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

The aim of our study was to evaluate the association between the expression of E-cadherin and clinical prognostic factors in uterine endometrioid adenocarcinoma of different histological grade. We have studied 104 postmenopausal women with diagnosis of endometrioid adenocarcinoma. We evaluated the presence of obesity and vaginal bleeding. Surgical specimens were fixed in 10% neutral buffered formalin solution and embedded in paraffin. 4 mm sections were stained by hematoxylin-eosin, von Gieson, and histological type of cancer, metastatic involvement of lymph nodes and depth of myometrial invasion were evaluated. Histological grade of cancer was assessed by FIGO grading system. All samples were analyzed by immunohistochemistry for E-cadherin (Dakocytomation). We assessed the number of E-cadherin-positive and negative tumor cells and degree of positivity (low, moderate, high). Histological study by hematoxylin-eosin has showed grade 1 endometrioid carcinoma in 35 cases (33.7%, group I), grade 2 adenocarcinoma in 44 cases (42.3%, group II), and grade 3 adenocarcinoma in 25 cases (24%, group III). Our results suggest that the loss of E-cadherin expression is associated with a higher histological grade of uterine endometrioid adenocarcinoma, depth of myometrial invasion, lymph node positivity, coexistence of obesity and vaginal bleeding. It seems that local invasion and metastatic spread of tumor should be preceded by the loss of E-cadherin expression in tumor cells, which progressively occurs in carcinogenesis. Therefore, E-cadherin negativity can be used as a poor prognostic factor and more aggressive chemotherapy regimen should be used.
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PMID:The expression of cadherin e and clinical prognostic factors in uterine endometrioid adenocarcinoma. 1636 55

Orlistat is an anti-obesity agent that increases the fecal fat excretion, which promotes colon carcinogenesis. Therefore, the present study was designed to verify the effects of Orlistat on the formation of rat colonic aberrant crypt foci (ACF) and cell proliferation evaluated by the PCNA method. Male Wistar rats received either a standard diet or a high fat diet (HFD), supplemented or not with Orlistat (200mg/kg chow) and two doses of the carcinogen dimethyl-hydrazine (25mg/Kg). After 30 days, Orlistat was associated to a significant increase in the number of colonic ACFs and cell proliferation in DMH-treated animals, independently of the HFD.
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PMID:The anti-obesity agent Orlistat is associated to increase in colonic preneoplastic markers in rats treated with a chemical carcinogen. 1637 80

Gallbladder cancer is a relatively rare neoplasm that shows, however, high incidence rates in certain world populations. The interplay of genetic susceptibility, lifestyle factors and infections in gallbladder carcinogenesis is still poorly understood. Age-adjusted rates were calculated by cancer registry-based data. Epidemiological studies on gallbladder cancer were selected through searches of literature, and relative risks were abstracted for major risk factors. The highest gallbladder cancer incidence rates worldwide were reported for women in Delhi, India (21.5/100,000), South Karachi, Pakistan (13.8/100,000) and Quito, Ecuador (12.9/100,000). High incidence was found in Korea and Japan and some central and eastern European countries. Female-to-male incidence ratios were generally around 3, but ranged from 1 in Far East Asia to over 5 in Spain and Colombia. History of gallstones was the strongest risk factor for gallbladder cancer, with a pooled relative risk (RR) of 4.9 [95% confidence interval (CI): 3.3-7.4]. Consistent associations were also present with obesity, multiparity and chronic infections like Salmonella typhi and S. paratyphi [pooled RR 4.8 (95% CI: 1.4-17.3)] and Helicobacter bilis and H. pylori [pooled RR 4.3 (95% CI: 2.1-8.8)]. Differences in incidence ratios point to variations in gallbladder cancer aetiology in different populations. Diagnosis of gallstones and removal of gallbladder currently represent the keystone to gallbladder cancer prevention, but interventions able to prevent obesity, cholecystitis and gallstone formation should be assessed.
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PMID:Gallbladder cancer worldwide: geographical distribution and risk factors. 1639 65

