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)

Salicylate and its pro-drug form aspirin are widely used medicinally for their analgesic and anti-inflammatory properties, and more recently for their ability to protect against colon cancer and cardiovascular disease. Despite the wide use of salicylate, the mechanisms underlying its biological activities are largely unknown. Recent reports suggest that salicylate may produce some of its effects by modulating the activities of protein kinases. Since we have previously shown that the farnesyltransferase inhibitor l-744, 832 inhibits cell proliferation and p70(s6k) activity, and salicylate inhibits cell proliferation, we examined whether salicylate affects p70(s6k) activity. We find that salicylate potently inhibits p70(s6k) activation and phosphorylation in a p38 MAPK-independent manner. Interestingly, low salicylate concentrations (</=250 microm) inhibit p70(s6k) activation by phorbol myristate acetate, while higher salicylate concentrations (>/=5 mm) are required to block p70(s6k) activation by epidermal growth factor + insulin-like growth factor-1. These data suggest that salicylate may selectively inhibit p70(s6k) activation in response to specific stimuli. Inhibition of p70(s6k) by salicylate occurs within 5 min, is independent of the phosphatidylinositol 3-kinase pathway, and is associated with dephosphorylation of p70(s6k) on its major rapamycin-sensitive site, Thr(389). A rapamycin-resistant mutant of p70(s6k) is resistant to salicylate-induced Thr(389) dephosphorylation.
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PMID:Salicylate-induced growth arrest is associated with inhibition of p70s6k and down-regulation of c-myc, cyclin D1, cyclin A, and proliferating cell nuclear antigen. 1099 86

Reducing dietary saturated fat by 7% of energy, a realistic target, would reduce serum cholesterol by 10% and mortality from ischemic heart disease by 25-30%. Randomized trials show that this mortality reduction is attained rapidly, usually by the third year after initial reduction of dietary saturated fat intake. Dietary change in adulthood may therefore reverse the adverse health effects of a high-fat diet in childhood. In the absence of such change, however, dietary fat in childhood may increase the risk of cardiovascular disease in adult life because of a longer duration of exposure to a high-fat diet. Assessing the effects of diet on cancer risk is more difficult. The intermediary markers of risk that are analogous to serum cholesterol are less satisfactory and there are negligible trial data. Cohort studies of diet and cancer, although subject to bias, do not favor a direct causal relation between dietary fat and cancer. But a reduction in risk is likely when dietary fat is reduced as part of a general change toward a healthier diet. The trend toward increased energy intake and body size in childhood and relatively low dietary fiber contribute to the decreasing age at menarche, which is associated with an increased risk of breast cancer. Low dietary fiber, low fruit and vegetable consumption, and high red meat consumption are associated with colon cancer and other cancers, and important causal effects of diet on cancer are likely. As with cardiovascular disease, this dietary trend that is commenced in childhood is likely to increase age-specific rates of colon cancer in adult life, but the risk may be reversed with later dietary change.
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PMID:Dietary fat and adult diseases and the implications for childhood nutrition: an epidemiologic approach. 1106 71

Hyperhomocysteinemia, a risk factor for cardiovascular disease, is caused by nutritional and/or genetic disruptions in homocysteine metabolism. The most common genetic cause of hyperhomocysteinemia is the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. This variant, with mild enzymatic deficiency, is associated with an increased risk for neural tube defects and pregnancy complications and with a decreased risk for colon cancer and leukemia. Although many studies have reported that this variant is also a risk factor for vascular disease, this area of investigation is still controversial. Severe MTHFR deficiency results in homocystinuria, an inborn error of metabolism with neurological and vascular complications. To investigate the in vivo pathogenetic mechanisms of MTHFR deficiency, we generated mice with a knockout of MTHFR: Plasma total homocysteine levels in heterozygous and homozygous knockout mice are 1.6- and 10-fold higher than those in wild-type littermates, respectively. Both heterozygous and homozygous knockouts have either significantly decreased S-adenosylmethionine levels or significantly increased S-adenosylhomocysteine levels, or both, with global DNA hypomethylation. The heterozygous knockout mice appear normal, whereas the homozygotes are smaller and show developmental retardation with cerebellar pathology. Abnormal lipid deposition in the proximal portion of the aorta was observed in older heterozygotes and homozygotes, alluding to an atherogenic effect of hyperhomocysteinemia in these mice.
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PMID:Mice deficient in methylenetetrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid deposition. 1118 67

