Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Butyrate is a short chain fatty acid (SCFA) produced by bacterial fermentation of dietary fibers in the colon lumen which severely affects the proliferation of colon cancer cells in in vitro experiments. Although butyrate is able to interfere with numerous cellular targets including cell cycle regulator expression, little is known about butyrate metabolism and its possible involvement in its effect upon colon carcinoma cell growth. In this study, we found that HT-29 Glc-/+ cells strongly accumulated and oxidized sodium butyrate without producing ketone bodies, nor modifying oxygen consumption nor mitochondrial ATP synthesis. HT-29 cells accumulated and oxidized sodium acetate at a higher level than butyrate. However, sodium butyrate, but not sodium acetate, reduced cell growth and increased the expression of the cell cycle effector cyclin D3 and the inhibitor of the G1/S cdk-cyclin complexes p21/WAF1/Cip1, demonstrating that butyrate metabolism downstream of acetyl-CoA synthesis is not required for the growth-restraining effect of this SCFA. Furthermore, HT-29 cells modestly incorporated the 14C-labelled carbon from sodium butyrate into cellular triacylglycerols and phospholipids. This incorporation was greatly increased when D-glucose was present in the incubation medium, corresponding to the capacity of hexose to circulate in the pentose phosphate pathway allowing NADPH synthesis required for lipogenesis. Interestingly, when HT-29 cells were cultured in the presence of sodium butyrate, their capacity to incorporate 14C-labelled sodium butyrate into triacylglycerols and phospholipids was increased more than twofold. In such experimental conditions, HT-29 cells when observed under an electronic microscope, were found to be characterized by an accumulation of lipid droplets in the cytosol. Our data strongly suggest that butyrate acts upon colon carcinoma cells upstream of acetyl-CoA synthesis. In contrast, the metabolism downstream of acetyl-CoA [i.e. oxidation in the tricarboxylic acid (TCA) cycle and lipid synthesis] likely acts as a regulator of butyrate intracellular concentration.
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PMID:Butyrate metabolism upstream and downstream acetyl-CoA synthesis and growth control of human colon carcinoma cells. 1102 87

We hypothesized that the tolerance for nutrient deprivation as well as angiogenesis might be an important factor for tumor progression under hypovascular conditions. When normal human fibroblasts were subjected to extreme nutrient starvation by culturing in a medium without serum, glucose, and amino acids, cells died within 24 h. When substituted with liver cancer cell lines HepG2, Hep3B, HLE, and HuH-7, cell death occurred within 36 h. In contrast, four of six pancreas cancer cell lines, PANC-1, AsPC-1, BxPC-1, and KP-3, survived for remarkably longer periods; >50% of the cells survived, even after starvation for 48 h. Among three gastric cancer cell lines, MKN28, MKN45, and MKN74, only the most poorly differentiated MKN45 cells survived >36 h. More than 50% of the cells in colon cancer cell lines SW480, WiDr, and DLD-1 survived after 36 h, and the most undifferentiated SW480 cell line survived longest. We examined the possible involvement of PKB/Akt expression in the survival of various cell lines under nutrient starvation conditions. High expression of PKB/Akt was found to be associated with tolerance for nutrient starvation. When Akt antisense RNA expression vectors were introduced into PANC-1 cells, the tolerance was partially but significantly diminished by vectors for Akt1 and Akt2 but not Akt3. Because elimination of the tolerance might serve as a new strategy for cancer therapy, several compounds were tested for this purpose, and troglitazone, an insulin sensitizer, as well as LY294002, a phosphatidylinositol 3-kinase inhibitor, were found to kill PANC-1 cells only under nutrient starvation conditions.
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PMID:Remarkable tolerance of tumor cells to nutrient deprivation: possible new biochemical target for cancer therapy. 1108 46