There is increasing evidence that dysregulation of energy homeostasis is associated with colorectal carcinogenesis. Epidemiological data have consistently demonstrated a positive relation between increased body size and colorectal malignancy, whereas mechanistic studies have sought to uncover obesity-related carcinogenic pathways. The phenomenon of "insulin resistance" or the impaired ability to normalize plasma glucose levels has formed the core of these pathways, but other mechanisms have also been advanced. Obesity-induced insulin resistance leads to elevated levels of plasma insulin, glucose and fatty acids. Exposure of the colonocyte to heightened concentrations of insulin may induce a mitogenic effect within these cells, whereas exposure to glucose and fatty acids may induce metabolic perturbations, alterations in cell signaling pathways and oxidative stress. The importance of chronic inflammation in the pathogenesis of obesity has recently been highlighted and may represent an additional mechanism linking increased adiposity to colorectal carcinogenesis. This review provides an overview of the epidemiology of body size and colorectal neoplasia and outlines current knowledge of putative mechanisms advanced to explain this relation. Family based studies have shown that the propensity to become obese is heritable, but this is only manifest in conditions of excess energy intake over expenditure. Inheritance of a genetic profile that predisposes to increased body size may also be predictive of colorectal cancer. Genomewide scans, linkage studies and candidate gene investigations have highlighted more than 400 chromosomal regions that may harbor variants that predispose to increased body size. The genetics underlying the pathogenesis of obesity are likely to be complex, but variants in a range of different genes have already been associated with increased body size and insulin resistance. These include genes encoding elements of insulin signaling, adipocyte metabolism and differentiation, and regulation of energy expenditure. A number of investigators have begun to study genetic variants within these pathways in relation to colorectal neoplasia, but at present data remain limited to a handful of studies. These pathways will be discussed with particular reference to genetic polymorphisms that have been associated with obesity and insulin resistance.
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PMID:Obesity and colorectal cancer: epidemiology, mechanisms and candidate genes. 1642 29

Obesity is a worldwide problem which impacts the risk and prognosis of some of the more common forms of cancer, including breast cancer in post-menopausal women. As the basis for understanding the potential mechanisms of obesity and cancer relationship has advanced, a number of new hypotheses have emerged. The adipocytokines are a complex group of biologically active polypeptides. Leptin is a growth hormone, secreted by adipose tissue, whose levels are normally elevated in obese individuals and may have a promoting effect on carcinogenesis and metastasis of breast cancer, possibly in an autocrine manner. Leptin interferes with the insulin signaling pathway and in type 2 diabetes plasma leptin levels are found to be correlated with the degree of insulin resistance, a relationship independent of body mass. This relationship might provide a mechanistic explanation for promotion potential.
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PMID:Obesity, breast cancer and the role of adipocytokines. 1643 10

We have recently proposed lipid peroxidation as a unifying mechanistic pathway by which several seemingly unrelated risk/protective factors (obesity, hypertension, diabetes, smoking, oophorectomy/hysterectomy, parity, antioxidants) affect renal cell carcinoma development. In experimental studies, increased lipid peroxidation is a principal mechanistic pathway in renal carcinogenesis induced by different chemicals. In this communication, we provide additional lines of evidence that further support a role for lipid peroxidation on renal cell cancer development. (1) Lipid peroxidation may explain the role of other risk (analgesic use, pre-eclampsia) or protective (alcohol intake, oral contraceptives) factors for renal cell carcinoma. (2) Additional experimental evidence supports lipid peroxidation as an important mechanism in renal carcinogenesis, and (3) Existing evidence support a cross-talk between the lipid peroxidation pathway and other pathways that are relevant to renal carcinogenesis, such as apoptosis, VHL, and possibly other pathways.
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PMID:Lipid peroxidation and renal cell carcinoma: further supportive evidence and new mechanistic insights. 1645 3

Prostate cancer, the third most common cancer in men worldwide, varies substantially according to geographic region and race/ethnicity. Obesity and associated endocrine variation are foremost among the risk factors that may underlie these regional and ethnic differences. The association between obesity and prostate cancer incidence is complex and has yielded inconsistent results. Studies that have linked obesity with prostate cancer mortality, advanced stage disease, and higher grade Gleason score, however, have produced more consistent findings, indicating that obesity may not necessarily increase the risk of prostate cancer, but may promote it once established. Additionally, metabolic syndrome, which includes disturbed glucose metabolism and insulin bioactivity, may also be associated with prostate carcinogenesis. Adipokines, defined as biologically active polypeptides produced by adipose tissue, have been linked with a number of carcinogenic mechanisms, including angiogenesis, cell proliferation, metastasis, and alterations in sex-steroid hormone levels. A number of emerging studies have implicated the role of adipokines in prostate carcinogenesis. This review explores the specific roles of several adipokines as putative mediating factors between obesity and prostate cancer with particular attention to leptin, interleukin-6 (IL-6), heparin-binding epidermal growth factor-like growth factor (HB-EGF), vascular endothelial growth factor (VEGF) and adiponectin.
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PMID:Obesity, adipokines, and prostate cancer (review). 1646 80

