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)

Over a 7 year period, 85 cancer patients were managed by the nutrition service of St. Joseph's Hospital, Toronto. All these patients were nutritionally depleted, had obstruction to the gastrointestinal tract, or had postoperative complications such as enterocutaneous fistulas, evisceration or intraabdominal sepsis, which left total parenteral nutrition (TPN) as the only means of achieving positive nitrogen balance. A prospective study started in 1970 has found that when cancer was resectable and TPN was started preoperatively and continued postoperatively (24 patients-group 1) until the patient could take a normal diet, no deaths or significant complications occurred. When TPN was first started after life-threatening complications had occurred (53 depleted patients-group 2), the mortality was 17.0%. This mortality was only 4.5% after complications following operations for colon cancer, but was much higher with esophageal, pancreatic and bladder cancer, and especially after complications following surgery where radiotherapy had previously been given to abdomen or pelvis. When TPN was used in inoperable, cachectic patients (8 patients-group 3) to permit them to tolerate radiotherapy or chemotherapy, the mortality was 37.5%. This latter group is small, but TPN is worthwhile in selected patients where significant palliation and improvement in the quality of life can occur.
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PMID:Specialized nutritional support in the cancer patient: is it worthwhile? 41 70

Biologically significant levels of IL-2 activity were produced by isolated lamina propria mononuclear cells (LPMC) from normal intestine (n = 12), cancer-bearing colons (n = 35) and inflammatory bowel disease (IBD) affected tissue (n = 12). The levels of IL-2 produced were similar for all three sources of LPMC (normal 252 +/- 48 U/ml, IBD-affected mucosa 197 +/- 42 U/ml and colon cancer 285 +/- 43 U/ml). These levels were significantly greater than those produced by peripheral blood mononuclear cells (20 +/- 5 U/ml, P less than 0.01) on a per cell basis. In mucosa from cancer-bearing colons the amount of IL-2 produced by LPMC was unaffected by the invasiveness of the colon cancer. LPMC IL-2 production was markedly suppressed by drugs used in IBD therapy. 5-Aminosalicylic acid (5-ASA) reduced activity in a dose-dependent fashion. At a dose equivalent to the faecal therapeutic level of 0.5 mg/ml activity, IL-2 production by LPMC was suppressed to 3.4% of controls. Similarly, exposure of LPMC to cyclosporin A (CyA) and hydrocortisone (HC) at therapeutic levels reduced IL-2 activity to less than 1% of controls. The major producers of IL-2 activity were shown to be CD3+ T lymphocytes and those bearing the activation markers IL-2R and TFR. Suppression of mucosal IL-2 production represents an important therapeutic mechanism of drugs used in the management of IBD including HC, 5-ASA and CyA. These results suggest that mucosal T cells produce appreciable levels of IL-2 activity that may be important in maintaining immune homeostasis in the normal intestine, provide anti-neoplastic cytotoxic activity and contribute to the inflammatory events that characterize the mucosal lesions of IBD.
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PMID:IL-2 production by intestinal lamina propria cells in normal inflamed and cancer-bearing colons. 156

One-stage subtotal colectomy of an acutely obstructed left colon would improve quality of life while shortening the length of hospitalization. Prohibitive mortality rates, however, are ascribed to such an approach. Analyzing the Senior Author's experience we compared the one-stage approach versus the multi-stage resections concerning operative mortality and morbidity rates and the duration of hospitalization. Forty-nine of 291 (17%) large bowel cancers presented acute left-sided obstruction requiring emergency surgery. Colostomy alone was performed in 18 (37%), multi-stage colectomy in 20 (41%, Group A) and one-stage subtotal colectomy in 11 (22%, Group B, all of them after 1979), the years under scrutiny being from 1973 through Sept. 1990. Both groups were comparable in age and sex distribution, TNM staging and ASA classification. Operative mortality and morbidity rates were 10% and 30% in Group A, 9% and 18% in Group B, respectively. The average length of hospitalization was 21.25 days (14-30) in Group A, 9.18 days (7-14) in Group B. Whenever an experienced surgical team is available and in the absence of contra-indications (local factors precluding a swift dissection, hemodynamic instability, gangrenous bowel) a one-stage subtotal colectomy, taking advantage of a better healing ileo-sigmoid or ileo-rectal anastomosis, carries acceptable mortality and morbidity rates while enhancing the quality of life and shortening the length of hospitalization. It should be considered the choice procedure, provided selection requirements and technical demands are met. An evaluation of the Senior Author's team experience (1973-90) in the management of acutely obstructing left colon cancer (49/291 or 17%) provides information on multi-stage resections and one-stage subtotal colectomy (Group A and B) as regards operative mortality (10% in Group A, 9% in Group B) as well as length of hospitalization (21 days in Group A, 9 days in Group B).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Surgical management of acute, malignant obstruction of the left colon with colostomy]. 178 65

