Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

Although obesity is known as a risk factor for several human cancers, the association of obesity with cancer recurrence and metastasis remains to be characterized. Here, B16-BL6 melanoma and Lewis lung carcinoma cells were intravenously injected into diabetic (db/db) and obese (ob/ob) mice. The number of experimental lung colonies was markedly promoted in these mice when compared with C57BL/6 mice. In contrast, tumor growth at the implanted site was comparable when cells were inoculated orthotopically. The use of B16-BL6 cells stably transfected with the luciferase gene revealed that the increased metastasis reflected a difference mainly within 6 hr after the intravenous inoculation of tumor cells. Administration of recombinant leptin in ob/ob mice abolished the increase in metastasis early on as well as the decrease in the splenic NK cell number. In addition, depletion of NK cells by an anti-asialo-GM1 antibody abrogated the enhanced metastasis in db/db mice. These results demonstrate that metastasis is markedly promoted in diabetic and obese mice mainly because of decreased NK cell function during the early phase of metastasis.
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PMID:Severe pulmonary metastasis in obese and diabetic mice. 1699 95

Guggulsterone is a plant polyphenol traditionally used to treat obesity, diabetes, hyperlipidemia, atherosclerosis, and osteoarthritis, possibly through an anti-inflammatory mechanism. Whether this steroid has any role in cancer is not known. In this study, we found that guggulsterone inhibits the proliferation of wide variety of human tumor cell types including leukemia, head and neck carcinoma, multiple myeloma, lung carcinoma, melanoma, breast carcinoma, and ovarian carcinoma. Guggulsterone also inhibited the proliferation of drug-resistant cancer cells (e.g., gleevac-resistant leukemia, dexamethasone-resistant multiple myeloma, and doxorubicin-resistant breast cancer cells). Guggulsterone suppressed the proliferation of cells through inhibition of DNA synthesis, producing cell cycle arrest in S-phase, and this arrest correlated with a decrease in the levels of cyclin D1 and cdc2 and a concomitant increase in the levels of cyclin-dependent kinase inhibitor p21 and p27. Guggulsterone-induced apoptosis as indicated by increase in the number of Annexin V- and TUNEL-positive cells, through the downregulation of anti-apoptototic products. The apoptosis induced by guggulsterone was also indicated by the activation of caspase-8, bid cleavage, cytochrome c release, caspase-9 activation, caspase-3 activation, and PARP cleavage. The apoptotic effects of guggulsterone were preceded by activation of JNK and downregulation of Akt activity. JNK was needed for guggulsterone-induced apoptosis, inasmuch as inhibition of JNK by pharmacological inhibitors or by genetic deletion of MKK4 (activator of JNK) abolished the activity. Overall, our results indicate that guggulsterone can inhibit cell proliferation and induce apoptosis through the activation of JNK, suppression of Akt, and downregulation of antiapoptotic protein expression.
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PMID:Guggulsterone inhibits tumor cell proliferation, induces S-phase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products. 1747 22

The development of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands for the treatment of diseases including metabolic syndrome, diabetes and obesity has been hampered due to contradictory findings on their potential safety. For example, while some reports show that ligand activation of PPARbeta/delta promotes the induction of terminal differentiation and inhibition of cell growth, other reports suggest that PPARbeta/delta ligands potentiate tumorigenesis by increasing cell proliferation. Some of the contradictory findings could be due in part to differences in the ligand examined, the presence or absence of serum in cell cultures, differences in cell lines or differences in the method used to quantify cell growth. For these reasons, this study examined the effect of ligand activation of PPARbeta/delta on cell growth of two human cancer cell lines, MCF7 (breast cancer) and UACC903 (melanoma) in the presence or absence of serum using two highly specific PPARbeta/delta ligands, GW0742 or GW501516. Culturing cells in the presence of either GW0742 or GW501516 caused upregulation of the known PPARbeta/delta target gene angiopoietin-like protein 4 (ANGPTL4). Inhibition of cell growth was observed in both cell lines cultured in the presence of either GW0742 or GW501516, and the presence or absence of serum had little influence on this inhibition. Results from the present studies demonstrate that ligand activation of PPARbeta/delta inhibits the growth of both MCF7 and UACC903 cell lines and provide further evidence that PPARbeta/delta ligands are not mitogenic in human cancer cell lines.
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PMID:Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines. 1805 22

