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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both animal and human studies indicate that increased caloric intake and increases in body weight and obesity are associated with increased risk of cancer of the breast, endometrium, ovaries, colon, rectum and prostate. Recent animal studies indicate that it is the total caloric intake, rather than the percent of fat in the diet, that is associated with tumorigenesis and carcinogenesis, and that tumor development depends on a complex interaction involving energy intake, energy expenditure, energy retention within the body (body fat vs lean body mass) and body size. Omega-3 fatty acids inhibit tumorigenesis and tumor growth in many cancer models in rodents. Exercise diminishes tumor formation in mice, rats and humans. Exercise delays mortality from all causes, and life-long exercise is associated with decreased cancers of the breast and reproductive system in women, and cancer of the colon in women and men.
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PMID:Nutritional cancer risks derived from energy and fat. 332 85

Recent findings indicate that obese (ob/ob) mice suffer a low incidence of lung metastasis and survive longer than lean (+/?) littermates following injection with B16 melanoma cells [34]. The present study examined the food intake of obese and lean mice during the growth of this tumor. Mice from both groups increased their food intake by small and approximately equal amounts during the first three quarters of the survival period following injection with 10(6) cells, and body weights remained fairly stable. During the final quarter, however, obese mice became anorexic whereas lean mice became intensely hyperphagic; body weights changed accordingly. Thus, food intake is differentially affected by tumor growth in this form of genetic obesity.
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PMID:Food intake during tumor growth: anorexia in genetically obese ob/ob mice and hyperphagia in lean mice. 659 52

The poor prognosis of obese women with carcinoma of the breast has yet to find a satisfactory explanation. It is suspected that the hormonal milieu of these patients may favor tumor growth. This investigation explored the relationship between obesity, urinary estrogen excretion, and tumor estrogen receptors (ER) in women treated with mastectomy for carcinoma of the breast. The ER levels determined from the primary cancers of 129 women treated with mastectomy were compared with the obesity index (O.I.) of these patients, i.e., weight in pounds/height in inches. In addition, 24-hour total urinary estrogen determinations were performed in 30 postmenopausal women and compared with their O.I. and ER. A weak direct correlation was found between ER and O.I. in postmenopausal women. The urinary estrogens of postmenopausal women were correlated directly with obesity index, but no relationship could be established between urinary estrogens and the ER content of breast cancers. It is concluded that the excess estrogen production of obese women may be responsible for their poor prognosis by promoting tumor growth. The high tumor ER concentrations associated with obesity suggest a high frequency of hormonally sensitive tumors.
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PMID:Obesity, estrogen production, and tumor estrogen receptors in women with carcinoma of the breast. 683 4

The effect of obesity and fat distribution on survival of breast cancer patients was studied prospectively in 241 women with a natural menopause who participated in a breast cancer screening project, the DOM-project in Utrecht, The Netherlands. Mean follow-up time was 9.1 years and endpoint of interest was death from breast cancer. Fat distribution was assessed by contrasting groups of subscapular and triceps skinfold thickness. No significant differences in survival time between more obese (Quetelet's index > or = 26 kg/m2) and leaner (Quetelet's index < 26 kg/m2) patients or between patients with central fat distribution and patients with peripheral fat distribution were observed. Analyses were stratified by axillary node status, estrogen receptor status, and way of detection (by first screening or afterwards). Results of the stratified analyses were suggestive of a modifying effect of these factors. The absence of an association between obesity and survival time might be explained by two counteracting mechanisms. On the one hand obesity might be related to impaired survival, due to a tumor growth promoting effect of extra-ovarian estrogens. On the other hand obesity might be related to improved survival in a screened population, because obese patients profit more from screening by earlier detection of tumors than leaner counterparts.
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PMID:Obesity and subcutaneous fat patterning in relation to survival of postmenopausal breast cancer patients participating in the DOM-project. 764 30