Prostaglandins (PG) have been implicated in the pathogenesis of cancer and play an important role in immune regulation. Colon cancer is associated with elevated levels of PGE2, while aspirin, the prototypical inhibitor of PG synthesis, appears to reduce the incidence of colon cancer by 50%. We have observed that in human colon cancer the expression of HLA class I and II antigens is reduced or lost; loss of HLA antigens is suspected to be a mechanism by which the malignant cell escapes the immune surveillance. We investigated the effect of these eicosanoids on the expression of HLA antigens in human colon adenocarcinoma cell lines. PGE2 down-regulated the expression of the class II antigen HLA-DR in SW1116 cells (65% reduction at 2.8 x 10(-8) M). This effect was dose- and time-dependent, reversible, and specific (PGF2 alpha and LTB4 had no effect; the expression of carcinoembryonic antigen and class I genes were not affected). Aspirin induced the expression of HLA-DR in HT29 cells, a cell line not expressing constitutively HLA-DR. The reduction of HLA-DR by PGE2 was accompanied by reduced messenger RNA (mRNA) levels of HLA-DR alpha and reduced transcription of the corresponding gene. In contrast to HLA-DR, none of these three eicosanoids affected the expression of HLA class I genes, as assessed via determination of protein expression by fluorescence flow cytometric analysis and evaluation of the corresponding class I mRNA levels. We conclude that PGE2 specifically down-regulates the expression of HLA-DR, while it does not affect the expression of class I antigens.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostaglandin E2 down-regulates the expression of HLA-DR antigen in human colon adenocarcinoma cell lines. 772 22

Epidemiological studies have suggested that increased intake of calcium (Ca) or aspirin (ASA) is associated with a reduced risk for colon cancer. To delineate a possible mechanism of action, the present study used male F344 rats in an azoxymethane (AOM)-induced colon tumor model to study the single and interactive effects of Ca and ASA on cholic acid-promoted experimental colon carcinogenesis. Following initiation with AOM, a promotion diet containing 0.5% cholic acid was fed for 34 weeks until the adenoma development stage. Cholic acid was used as a surrogate for high-fat diets and to promote carcinogenesis. Diets were supplemented with CaCO3 (2% Ca by weight), 250 p.p.m. ASA, or both. After 34 weeks, the diets were switched during the progression stage and rats were killed at week 51. Several intermediate endpoints were examined during the course of AOM carcinogenesis to determine their reliability as predictors of colon cancer risk. Intermediate endpoints included colon crypt height measurement, colon mucosal ornithine decarboxylase (ODC) and colon mucosal protein kinase C (PKC) activities. The biomarkers were examined at the beginning of the study at 2 weeks, and thereafter at 5, 15, 30 and 40 weeks of dietary treatment. Animals were necropsied at week 51 and tumor incidence and numbers were analyzed for correlation with biomarkers. Survival was highest in the group fed CaCO3 during the promotion stage and tumor burden was lowest in groups fed CaCO3 during this stage. Supplementation during the progression stage was ineffective. The cholic acid promotion model resulted in increased ODC which was inhibited by intervention during the promotion stage with Ca, but not ASA. PKC was also activated by cholic acid feeding, and this effect was modulated by intervention in the promotional stage with Ca or ASA. Colon tumor incidence and burden was increased by cholic acid promotion and decreased by Ca, but not affected by ASA. In summary, Ca is a more effective chemopreventive agent in cholic acid-promoted colon carcinogenesis than ASA, impacting both incidence and tumor number. Colonic ODC, but not PKC may be a suitable predictor of risk and response in chemoprevention trials for colon cancer.
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PMID:Chemopreventive effects of calcium but not aspirin supplementation in cholic acid-promoted colon carcinogenesis: correlation with intermediate endpoints. 772 52