Insulin resistance is associated with a plethora of chronic illnesses, including Type 2 diabetes, dyslipidemia, clotting dysfunction, and colon cancer. The relationship between obesity and insulin resistance is well established, and an increase in obesity in Western countries is implicated in increased incidence of diabetes and other diseases. Central, or visceral, adiposity has been particularly associated with insulin resistance; however, the mechanisms responsible for this association are unclear. Our laboratory has been studying the physiological mechanisms relating visceral adiposity and insulin resistance. Moderate fat feeding of the dog yields a model reminiscent of the metabolic syndrome, including visceral adiposity, hyperinsulinemia, and insulin resistance. We propose that insulin resistance of the liver derives from a relative increase in the delivery of free fatty acids (FFA) from the omental fat depot to the liver (via the portal vein). Increased delivery results from 1) more stored lipids in omental depot, 2) severe insulin resistance of the central fat depot, and 3) possible regulation of visceral lipolysis by the central nervous system. The significance of portal FFA delivery results from the importance of FFA in the control of liver glucose production. Insulin regulates liver glucose output primarily via control of adipocyte lipolysis. Thus, because FFA regulate the liver, it is expected that visceral adiposity will enhance delivery of FFA to the liver and make the liver relatively insulin resistant. It is of interest how the intact organism compensates for insulin resistance secondary to visceral fat deposition. While part of the compensation is enhanced B-cell sensitivity to glucose, an equally important component is reduced liver insulin clearance, which allows for a greater fraction of B-cell insulin secretion to bypass liver degradation, to enter the systemic circulation, and to result in hyperinsulinemic compensation. The signal(s) resulting in B-cell up-regulation and reduced liver insulin clearance with visceral adiposity is (are) unknown, but it appears that the glucagon-like peptide (GLP-1) hormone plays an important role. The integrated response of the organism to central adiposity is complex, involving several organs and tissue beds. An investigation into the integrated response may help to explain the features of the metabolic syndrome.
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PMID:Central role of the adipocyte in the metabolic syndrome. 1121 41

Hyperinsulinemia may be related to colon carcinogenesis. Several studies have suggested that diabetes mellitus is related to increased risk of colon cancer. We examined cross-sectionally the relation of fasting plasma insulin levels and glucose tolerance status to colon adenomas. In a consecutive series of 951 men undergoing total colonoscopy for a health examination at the Japan Self Defense Forces Fukuoka Hospital from April 1998 to August 1999, we identified 233 cases of colon adenomas and 497 controls with normal colonoscopy. Glucose tolerance status was determined by a 75-g oral glucose tolerance test, and subjects were classified as normal, impaired glucose tolerance (IGT) or non-insulin dependent diabetes mellitus (NIDDM). Plasma insulin levels were measured after subjects had fasted overnight. Logistic regression analysis and analysis of covariance was used to control for age and obesity. While plasma insulin levels were unrelated to colon adenomas, NIDDM was associated with a significantly increased risk of colon adenomas. There was no association between IGT and colon adenomas. NIDDM was more strongly associated with proximal colon adenomas. The findings suggest that long-term hyperinsulinemic status associated with NIDDM may increase the risk of colon adenomas, and subsequently of colon cancer.
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PMID:Glucose intolerance, plasma insulin levels, and colon adenomas in Japanese men. 1150 14

Neoangiogenesis and enhanced glucose metabolism in neoplasms are likely to be activated by the same biochemical stimulus; hypoxia. A correlation between these two parameters has been postulated. The objective of this study was to evaluate the relationship between Fluoro-desoxi-glucose uptake at positron emission tomography scan and angiogenesis in lung metastasis. Fluoro-desoxi-glucose activity, expressed as a standard uptake value, and microvessel intratumoural density, were retrospectively calculated in a series of 43 lung metastasis resected in 19 patients. Primary sites were colorectal cancer in 16 metastases, sarcoma in eight, gynaecological in four and other sites in 15. The correlation between the two parameters was tested by logistic regression and multivariate analysis. Positron emission tomography scan was positive in 17 patients (sensitivity 89%). No correlation was observed between standard uptake value and microvessel intratumoural density in this series of lung metastasis. Positron emission tomography negative and positive nodules presented comparable value of microvessel intratumoural density (12.9 vs 11.3). Standard uptake value was significantly correlated with nodules size and was higher in colon cancer metastasis than in sarcoma ones. Microvessel intratumoural density was independent from nodule size but significantly higher in sarcoma than in colon cancer metastasis. The lack of correlation was confirmed by multivariate analysis after adjustment for tumour type and nodules size. The present study demonstrated that positron emission tomography scan is positive in a high proportion of patients regardless of microvessel density. Glucose uptake and angiogenesis appear to be independent biological features in lung metastasis. This observation may have implications for future antiangiogenic therapies.
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PMID:Fluoro-deoxi-glucose uptake and angiogenesis are independent biological features in lung metastases. 1198 69

