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)

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause damage in the upper gastrointestinal (GI) tract by impairing the ability of the mucosa to resist and respond to injury. Many of these effects of NSAIDs can be attributed to their ability to suppress mucosal prostaglandin synthesis. Selective inhibitors of cyclooxygenase (COX)-2 are less likely to disrupt mucosal defence and do not interfere with platelet aggregation. Thus, their use is associated with a reduced incidence of serious GI adverse events; however, a significant risk of such events still persists. At least in animal models, selective COX-2 inhibitors interfere with ulcer healing to the same extent as conventional NSAIDs. In contrast, COX-inhibiting nitric oxide donors (CINODs) produce anti-inflammatory and analgesic effects comparable or superior to those of NSAIDs, but with greatly reduced GI toxicity. Unlike NSAIDs and selective COX-2 inhibitors, CINODs do not interfere with ulcer healing. Moreover, because CINODs suppress the activity of both COX-1 and COX-2, they do not share with selective COX-2 inhibitors the lack of cardioprotection afforded by significant suppression of platelet aggregation. Because of their safety profile, CINODs may be particularly useful for long term prevention applications, such as for colon cancer, cardiovascular disease and Alzheimer's disease.
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PMID:Mechanisms of nonsteroidal anti-inflammatory drug-induced gastrointestinal injury and repair: a window of opportunity for cyclooxygenase-inhibiting nitric oxide donors. 1505 99

Controversy exists as to the role of female reproductive hormones in asthma and COPD and, specifically, the effect of hormone replacement therapy (HRT) on these disorders. The differential incidence of asthma over the menstrual life cycle suggests an effect of female reproductive hormones on asthma; less data are available for COPD. Estrogen and progesterone have protean effects at the cellular level, consistent with potentially harmful and beneficial effects in lung disease. Large epidemiologic studies show an increased risk of development of asthma with the use of HRT but no consistent effects on COPD. Clinical and epidemiologic studies of exacerbations are limited, but suggest either a harmful effect or no effect of HRT on exacerbations of asthma and COPD. HRT appears to increase the risk of development of asthma but is not associated with the loss of lung function characteristic of COPD. Because the development of asthma is rare in postmenopausal women, the absolute increase in risk among women without asthma is modest. Physicians may wish to avoid HRT therapy in patients with difficult to control asthma and COPD. Clinical decisions to start or continue HRT among women without asthma or COPD should be based on the effects of HRT on more common diseases such as cardiovascular disease, breast cancer and osteoporosis, non-vertebral fractures and colon cancer.
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PMID:Hormone replacement therapy and obstructive airway diseases. 1517 88

Developing policy and strategic initiatives to increase population levels of physical activity (PA) requires constant referral to the epidemiological evidence base. This paper updates the evidence that PA confers a positive benefit on health, using research studies in the peer-reviewed scientific literature published between 2000-2003. Areas covered include updates in all-cause mortality and in cardiovascular disease prevention, diabetes, stroke, mental health, falls and injuries, and in obesity prevention. Recent evidence on PA and all-cause mortality replicates previous findings, and is consistent with current Australian moderate PA recommendations. Recent papers have reinforced our understanding of the cardiovascular protective effects of moderate PA, with new evidence that walking reduces the risk of CVD and, in two studies, at least as much as vigorous activity. The evidence base for protective effects of activity for women, older adults and for special populations has strengthened. Cancer prevention studies have proliferated during this period but the best evidence remains for colon cancer, with better evidence accumulating for breast cancer prevention, and uncertain or mixed evidence for the primary prevention of other cancers. Important new controlled-trial evidence has accumulated in the area of type 2 diabetes: moderate PA combined with weight loss, and a balanced diet can confer a 50-60% reduction in risk of developing diabetes among those already at high risk. Limited new evidence has accumulated for the role of PA in promoting mental health and preventing falls.
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PMID:Updating the evidence that physical activity is good for health: an epidemiological review 2000-2003. 1521 97