A retrospective analysis was carried out on 56 pts., (37 M, 19 F), mean age 64 yrs., operated for moderate to severe obstruction due to left colon carcinoma. Clinical and pathological features, treatment and results were compared with those of 108 pts. with left colon cancer who underwent elective surgery. Mean duration of obstructive symptoms was 5.3 days and mean delay between admission and operation was 1.15 days. Site and nature of the obstruction were assessed pre-operatively in 80.3% of the pts. Distribution of tumor localization was similar in the two groups. ASA risk was statistically higher in pts. with obstruction. Staging according to the Astler-Coller (mod. 1978) classification, showed a greater incidence of more advanced stages in the obstructing tumors. In the group with obstruction a three stage surgery was carried out in 18 pts. (32.1%), a two stage in 6 (10.7%), a primary resection in 6 (10.7%) and a decompressive colostomy in 26 (46.5%). Radicality and resectability rates were 50% and 53.6% vs 69.4% and 82.4% in elective surgery. Mean post-operative stay was 42 and 21 days respectively in the two groups. Overall post-operative death rate was 19.6% vs 9.2%, and 3.3% vs 7.8% after resective surgery. Post-operative complications accounted for 21.4% vs 21.3%. 5-year survival rate after curative surgery was 47.8% vs 76.8%. On the basis of their results and on Literature reports the Authors suggest a reevaluation of a staged surgical treatment for obstructing left colon cancer based on primary decompression following an E.L. when needed. Consequent resection and intestinal reconstruction should be performed after 2-3 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Surgery of the obstructive complication of carcinoma of the left colon. The clinical problems and the authors' personal experience with 56 surgical cases]. 784 71

Aspirin and other nonsteroidal antiinflammatory drugs inhibit prostaglandin synthesis and tumor growth in many experimental systems, but it is unclear which of these tumor models are relevant to humans. We have reported reduced risk of fatal colon cancer among persons who used aspirin in a large prospective study. This analysis examines other fatal cancers in relation to aspirin among 635,031 adults in that study who provided information in 1982 on the frequency and duration of their aspirin use and did not report cancer. Death rates were measured through 1988. Death rates decreased with more frequent aspirin use for cancers of the esophagus, stomach, colon, and rectum but not generally for other cancers. For each digestive tract cancer, death rates were approximately 40% lower among persons who used aspirin 16 times/month or more for at least 1 year compared to those who used no aspirin. The trend of decreasing risk with more frequent aspirin use was strongest among persons who had used aspirin for 10 years or more; it remained statistically significant, except for esophageal cancer, in multivariate analyses that adjusted for other known risk factors. Biases such as early detection or aspirin avoidance among cases do not appear to explain the results. Our data suggest that regular, prolonged use of aspirin may reduce the risk of fatal cancer of the esophagus, stomach, colon, and rectum. Future epidemiological and basic research should examine all digestive tract cancers in considering the chemopreventive or therapeutic potential of nonsteroidal antiinflammatory drugs.
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PMID:Aspirin use and risk of fatal cancer. 826 25

Aspirin and other NSAIDs reduce the incidence of and mortality from colon cancer, but their mechanism of action remains unknown. We evaluated the effect of aspirin (ASA) and three other structurally unrelated NSAIDs (indomethacin, naproxen, and piroxicam) on cell proliferation, cell cycle phase distribution, and the development of apoptosis in HT-29 colon adenocarcinoma cells in vitro. All of the NSAIDs examined reduced the proliferation and altered the morphology of these cells in a time- and concentration-dependent manner. In addition, they altered the cell cycle phase distribution of these cells. They increased the proportion of cells in the G0/G1 phase and reduced the proportion in the S phase of the cell cycle. ASA and indomethacin also reduced the percentage of cells in the G2/M phase, whereas naproxen and piroxicam did not. Parallel to their effect on cell cycle, ASA and indomethacin also reduced the levels of p34cdc2 and p33cdk2, two cyclin-dependent kinases that are important for cell cycle progression. Finally, all the NSAIDs analyzed, except ASA, induced apoptosis in these cells. There as a rough correlation between the relative potency of these compounds in inducing apoptosis and their effectiveness in retarding cell proliferation. Our findings indicate that NSAIDs can reduce the proliferation of HT-29 colon cancer cells in vitro. In addition, they cause cell cycle quiescence and apoptosis, both of which could account for their anti-proliferative effect. These findings suggest possible mechanisms for the cancer preventive effects of these compounds in humans.
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PMID:Nonsteroidal antiinflammatory drugs inhibit the proliferation of colon adenocarcinoma cells: effects on cell cycle and apoptosis. 854 62

