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

Examining the relationship between health outcomes and environmental exposures requires summary measures, or indicators. To advance the use of indicators, the Johns Hopkins Center for Excellence in Environmental Public Health Tracking piloted three pairs of indicators: 1) air toxics and leukemia in New Jersey, 2) mercury emissions and fish advisories in the United States, and 3) urban sprawl and obesity in New Jersey. These analyses illustrate the feasibility of creating environmental hazard, exposure, and health outcome indicators, examining their temporal and geographic trends, and identifying their temporal and geographic relationships. They also show the importance of including appropriate caveats with the findings. The authors' investigations demonstrate how existing environmental health data can be used to create meaningful indicator measures to further the understanding of environment-related diseases and to help prioritize and guide interventions. Indicators are the foundation of environmental public health tracking, and increased use and development of them are necessary for the establishment of a nationwide tracking network capable of linking environmental exposures and health outcomes.
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PMID:Tracking health and the environment: a pilot test of environmental public health indicators. 1818 34

Excess body weight (overweight and obesity) is characterized by chronic hyperinsulinaemia and insulin resistance, and is implicated both in cancer risk and cancer mortality. The list of cancers at increased risk of development in an "obesogenic" environment include common adult cancers such as endometrium, post-menopausal breast, colon and kidney, but also less common malignancies such as leukaemia, multiple myeloma, and non-Hodgkin's lymphoma. The pathophysiological and biological mechanisms underpinning these associations are only starting to be understood. Insulin resistance is at the heart of many, but there are several other candidate systems including insulin-like growth factors, sex steroids, adipokines, obesity-related inflammatory markers, the nuclear factor kappa beta (NF-kappa B) system and oxidative stresses. With such as diversity of obesity-related cancers, it is unlikely that there is a "one system fits all" mechanism. While public health strategies to curb the spread of the obesity epidemic appear ineffective, there is a need to better understand the processes linking obesity and cancer as a pre-requisite to the development of new approaches to the prevention and treatment of obesity-related cancers.
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PMID:Obesity and cancer: pathophysiological and biological mechanisms. 1846 61

The zeta chain-associated 70-kDa protein (ZAP-70) of tyrosine kinase plays a critical role in T cell receptor-mediated signal transduction and the immune response. A high level of ZAP-70 expression is observed in leukemia, which suggests ZAP-70 as a logical target for immunomodulatory therapies. (-)-Epigallocatechin gallate (EGCG) is one of the major green tea catechins that is suggested to have a role as a preventive agent in cancer, obesity, diabetes, and cardiovascular disease. Here we identified ZAP-70 as an important and novel molecular target of EGCG in leukemia cells. ZAP-70 and EGCG displayed high binding affinity (Kd = 0.6207 micromol/liter), and additional results revealed that EGCG effectively suppressed ZAP-70, linker for the activation of T cells, phospholipase Cgamma1, extracellular signaling-regulated kinase, and MAPK kinase activities in CD3-activated T cell leukemia. Furthermore, the activation of activator protein-1 and interleukin-2 induced by CD3 was dose-dependently inhibited by EGCG treatment. Notably, EGCG dose-dependently induced caspase-mediated apoptosis in P116.cl39 ZAP-70-expressing leukemia cells, whereas P116 ZAP-70-deficient cells were resistant to EGCG treatment. Molecular docking studies, supported by site-directed mutagenesis experiments, showed that EGCG could form a series of intermolecular hydrogen bonds and hydrophobic interactions within the ATP binding domain, which may contribute to the stability of the ZAP-70-EGCG complex. Overall, these results strongly indicated that ZAP-70 activity was inhibited specifically by EGCG, which contributed to suppressing the CD3-mediated T cell-induced pathways in leukemia cells.
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PMID:(-)-Epigallocatechin gallate regulates CD3-mediated T cell receptor signaling in leukemia through the inhibition of ZAP-70 kinase. 1868 87

