Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:036187 (gut)
 73,132 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

According to the hypothesis being tested by this laboratory, bacteria (in particular, certain clostridia) metabolize the bile acids to give unsaturated products that are important in the causation of colorectal cancer. In this paper, various dietary regimens are discussed in terms of their effect on the fecal steroid concentration and on the gut bacterial flora. The diets considered include high- and low-fiber, high- and low-meat, and high- and low-fat diets.
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PMID:Metabolic epidemiology of dietary factors in large bowel cancer. 110 51

Gut-associated lymphoid cells are modulated by several gut hormones. We postulated that lymphokine-associated-killer (LAK) cell cytotoxicity of lymphocytes isolated from the gut mucosa may be increased by substance P (SP). Intestinal lamina propria mononuclear cells (LPMC) and colonic cancer cells were isolated from operative specimens by successive mechanical and enzymatic dissociation methods. Effector LAK cells were induced by culturing LPMC with recombinant interleukin-2 at a concentration of 250 U/ml. Substance P (10(-5) M) was added to the culture medium. Targets consisted of fresh colon cancer cells, HT-29 (cultured human colon cancer cell line), and control cell lines. After 4 days of incubation, cytotoxicity was measured using a 4-h 51Cr release assay. LAK cells alone showed moderate cytotoxicity against HT-29 and none against fresh colon cancer cells. LAK cells generated in the presence of substance P showed moderate cytotoxicity against HT-29 and strong cytotoxicity against fresh colorectal cancer cells. The percentage of cytotoxicity +/- SEM at various effector to target ratios was [(*) denotes P < 0.05 compared with above]: [table: see text] We conclude that substance P significantly increases LAK cell cytotoxicity against fresh colon cancer cells, but not against cultured cells.
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PMID:Substance P increases in vitro lymphokine-activated-killer (LAK) cell cytotoxicity against fresh colorectal cancer cells. 127 74

Increased concentrations of fecal bile acids have been suggested to be associated with increased risk of colorectal cancer. Fecal bile acid profiles were determined in 12 healthy Finnish women who included in their normal diets for 2-week periods in turn three different types of bread, 200-300 g/day. The breads contained either low-fiber wheat, whole-meal wheat, or whole-grain rye. During consumption of rye bread, the total mean concentration of fecal free bile acids was 4.77 +/- 0.90 mumol/g of dry feces (mean +/- SEM), which was much lower than with the normal omnivorous diet (8.05 +/- 1.56 mumol/g) or during administration of the low-fiber wheat bread (8.83 +/- 1.56 mumol/g) or the whole-meal wheat bread (7.88 +/- 1.34 mumol/g) (P less than 0.05). This decrease was mainly caused by increased proportions of saponifiable bile acids (P less than 0.01). During intake of the whole-grain rye bread, 46% +/- 3% of the fecal bile acids were in their saponifiable forms; this percentage was 30% +/- 3% during the control period, 30% +/- 4% during the low-fiber wheat bread period, and 27% +/- 4% during the whole-meal wheat bread period. It is concluded that the type of bread significantly effects concentrations of cocarcinogenic and comutagenic free lithocholic and deoxycholic acids by changing modes of conjugation in the gut.
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PMID:Fecal bile acid metabolic pattern after administration of different types of bread. 132 33

To detect and measure occult gastrointestinal bleeding, we have measured haemoglobin concentrations (by HemoQuant) in the clear fluid obtained after whole-gut lavage. In subjects with healthy gastrointestinal tracts, lavage-fluid haemoglobin concentrations were 0.5-5.1 mg/L, equivalent to daily blood loss of 0.1-1.1 mL. High concentrations were found for patients with colorectal cancer, severe diverticular disease, and rectal varices, in seven of sixteen patients with active inflammatory bowel disease, and in four patients with iron-deficiency anaemia thought to be due to gastrointestinal bleeding. In these four patients, estimated blood loss ranged from 2.6-24.5 mL per day. This method could have various research and clinical applications.
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PMID:Haemoglobin in gut lavage fluid as a measure of gastrointestinal blood loss. 136 92

