154,528 research outputs found
Hyperspectral texture analysis for colon tissue biopsy classification
Get PDFDiagnosis 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
Get PDFDiagnosis 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
Diabetes alone should not be a reason for withholding adjuvant chemotherapy for stage III colon cancer
Get PDFBackground: 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
New Marker of Colon Cancer Risk Associated with Heme Intake: 1,4-Dihydroxynonane Mercapturic Acid
Get PDFBackground: 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
Glycemic index, nutrient density, and promotion of aberrant crypt foci in rat colon
Get PDFWe speculated that a diet with a high glycemic index (GI), or a diet with a low nutrient density (nutrient-to-calorie ratio), would enhance colon carcinogenesis, presuma-bly via increased insulin resistance. Forty-eight female Sprague -Dawley rats (SD) received an azoxymethane injection (20mg /kg) and were randomized to 5 groups given an AIN76 diet containing (1) 65% starch by wt. (2) 65% glucose, GI=100, (3) 65% fructose, GI=23, (4) 82% starch, or (5) 39% oil and 39% sucrose. The nutrient density was halved in 45 diets compared to 13 diets. Promotion was assessed by the multi-plicity (number of crypts) of aberrant crypt foci (ACF), an early marker of colon carcinogenesis. Insulin resistance was estimated by (blood insulin x blood glucose), by plasma triglycerides, and by visceral fat. To confirm the results in another rat strain, the whole experiment was duplicated in 48 female Fischer F344 rats. Results show that: (i) ACF multiplicity was not different in glucose- and fructose-fed rats (p>0.7): diets with contrasting GI had the same effect on ACF growth. (ii) Diets of low nutrient density increased visceral fat (p<0.05), but reduced the ACF size in F344 (p<0.001, no reduction in SD). (iii) Indirect insulin resistance markers (FIRI index, blood triglycerides, visceral fat) did not correlate with ACF multiplicity. These results do not support the hypothesis that diets with a high glycemic index, or of low nutrient density, or diets that increase some indirect insulin resistance markers, can promote colon carcinogenesis in female rats
Dehydroalanine and Lysinoalanine in Thermolyzed Casein do not Promote Colon Cancer in the Rat
Get PDFThermolysis 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
Calcium Carbonate Suppresses Haem Toxicity Markers without Calcium Phosphate Side Effect on Colon Carcinogenesis
Get PDFRed 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
Colonic Protein Fermentation and Promotion of Colon Carcinogenesis by Thermolyzed Casein
Get PDFThermolyzed 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
Red meat and colon cancer : should we become vegetarians, or can we make meat safer ?
Get PDFThe effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer
Evidence for Two Modes of Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia in Human Colon Cancer Cells
Get PDFColorectal cancer is the third leading cause of cancer-related mortality in the world-- the main cause of death from colorectal cancer is hepatic metastases, which can be treated with isolated hepatic perfusion (IHP). Searching for the most clinically relevant approaches for treating colorectal metastatic disease by isolated hepatic perfusion (IHP), we developed the application of oxaliplatin concomitantly with hyperthermia and humanized death receptor 4 (DR4) antibody mapatumumab (Mapa), and investigated the molecular mechanisms of this multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this study, that the synergistic effect of the multimodality treatment-induced apoptosis was caspase dependent and activated death signaling via both the extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was activated by c-Jun N-terminal kinase (JNK) signaling which led to Bcl-xL phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL, which contributed to the intrinsic pathway. The downregulation of cellular FLICE inhibitory protein long isoform (c-FLIPL) in the extrinsic pathway was accomplished through ubiquitination at lysine residue (K) 195 and protein synthesis inhibition. Overexpression of c-FLIPL mutant (K195R) and Bcl-xL mutant (S62A) completely abrogated the synergistic effect. The successful outcome of this study supports the application of multimodality strategy to patients with colorectal hepatic metastases who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway. © 2013 Song et al
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