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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between vitamin supplement use and colon cancer was assessed in a population-based case-control study among men and women aged 30-62 years. Cases were 251 men and 193 women diagnosed with colon cancer in 1985-1989 in three counties in the Seattle metropolitan area who were identified from the Surveillance, Epidemiology, and End Results cancer registry. Controls were 233 men and 194 women identified by random digit dialing. Supplement use was assessed by questions on frequency, duration, and dose per day (for individual supplements) or type (for multivitamins) during the 10-year period ending 2 years before diagnosis. All results were adjusted for age and sex and were not confounded by other measured behaviors. The average daily intake of supplemental vitamins A, C, E, folic acid, calcium, and multivitamins during the reference period were each associated with reduced risk of colon cancer (all P for trend < 0.03). The strongest associations were for use of vitamin E (odds ratio, 0.43; 95% confidence interval, 0.26-0.71 for > or = 200 IU/day versus none) and multivitamins (odds ratio, 0.49; 95% confidence interval, 0.35-0.69 for daily use versus no use; both P for trend < 0.001). These two associations were also significant using a stricter test of trend limited to supplement users, which reduces the effect of colinearity among these exposures. Because almost all vitamin D supplementation comes from multivitamin pills, the association of vitamin D use with colon cancer could not be distinguished from that of multivitamin use. Clinical trials or cohort studies with long-term assessment would be needed before public health recommendations could be made about supplement use.
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PMID:Relationship between vitamin and calcium supplement use and colon cancer. 933 57

Although vitamin E can block mutagenesis and cell transformation in vitro and can reduce the number of chemically induced colonic adenomas in mice, previous clinical trials have found no protective effect of vitamin E supplements against colorectal adenomas, and epidemiological studies have found only weak protective effects of dietary or plasma alpha-tocopherol against colorectal cancer. We previously examined first diagnosis of colorectal adenomas in a sigmoidoscopy screening population and failed to find a protective effect of dietary vitamin E. Because measurements of dietary intake may not be a good proxy of vitamin E status, we assayed plasma alpha- and gamma-tocopherol concentration for 332 subjects with colorectal adenomas and 363 control subjects from this previous sigmoidoscopy-based study. Increasing alpha-tocopherol and decreasing gamma-tocopherol levels were associated with decreased occurrence of large (> or = 1 cm) but not of small (<1 cm) adenomas; however, after adjustment for potential confounding variables, these trends were not statistically significant. A strong trend (P = 0.02) was observed by using the alpha-tocopherol:gamma-tocopherol ratio, which may be a more sensitive indicator of alpha-tocopherol intake. Subjects in the highest versus lowest quintile of alpha-tocopherol: gamma-tocopherol ratio had an odds ratio of 0.36 (95% confidence interval, 0.14-0.95) for large adenomas. The finding that a high alpha-tocopherol:gamma-tocopherol ratio is associated with decreased occurrence of large, but not of small, colorectal adenomas is consistent with previous findings that alpha-tocopherol may be protective against colon cancer. A high plasma alpha-tocopherol:gamma-tocopherol ratio may be a better predictor of decreased cancer risk than high plasma alpha-tocopherol alone.
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PMID:Plasma tocopherol and prevalence of colorectal adenomas in a multiethnic population. 948 18

The role of vitamin E in the etiology and prevention of colon cancer is not clear. It is possible that various forms of vitamin E may act differently in colon tissue and may be effective chemopreventive agents. Previous reports of vitamin E and colon cancer have focused on alpha-tocopherol and have not considered other dietary forms of vitamin E. Data from a study of 1,993 cases and 2,410 controls were used to evaluate the associations between the four most common forms of dietary vitamin E and supplemental vitamin E and colon cancer. After adjusting for other health and life-style factors, we did not observe a statistically significant association between dietary tocopherols and colon cancer. There were, however, suggestions of an inverse association between total alpha-tocopherol equivalents and colon cancer among women diagnosed with colon cancer before the median age of the control population, 67 years [odds ratio (OR) = 0.66, 95% confidence interval (CI) = 0.36-1.22] and a direct association between gamma-tocopherol and colon cancer among these women (OR = 1.44, 95% CI = 0.92-1.93). Women diagnosed with colon cancer when > or = 67 years of age appeared to have some protection from use of vitamin E supplements (OR = 0.80, 95% CI = 0.56-1.15). These data offer only limited support for a protective effect of vitamin E and colon cancer after adjustment for other health and life-style factors.
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PMID:Vitamin E and colon cancer: is there an association? 963 91

The best preventive care consists of a combination of office-based services: patient education, life style counseling, clinical vigilance through routine check ups, and the administration of timely screening. In a healthcare environment of tightened resources, tighter schedules, and increased patient demand for your time, it is nevertheless possible to offer substantive preventive care for older patients in an efficient and cost effective manner. Interventions for cardiovascular disease include weight loss, a low-fat diet, vitamin E, and folic acid. Screening is recommended for breast, cervical, and colon cancer, but prostate cancer screening is controversial. The value of mammograms in women over age 50 is well-established. Preventive measures for osteoporosis include calcium and vitamin D, estrogen replacement, and weight-bearing exercise.
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PMID:Simple, sensible preventive measures for managed care settings. 979 Nov 97

