Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevention of cancer by agents in our diet has led to the concept that oxygen radicals are a necessary component of a variety of human cancers including breast, colon and prostatic cancer. These cancers are putatively promoted by estradiol, bile acids and androgens. Epidemiological studies have shown that these cancers are suppressed in vegetarian populations. Vegetable components that may be responsible for this cancer prevention are Vitamin A, retinoids and protease inhibitors (PIs). These agents have been shown to suppress the formation of hydrogen peroxide in promoter-induced neutrophils. They also have been shown to block two-stage carcinogenesis and breast cancer when fed to animals. PIs also suppress experimentally-induced colon cancer and spontaneous liver cancer. Moreover, a new series of cancer-preventive agents, Sarcophytols (isolated by Fujiki and co-workers), are capable of suppressing two-stage carcinogenesis, breast and colon cancers in rodents when given in low concentrations. Sarcophytols were also active suppressors of H2O2 formation of 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced neutrophils. These observations point to an essential role of oxygen radicals in carcinogenesis. Suppression of the oxygen radical response of neutrophils in relation to cancer preventive agents is a facile assay of these important substances. The mechanism of action of oxygen radicals in promoting carcinogenesis is a multiple one, including: (1) activation of oncogenes, (2) modification of DNA bases, and (3) formation of single-strand breaks leading to poly(ADP)ribose polymerase activation.
 ...
PMID:Prevention of cancer by agents that suppress oxygen radical formation. 206 Aug 47

A search of the literature using National Library of Medicine databases and individual cancer journal articles yielded over 500 compounds with published chemopreventive activity in animals. From these, an initial 16 agents or agent combinations have been evaluated in the following animal tumor models: mouse skin papillomas/carcinomas induced by 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate; rat breast adenocarcinoma induced by N-methyl-N-nitrosourea or 7,12-dimethylbenz(a)anthracene; hamster lung carcinoma induced by N-methyl-N-nitrosourea or diethylnitrosamine; mouse bladder papillary carcinoma induced by N-butyl-N-(4-hydroxybutyl)nitrosamine; and rat and mouse colon cancer induced by azoxymethane/methylazoxymethanol acetate. Some of the most interesting positive results observed include 4-hydroxyphenyl retinamide plus tamoxifen in breast cancer, piroxicam in colon cancer, dimethylfluoroornithine in breast and bladder cancer, oltipraz in lung cancer, dehydroepiandrosterone in colon cancer, and molybdate in bladder cancer. Eighteen human intervention trials in progress are described that involve the following agents: beta-carotene (eight trials). Retinol/retinoic acid (seven trials), vitamins C and E (three trials), 4-hydroxyphenyl retinamide (one trial), piroxicam (one trial), and calcium (one trial). By organ site these studies involve cancer of the lung (six studies), skin (five studies), colon (four studies), breast (one study), and uterine cervix (two studies).
 ...
PMID:Identification of candidate cancer chemopreventive agents and their evaluation in animal models and human clinical trials: a review. 240 15

The possible association between the risk of breast cancer, blood level, and dietary intake of preformed Vitamin A (retinol) and beta-carotene was investigated in a case-control study carried out from May 1982 to June 1985. The patients studied were 214 previously untreated individuals with T1-2, N0-1, M0 breast cancer admitted to the National Cancer Institute of Milan and 215 controls admitted for conditions other than neoplastic or metabolic disorders. Both cases and controls were selected from an age group ranging from 30 to 65 years old. Plasma levels of retinol and beta-carotene were tested from blood samples drawn during the first day after admission to the hospital. A questionnaire about diet was used to estimate the mean intake of 69 food items from which a daily dietary index of retinol and beta-carotene intake was computed. Information relating to the woman's history, socioeconomic status, and known risk factors for breast cancer was also collected. No association was found between beta-carotene (in the diet or blood) or dietary retinol and the risk of breast cancer. As for blood retinol, our data show a significant trend of increasing risk with higher levels; multivariate relative risk for subsequent serum levels based on the control quintiles, are 1, 1.5, 1.8, 1.7; (test for linear trend: chi-square = 8.26). Thus, these findings, together with the results of other studies, suggest that retinol and beta-carotene are unlikely to be related to the risk of breast cancer.
 ...
PMID:The relationship of dietary intake and serum levels of retinol and beta-carotene with breast cancer. Results of a case-control study. 333 44