Previous studies of leptin with cardiovascular disease (CVD) risk factors have been limited by clinical samples or lack of representation of the general population. This cross-sectional study, designed to examine whether leptin or insulin may mediate the endogenous relation of obesity with metabolic, inflammatory, and thrombogenic cardiovascular risk factors, included 522 men and 514 women aged >or=40 years who completed a physical examination during the third National Health and Nutrition Examination Survey. Participants were free of existing CVD, cancer (except non-melanoma skin cancer), diabetes, or respiratory disease. In multivariable analyses adjusted for race/ethnicity and lifestyle factors, waist circumference (WC) was positively associated with blood pressure, triglyceride, LDL cholesterol, total cholesterol:HDL ratio, apolipoprotein B, C-reactive protein (CRP), and fibrinogen concentrations, and negatively associated with HDL cholesterol and apolipoprotein A1 levels. The associations of WC with the metabolic CVD risk factors were largely attenuated after adjustment for insulin levels, while the associations of WC with the inflammatory and thrombogenic factors (CRP and fibrinogen, respectively) were largely explained by adjustment for leptin concentrations. However, leptin levels were not independently associated with CRP and fibrinogen in men and CRP in women when adjusted for WC. Positive associations of leptin and insulin with fibrinogen in women, independent of WC, were noted. These results suggest that insulin may be an important mediator of the association of obesity with metabolic but not inflammatory or thrombogenic CVD risk factors, while leptin does not appear to influence cardiovascular risk through a shared association with these risk factors. However, we cannot rule out the possibility that leptin and insulin influence cardiovascular risk in women through independent effects on fibrinogen concentrations.
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PMID:The relation of leptin and insulin with obesity-related cardiovascular risk factors in US adults. 1816 70

Gout patients might be at an increased risk of cancer because of obesity and heavy alcohol drinking, but uric acid has antioxidant properties, which may protect against carcinogenesis. We compared the incidence of cancer among 16 857 gout patients admitted to hospitals in Sweden during 1965-1995 with that of the national population. A total of 1425 malignant neoplasms were diagnosed in gout patients (standardized incidence ratio 1.25, 95% confidence limits 1.18, 1.31). The incidence of cancers of the oral cavity and pharynx, colon, liver and biliary tract, pancreas, lung, skin (melanoma and nonmelanoma), endometrium and kidney, as well as of malignant melanoma was increased among gout patients. With the exception of lung cancer, the risk remained elevated during the entire follow-up. This study provides no evidence of a protective effect of uric acid. Hyperuricemia may be an early manifestation of the carcinogenic process.
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PMID:A prospective study of gout and cancer. 1933 60