Accumulating evidence supports a role for obesity in the etiology of multiple myeloma (MM). The distinct possibility exists that obesity may be linked to MM through altered adipokine secretion and circulating levels, one of which, adiponectin, has a protective role in several malignancies, including leukemia. In this case-control study, we investigated the role of serum adiponectin, resistin, and leptin levels in the etiopathogenesis of MM and we explored their association with several established prognostic factors. Seventy three patients with incident, histologically confirmed MM and 73 controls matched on gender and age were studied between 2001 and 2007, and blood samples were collected. Serum adiponectin, leptin, resistin, as well as MM prognostic parameters were determined. Statistical analysis of the data was performed using univariate and multivariate analyses. Lower serum adiponectin and resistin levels were associated with higher risk of MM by bivariate analysis and after adjusting for age, gender, BMI, and serum levels of leptin (p < 0.0001). Adiponectin may have a protective role in MM, whereas leptin was not associated with risk for MM at a comparable level of significance and resistin levels may be decreased via a compensatory mechanism. Further studies are needed to confirm these associations and to explore the mechanisms underlying adiponectin's role in MM and plasma cell dyscrasias.
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PMID:Low circulating adiponectin and resistin, but not leptin, levels are associated with multiple myeloma risk: a case-control study. 1881 45

Obesity is a common complication of treatment for some childhood cancers, particularly acute lymphoblastic leukaemia (ALL) and craniopharyngioma. Evidence-based guidance is available for the general paediatric population on the diagnosis, aetiology, consequences, prevention and treatment of obesity, and this should be considered as the starting point for considering such issues in patients with malignancy. In ALL, a high proportion of patients show rapid and excessive weight gain soon after diagnosis which originates partly in lifestyle, in particular via markedly reduced levels of physical activity. Good evidence on risk factors for obesity in ALL is available, and the natural history and aetiology of obesity in ALL are now fairly well understood, while for craniopharyngioma the natural history is reasonably well understood. Understanding the natural history and aetiology of obesity should facilitate preventive interventions in the future. Evidence on preventive interventions is required urgently, and it should focus on promotion of a reduction in sedentary behaviour and increases in physical activity. Such interventions should be helpful in obesity prevention, but could also have a wide range of additional benefits in the prevention or amelioration of other late effects of treatment.
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PMID:Obesity during and after Treatment for Childhood Cancer. 1929 3

Adult survivors of childhood cancer, particularly brain tumours and acute lymphoblastic leukaemia demonstrate evidence of increased rates of metabolic complications and cardiovascular disease in later life. Evidence is accumulating that risk factors for these complications include obesity, physical inactivity, lipid abnormalities, insulin resistance and development of the metabolic syndrome. Cranial radiotherapy-induced growth hormone deficiency, other direct adverse effects of radiotherapy and anthracycline-induced left ventricular dysfunction are clearly identified risk factors for developing these complications. Growth hormone replacement, where appropriate, has been of some benefit in reducing the prevalence of metabolic complications in some long-term survivors. In others, it is clear that multidisciplinary interventions will need to be developed which focus on modifying aspects of lifestyle including increasing levels of habitual physical activity, improving diet and prevention of smoking along with the use of lipid-lowering medication.
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PMID:Metabolic disorders. 1929 4

Excess body weight in combination with physical inactivity is a major determinant for the development of insulin resistance with associated hyperglycaemia and hyperinsulinaemia and further leads to tumour development. Several prospective epidemiological studies have shown a direct association between excess weight and common malignancies, such as colon, breast (post-menopausal), endometrial, gallbladder, pancreatic, kidney and oesophageal cancers, but also less frequent malignancies, such as leukaemia, multiple myeloma and non-Hodgkin lymphoma. Insulin resistance and hyperinsulinaemia are certainly key biological mechanisms underlying the relationship between adiposity and tumour development. The anti-diabetic drug, metformin, in addition to reduction of insulin resistance has also shown anti-tumour properties, and is increasingly being considered as a drug to prevent and treat obesity-related cancers. Several biological pathways have been involved in the association between excess body weight, insulin resistance and cancer, such as chronic low-grade inflammation, glucose toxicity, AGE product metabolism and the adenosine monophosphate kinase pathway.
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PMID:Obesity related hyperinsulinaemia and hyperglycaemia and cancer development. 1948 4