Ad libitum (AL) overfeeding is the most significant, uncontrolled variable affecting the outcome of the current rodent bioassay. There is a highly significant correlation between AL food consumption, the resultant obesity and body weight, and low 2-yr survival in rodents. AL feeding of diets with lowered protein, metabolizable energy (ME), and increased fiber does not improve survival. Only dietary restriction (DR) of all diets tested significantly improves survival and delays the onset of spontaneous degenerative disease (i.e., nephropathy and cardiomyopathy) and diet-related tumors. Moderate DR results in an incidence of spontaneous tumors similar to AL-fed rats, but the tumors are found incidentally and do not cause early mortality. There is a decreased age-adjusted incidence of pituitary and mammary gland tumors in moderate DR-fed rats, but tumor growth time is similar between AL and DR rats with only a delay in tumor onset time seen in DR-fed groups. Moderate DR does not significantly alter drug-metabolizing enzyme activities nor the toxicologic response to 5 pharmaceuticals tested at maximum tolerated doses (MTDs). However, moderate DR-fed rats did require much higher doses of 4 additional pharmaceutical compounds before classical MTDs were produced. Toxicokinetic studies of 2 of these compounds demonstrated equal or higher steady-state systemic exposures to parent drug and metabolites in moderate DR-fed rats. Markers of oxidative stress (lipid peroxidation, protein oxidation) are decreased and cytoprotective anti-oxidant markers are preserved in moderate DR-fed rats. But moderate DR does not delay reproductive senescence in female rats. Only marked DR delays reproductive senescence compared to AL and moderate DR-fed female rats. These and other data indicate that moderate DR is the most appropriate method of dietary control for the rodent bioassay when used to assess pharmaceuticals for human safety and compounds for risk assessment.
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PMID:The effects of diet, ad libitum overfeeding, and moderate dietary restriction on the rodent bioassay: the uncontrolled variable in safety assessment. 899 7

Although reduced biological activity of the obese gene product, leptin, has been associated with obesity, little information is available concerning leptin alterations during anorexia. Therefore, we measured circulating leptin concentrations and hypothalamic leptin binding in anorectic tumor-bearing and pair-fed control rats. Plasma concentrations of leptin decreased in tumor-bearing rats early in the course of tumor growth, and fell to nearly non-detectable levels during severe anorexia. The pair-fed control rats that ate the same amount of food as did the anorectic tumor-bearing rats exhibited a 50% decrease in plasma leptin concentration. Concentrations of free fatty acids were elevated in both tumor-bearing and pair-fed groups, while circulating levels of triglycerides were increased only in anorectic tumor-bearing rats. Leptin receptor density was doubled in the hypothalamus of tumor bearing rats, while binding affinity was decreased by 50%. These results suggest that peripheral leptin production is down-regulated, perhaps due to increased lipolysis in tumor-bearing rats. It appears that hypothalamic leptin systems up-regulate receptor numbers in response to decreased blood leptin level, however, the decrease in binding affinity may compensate for these alterations. Therefore, the influence of leptin on hypothalamic neuropeptide Y feeding systems may be minimal in anorectic tumor-bearing rats.
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PMID:Reciprocal changes in hypothalamic receptor binding and circulating leptin in anorectic tumor-bearing rats. 972 52

Cancer is a leading cause of mortality in the United States. Despite much research on specific carcinogens, the cause of many cancers remains unclear. The identification of novel causative agents offers the potential for cancer prevention. Diseases such as obesity and diabetes mellitus, characterized by hyperinsulinemia, are associated with increased risk of endometrial, colorectal, and breast carcinomas. There is increasing evidence that insulin is a growth factor for tumor formation. The mechanisms underlying insulin-mediated neoplasia may include enhanced DNA synthesis with resultant tumor cell growth, inhibition of apoptosis, and altered sex hormone milieu. The reduced insulin levels seen with physical activity, weight loss, and a high fiber diet may account for decreased cancer risk. The role of newer drugs that restore sensitivity to insulin, thereby reducing hyperinsulinemia, is an exciting potential area of cancer prevention. In this review, we discuss the potential role of insulin as a tumor growth factor.
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PMID:Insulin: a novel factor in carcinogenesis. 1190 58