Colorectal cancer is a major cause of death in the United States, where it accounts for approximately 57,000 deaths per year. Thus, the prevention of this disease would have a significant impact on public health. Chemoprevention is defined as the use of natural or pharmacologic agents to disrupt the process of carcinogenesis. Substances explored as chemopreventive agents in colorectal cancer include: (1) the nonsteroidal anti-inflammatory drugs (NSAIDS), which may inhibit the evolution and formation of adenomas by their inhibition of cyclooxygenase and decrease of prostaglandin synthesis; (2) antioxidants, such as vitamin E or C, which may modulate carcinogenic substances; and (3) folate and calcium, which may interfere with tumor cell growth and replication. Dietary intervention can be accomplished by decreasing fat intake and increasing fiber consumption, both of which have been linked to a lower incidence of colon cancer in multiple epidemiologic studies. This field is continuing to evolve. Hopefully, ongoing research efforts will offer a better understanding of the role of these and other substances in chemoprevention. This article summarizes the available data regarding dietary and pharmacologic approaches to colorectal cancer chemoprevention.
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PMID:Chemoprevention of colorectal cancer: dietary and pharmacologic approaches. 1002 3

More than 40 promising agents and agent combinations are being evaluated clinically as chemopreventive drugs for major cancer targets. A few have been in vanguard, large-scale intervention trials--for example, the studies of tamoxifen and fenretinide in breast, 13-cis-retinoic acid in head and neck, vitamin E and selenium in prostate, and calcium in colon. These and other agents are currently in phase II chemoprevention trials to establish the scope of their chemopreventive efficacy and to develop intermediate biomarkers as surrogate end points for cancer incidence in future studies. In this group are fenretinide, 2-difluoromethylornithine, and oltipraz. Nonsteroidal anti-inflammatories (NSAID) are also in this group because of their colon cancer chemopreventive effects in clinical intervention, epidemiological, and animal studies. New agents are continually considered for development as chemopreventive drugs. Preventive strategies with antiandrogens are evolving for prostate cancer. Anti-inflammatories that selectively inhibit inducible cyclooxygenase (COX)-2 are being investigated in colon as alternatives to the NSAID, which inhibit both COX-1 and COX-2 and derive their toxicity from COX-1 inhibition. Newer retinoids with reduced toxicity, increased efficacy, or both (e.g., 9-cis-retinoic acid) are being investigated. Promising chemopreventive drugs are also being developed from dietary substances (e.g., green and black tea polyphenols, soy isoflavones, curcumin, phenethyl isothiocyanate, sulforaphane, lycopene, indole-3-carbinol, perillyl alcohol). Basic and translational research necessary to progress in chemopreventive agent development includes, for example, (1) molecular and genomic biomarkers that can be used for risk assessment and as surrogate end points in clinical studies, (2) animal carcinogenesis models that mimic human disease (including transgenic and gene knockout mice), and (3) novel agent treatment regimens (e.g., local delivery to cancer targets, agent combinations, and pharmacodynamically guided dosing).
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PMID:Progress in cancer chemoprevention. 1066 77

Chemoprevention is a recently introduced and rapidly growing area of oncology that is identifying agents with a potentially preventive role in cancer. Several clinical trials have recently shown the feasibility of this approach in reducing the risk of major human cancers. In the USA, a large trial that demonstrated a reduction of approximately 50% in the risk of developing breast cancer led to Food and Drug Administration (FDA) approval of tamoxifen as a preventive agent in women at increased risk. Although the results could not be reproduced in two smaller European trials, further investigations into this agent are clearly warranted. Raloxifene, another selective oestrogen receptor modulator which has reduced the risk of breast cancer in a trial in women with osteoporosis, is being compared with tamoxifen in a large primary prevention trial in at-risk women. Retinoids are a group of compounds that have proved especially effective in reducing the occurrence of second primary tumours in subjects with skin, head and neck or liver cancer. Fenretinide, a synthetic retinoic acid derivative, has recently been shown to decrease the occurrence of a second breast malignancy in premenopausal women. Results with non-steroidal anti-inflammatory drugs (NSAIDs) have proved consistently encouraging in epidemiological studies in lowering the incidence of colorectal cancer. Clinical trials with selective cyclo-oxygenase inhibitors potentially devoid of gastrointestinal (GI) toxicity are currently underway in at-risk subjects. Calcium and selenium have also received much attention as chemopreventive agents. Originally investigated against skin cancer, selenium showed efficacy in reducing prostate, lung and colon cancer incidence. Similarly, vitamin E was effective in reducing prostate cancer incidence and mortality in a lung cancer prevention trial in heavy smokers. The challenges of conducting well-designed and unequivocal chemoprevention trials are considerable, but advances in techniques of identification of at-risk subjects and establishing surrogate endpoint biomarkers should contribute greatly to future studies. Current knowledge suggests that a pharmacological approach to preventing cancer, using natural or synthetic agents, could become an important way forward.
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PMID:Recent advances in cancer chemoprevention, with emphasis on breast and colorectal cancer. 1076 41