Obesity is associated with increased cancer incidence and mortality. We have previously found that obesity in children is associated with a 50% increased recurrence of acute lymphoblastic leukemia (ALL) in high-risk patients. We have therefore developed novel in vivo and in vitro preclinical models to study the mechanism(s) of this association. Obesity increased relapse after monotherapy with vincristine (P = 0.03) in obese mice injected with syngeneic ALL cells. This occurred although the drug was dosed proportionally to body weight, equalizing blood and tissue drug levels. In coculture, 3T3-L1 adipocytes significantly impaired the antileukemia efficacy of vincristine, as well as three other chemotherapies (P < 0.05). Interestingly, this protection was independent of cell-cell contact, and it extended to human leukemia cell lines as well. Adipocytes prevented chemotherapy-induced apoptosis, and this was associated with increased expression of the two prosurvival signals Bcl-2 and Pim-2. These findings highlight the role of the adipocyte in fostering leukemia chemotherapy resistance, and may help explain the increased leukemia relapse rate in obese children and adults. Given the growing prevalence of obesity worldwide, these effects are likely to have increasing importance to cancer treatment.
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PMID:Adipocytes impair leukemia treatment in mice. 1977 40

Epidemiological studies have provided convincing evidence that obesity increases the risk for cancers of the oesophagus (adenocarcinoma), colon, pancreas, breast (post-menopausal), endometrium and kidney. The magnitude of the increase in risk varies between cancer sites. For an increase in BMI of 10 kg/m2 relative risks are approximately 2.3 for adenocarcinoma of the oesophagus, 1.5 for colon cancer in men, 1.2 for colon cancer in women, 1.4 for post-menopausal breast cancer, 2.9 for endometrial cancer and >1.5 for kidney cancer, while the size of the effect on cancer of the pancreas is uncertain. There is also evidence that obesity increases the risks for cancers of the gallbladder, malignant melanoma, ovary, thyroid, non-Hodgkin lymphoma, multiple myeloma and leukaemia. Estimates of the percentage of cancers that can be attributed to excess body weight suggest that in the UK and similar countries approximately 5% of all cancers are attributable to overweight and obesity.
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PMID:Symposium 1: Overnutrition: consequences and solutions. Obesity and cancer risk. 1995 65

Obesity is associated with poorer outcome from many cancers, including leukemia. One possible contributor to this could be suboptimal chemotherapy dosing in obese patients. We have previously found that vincristine (VCR) is less effective in obese compared to non-obese mice with leukemia, despite weight-based dosing. In the present study, we administered (3)H-VCR to obese and control mice to determine whether obesity would cause suboptimal VCR exposure. Blood VCR concentrations were fitted with a three-compartment model using pharmacokinetic analysis (two-stage PK) in three subsets of VCR concentrations vs. time method. Tissue and blood VCR concentrations were also analyzed using non-compartmental modeling. Blood VCR concentrations showed a triexponential decay and tended to be slightly higher in the obese mice at all time-points. However, the t(1/2,beta) and t(1/2,gamma) were shorter in the obese mice (9.7 min vs. 44.5 min and 60.3h vs. 85.6h, respectively), resulting in a lower AUC(0-infinity) (13,099 ng/m Lh vs. 15,384 ng/mL h). Had the dose of VCR been "capped", as is done in clinical practice, the AUC(0-infinity) would have been 36% lower in the obese mice than the controls. Tissue disposition of VCR revealed a biexponential decay from spleen, liver, and adipose. Interestingly, VCR slowly accumulated in the bone marrow of control mice, but had a slow decay from the marrow in the obese mice. Thus, obesity alters VCR PK, causing a lower overall exposure in circulation and bone marrow. Given the high prevalence of obesity, additional PK studies should be performed in obese subjects to optimize chemotherapy dosing regimens.
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PMID:Diet-induced obesity alters vincristine pharmacokinetics in blood and tissues of mice. 2008 1


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