation and that the potentially toxic products of this fermentation promote colon carcinogenesis). We found that the thermolysis of casein reduces its digestibility and increases colonic protein fermentation, as assessed by fecal ammonium and urinary phenol, cresol, and indol-3-ol. Thermolysis of two other proteins, soy and egg white protein, also increases colonic protein fermentation with increased fecal ammonia and urinary phenols, and thermolysis of all three proteins increases the levels of ammonia and butyric, valeric, and i-valeric acids in the cecal contents. We found, however, that the increased protein fermentation observed with thermolysis is not associated with pro-motion of colon carcinogenesis. With casein, the kinetics of protein fermentation with increasing thermolysis time are clearly different from the kinetics of promotion of ACF growth. The formation of the fermentation products was highest when the protein was thermolyzed for one hour, whereas promotion was highest for protein that had been thermolyzed for two or more hours. With soy and egg white, thermolysis increased colonic protein fermentation but did not promote colon carcinogenesis. Thus, although thermolysis of dietary casein increases colonic protein fermentation, products of this fermentation do not appear to be responsible for the promotion of colon carcinogenesis. Indeed, the results suggest that protein fermentation products do not play an important role in colon cancer promotion
Meat and fish consumption, APC gene mutations and hMLH1 expression in colon and rectal cancer: a prospective cohort study (The Netherlands).
No full textOBJECTIVE: The aim of this study was to investigate the associations between meat and fish consumption and APC mutation status and hMLH1 expression in colon and rectal cancer. METHODS: The associations were investigated in the Netherlands Cohort Study, and included 434 colon and 154 rectal cancer patients on whom case-cohort analyses (subcohort n = 2948) were performed. RESULTS: Total meat consumption was not associated with the endpoints studied. Meat product (i.e. processed meat) consumption showed a positive association with colon tumours harbouring a truncating APC mutation, whereas beef consumption was associated with an increased risk of colon tumours without a truncating APC mutation (incidence rate ratio (RR) highest versus lowest quartile of intake 1.61, 95% confidence interval (CI) 0.96-2.71, p-trend = 0.04 and 1.58, 95% CI 1.10-2.25, p-trend = 0.01, respectively). Consumption of other meat (horsemeat, lamb, mutton, frankfurters and deep-fried meat rolls) was associated with an increased risk of rectal cancer without a truncating APC mutation (RR intake versus no intake 1.79, 95% CI 1.10-2.90). No associations were observed for meat consumption and tumours lacking hMLH1 expression. CONCLUSIONS: Our data indicate that several types of meat may contribute differently to the aetiology of colon and rectal cancer, depending on APC mutation status but not hMLH1 expression of the tumour
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