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 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Approximately 20% of all deaths in the United States are due to cancer. Cancers of the hormonal tissues such as breast, uterus, ovary in women and prostate in men account for about 8% and 5% of total mortality and 30% and 11% of cancer mortality in women and men, respectively. Diet is considered to be a major and important environmental factor contributing to cancers of hormonal tissues. Breast, uterus, and ovary cancers in women and prostate cancers in men were positively correlated with high fat consumption, high body weight (body mass), body fat, and obesity. A major mechanism for development of these cancers appears to be mediated through increased levels of hormones, especially estrogens. Adipose tissue is considered to be one of the major sources of extraglandular estrogen, produced by aromatization of androgen precursors. Weight reduction decreases the estrogen levels possibly due to a decrease in body fat, thus decreasing the risk for cancers of the hormonal tissues. Dietary fiber may modify the risk for these cancers by influencing estrogen metabolism, recirculation, and excretion. Vitamin A and its precursors may decrease the risk for prostate cancer. Iodine deficiency may increase the risk for thyroid neoplasms in humans and experimental animals. Tumors of the hormonal tissues are the most common tumors in laboratory rodents, especially rats and mice. Incidences of mammary and anterior pituitary tumors had significant and positive correlation with body weight in rats and mice. Lowering the body weight by either decreased caloric intake or other means (e.g., exercise, increased fiber consumption) markedly lowered the incidences of these tumors in laboratory rodents. Laboratory studies indicated that mammary tumor rates in rats may not depend on the amount of fat consumed per day. The mammary tumor-promoting effect of fat may be due to complex interactions involving energy intake and energy retention (body mass) mediated through paracrine, endocrine, and neurohormonal mechanisms. Dietary protein may influence chemically induced tumors by affecting the metabolism of chemicals through enzyme induction. Thus, environmental factors such as diet are considered to be major and important factors for tumors of the hormonal tissues such as breast, uterus, and ovary in women and prostate in men. Diet and associated body weight are considered to be the major factors for tumors of hormonal tissues such as mammary and pituitary glands in rodents, especially rats. Modification of diet and a decrease in caloric intake may markedly decrease the incidence or delay the development of tumors of hormonal tissues in humans and in experimental animals.
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PMID:Influence of diet on tumors of hormonal tissues. 877 7

Vitamin A (retinol) and its derivatives, the retinoids, have been implicated as chemopreventive and differentiating agents in a variety of cancers, including that of the prostate. Very little is known about the physiological role of retinoids in the prostate. Here we show that normal prostate, benign prostate hyperplasia (BPH), and prostate carcinoma tissues contain endogenous retinol and its biologically active metabolite retinoic acid. In our studies, the concentration of retinol was 2-fold elevated in BPH compared with the other two tissues. In contrast, prostate carcinoma tissue contained five to eight times less retinoic acid than normal prostate or BPH. Moreover, we found that prostate tissue expresses dehydrogenases capable of converting retinol to retinoic acid through retinaldehyde as an intermediate. Formation of retinal from retinol takes place in microsomes, and the conversion of retinal to retinoic acid occurs in the cytosol. Furthermore, we found that the nuclear retinoic acid receptors alpha, beta, and gamma are expressed in normal and tumor samples. These studies establish a role for retinoids in the physiology of the prostate and possibly also in the pathophysiology of prostate cancer.
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PMID:Abnormal level of retinoic acid in prostate cancer tissues. 896 49

