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)

The reproductive hormone, estrogen, contributes to the development of breast cancer by binding to the estrogen receptor (ER) in the nucleus, triggering cell growth and tumor promotion. In addition to its role in regulating target genes and signaling pathways involved in cell cycle progression, the ER-signaling pathway may regulate the expression of chromatin-remodeling gene, Metastasis-associated 3 (MTA3), or interact with chromatin-remodeling protein, Metastasis-associated 1 (MTA1). The invasion-suppressor gene, E-Cadherin (E-Cad), has recently been identified as a downstream target gene regulated by the ER-MTA3 pathway via the transcriptional repressor, Snail, and the ER-MTA3-Snail-E-Cad pathway has therefore been evoked to explain the clinical observation that ER expression in breast cancer is generally associated with a better clinical outcome. Since E-Cad may play an initiating role during breast tumorigenesis, we hypothesized that this ER-signaling pathway may also determine susceptibility to breast cancer, and examined this in a multigenic case-control study of 468 incident breast cancer patients and 470 healthy controls by genotyping the single nucleotide polymorphisms (SNPs) in five genes (ER, MTA3, Snail, E-Cad, and MTA1) in the ER-signaling pathways. Support for this hypothesis came from the observations that (a) with the exception of Snail, which interacted differently with reproductive risk factors in relation to breast cancer risk, there was a joint effect of the SNPs of these genes and estrogen-related risk factors (age at first full-term pregnancy and obesity, measured by the body mass index) on breast cancer risk (p < 0.05); (b) a trend toward increased risk of developing breast cancer was seen in women harboring a greater number of putative high-risk genotypes of these genes in ER-signaling pathways; (c) this association between risk and the number of putative high-risk genotypes was stronger and more significant in women thought to have experienced higher estrogen level, i.e., obese women; and (d) the risk effect conferred by obesity was only significant in women with a higher number of putative high-risk genotypes of the ER-signaling genes. These epidemiological findings highlight the role of newly identified novel ER-related pathways in breast cancer development and provide a more comprehensive picture of the tumorigenic effect of estrogen in breast cancer development.
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PMID:Breast cancer risk associated with genotypic polymorphism of the genes involved in the estrogen-receptor-signaling pathway: a multigenic study on cancer susceptibility. 1650 42

A relatively young patient with chronic gastroesophageal reflux disease (GERD), obesity, smoking, and alcohol intake presented with widespread metastatic disease in lymph nodes, liver and lungs from a lower esophageal adenocarcinoma extending into the gastroesophageal junction associated with Barrett's mucosa and dysplasia.A complete response was achieved with six cycles of chemotherapy that sustained for more than 4 years without further recurrence. Unfortunately, there was presence of esophageal metaplasia after complete response which eventually converted to low to high grade dysplasia and ultimately to a second primary localized lower esophageal adenocarcinoma that was treated with thoracoabdominal esophagectomy and lymphadenectomy. No evidence of disease recurrence was seen 2 years later. The pathogenesis of a recent increase in the incidence of GERD, Barrett's esophagus and lower esophageal adenocarcinoma are discussed. Surgery, radiotherapy and combination chemotherapy are effective in the early stages leading to tumor shrinkage and prolongation of life and even cure in some cases. Lower esophageal adenocarcinoma is frequently associated with Barrett's high-grade dysplasia. Since there has been a dramatic increase in the incidence of Barrett's dysplasia, appropriate surveillance with upper gastrointestinal endoscopy and preventive strategies, such as the use of aspirin, cyclo-oxygenase II inhibitors and other nonsteroidal antiinflammatory drugs known to be chemopreventive agents against colon, esophagus, gastric and bladder cancers, need to be studied.
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PMID:Esophageal adenocarcinoma arising from Barrett's dysplasia: a case report of double occurrence and prolonged survival after chemotherapy. 1698 98

Gastric adenocarcinoma is the most common malignancy of the upper gastrointestinal tract. During the past two decades it has migrated toward the gastroesophageal junction. Gastroesophageal reflux and obesity may play a role. Recent research suggests that a number of biologic and molecular differences exist in patients with gastric cancer. Further investigation in these areas may help in predicting outcome and directing therapy. Gastric cancer is not a curable condition when metastases are present. However, postoperative chemotherapy plus chemoradiotherapy, in the Intergroup trial 0116, prolonged the overall and disease-free survival rates of patients after a curative (R0) resection. It should be considered the new standard of care in patients with gastric cancer who have undergone curative resection with stage Ib-IV disease. Preoperative therapy strategies may increase the likelihood of R0 resection and remain an area of active investigation. Finally, development of more active agents is needed for the treatment of metastatic tumors.
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PMID:Gastric cancer. 1703 Nov 30

Renal cell carcinoma (RCC) accounts for about 3% of all adult malignancies and its incidence is increasing. Smoking, obesity, and end-stage renal disease are important risk factors. Localized RCC may be cured with surgical excision. However, over one-third of patients eventually develop metastatic disease. While chemotherapy and radiation therapy are relatively ineffective for RCC, immunotherapy modestly extends survival and may lead to tumor regression and long-term survival in a small minority of patients. Recently, research into the pathology of genetic syndromes associated with RCC has led to remarkable advances in our understanding of the pathogenesis of sporadic RCC. Rational therapeutic agents developed from this understanding have established new treatment paradigms for this disease.
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PMID:Renal cell carcinoma: current status and emerging therapies. 1732 29