Cyclooxygenase-2 (COX-2)-catalysed synthesis of prostaglandin E2 plays a key role in inflammation and its associated diseases, such as cancer and cardiovascular disease. There are numerous reports demonstrating that flavonoids inhibit COX-2 activity. However, transcriptional regulation of COX-2 can also be important. Nobiletin, amentoflavone, quercetin, quercetin penta-acetate, flavone, resveratrol, apigenin, chrysin, kaempferol, galangin, and genistein have been reported to modulate COX-2 transcription in a wide variety of systems. Here, we briefly review the literature on regulation of COX-2 transcription by flavonoids, and report some new preliminary data on Vitamin E and quercetin conjugates. Quercetin, quercetin 3-glucuronide, quercetin 3'-sulfate and 3'methylquercetin 3-glucuronide reduced COX-2 mRNA expression in both unstimulated and interleukin-1beta stimulated colon cancer (Caco2) cells. Quercetin and quercetin 3'-sulfate, unlike quercetin 3-glucuronide and 3'methylquercetin 3-glucuronide, also inhibited COX-2 activity. In contrast, tocopherols (alpha-tocopherol, alpha-tocopherol acetate, and gamma-tocopherol at 10microM) did not affect COX-2 mRNA expression in unstimulated Caco2 cells. However, the tocopherols inhibited COX-2 activity showing that the tocopherols act post-transcriptionally on activity, whereas quercetin and some quercetin conjugates affect both the transcription and activity of COX-2. Flavonoid modulation of COX-2 transcription may therefore be an important mechanism in anti-carcinogenesis.
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PMID:Effect of flavonoids and vitamin E on cyclooxygenase-2 (COX-2) transcription. 1522 97

A nutrition rich in fibre has a preventive effect against constipation, colon diverticulosis, carcinoma of the large bowel and stomach, type 2-diabetes, metabolic syndrome and cardiovascular disease. In case of constipation, diverticulosis and diabetes this effect solely depends on dietary fibre. Regarding carcinomas and cardiovascular diseases, so far unknown factors integrated in or associated with fibre-rich food may also contribute to the preventive effect. Therapy with dietary fibre is indicated for constipation, colon diverticulosis, diarrhea, diabetes, and hypercholesterinemia. The individual dietary fibres differ substance-specifically. Food-integrated dietary fibre such as whole-grain bread, vegetables and fruit have their place in prevention. Dietary fibre preparations such as wheat bran, flax seed or sugar-beet fibre are useful in the treatment of constipation, colon diverticulosis and adiposity. Oat bran is preferentially used in hypercholesterinemia. Purified dietary fibres such as cellulose, guar, psyllium, and beta-glucan have an anti-diabetic, all viscous fibres an anti-lipaemic effect. The therapeutic dosages of dietary fibre preparations are 20-40 g/day and of purified fibres substances 10-20 g/day respectively.
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PMID:[Dietary fibre: more than a matter of dietetics. II. Preventative and therapeutic uses]. 1547 Nov 77

The Women's Health Initiative (WHI) hormone replacement therapy (HRT) estrogen plus progestin (E+P) and estrogen-only arms are part of a large NIH-sponsored randomized controlled trial (RCT). Both arms were terminated prematurely after 5 and 8 yr, respectively. The E+P arm showed non-statistically significant increased incidences of cardiovascular events and breast cancer, whereas the E-only arm did not. Both arms showed an increased rate of thromboembolic events and stroke. Both arms showed protection against fractures and with protection against colon cancer only in the E+P arm. These results have been widely generalized as indicating a negative risk/benefit ratio for HRT in menopausal women. The WHI results are at odds with results of large epidemiological studies that showed protection against cardiovascular disease. Although the latter data are, in part, confounded by a "healthy user bias," much of the inconsistency may be explained by the fact that women in the latter studies initiated HRT at the menopausal transition, whereas the WHI trial was conducted in older women (mean age 63.3), who were, on average, approx 12 yr postmenopausal. In addition, older trials included women on either unopposed estrogen therapy (ERT) or cyclic HRT regimens. Whatever other forces may have been at work, observational and experimental evidence supports the conclusion that estrogen's atheropreventive effects predominate early, in the absence of vulnerable plaque to be ruptured or thrombotic episodes propagated by narrowed lumens and intravascular turbulence. On the contrary, age-related adverse effects of HRT may prevail once complex atheromas and luminal narrowing/irregularity are established. It is known that prevalence of subclinical "at-risk" atherosclerotic lesions increases in women during the first 5-10 yr after menopause. Furthermore, animal and clinical evidence supports the use of lower doses of estrogen than were employed in the WHI in older/longer postmenopausal women.
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PMID:Is the WHI relevant to HRT started in the perimenopause? 1554 85

Nutritional challenges are particularly relevant to women. Almost 62% of women are overweight; of these women, 33% are obese. The incidence of obesity is even greater in non-Hispanic Black and Mexican American women. Women who are overweight or obese experience a greater number of adverse health outcomes, including an increased incidence of cardiovascular disease and breast and colon cancer. Dietary patterns influence health outcomes, with a heart-healthy pattern having the most positive health outcomes. Health care providers should encourage women to consume a diet high in fruits and vegetables and low in total and saturated fats.
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PMID:Obesity and nutrition in women throughout adulthood. 1556 71