We tested the effects of feeding a diet very high in fiber from fruit and vegetables. The levels fed were those, which had originally inspired the dietary fiber hypothesis related to colon cancer and heart disease prevention and also may have been eaten early in human evolution. Ten healthy volunteers each took 3 metabolic diets of 2 weeks duration. The diets were: high-vegetable, fruit, and nut (very-high-fiber, 55 g/1,000 kcal); starch-based containing cereals and legumes (early agricultural diet); or low-fat (contemporary therapeutic diet). All diets were intended to be weight-maintaining (mean intake, 2,577 kcal/d). Compared with the starch-based and low-fat diets, the high-fiber vegetable diet resulted in the largest reduction in low-density lipoprotein (LDL) cholesterol (33% +/- 4%, P <.001) and the greatest fecal bile acid output (1.13 +/- 0.30 g/d, P =.002), fecal bulk (906 +/- 130 g/d, P <.001), and fecal short-chain fatty acid outputs (78 +/- 13 mmol/d, P <.001). Nevertheless, due to the increase in fecal bulk, the actual concentrations of fecal bile acids were lowest on the vegetable diet (1.2 mg/g wet weight, P =.002). Maximum lipid reductions occurred within 1 week. Urinary mevalonic acid excretion increased (P =.036) on the high-vegetable diet reflecting large fecal steroid losses. We conclude that very high-vegetable fiber intakes reduce risk factors for cardiovascular disease and possibly colon cancer. Vegetable and fruit fibers therefore warrant further detailed investigation.
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PMID:Effect of a very-high-fiber vegetable, fruit, and nut diet on serum lipids and colonic function. 1128 49

Estrogen replacement therapy either with (HRT) or without (ERT) accompanying progesterone is routinely offered to well women at the time of menopause, in order to relieve vasomotor symptoms, (hot flashes), reduce urogenital atrophy and reduce the risks of cardiovascular disease, osteoporosis and perhaps colon cancer and Alzheimer's disease. It is generally felt however, that women with a previous diagnosis of breast cancer are not suitable candidates for such therapy since either estrogen or progesterone may be associated with an increased risk of cancer recurrence. There are however, a variety of approaches to menopausal therapy in such women. A careful history must first be taken in order to identify the symptoms or conditions of concern. Vasomotor symptoms can be reduced by the use of other medications such as the antidepressant venlafaxine (Effexor). Estring, a vaginal estrogen ring can be used to reduce genitourinary symptoms, with little systemic estrogen absorption. Osteoporosis can be prevented or treated with calcium supplements, exercise, improved diet, bisphosphonates and/or selective estrogen receptor modulators (SERMs) while cardiovascular risk can be reduced by diet and exercise, as well as the appropriate use of lipid lowering and antihypertensive medications.
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PMID:The role of hormone replacement therapy in women with a previous diagnosis of breast cancer and a review of possible alternatives. 1133 40

Today, clinicians are challenged to address a woman's contraceptive needs during her reproductive and perimenopausal years and then provide her with a menopausal therapeutic option. This option should offer optimal symptom relief, noncontraceptive health benefits, and a good tolerability profile. The benefits of hormone replacement therapy include control of vasomotor symptoms, reduction of vulvovaginal atrophy, and protection against osteoporosis. Research also points to emerging hormone replacement therapy benefits such as protection against cardiovascular disease, colon cancer, and Alzheimer's disease. One of the primary considerations in the transition from oral contraceptive use to hormone replacement therapy is the tolerability profile of the progestin component of the hormone replacement therapy. Because progestin-related side effects are among the main reasons for discontinuation of hormone replacement therapy, the selection of a formulation that contains the same well-tolerated progestin as in the woman's oral contraceptive can be particularly important to successful use of hormone replacement therapy. Currently in the United States continuous combined hormone replacement therapy is available in 3 formulations and 1 continuous estrogen/intermittent progestin formulation. Although direct comparative trials are lacking, available data suggest that the new, continuous 17beta-estradiol/intermittent norgestimate hormone replacement therapy formulation may offer advantages over regimens that contain older progestins with metabolic disadvantages.
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PMID:Combined oral hormone replacement therapy formulations. 1152 Nov 21

Estrogen used alone (estrogen replacement therapy [ERT]) or with the addition of progesterone (hormone replacement therapy [HRT]) is known to be effective in reducing menopausal symptoms including hot flashes, vaginal dryness and urinary symptoms. It has been traditionally contraindicated, however, in women with a previous diagnosis of breast cancer because of fear that it may increase the risk of recurrence. There are considerable basic scientific data but little methodologically strong observational data and none from randomized studies concerning the use of ERT in women with a prior diagnosis of breast cancer. From our knowledge of the physiology of breast cancer, however, estrogen and/or progestational agents should be used with caution in women with a previous diagnosis of breast cancer. There are currently many alternatives to ERT/HRT in the prevention of menopausal symptoms such as vitamin E, clonidine and selective serotonin reuptake inhibitor antidepressants such as venlafaxine. There are also a variety of other approaches to the prevention of osteoporosis and cardiovascular disease including bisphosphonates, diet, and exercise; and diet, exercise, and statins, respectively. Other suggested beneficial effects of estrogen such as colon cancer prevention can be approached by the use of aspirin or the non-steroidals. Several trials of ERT/HRT used for 2 years versus no therapy in menopausal women with a previous diagnosis of breast cancer are ongoing in Europe and Britain, and should give us stronger data as to the role of HRT in this setting.
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PMID:Hormone replacement in women with a history of breast cancer. 1152 54