It is well known that chronic inflammation of the colon and rectum is associated with an increased risk of colorectal cancer, but the mechanisms by which inflammation promotes neoplasia remain undefined. The authors propose that inflammatory neutrophils may produce carcinogenic nitrosamines via the L-arginine-dependent formation of nitrogen oxides such as nitric oxide. Therefore, the objectives of the study were to characterize the L-arginine-dependent formation of nitrogen oxides by inflammatory (elicited) neutrophils using conditions that more closely mimic the extravascular (i.e., interstitial) compartment of the gut and to characterize the neutrophil-dependent N-nitrosation of a model amine to yield its nitrosamine derivative. In the absence of any metabolic activation, adherent, inflammatory neutrophils (2 x 10(6) cells) produced 12.8 +/- 1.4 mumol/L of nitrite during a 4-hour incubation period. Omission of L-arginine and/or inhibition of nitric oxide synthase by the addition of 1 mmol/L NG-nitro-L-arginine methyl ester (L-NAME) resulted in 35%-78% inhibition of nitrite production, suggesting that nitrite was derived from nitric oxide. By comparison, neither circulating rat neutrophils nor elicited rat macrophages produced significant amounts of nitrite under the same conditions. Furthermore, elicited neutrophils (2 x 10(6) cells) were capable of N-nitrosating 2,3-diaminonaphthalene to yield its nitrosamine derivative 1-naphtho-2,3-triazole (282 +/- 12 nmol/L) in a time- and cell-dependent pattern similar to that of nitrite production. Addition of a variety of antioxidants (e.g., ascorbic acid, reduced glutathione, alpha-tocopherol analog), 5-aminosalicylic acid, or L-NAME resulted in 80%-85% inhibition of neutrophil-mediated nitrosamine formation. Taken together, these data suggest that inflammatory neutrophils may represent an important metabolic source of endogenous carcinogens during times of active intestinal inflammation.
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PMID:Neutrophil-mediated nitrosamine formation: role of nitric oxide in rats. 139 83

Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and interleukin-2 (IL2) can induce regression of tumor metastases in animal models and in human metastatic malignant melanoma. We investigated the potential of colorectal cancer TIL as a source of killer cells and the effect of tumor necrosis factor alpha (TNF alpha) in combination with IL2 on their cytotoxic activity. Tumor-infiltrating lymphocytes were isolated from surgical specimens using a mechanical and enzymatic dissociation process. Autologous lamina propria mononuclear cells (LPMC) were used as control. Tumor-infiltrating lymphocytes and LPMC were cultured in the presence of IL2 with/without TNF alpha (1000 U/ml each) for 5 to 8 weeks. Cytotoxicity (% lysis) was tested against Daudi target cells in a 4-hr 51Cr-release assay. The combination of IL2 and TNF alpha resulted in a significantly greater-fold expansion of TIL than IL2 alone (P less than 0.01). Lamina propria mononuclear cells expanded less than TIL, and TNF alpha had an inhibitory effect on their growth (P less than 0.05). Tumor-infiltrating lymphocytes and LPMC showed comparable cytotoxicity when cultured with IL2 alone. However, the addition of TNF alpha augmented the killer activity of TIL while inhibiting that of LPMC (P = 0.035). These results indicate that TNF alpha selectively increases the IL2-induced growth and cytotoxic function of colorectal cancer TIL, but not those of gut mucosal lymphoid cells, suggesting that TIL and LMPC differ in their response to TNF alpha. Therefore, this combination of cytokines may hold more promise than single agents for the immunotherapy of colorectal cancers with TIL.
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PMID:Resident research award: tumor necrosis factor alpha selectively enhances growth and cytotoxic activity of tumor infiltrating lymphocytes from human colorectal cancer. 154 66

Three cases of primary signet-ring cell carcinoma of the rectum are described. They accounted for 0.2% of the 1531 cases of colorectal adenocarcinoma in the 12 yr period from 1972-1983 in the University Department of Pathology at Queen Mary Hospital. The patients were young, aged 18, 24 and 27 yr respectively, in striking contrast to the mean age of 62 in patients with the usual types of colorectal cancer. They were also younger than most patients with this tumour in the literature. They presented with alteration of bowel habit, blood and mucus in stool, and weight loss. Pathological features included constrictive narrowing of the gut lumen by intestinal wall thickened by a desmoplastic reaction to diffusely infiltrating signet-ring carcinoma cells, widespread lymph node and peritoneal metastases, and absent hepatic metastasis. Microscopically, the mucosa was largely intact, but had multifocal tumour involvement. This peculiar feature was responsible for three consecutive negative biopsies in one case. Care in distinguishing it from mucinous adenocarcinoma is emphasized. All three patients presented with Dukes' C lesions. The prognosis is poor.
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PMID:Primary colorectal signet-ring cell carcinoma in young patients: report of 3 cases. 298 77