Epidemiologic studies of diet and cancer have been facilitated in Hawaii by the multiethnic composition of its population and the consequent heterogeneity in dietary intakes. Studies of migrant populations, particularly the Japanese, have firmly supported the conclusions that environmental factors are of predominant etiologic significance for most major sites of cancer, and that these factors may exert their influences at particular periods of life. Recent observations on Filipino migrants reproduce most of the findings in the Japanese, although they do not show the same abrupt increase in colon cancer rates to the high levels found in Caucasians. Data on dietary intakes in these populations support several of the prevailing hypotheses regarding the etiology of certain gastrointestinal and hormone-dependent cancers. Several case-control studies of diet and cancer have been completed or are ongoing in Hawaii. Some of these have included comparable studies in Japan, but the findings in Hawaii have generally not been reproduced in Japan. Weak associations with dietary fat have been found in Hawaii for breast cancer (particularly in Japanese women) and for prostate cancer (particularly in men greater than or equal to 70 years of age). Vitamin A (especially carotene) has been shown to be inversely associated with lung cancer risk in men, but positively associated with prostate cancer risk in older men. Vitamin C may be inversely related to bladder cancer risk, but has shown no relationship to lung or prostate cancer risk. These and other findings are discussed in terms of future needs for epidemiologic research in this field.
 ...
PMID:Multiethnic studies of diet, nutrition, and cancer in Hawaii. 391

In this study plasma levels of vitamin A, carotenoids, retinol binding protein (RBP), prealbumin (PA), HDL-and total cholesterol were determined in 33 subjects with breast cancer and compared to those of a group of healthy subjects previously described. Plasma levels of vitamin A and carotene were determined by a spectrophotometric method using trifluoroacetic acid, plasma RBP and PA by single radial immunodiffusion, and HDL-and total cholesterol by enzymatic colorimetry. Mean plasma values of vitamin A, carotene and HDL-cholesterol were lower (P less than 0.01) than in the control group, the same applies to the RBP and PA mean levels (P less than 0.05). On the contrary, the mean value of total cholesterol was higher (P less than 0.01) in the patients than in the control group. Vitamin A plasma levels were significantly related to RBP and PA. No significant statistical correlation was found between clinical stage and vitamin A plasma levels.
 ...
PMID:[Plasma values of vitamin A and its binding proteins (retinol binding proteins and prealbumin), carotene, total cholesterol and HDL-cholesterol in subjects with breast carcinoma]. 392 40

A specific retinoic acid-binding protein was demonstrated by sucrose density gradient centrifugation and saturation binding analysis in MCF-7 human breast cancer cells. In contrast, retinol-binding protein could not be detected in this cell line. By Scatchard analysis, this retinoic acid-binding protein was found to have a dissociation constant (Kd) of 154 nM and to bind a maximum of 14 pmoles of [3H] retinoic acid per milligram of cytoplasmic protein. Experiments with intact attached cells revealed the Kd to be 125 nM, which is very close to the value obtained for cytoplasmic extract. The binding of [3H] retinoic acid was abolished by unlabeled retinoic acid. Retinal and alpha-retinoic acid competed for binding sites but were less potent than unlabeled retinoic acid. Retinol, retinyl acetate, and the analog Ro 10-9359 showed little of no competition for the retinoic acid-binding site. A specific retinoic acid-binding protein was also demonstrated by gel electrophoresis. The presence of retinoic acid binding protein in MCF-7 cells suggests that the biologic effects of retinoic acid may be mediated by this specific protein.
 ...
PMID:Retinoic acid-binding protein in a human cell (MCF-7) from breast carcinoma. 624 68

In a prospective study of 5,004 women in Guernsey, plasma samples were collected and stored. Retinol, beta-carotene and vitamin E levels were later measured in the samples from 39 women who subsequently developed breast cancer and from 78 controls who did not develop cancer. Plasma retinol levels were not related to the risk of breast cancer, mean levels among cases and controls being 485 micrograms l-1 and 479 micrograms l-1 respectively. Plasma vitamin E levels showed a clear association, low levels being associated with a significantly higher risk of cancer. The mean vitamin E levels among cases and controls were 4.7 mg l-1 and 6.0 mg l-1 respectively (P less than 0.025), and the risk of breast cancer in women with vitamin E levels in the lowest quintile was about 5-times higher than the risk for women with levels in the highest quintile (P less than 0.01). beta-carotene levels showed a tendency to be lower in women who developed cancer than in controls (36 micrograms l-1 among cases compared with 50 micrograms l-1 among controls) but the difference was not statistically significant.
 ...
PMID:Plasma retinol, beta-carotene and vitamin E levels in relation to the future risk of breast cancer. 670 7