Chemoprevention refers to the use of specific natural or synthetic chemical agents to reverse, suppress, or prevent the progression to invasive cancer. The ideal chemopreventive agent is safe and nontoxic over the long term. It should be easy to take and demonstrated to be effective in randomized trials in humans. Aspirin and NSAIDs meet many of the criteria for an ideal agent. The literature on aspirin and NSAIDs makes it clear that these agents can prevent colorectal cancer and precursor adenomas. That does not mean that we should make general recommendations for their use. First, we do not know the proper dose or duration. More important, these medications are accompanied by adverse effects that can be considerable. Indeed, the Medical Letter, an authoritative, unbiased publication on drugs and therapeutics, concluded that "for primary prevention in low-risk patients, more studies are required to establish whether the beneficial effect of aspirin is great enough to compensate for the possible increased risk of hemorrhagic stroke." These recommendations were directed at the use of these medications for prevention of myocardial infarction, but the same conclusions apply to colorectal cancer: although aspirin may prevent the disease, it may increase the risk of hemorrhagic strokes or cause other adverse effects. We must accurately balance the benefits and risks of these drugs, based on the results of ongoing randomized studies, before recommending aspirin for prevention of colorectal cancer. Is there anything that we can recommend to our patients for prevention of colorectal cancer? Based on observational epidemiologic studies, it is clear that individuals who consume a diet high in vegetables and natural fibers and low in fat have a reduced risk of colon cancer and polyps. Optimal nutrient intakes for the prevention of cancer might be more readily achieved via food fortification or supplementation, but this requires more research. Regular physical exercise and maintenance of normal body weight are also protective. Until the results of definitive studies of chemopreventive agents are available, we can recommend that our patients eat a sensible diet, exercise, and avoid obesity. Such an approach should protect them from cardiovascular disease, an even deadlier condition than colorectal cancer. In the future, we need randomized prevention trials that, for logistic reasons, may need to focus on the occurrence and progression of colorectal adenomas rather than carcinoma itself. Studies that test more than one compound at a time, using factorial designs, will be more efficient. We will need better information about duration and dose, adverse side effects, molecular mechanisms, and cellular sites of NSAID activity. Ultimately, we will need to know more about the biology and molecular biology of colorectal cancer and its precursors. That information will, perhaps, permit us to design agents to interrupt the pathway to cancer and to use intermediate markers more intelligently.
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PMID:Aspirin and other nonsteroidal anti-inflammatory agents in the prevention of colorectal cancer. 879 Nov 32

Several lines of evidence suggest that long-term treatment with non-steroidal anti-inflammatory drugs may reduce the risk of colon cancer and the size and number of colonic polyps in patients with familial adenomatous polyposis. Aspirin has also been shown to inhibit cell proliferation in human tumor cell lines and to induce apoptosis in colonic mucosa of familial polyposis patients. To elucidate the molecular mechanisms of the antiproliferative action of aspirin, we studied the effects of aspirin on cell growth and differentiation of the human colon carcinoma Caco-2 cell line. These cells represent a useful tool for studying the mechanisms involved in the regulation of cell growth and differentiation of intestinal epithelial cells since they spontaneously differentiate into polarized cells, expressing brush border enzymes. We show in this study that aspirin (0.1-10 mM) induces a profound inhibition of cell replication as assessed either by cell counts or thymidine incorporation. Moreover, aspirin concentrations of 5 and 10 mM induce apoptosis, whereas concentrations of 1 and 2 mM do not. The inhibition of growth is associated with a dose-dependent reduction in insulin-like growth factor II mRNA expression and with an increase in sucrase activity (a brush border enzyme) and apolipoprotein A-I mRNA expression, 2 specific markers of the differentiative status of this cell line. Our data thus show that aspirin-dependent inhibition of cell growth is associated with the enterocyte-like differentiation of Caco-2 cells.
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PMID:Effect of aspirin on cell proliferation and differentiation of colon adenocarcinoma Caco-2 cells. 939 70


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