Archival reports demonstrate that black females are in the minority of reported breast cancer cases, yet are given a significantly poorer prognosis than their white counterparts. Numerous studies have been conducted in an attempt to explain this discrepancy. In the past, socio-economic variables such as economic status and access to adequate health care have been the focus of attention. More recently there has been a shift to understanding the racial differences in genotype, as well as hormones related to tumor growth. In the present report, we explore the effects of increased estrogen levels as a precursor to the detrimental effects of breast cancer in African American women when compared to Caucasian women. Furthermore we will explore the effects of increased estrogen levels on the apoptotic events of p53 and Bcl-2 proteins. We conclude with a discussion regarding the antagonistic behavior of varying isoforms of estrogen receptors, and their relationship to nitric oxide (NO) as a free radical. The main focus of this paper is to address the many carcinogenic pathways that are instigated by estrogen and those which may be linked to obesity. By determining the relative concentration of estrogen and related proteins within black and white populations we hope to better understand the above mentioned disparity.
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PMID:Risk factors for breast cancer and the prognosis of African American women: estrogen's role. 1282 61

Uterine leiomyomas, or fibroids, represent a major public health problem. It is believed that these tumors develop in the majority of American women and become symptomatic in one-third of these women. They are the most frequent indication for hysterectomy in the United States. Although the initiator or initiators of fibroids are unknown, several predisposing factors have been identified, including age (late reproductive years), African-American ethnicity, nulliparity, and obesity. Nonrandom cytogenetic abnormalities have been found in about 40% of tumors examined. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has only recently been explored. Growth factors with mitogenic activity, such as transforming growth factor- (subscript)3(/subscript), basic fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I, are elevated in fibroids and may be the effectors of estrogen and progesterone promotion. These data offer clues to the etiology and pathogenesis of this common condition, which we have analyzed and summarized in this review.
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PMID:Etiology and pathogenesis of uterine leiomyomas: a review. 1282 76

Some studies suggest that several tumors have a greater incidence in those patients with a high fat diet, such as colon, breast, and prostate. However, we wanted to determine the effects of obesity alone, independent of diet, on the progression of prostate tumor growth. Using a genetic model of obese and lean Zucker rats, we wanted to demonstrate any sera differences in the concentration of basic fibroblast growth factor (FGF-2) and vascular endothelial cell growth factor (VEGF), two important factors involved in the growth and progression of prostate cancer. We also wanted to investigate if there were any differences in immune function between the two sera, which could also account for uninhibited tumor growth, as well as differences in mitogenic stimulation. Female Zucker rat obese and lean sera were analyzed using ELISA assays for FGF-2, VEGF, and macrophage inflammatory protein-1 alpha (MIP-1a), as a measure of macrophage function. In addition, the sera of lean and obese sera were plated on wells growing LNCaP prostate cancer cells to determine differences in mitogenicity. We found a greater concentration of FGF-2 in the sera from obese Zucker rats compared to lean Zucker rats: 6.32+/-0.56 vs 3.48+/-0.34 pg/ml, respectively, P<0.05). We also demonstrated a greater concentration of VEGF in obese rat sera compared to lean sera: 54.4+/-4.1 vs 38.0+/-2.9 pg/mL, respectively, P<0.05). We detected a trend in mitogenic stimulation among LNCaP cells along the higher concentrations of the dose-response curve (0.72+/-0.06 vs 0.51+/-0.5). However, this was not statistically significant. In addition, we did not find a significant difference in MIP-1a macrophage activity levels between sera. To conclude, we speculate that the greater concentrations of VEGF and FGF-2 in the sera of obese rodents vs lean rodents may account for some of the differences seen in obesity-related tumor growth seen in the human condition. However, the lack of any sera differences of immune function, as measured by macrophage activity, as well as no significant differences on mitogenic proliferation on LNCaP prostate cancer cells, suggests that other mechanisms may exist to explain differences seen in obesity-related prostate tumor biology.
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PMID:Immune function, mitogenicity, and angiogenic growth factor concentrations in lean and obese rodent sera: implications in obesity-related prostate tumor biology. 1466 68


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