Peroxisome Proliferator Activated Receptor-gamma (PPAR-gamma) is a ligand-activated transcription factor belonging to the steroid receptor superfamily. It is a key regulator of adipogenic differentiation and glucose homeostasis, the ligands of which have also been demonstrated to induce differentiation in human breast, lung and colon cancer cell lines. In the present study, PPAR-gamma expression in cases of non-small cell lung carcinoma (NSCLC) was examined immunohistochemically and was correlated with tumor histological type and grade. Primary tumor samples from 147 patients with NSCLC were immunostained using a monoclonal antibody against PPAR-gamma. Positive PPAR-gamma immunostaining was prominent in 61 out of 147 cases (42%) and negative in the rest. PPAR-gamma positivity was prominent in 37 out of 79 cases (47%) of squamous cell lung carcinoma and in 24 out of 68 ones (35%) of lung adenocarcinoma. PPAR-gamma positivity was most frequently observed in squamous cell tumors (P=0.021) and in tumors of high histological grade of both histological types (P=0.041). Well-differentiated adenocarcinoma cases presented increased frequency for PPAR-gamma positivity compared with moderately and poorly differentiated ones (P=0.001). The intensity and pattern of PPAR-gamma staining in tumor cells were not correlated with histopathological parameters in PPAR-gamma positive cases of NSCLC examined. Our findings support evidence for participation of this protein in the biological mechanisms underlying the carcinogenic evolution in the lung, suggesting also the importance of specific PPAR-gamma ligands as future therapeutic approach in lung cancer.
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PMID:Expression of peroxisome proliferator activated receptor-gamma in non-small cell lung carcinoma: correlation with histological type and grade. 1200 33

Positron emission tomography (PET) with [18F]-fluorodeoxyglucose (FDG) is a tool for the imaging and evaluation of glucose metabolism. This technique has recently become available in more than thirty hospitals and has been approved under Japan's national health insurance program. FDG uptake correlates with glucose utilization in tissue and is widely used for evaluating malignant tumors as well as brain function and myocardial viability. FDG-PET is useful for the diagnosis of lung cancer, colon cancer, esophageal cancer, malignant lymphoma, malignant melanoma, head and neck cancer, myocardial viability, and epileptic focus. A brief summary of the application and utility of FDG-PET for esophageal carcinoma is described in this article. Because of its limited spatial resolution, FDG-PET is not able to evaluate the invasiveness of primary tumors and small lesions. However, the uptake of FDG correlates with the aggressiveness of the tumor and the prognosis of patients with esophageal carcinoma. The sensitivity, specificity, and accuracy of lymph node staging is higher than that with CT. FDG-PET has the advantage of being able to detect distant metastases on a single occasion. Evaluation of the response to therapy and of recurrence is also possible by means of FDG-PET. There is some normal uptake and physiological distribution of FDG in many organs. Physiological status has an effect on the uptake of FDG in normal organs, and, consequently, on lesion uptake. Understanding of these characteristics makes this procedure a useful diagnostic modality for the management of patients with esophageal carcinoma.
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PMID:[Current status of nuclear medicine. Clinical application of FDG-PET for cancer diagnosis. Esophageal cancer]. 1207 32

Previously we have demonstrated an impairment in the activity of alpha-L-fucosidase in colon tumours. In order to establish an in vitro model to study this enzyme in colon cancer, we have determined the activity and properties of the enzyme during the differentiation of HT-29 colon cancer cells. Cultures were committed to differentiate into enterocyte-like cells by placing them in a culture medium without glucose for 18-21 days. The state of differentiation was evaluated by assaying the activity of enterocytic marker enzymes, and the acquisition of enterocyte morphology was assessed by electron microscopy. The alpha-L-fucosidase activity was determined using a fluorometric method. Intracellular levels of alpha-L-fucosidase activity are lower in non-differentiated cells (3.0 +/- 1.01 U/mg) than in differentiated ones (9.2 +/- 4.09 U/mg) (P < 0.001). This variation is not due to a greater secretion of the enzyme to the culture medium, and properties such as pH optimum or the affinity towards substrate are not dependent on differentiation. The enzyme however, is more stable at acidic pH and at high temperatures, and V(max) is higher in differentiated cells. Moreover, in undifferentiated cells the enzyme is mainly in a monomeric form whereas multimeric forms of the enzyme appear only upon differentiation. Most of these changes are very similar to those previously observed between normal colon tissue and colon tumours. Thus, we suggest that differentiation of HT-29 colon cancer cells could be used as a model to study the alterations of the enzyme alpha-L-fucosidase during the progression of the tumoural process.
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PMID:Activity and properties of alpha-L-fucosidase are dependent on the state of enterocytic differentiation of HT-29 colon cancer cells. 1212 80