Physical activity is crucial for maintaining normal structure and function of metabolic processes and body organs, such as the heart and muscles. Lack of regular activity leads to the deterioration of these organs, thereby increasing levels of morbidity and mortality. Physical activity is associated with lower incidence of total mortality and mortality from heart diseases. It also inhibits high blood pressure, diabetes mellitus, colon cancer and probably breast cancer, osteoporosis, mental depression, and improves quality of life. While the favorable outcomes are usually related to activity level in a dose-response pattern, the greatest benefit is observed in the transition from sedentary to moderately active lifestyle. Despite possible direct and indirect adverse effects of physical activity, the benefits markedly outweigh the risk. In order to benefit from physical activity, people should perform activities that involve large muscle mass, at moderate intensity, during most of the week, or at least 3 days/week, for about 30 minutes a day. It is desirable to add strength and flexibility exercises. The need for medical screening prior to initiation of activity is questionable, and there are no solid recommendations. In the opinion of the authors, at all ages people should be aware of whether they possess one or more risk factors for cardiovascular disease. Young healthy people free of risk factors may start activity, gradually, without special preparations or screening. However, men and women above the age of 45 or 50 years, respectively, or younger, if a risk factor is present, should consult their family physician or a specialist in order to perform relevant screening and obtain instructions on the desired nature of recommended physical activity, its length and intensity.
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PMID:[By the sweat of your brow shall you eat bread: a blessing or a curse?]. 1571 22

Overweight and obesity increase the risk of developing several cancers. Once cancer develops, individuals may be at increased risk of recurrence and poorer survival if they are overweight or obese. A statistically significant association between overweight or obesity and breast cancer recurrence or survival has been observed in the majority of population-based case series; however, adiposity has been shown to have less of an effect on prognosis in the clinical trial setting. Weight gain after breast cancer diagnosis may also be associated with decreased prognosis. New evidence suggests that overweight/obesity vs normal weight may increase the risk of poor prognosis among resected colon cancer patients and the risk of chemical recurrence inprostate cancer patients. Furthermore, obese cancer patients are at increased risk for developing problems following surgery, including wound complication, lymphedema, second cancers, and the chronic diseases affecting obese individuals without cancer such as cardiovascular disease and diabetes. Mechanisms proposed to explain the association between obesity and reduced prognosis include adipose tissue-induced increased concentrations of estrogens and testosterone, insulin, bioavailable insulin-like growth factors, leptin, and cytokines. Additional proposed mechanisms include reduced immune functioning, chemotherapy dosing, and differences in diet and physical activity in obese and nonobese patients. There have been no randomized clinical trials testing the effect of weight loss on recurrence or survival in overweight or obese cancer patients, however. In the absence of clinical trial data, normal weight, overweight, and obese patients should be advised to avoid weight gain through the cancer treatment process. In addition, weight loss is probably safe, and perhaps helpful, for overweight and obese cancer survivors who are otherwise healthy.
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PMID:Obesity and cancer: the risks, science, and potential management strategies. 1605 36

The introduction of celecoxib (Celebrex, Figure 1; GD Searle and Co) as the first cyclooxygenase (COX)2 selective inhibitor in the US and the expected introduction of rofecoxib (Vioxx; Merck and Co Inc) as the first COX2 inhibitor with an acute pain indication, has prompted interest in this class of drugs as a possible therapeutic improvement on dual COX1/COX2 inhibitor NSAIDs, currently on the market. Recognition that the COX-2 enzyme may have a broader role than pain and inflammation has led to studies investigating the efficacy of COX-2 inhibitors for Alzheimer's disease (AD), stroke, cardiovascular disease and colon cancer. Speakers at the second annual conference sponsored by IBC, addressed issues ranging from the basic concepts of COX2 specificity versus selectivity, pathways and regulatory factors related to COX2 expression, the principles underlying the possible broad implications of the COX2 mechanisms, as well as summaries of recently completed clinical trials supporting the clinical efficacy and safety of COX2 inhibitors in humans. The timeliness of this meeting is emphasized by the recent approval of rofecoxib by the FDA Arthritis Advisory panel and the initial reports in the media of toxicity attributed to celecoxib. Preclinical and limited clinical data presented suggest possible therapeutic roles for selective COX2 inhibitors in neurodegeneration due to both AD and stroke, the prevention and treatment of colon cancer, prevention of premature labor, as well as pain and inflammation.
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PMID:COX-2 inhibitors--IBC conference. 12-13 April 1999, Coronado, CA, USA. 1612 36


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