Vitamin A and its analogues (retinoids) regulate the differentiation of epithelial tissues. Retinoids inhibit the induction of rat mammary cancers by carcinogens in vivo, and cellular binding proteins for retinoids have been demonstrated in some human breast cancer samples. In this study, we examined the model system of human breast cancer cell lines in long-term tissue culture for effects of retinoids on growth and for the presence of cellular retinoid binding proteins. Retinoic acid and retinol inhibit the growth of of MCF-7, Hs578T, and ZR-75-B cell lines. Retinoic acid is more potent than retinol in this regard: 50% growth inhibition is achieved by 6 nM retinoic acid in ZR-75-B and by 700 nM in MCF-7 and Hs578T, whereas 5-8 muM retinol is required in all three cell lines. The time to onset of growth inhibition varies markedly between cell lines and is not related to cell density or doubling time. Retinoic acid increases the doubling time of MCF-7 and ZR-75-B by two- to threefold, but causes cell death in Hs578T. The growth inhibition is reversible in every cell line by removal of retinoic acid. Specific and distinct binding of [(3)H]retinoic acid and [(3)H]retinol is present in cytosols of MCF-7 and Hs578T cells as assessed by sucrose density gradient centrifugation. In ZR-75-B, [(3)H]retinoic acid binding was present, but no binding of [(3)H]retinol was detectable. This study reveals that retinoids may play an important role in the regulation and treatment of human breast cancer and that human breast cancer cell lines represent a useful model to study this role.
 ...
PMID:Binding of retinoids to human breast cancer cell lines and their effects on cell growth. 718 72

Vitamin A concentration in breast adipose tissue as a risk factor for breast cancer was studied by assessing the vitamin A concentration in breast adipose tissue of women with benign breast disease (n = 45) and of those with breast cancer (n = 36). No significant differences in vitamin A concentration between the two groups were found either in premenopausal or postmenopausal subjects. The same was true with the dietary intake of vitamin A in these two groups of women. The vitamin A concentration in breast adipose tissue had a significant correlation with the dietary intake in breast cancer cases only (r = 0.42, p < 0.01). The present results support the previous suggestion that vitamin A is unlikely to be related to the risk of breast cancer.
 ...
PMID:Vitamin A concentration in breast adipose tissue of breast cancer patients. 765 53

Vitamin A and its metabolites play a crucial role in regulating the differentiation and proliferation of epithelial cells, and are potent inducers of apoptosis. The effects of retinoids are thought to be mediated through the metabolite retinoic acid, which binds to nuclear retinoic acid receptors that then interact with specific retinoic acid response elements. The development of cancers involves alterations in growth and differentiation of cells as a result of carcinogen-induced damage to DNA of regulatory genes. Most of the results from experimental animal studies indicate that retinoids are effective in preventing or suppressing cancers. Although the relationship between preformed vitamin A in the diet and epithelial cancers remains to be further clarified, a high intake of vegetables and fruits has been consistently associated with a lower risk of these cancers. This interesting biological activity profile of retinoids has prompted investigators to study them in the chemoprevention of epithelial cancers and in the treatment of advanced cancers. Although the therapeutic response of retinoids against advanced cancers is disappointing, they have emerged as promising chemopreventive agents, particularly in head and neck sites. Both natural and synthetic analogues of vitamin A have been shown to be effective in suppressing micronucleated cells, reversing oral leukoplakia, and preventing new and recurrent lesions in subjects with oral leukoplakia, as well as in reducing the occurrence of second primaries in treated head and neck cancer patients. They have not been consistently effective in suppressing either bronchial atypia or metaplasia, nor have they been proven effective in reducing the occurrence of recurrent lesions in treated skin cancer patients, although some activity has been demonstrated in reducing lesion counts in actinic keratoses. Vitamin A in combination with other micronutrients has not reduced incidence and mortality from oesophageal and stomach cancers. A synthetic retinoid, fenretinide, is currently being evaluated in preventing contralateral breast cancer in treated breast cancer patients. Toxicity has been a major concern with retinoids, as prolonged administration is required in chemoprevention studies. Available evidence indicates that natural analogues of retinoids are less toxic than synthetic compounds such as isotretinoin. Large studies are currently evaluating retinoids in the prevention of head and neck cancers and lung cancers. The outcome of these studies will be important in directing future research initiatives and in forming policies regarding the use of vitamin A compounds in the prevention of cancers.
 ...
PMID:Retinoids as cancer-preventive agents. 892 19


1 2 3 Next >>