Dietary fiber consists of the structural and storage polysaccharides and lignin in plants that are not digested in the human stomach and small intestine. A wealth of information supports the American Dietetic Association position that the public should consume adequate amounts of dietary fiber from a variety of plant foods. Recommended intakes, 20-35 g/day for healthy adults and age plus 5 g/day for children, are not being met, because intakes of good sources of dietary fiber, fruits, vegetables, whole and high-fiber grain products, and legumes are low. Consumption of dietary fibers that are viscous lowers blood cholesterol levels and helps to normalize blood glucose and insulin levels, making these kinds of fibers part of the dietary plans to treat cardiovascular disease and type 2 diabetes. Fibers that are incompletely or slowly fermented by microflora in the large intestine promote normal laxation and are integral components of diet plans to treat constipation and prevent the development of diverticulosis and diverticulitis. A diet adequate in fiber-containing foods is also usually rich in micronutrients and nonnutritive ingredients that have additional health benefits. It is unclear why several recently published clinical trials with dietary fiber intervention failed to show a reduction in colon polyps. Nonetheless, a fiber-rich diet is associated with a lower risk of colon cancer. A fiber-rich meal is processed more slowly, which promotes earlier satiety, and is frequently less calorically dense and lower in fat and added sugars. All of these characteristics are features of a dietary pattern to treat and prevent obesity. Appropriate kinds and amounts of dietary fiber for the critically ill and the very old have not been clearly delineated; both may need nonfood sources of fiber. Many factors confound observations of gastrointestinal function in the critically ill, and the kinds of fiber that would promote normal small and large intestinal function are usually not in a form suitable for the critically ill. Maintenance of body weight in the inactive older adult is accomplished in part by decreasing food intake. Even with a fiber-rich diet, a supplement may be needed to bring fiber intakes into a range adequate to prevent constipation. By increasing variety in the daily food pattern, the dietetics professional can help most healthy children and adults achieve adequate dietary fiber intakes.
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PMID:Position of the American Dietetic Association: health implications of dietary fiber. 1214 67

Our data suggest that lymph-node size is not a reliable indicator for lymph-node metastasis in gastric, esophageal, and colon cancer. Despite a significant difference in diameter of metastatic and non-metastatic nodes, the accurate evaluation of lymph-node metastasis in gastro-intestinal carcinoma cannot be determined by nodal size, because the majority of counted lymph nodes is ?5 mm and the frequency of small lymph-node metastases is high. Therefore imaging techniques using the size as criterion of nodal infiltration can not exactly assess the nodal status of patients with gastro-intestinal carcinomas. For rational lymphadenectomy, the value of sentinel node biopsy in gastro-intestinal cancer is now discussed. At the moment it is too early to apply sentinel node biopsy in order to reduce the extent of lymphadenectomy in these carcinomas [11]. Recent interest has focused on PET scanning in the detection of lymph-node metastases. PET represents a potentially ideal imaging modality for malignancy. It allows a quick and simultaneous assessment of both local and distant sites and, as a result of avid uptake of the glucose moiety, may potentially identify small tumor loads. There are only limited experience in detecting lymph-node metastases in gastro-intestinal carcinoma and the results of the published reports are controversially discussed [12, 13]. Our data demonstrate a high frequency of small lymph-node metastases in gastro-intestinal carcinoma and suggest that a careful histological search for small lymph-node metastases should be undertaken to avoid false-negative lymph-node staging. These results emphasize that a reliable pathological staging of gastro-intestinal cancer must be based on a standardized systematic lymphadenectomy because lymph-node sampling based on lymph-node size is not sufficient.
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PMID:Preoperative lymph-node staging in gastrointestinal cancer--correlation between size and tumor stage. 1223 85


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