The authors conducted a case-control study among the multi-ethnic population of Hawaii to examine the role of dietary soy, fiber, and related foods and nutrients on the risk of endometrial cancer. Endometrial cancer cases (n = 332) diagnosed between 1985 and 1993 were identified from the five main ethnic groups in the state (Japanese, Caucasian, Native Hawaiian, Filipino, and Chinese) through the rapid-reporting system of the Hawaii Tumor Registry. Population controls (n = 511) were selected randomly from lists of female Oahu residents and matched to cases on age (+/-2.5 years) and ethnicity. All subjects were interviewed using a diet history questionnaire that included over 250 food items. Non-dietary risk factors for endometrial cancer included nulliparity, never using oral contraceptives, fertility drug use, use of unopposed estrogens, a history of diabetes mellitus or hypertension, and a high Quetelet's index (kg/cm2). Energy intake from fat, but not from other sources, was positively associated with the risk of endometrial cancer. The authors also found a positive, monotonic relation of fat intake with the odds ratios for endometrial cancer after adjustment for energy intake. The consumption of fiber, but not starch, was inversely related to risk after adjustment for energy intake and other confounders. Similar inverse gradients in the odds ratios were obtained for crude fiber, non-starch polysaccharide, and dietary fiber. Sources of fiber, including cereal and vegetable and fruit fiber, were associated with a 29-46% reduction in risk for women in the highest quartiles of consumption. Vitamin A and possibly vitamin C, but not vitamin E, were also inversely associated with endometrial cancer, although trends were not strong. High consumption of soy products and other legumes was associated with a decreased risk of endometrial cancer (p for trend = 0.01; odds ratio = 0.46, 95% confidence interval 0.26-0.83) for the highest compared with the lowest quartile of soy intake. Similar reductions in risk were found for increased consumption of other sources of phytoestrogens such as whole grains, vegetables, fruits, and seaweeds. Ethnic-specific analyses were generally consistent with these results. The observed dietary associations appeared to be largely independent of other risk factors, although the effects of soy and legumes on risk were limited to women who were never pregnant or who had never used unopposed estrogens. These data suggest that plant-based diets low in calories from fat, high in fiber, and rich in legumes (especially soybeans), whole grain foods, vegetables, and fruits reduce the risk of endometrial cancer. These dietary associations may explain in part the reduced rates of uterine cancer in Asian countries compared with those in the United States.
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PMID:Association of soy and fiber consumption with the risk of endometrial cancer. 927 Apr 8

Vitamin A or its synthetic analogues are potent in controlling cell differentiation and in preventing epithelial cancer in experimental animals. Although some community-based studies have found that high serum retinol levels in prediagnostic sera were associated with reduced risk for cancer, other reports in humans have not confirmed this finding. This study is to evaluate the preoperative serum vitamin A level in breast cancer patients in Taiwan. The serum specimens were collected from 106 female cases of breast cancer (aged 30 to 70 years), 32 female cases of benign breast disease (aged 29 to 57 years), and 40 healthy females (aged 22 to 52 years). The serum vitamin A levels were measured by colorimetic analysis. The results showed the mean value of the vitamin A level was 140.4 +/- 65.7 micrograms/dl in the breast cancer group comparing to 145.2 +/- 44.2 micrograms/dl in the benign breast disease group, 144.0 +/- 30.0 micrograms/dl in the control group (P > 0.05). The characteristics of the breast cancer group were analyzed and they revealed that serum vitamin A levels did not bear statistically significant differences in age, duration, steroid receptor, tumor size and menopausal state. (P > 0.05) In conclusion, the serum vitamin A levels were not decreased in early breast cancer patients. The serum vitamin A levels were significantly decreased in the metastatic breast cancer group, especially in liver metastatic women. (P < 0.05). Postoperative vitamin A supplement may have potential benefit to metastatic breast cancer patients.
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PMID:Serum vitamin A level in breast cancer patients. 983 62

Vitamin A and its derivatives (collectively referred to as retinoids) are required for many fundamental life processes, including vision, reproduction, metabolism, cellular differentiation, hematopoesis, bone development, and pattern formation during embryogenesis. There is also considerable evidence to suggest that natural and synthetic retinoids have therapeutical effects due to their antiproliferative and apoptosis-inducing effects in human diseases such as cancer. Therefore it is not surprising that a significant amount of research was dedicated to probe the molecular and cellular mechanisms of retinoid action during the past decade. One of the cellular mechanisms retinoids have been implicated in is the initiation and modulation of apoptosis in normal development and disease. This review provides a brief overview of the molecular basis of retinoid signaling, and focuses on the retinoid-regulation of apoptotic cell death and gene expression during normal development and in pathological conditions in vivo and in various tumor cell lines in vitro.
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PMID:Retinoid-induced apoptosis in normal and neoplastic tissues. 1020 Apr 39