Calcium and antioxidant vitamins, such as A, C, and E, have been shown to reduce colorectal epithelial proliferation and thereby to act as possible chemoprotective agents in colorectal cancer. We investigated the effects of an intervention with calcium and vitamins on cell proliferation in the colonic mucosa of patients operated on for colorectal cancer. Patients with resected colorectal cancer Dukes' stage B-C were randomized to receive daily 30,000 IU of axerophthol palmitate (vitamin A) plus 1 g ascorbic acid (vitamin C) plus 70 mg of dl-alpha-tocopherol acetate (vitamin E) and 2 g natural calcium daily or indistinguishable placebo for 6 months. At the time of surgery and after 6 and 12 months of treatment, cell kinetics of normal colonic mucosa were assessed by using proliferating cell nuclear antigen (PCNA). Ninety patients were enrolled and 77 were assessable: 34 in the treatment group and 43 in the placebo group. A significant reduction of mean total PCNA labeling index (PCNALI) was evident in both groups after 6 months (vitamins/calcium, from 16.11 +/- 2.43 to 10.71 +/- 2.81; placebo, from 17.30 +/- 2.63 to 12.53 +/- 3.40). The difference in the percentage of reduction of mean PCNALI between baseline and after 6 months was not statistically significant in the treatment and placebo groups: 34% and 28%, respectively. A second control, 6 months after discontinuation of vitamin and calcium supplementation, showed a further decrease of mean total PCNALI in both groups, but this was not statistically significant. Our randomized trial showed that calcium and vitamin supplementation does not reduce cell kinetics of colon epithelium. Furthermore, this study suggests the need for extreme caution in the interpretation and publication of studies on chemoprotectants in colon cancer without a control group.
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PMID:Effects of calcium and vitamin supplementation on colon cell proliferation in colorectal cancer. 1083 24

To better understand the anticancer activity of Levamisole (LMS), which serves as an adjuvant in colon cancer therapy in combination with 5-Fluorouracil, this study analyses LMS' ability to induce apoptosis and growth arrest in cultured human micro- and macrovascular endothelial cells (ECs) and fibroblasts. Cells exposed (24 h) to Levamisole (range: 0.5 - 2 mmol l(-1)) alone or in combination with antioxidants (10 mmol l(-1) glutathione or 5 mmol l(-1) N-Acetylcysteine or 0.1 mmol l(-1) Tocopherol) were evaluated for apoptosis ((3)H-thymidine assays, in situ staining), mRNA/protein expression (Northern/Western blot), and proliferation ((3)H-thymidine incorporation). Levamisole dose-dependently increased apoptosis in ECs to 230% (HUVECs-human umbilical vein ECs), 525% (adult human venous ECs) and 600% (human uterine microvascular ECs) but not in fibroblasts compared to control cells (set as 100%). Levamisole increased in ECs integrin-dependent matrix adhesion, inhibited proliferation (-70%), reduced expression of survival factors such as clusterin (-30%), endothelin-1 (-43%), bcl-2 (-34%), endothelial NO-synthase (-32%) and pRb (Retinoblastoma protein: -89%), and increased that of growth arrest/death signals such as p21 (+73%) and bak (+50%). LMS (2 mmol l(-1))-induced apoptosis was inhibited by glutathione (-50%) and N-Acetylcysteine (-36%), which also counteracted reduction by Levamisole of pRb expression, suggesting reactive oxygen species and pRb play a role in these processes. The ability of LMS to selectively induce apoptosis and growth arrest in endothelial cells potentially hints at vascular targeting to contribute to Levamisole's anticancer activity.
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PMID:Levamisole induced apoptosis in cultured vascular endothelial cells. 1113 34

The vitamin E analog alpha-tocopheryl succinate (alpha-TOS) can induce apoptosis. We show that the proapoptotic activity of alpha-TOS in hematopoietic and cancer cell lines involves inhibition of protein kinase C (PKC), since phorbol myristyl acetate prevented alpha-TOS-triggered apoptosis. More selective effectors indicated that alpha-TOS reduced PKCalpha isotype activity by increasing protein phosphatase 2A (PP2A) activity. The role of PKCalpha inhibition in alpha-TOS-induced apoptosis was confirmed using antisense oligonucleotides or PKCalpha overexpression. Gain- or loss-of-function bcl-2 mutants implied modulation of bcl-2 activity by PKC/PP2A as a mitochondrial target of alpha-TOS-induced proapoptotic signals. Structural analogs revealed that alpha-tocopheryl and succinyl moieties are both required for maximizing these effects. In mice with colon cancer xenografts, alpha-TOS suppressed tumor growth by 80%. This epitomizes cancer cell killing by a pharmacologically relevant compound without known side effects.
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PMID:Induction of cancer cell apoptosis by alpha-tocopheryl succinate: molecular pathways and structural requirements. 1115 56


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