Technological advances have reduced and refined man's plant food intake and consequently brought about an unprecedented decline in his consumption of dietary fibre (DF). The emergence of certain diseases selectively in regions which have been affected the most by this dietary change has led to an enhanced awareness of the functions of DF. DF is a heterogeneous group of substances which resist digestion by the endogenous enzymes of the human gut, although they are fermented to a substantial extent by the bacterial flora of the large intestine. Chemically, DF essentially consists of nonstarch polysaccharides and lignin, and its major constituents are cellulose, hemicelluose, lignin and pectin. The physiological effects of DF are attributable largely to its physicochemical properties. DF primarily affects gastrointestinal (GI) function; its effects are observable at all stages from ingestion through defaecation. It restricts caloric intake, shows gastric and small intestinal transit, and affects the activity of digestive enzymes and release of GI hormones. Its overall impact is to reduce apparent digestibility of nutrients marginally but consistently. In the large intestine, DF accelerates transit, supports bacterial growth and serves to hold water. As a result, the faecal weight and water content increase, and the transit time generally becomes shorter. Secondary to its GI effects, DF attenuates postprandial glycaemia and has long term effects on glucose tolerance and lipoprotein metabolism. These effects have important implications in the aetiopathogenesis of constipation and its sequelae including diverticulosis, cholesterol gallstones, colorectal cancer, obesity, diabetes mellitus and atherosclerosis. DF has traditionally been used therapeutically for constipation; now its use in diabetes is also well established. Our appreciation of the role of DF in human nutrition has undergone a major change in the last two decades. From a redundant constituent of plant foods, it has now moved to the position of an essential nutrient, the deficiency of which seems to have serious consequences.
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PMID:Dietary fibre: consensus and controversy. 301 Mar 80

The incidence of colorectal cancer in the western hemisphere is though to be the result, in part, of environmental agents, and many studies strongly implicate diet as a determining factor. It is conceivable that the ingestion of genotoxic chemicals present in food or the endogenous formation of such substances in the gut may initiate colorectal cancer in humans. In the present study, 32P-postlabelling has been used to examine DNA from normal-appearing colonic mucosa obtained from (i) patients undergoing surgery for colorectal cancer and (ii) adult and fetal controls for the presence of aromatic DNA adducts.
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PMID:An aromatic DNA adduct in colonic mucosa from patients with colorectal cancer. 319 22

Patients with colorectal cancer respond poorly to in vivo immunotherapy with lymphokine-activated killer (LAK) cells generated from peripheral blood mononuclear cells (PBMC). We postulated that gut-derived immune cells could be a more relevant source of LAK cells directed against colorectal cancer. Intestinal lamina propria mononuclear cells (LPMC) and colonic adenocarcinoma cells were isolated from operative specimens by combination of mechanical and enzymatic dissociation methods. LAK cells were generated by culturing PBMC and LPMC with recombinant interleukin 2 (IL2), with and without OKT3 monoclonal antibody, in short- (4 days) and long-term (21 days) cultures. Other cultured tumor cells, normal intestinal fibroblasts, and hapten-modified autologous LPMC were used as control targets. Cytotoxicity was measured by a 4-hr 51Cr release assay. Short-term cultured LAK cells exhibited a strong to moderate degree of killing against normal intestinal fibroblasts, hapten-modified self cells, and four different tumor cell lines. Instead, fresh colon cancer cells were resistant to cytotoxicity, regardless of their degree of histologic differentiation and the autologous or allogeneic nature of the LAK cells. Long-term culture with IL2 remarkably increased LAK cell activity against all tumor targets, but not against colonic adenocarcinoma cells. The results of this study, showing that freshly isolated colon cancer cells are intrinsically resistant in vitro to highly activated cytotoxic effector cells, may explain the poor clinical results observed in human trials with in vivo administration of IL2 or LAK cells.
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PMID:Lymphokine-activated killer (LAK) cells from human intestinal mucosa: cytotoxic activity against tumor cell lines and modified self but not autologous and allogeneic colon cancer cells. 336 87


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