Insulin and insulin-like growth factor (IGF) axes are major determinants of proliferation and apoptosis and thus may influence carcinogenesis. In various animal models, modulation of insulin and IGF-1 levels through various means, including direct infusion, energy excess or restriction, genetically induced obesity, dietary quality including fatty acid and sucrose content, inhibition of normal insulin secretion and pharmacologic inhibition of IGF-1, influences colonic carcinogenesis. Human evidence also associates high levels of insulin and IGF-1 with increased risk of colon cancer. Clinical conditions associated with high levels of insulin (noninsulin-dependent diabetes mellitus and hypertriglyceridemia) and IGF-1 (acromegaly) are related to increased risk of colon cancer, and increased circulating concentrations of insulin and IGF-1 are related to a higher risk of colonic neoplasia. Determinants and markers of hyperinsulinemia (physical inactivity, high body mass index, central adiposity) and high IGF-1 levels (tall stature) are also related to higher risk. Many studies indicate that dietary patterns that stimulate insulin resistance or secretion, including high consumption of sucrose, various sources of starch, a high glycemic index and high saturated fatty acid intake, are associated with a higher risk of colon cancer. Although additional environmental and genetic factors affect colon cancer, the incidence of this malignancy was invariably low before the technological advances that rendered sedentary lifestyles and obesity common, and increased availability of highly processed carbohydrates and saturated fatty acids. Efforts to counter these patterns are likely to have the most potential to reduce colon cancer incidence, as well as cardiovascular disease and diabetes mellitus.
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PMID:Insulin, insulin-like growth factors and colon cancer: a review of the evidence. 1216 83

Recent promising trials that use low-dose CT for the early detection of lung cancer have reinvigorated the interest in screening approaches. At the same time the development of fast image acquisition techniques, such as multislice CT, have sparked renewed interest in cardiac imaging within the radiological community. In addition to special cardiac capabilities, multislice CT has several other features such as high acquisition speed and low-dose requirements that may make this modality a universal radiological screening tool. Non-invasive disease detection is the radiologist's domain. In this paper we identify criteria for effective screening and apply these criteria to screening approaches with multislice CT when used for detection of three disease entities: colon cancer; lung cancer; and cardiovascular disease.
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PMID:Multi-slice computed tomography as a screening tool for colon cancer, lung cancer and coronary artery disease. 1170 31

OBJECTIVES: To establish guidelines on the administration of hormone replacement therapy in Hong Kong for a primary audience of Fellows and Members of the Hong Kong College of Obstetricians and Gynaecologists and a secondary audience of all interested medical and paramedical personnel in Hong Kong. PARTICIPANTS: The Quality Assurance Committee established a consensus panel of four College Fellows who had expertise of treating menopausal women by giving hormone replacement therapy. All the panelists were qualified obstetricians and gynaecologists. EVIDENCE: The panelists drew their conclusions from the available scientific literature on hormone replacement therapy from Hong Kong and overseas. CONSENSUS PROCESS: The consensus reached within the panel was presented to the Quality Assurance Committee on 23 June 1998, and subsequently revised and presented three times. The final version was approved by the Quality Assurance Committee on 2 March 1999 and the Council of the Hong Kong College of Obstetrics and Gynaecology on 11 March 1999. CONCLUSIONS: The administration of hormone replacement therapy is effective in reducing the severity and frequency of menopausal hot flushes and sweating. Therapy protects against osteoporosis and reduces the risk of cardiovascular disease. There is some evidence to suggest that treatment also protects against Alzheimer's disease and carcinoma of the colon. The most serious problem attributed to using hormone replacement therapy is the possible increase in the risk of breast cancer development; the exact risk is unknown. Side effects include unwanted bleeding and breast tenderness and sensitivity. The risks and benefits of using hormone replacement therapy should be explained to postmenopausal women so that they can make an informed decision about using this treatment.
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PMID:Guidelines for the administration of hormone replacement therapy. The Hong Kong College of Obstetricians and Gynaecologists. 1182 92


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