Despite Otto Warburg's 1931 Nobel Prize for his work affirming the role of metabolism in carcinogenesis, there has been little further interest in this association between metabolism and cancer. Disinterest has, in part, been attributable to the notion that Warburg's description of a relation between a shift to glycolysis in carcinogenesis may be an epiphenomenon rather than a mechanistic determinant. By studying the critical cellular energy sensor AMP-activated protein kinase (AMPK), I postulate that the association between intermediary metabolism and tumours varies over time. Through accumulation of carbohydrates and pan-inhibition of AMPK, premalignant tumours may gain a replicative advantage through the repression of senescence. Conversely, malignant tumours, with a defective tumour suppressor contingent, undergo a "glycolytic switch", in part by tolerating a degree of AMPK activation, to mitigate substrate limitation. I contend that this Janus-faced relation with intermediary metabolism contributes to carcinogenesis; if proven, this finding would have important implications for public health, in that it would lend support to the idea that prevention of obesity, and caloric restriction and exercise could reduce the predisposition to cancer.
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PMID:Cancer's sweet tooth: the Janus effect of glucose metabolism in tumorigenesis. 1648 6

Several lifestyle factors affect a woman's risk of gynaecological cancer and-potentially-can be modified to reduce risk. This chapter summarises the evidence for the effect of lifestyle factors on the incidence of gynaecological malignancy. The incidence of obesity is increasing in the developed world such that it now contributes as much as smoking to overall cancer deaths. Women with a body mass index (BMI)>40 have a 60% higher risk of dying from all cancers than women of normal weight. They are also at increased risk from gynaecological cancer. Dietary factors significantly influence the risk of gynaecological cancer: fruit, vegetables and antioxidants reduce risk whereas high animal fat and energy intakes increase risk. Alcohol intake adversely affects breast cancer risk, possibly accounting for 4% of all breast cancers. Physical activity protects against ovarian, endometrial and postmenopausal breast cancer, independently of BMI. The oral contraceptive pill has a substantial and long-lasting effect on the prevention of ovarian and endometrial cancer and is one of the best examples of large-scale chemoprevention in the developed world. Childbearing is protective against ovarian, endometrial and breast cancer but increases the risk of cervical cancer. Smoking acts as a cofactor in cervical carcinogenesis and increases the risk of ovarian cancer, particularly mucinous tumours.
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PMID:The effect of lifestyle factors on gynaecological cancer. 1654 19

Increased visceral adipose tissue results in elevated plasma leptin, which are associated with increased risk of a number of obesity-related cancers. However, research is contradictory regarding the role of elevated plasma leptin in colon cancer risk. Having established that leptin induced proliferation in a murine model of preneoplastic (Apc(Min/+); IMCE) colon epithelial cells but not normal (Apc(+/+); YAMC) cells, we hypothesized that the leptin-associated IMCE cell proliferation was a result of autocrine interleukin-6 (IL-6) production and ensuing IL-6 receptor (IL-6R) signaling. Here we show, for the first time, that leptin induces elevated IL-6 production in IMCE cells but not in YAMC cells. IL-6 treatment induced cell proliferation in IMCE cells, but not in YAMC cells, in a concentration-dependent manner from 0.1 to 100 ng/ml (P < 0.05). Interleukin-6-induced IMCE cell proliferation was blocked by the addition of a neutralizing anti-IL-6R antibody. In addition, leptin-induced IMCE cell proliferation was blocked by the addition of an anti-IL-6R neutralizing antibody. Further, we elucidate a novel mechanism by which leptin activates TACE/ADAM17-associated IL-6R shedding and trans-IL-6 signaling in IMCE by induction of IL-6 production. IL-6 treatment of IMCE cells was associated with STAT3, ERK, p38, MEK and JAK2 activation and associated STAT3 nuclear activation and translocation. These data implicate leptin-induced IL-6 production, signaling and subsequent STAT3 activation as early events promoting the survival/proliferation of colon epithelial preneoplastic cells. The elucidation of the leptin-initiated mechanism of preneoplastic cell proliferation establishes a biologically plausible link between the adipocyte-specific cytokine leptin and obesity-associated colon cancer.
Carcinogenesis 2006 Jul
PMID:Interleukin-6 production induced by leptin treatment promotes cell proliferation in an Apc (Min/+) colon epithelial cell line. 1659 43


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