Vitamin A derivatives (retinoids) are potent regulators of embryogenesis, cell proliferation, epithelial cell differentiation and carcinogenesis [1]. In breast cancer cells, the effects of retinoids are associated with changes in the cadherin-beta-catenin adhesion and signaling system [2] [3]. beta-catenin is a component of the Wnt signaling pathway, which regulates several developmental pathways [4]. Increases in cytoplasmic beta-catenin and beta-catenin signaling are also associated with numerous cancers, and are particularly important in colon cancer [5]. The oncogenic and developmental effects of beta-catenin are mediated by its interaction with and activation of members of the LEF/TCF family of transcription factors [6] [7] [8]. Here, we shown that retinoic acid (RA) decreases the activity of the beta-catenin-LEF/TCF signaling pathway. This activity of RA was independent of the adenomatous polyposis coli (APC) tumor suppressor and ubiquitination-dependent degradation of cytoplasmic beta-catenin. Consistent with this finding, beta-catenin interacted directly with the RA receptor (RAR) in a retinoid-dependent manner, but not with the retinoid X receptor (RXR), and RAR competed with TCF for beta-catenin binding. The activity of RA on RAR-responsive promoters was also potentiated by beta-catenin. The data suggest that direct regulation of beta-catenin-LEF/TCF signaling is one mechanism whereby RA influences development, cell differentiation and cancer.
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PMID:Cross-regulation of beta-catenin-LEF/TCF and retinoid signaling pathways. 1060 66

Lung cancer is the leading cause of cancer death in the United States. The persisting grim lung cancer incidence and mortality figures argue powerfully for new approaches such as chemoprevention for controlling this disease. Retinoids are among the most intensively studied cancer chemoprevention agents, including in the lung. Several randomized clinical or translational chemoprevention trials (e.g., of retinoids, beta-carotene, or combined folic acid and vitamin B(12)) have been conducted in lung pre-malignancy. Retinoid studies have produced important data on molecular/cellular markers of lung carcinogenesis, e.g., loss of heterozygosity (LOH) at 3p and 9p and retinoic acid receptor-beta (RAR-beta). Two large randomized trials with a lung cancer endpoint, the Alpha-Tocopherol, Beta-Carotene (ATBC) Prevention Study and the Beta-Carotene and Retinol Efficacy Trial (CARET), found that beta-carotene (+/- retinol) was harmful (in smokers). Recently completed lung-second-primary-tumor-prevention trials include the retinoids retinyl palmitate and 13-cis-retinoic acid (13cRA) and N-acetylcysteine (NAC). Vitamin E and selenium show promise for lung cancer prevention, based on positive secondary/subset analyses of three large-scale, randomized National Cancer Institute (NCI) cancer prevention trials. Future directions of lung cancer chemoprevention include the study of molecular markers of risk and drug activity, molecular targeting study, improved imaging techniques (e.g., molecular imaging) and new drug delivery systems.
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PMID:Lung cancer chemoprevention. 1065 11

Vitamin A, its physiologic metabolites, and synthetic derivatives (retinoids) have been shown to have protective effects against the development of certain types of cancer. In addition, pharmacologic amounts of retinoids have been used with some success in the treatment of a few human tumors. The chemoprevention effect of retinoids is most likely exerted at the tumor-promotion phase of carcinogenesis. Retinoids block tumor promotion by inhibiting proliferation, inducing apoptosis, inducing differentiation, or a combination of these actions. Clinically, isotretinoin (13-cis-retinoic acid) significantly decreases the incidence of second primary tumors in patients with head-and-neck cancer and reduces appearance of non-melanoma skin cancer in patients with xeroderma pigmentosum. Retinoic acid has proved to be an effective treatment for promyelocytic leukemia. However, retinoid resistance limits its use as a single agent. Clinical trials are in progress to determine the efficacy of retinoids in treating other types of cancer such as neuroblastoma and breast carcinoma. The development of receptor-selective retinoids and selective inhibitors of retinoid metabolism may lead to further use of retinoids in both chemoprevention and treatment of cancer.
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PMID:Recent advances in the use of vitamin A (retinoids) in the prevention and treatment of cancer. 1111 36