Epidemiological studies suggest that obesity increases the risk of developing several cancers, including melanoma. Obesity increases the expression of angiogenic factors, such as leptin, that may contribute to tumor growth. However, a direct cause and effect relationship between obesity and tumor growth has not been clearly established and the role of leptin in accelerating tumor growth is unclear. Our objective in the present study was to examine the rate of melanoma tumor growth in lean and obese mice with leptin deficiency or high levels of plasma leptin. We injected 1 x 10(6) B16F10 melanoma cells subcutaneously into lean wild type (WT), obese melanocortin receptor 4 knockout (MC4R(-/-)), which have high leptin levels, obese leptin-deficient (ob(-/-)), pair fed lean ob(-/-), and lean ob(+/-) mice. Mean body weights were 29.7 +/- 0.3 g (WT), 46.3 +/- 1.9 g (MC4R(-/-)), 63.7 +/- 0.9 g (ob(-/-)), 30.5 +/- 1.0 g (pair fed ob(-/-)) and 31.6 +/- 1.7 g (ob(+/-)). Tumors were much larger in the obese leptin deficient ob(-/-) (5.1 +/- 0.9 g) and obese MC4R(-/-) (5.1 +/- 0.7 g) than in lean WT (1.9 +/- 0.3 g) and ob(+/-) (2.8 +/- 0.7 g) mice. Prevention of obesity by pair feeding ob(-/-) mice dramatically reduced tumor weight (0.95 +/- 0.2 g) to a level that was significantly lower than in WT mice of the same weight. Tumor VEGF levels were the highest in the obese mouse tumors (p < 0.05), regardless of the host leptin levels. Except for the lean ob(+/-), MC4R(-/-) and ob(-/-) melanomas had the highest VEGF receptor 1 and VEGF receptor 2 protein expression (p < 0.01 and p < 0.05), respectively. These results indicate that obesity markedly increases melanoma tumor growth rate by mechanisms that may involve upregulation of VEGF pathways. Although tumor growth does not require host leptin, melanoma tumor growth may be accelerated by leptin.
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PMID:Obesity promotes melanoma tumor growth: role of leptin. 1971 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 has been implicated in several inflammatory diseases and in different types of cancer. Chronic inflammation induced by exposure to ultraviolet (UV) radiation has been implicated in various skin diseases, including melanoma and nonmelanoma skin cancers. As the relationship between obesity and susceptibility to UV radiation-caused inflammation is not clearly understood, we assessed the role of obesity on UVB-induced inflammation, and mediators of this inflammatory response, using the genetically obese (leptin-deficient) mouse model. Leptin-deficient obese (ob/ob) mice and wild-type counterparts (C57/BL6 mice) were exposed to UVB radiation (120 mJ/cm(2)) on alternate days for 1 month. The mice were then euthanized and skin samples collected for analysis of biomarkers of inflammatory responses using immunohistochemistry, western blotting, ELISA and real-time PCR. Here, we report that the levels of inflammatory responses were higher in the UVB-exposed skin of the ob/ob obese mice than those in the UVB-exposed skin of the wild-type non-obese mice. The levels of UVB-induced cyclooxygenase-2 expression, prostaglandin-E(2) production, proinflammatory cytokines (i.e., tumor necrosis factor-alpha, interleukin-1beta, interleukin-6), and proliferating cell nuclear antigen and cell survival signals (phosphatidylinositol-3-kinase and p-Akt-Ser(473)) were higher in the skin of the ob/ob obese mice than the those in skin of their wild-type non-obese counterparts. Compared with the wild-type non-obese mice, the leptin-deficient obese mice also exhibited greater activation of NF-kappaB/p65 and fewer apoptotic cells in the UVB-irradiated skin. Our study suggests for the first time that obesity in mice is associated with greater susceptibility to UVB-induced inflammatory responses and, therefore, obesity may increase susceptibility to UVB-induced inflammation-associated skin diseases, including the risk of skin cancer.
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PMID:Leptin deficiency-induced obesity exacerbates ultraviolet B radiation-induced cyclooxygenase-2 expression and cell survival signals in ultraviolet B-irradiated mouse skin. 2057 Jun 90

Weight, weight gain, and obesity account for approximately 20% of all cancer cases. Evidence on the relation of each to cancer is summarized, including esophageal, thyroid, colon, renal, liver, melanoma, multiple myeloma, rectum, gallbladder, leukemia, lymphoma, and prostate in men; and postmenopausal breast and endometrium in women. Different mechanisms drive etiologic pathways for these cancers. Weight loss, particularly among postmenopausal women, reduces risk for breast cancer. Among cancer patients, data are less robust, but we note a long history of poor outcomes after breast cancer among obese women. While evidence on obesity and outcomes for other cancers is mixed, growing evidence points to benefits of physical activity for breast and colon cancers. Dosing of chemotherapy and radiation therapy among obese patients is discussed and the impact on therapy-related toxicity is noted. Guidelines for counseling patients for weight loss and increased physical activity are presented and supported by strong evidence that increased physical activity leads to improved quality of life among cancer survivors. The "Five A's" model guides clinicians through a counseling session: assess, advise, agree, assist, arrange. The burden of obesity on society continues to increase and warrants closer attention by clinicians for both cancer prevention and improved outcomes after diagnosis.
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PMID:Obesity and cancer. 2050 89

Recent population-based epidemiological studies strongly hint towards a link between obesity and its occurrence as well as progression of several cancers including melanoma. Although effects of obesity on breast, colon and liver cancers have been extensively investigated, the links between obesity and melanoma remain largely unexplored. Present study aimed to understand the effect of high fat diet-induced weight gain on susceptibility of C57BL/6J mice to melanoma. For this, mice routinely were fed on high fat diet for 6 months (HFD mice). Subsequently, mouse melanoma cells were injected subcutaneously in control as well as HFD mice and followed for tumor initiation and progression. We provide strong evidence that diet-induced obesity leads to increased melanoma progression in male C57BL/6J mice. We observed that increased melanoma progression is associated with enhanced Cav-1 and FASN expression in tumors from HFD mice. Cav-1 and FASN are co-ordinately regulated and Cav-1 interacts with FASN in melanoma cells. Enhanced levels of Cav-1, FASN and pAkt control melanoma cell proliferation. Our study establishes a causative relationship between diet-induced obesity and melanoma progression as well as demonstrates that obesity affects important tumorigenic pathways in melanoma.
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PMID:Diet-induced obesity increases melanoma progression: involvement of Cav-1 and FASN. 2138 14


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