Clinical and preclinical studies suggest that retinoids can inhibit the growth of a small percentage of human renal cancers (RCs), although the majority of RCs both in vitro and in vivo are retinoid resistant. Our recent studies indicate that the metabolism of retinol to retinyl esters is greatly reduced in human carcinoma cell lines of the oral cavity, skin, and breast as compared with their normal epithelial counterparts, suggesting that human carcinoma cells are retinoid deficient relative to normal epithelial cells. We considered whether retinoid resistance in RCs was related to an abnormality in retinoid metabolism. The metabolism of [3H]retinol and of [3H]retinoic acid (RA) was examined in RC cell lines and normal human kidney (NK) epithelial cells cultured in media, in RA, or in RA plus IFN-alpha. The expression of LRAT (lecithin:retinol acyltransferase) was assessed by Northern and Western analysis. Retinol and retinyl ester levels were determined in tissue samples of normal human kidney and renal cell carcinoma. NK cells esterified all of the 50 nM [3H]retinol in which they were cultured. In contrast, six of the seven RC cell lines metabolized only trace amounts of [3H]retinol to [3H]retinyl esters. Consistent with this relative lack of [3H]retinol esterification by the tumor cells, the tumor cells exhibited LRAT transcripts of aberrantly low sizes relative to those in normal epithelial cells. Moreover, the NK cells expressed abundant levels of LRAT protein by Western analysis, whereas the RC cells did not express LRAT protein. When samples of human kidney tumor tissue were compared with samples of normal kidney tissue from patients who had undergone surgery for primary RC, the normal kidney tissues contained much higher levels of retinol and retinyl esters (approximately 0.5-2 microg/gram wet weight) than the tumor tissues in all seven patients examined. Culture of the RC lines in IFN-alpha plus all-trans-RA, a combination therapy used clinically, resulted in higher intracellular levels of [3H]retinol and [3H]retinyl esters. The metabolism of [3H]RA was also examined in these RC lines versus NK cells. Although the NK epithelial cells metabolized [3H]RA, the majority of the RC lines metabolized [3H]RA at a much slower rate. Most of the RC lines metabolized only 10-30% of the 50 nM [3H]RA over 6 h of culture. These data indicate that RCs both in vitro and in vivo are retinol and retinyl ester deficient relative to the normal human kidney, and they suggest that the aberrant differentiation of the neoplastic renal cells results in part from a defect in retinoid metabolism.
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PMID:Reduced levels of retinyl esters and vitamin A in human renal cancers. 1128 61

Epidemiological studies have suggested that low levels of selenium are associated with a higher incidence of both lung and prostate cancer. We analyzed the selenium serum concentration in 356 Carotene and Retinol Efficacy Trial (CARET) participants who later developed lung cancer and 356 matched controls and in 235 prostate cancer cases and 456 matched controls. Serum samples were obtained a mean of 4.7 years before diagnosis for both tumor types. Controls were matched to cases by year of randomization, age, smoking status, treatment arm, exposure population (asbestos workers or cigarette smokers), and year of blood draw. In the control population (n = 820), significant predictors of low serum selenium concentration were current smoking status and East Coast locations of the study center. Overall, there was no significant difference in mean serum selenium in lung cancer cases versus controls (11.91 microg/dl versus 11.77 microg/dl) or prostate cancer cases versus controls (11.48 microg/dl versus 11.43 microg/dl). No statistically significant trend in odds ratio was seen across quartiles of serum selenium for lung cancer (P = 0.49) or prostate cancer (P = 0.69). In a subpopulation of 174 prostate cancer patients who had clinical and pathological staging material reviewed, there was no association between serum selenium and Gleason score or clinical or pathological stage. In the CARET population of current and former smokers consuming an ad libitum diet, the serum concentration of selenium was not a risk factor for either lung cancer or prostate cancer.
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PMID:Predictors of serum selenium in cigarette smokers and the lack of association with lung and prostate cancer risk. 1158 33


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