The skeleton is the most common site of metastasis in patients with advanced prostate cancer. Despite many advances in targeting skeletal metastases, the mechanisms behind the attraction of prostate cancer cells to the bone are not known. Osteoclast cathepsin K, due to its ability to effectively degrade bone matrix collagen I, has been implicated in colonization and growth of prostate tumours in the bone. Identification of new cathepsin K substrates in the bone microenvironment and the recent findings demonstrating its involvement in obesity and inflammation suggest additional roles for this enzyme in skeletal metastases of prostate cancer.
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PMID:Cathepsin K in the bone microenvironment: link between obesity and prostate cancer? 1763 27

In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all acknowledged risk factors, along with specific occupational and environmental factors. A familial history of renal carcinoma is also likely to increase the risk. Renal carcinoma may remain clinically occult for most of its course. The classic presentation of pain, haematuria, and flank mass occurs in only 9% of patients and is often indicative of advanced disease. Approximately 30% of patients with renal carcinoma present with metastatic disease, 25% with locally advanced renal carcinoma and 45% with localized disease. Metastases are typically found in the lung, soft tissue, bone, liver, cutaneous sites, and central nervous system. The most important staging technique is a computed tomography (CT) scan of the whole abdomen. Survival rates are more favourable for patients with tumours confined to the kidney. Five-year survival for patients with metastatic renal carcinoma is comprised between 0 and 20%. Radical nephrectomy is the standard intervention for renal cancer. Intrinsic resistance to chemotherapy has long been a hallmark of renal carcinoma. Limited options are available for the systemic therapy, and no chemotherapeutic regimen is accepted as a standard of care. Biologic agents represent the major effective therapies for widespread metastatic renal cancer. An antiangiogenic strategy, the neutralization of VEGF, can slow the growth rate of advanced cancer.
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PMID:Renal cancer. 1766 11

It has long been known that obesity modestly increases the risk of prostate cancer mortality. Only recently, however, have studies examined whether this association is due to an increased risk of aggressive disease and/or worse outcomes following initial diagnosis and treatment. This distinction is important, because if obesity increases the risk of metastasis and death following treatment, weight loss could be an effective adjunct treatment. We now have good evidence that obesity increases the risk of aggressive prostate cancer, but reduces the risk of low-grade, nonaggressive cancer. In addition, several studies have found that obesity increases the risk of biochemical recurrence following prostatectomy; however, the few studies that have examined more definitive end points, metastases and death, have been less consistent. Furthermore, there are no studies that have examined whether weight loss after diagnosis favorably affects prostate cancer outcome. While accepting the current limitations in our knowledge base, it is our opinion that it is appropriate for physicians to counsel their patients to lose weight following prostate cancer diagnosis and motivate this change in behavior by emphasising the likely benefit of improving long-term outcome.
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PMID:Obesity and prostate cancer mortality. 1792 21

PTP1B and T cell PTP (TC-PTP) are protein tyrosine phosphatases (PTPs) that share high sequence and structural homology yet play distinct physiological roles. While PTP1B plays a central role in metabolism and is an attractive drug target for obesity and type 2 diabetes, TC-PTP is necessary for the control of inflammation. In this review, we will discuss the growing evidence for the involvement of PTP1B in cancer, while proposing a role for TC-PTP in inflammation-induced tumorigenesis. Given the challenge of developing inhibitors specific for PTP1B alone, it is necessary to consider both enzymes and their roles in various cancer models.
Cancer Metastasis Rev 2008 Jun
PMID:PTP1B and TC-PTP: regulators of transformation and tumorigenesis. 1823 7

High dietary fat intake and obesity may increase susceptibility to certain forms of cancer. To study the interactions of dietary fat, obesity, and metastatic mammary cancer, we created a population of F(2) mice cosegregating obesity QTL and the MMTV-PyMT transgene. We fed the F(2) mice either a very-high-fat or a matched-control-fat diet and measured growth, body composition, age at mammary tumor onset, tumor number and severity, and formation of pulmonary metastases. SNP genotyping across the genome facilitated analyses of QTL and QTL x diet interaction effects. Here we describe development of the F(2) population (n = 615) which resulted from a cross between the polygenic obesity model M16i and FVB/NJ-TgN (MMTV-PyMT)(634Mul), effects of diet on growth and body composition, and QTL and QTL x diet and/or gender interaction effects for growth and obesity-related phenotypes. We identified 38 QTL for body composition traits that were significant at the genome-wide 0.05 level, likely representing nine distinct loci after accounting for pleiotropic effects. QTL x diet and/or gender interactions were present at 15 of these QTL, indicating that such interactions play a significant role in defining the genetic architecture of complex traits such as body weight and obesity.
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PMID:Genotype X diet interactions in mice predisposed to mammary cancer. I. Body weight and fat. 1828 34

High dietary fat intake and obesity may increase the risk of susceptibility to certain forms of cancer. To study the interactions of dietary fat, obesity, and metastatic mammary cancer, we created a population of F(2) mice cosegregating obesity QTL and the MMTV-PyMT transgene. We fed the F(2) mice either a very high-fat or a matched-control-fat diet, and we measured growth, body composition, age at mammary tumor onset, tumor number and severity, and formation of pulmonary metastases. SNP genotyping across the genome facilitated analyses of QTL and QTL x diet interaction effects. Here we describe effects of diet on mammary tumor and metastases phenotypes, mapping of tumor/metastasis modifier genes, and the interaction between dietary fat levels and effects of cancer modifiers. Results demonstrate that animals fed a high-fat diet are not only more likely to experience decreased mammary cancer latency but increased tumor growth and pulmonary metastases occurrence over an equivalent time. We identified 25 modifier loci for mammary cancer and pulmonary metastasis, likely representing 13 unique loci after accounting for pleiotropy, and novel QTL x diet interactions at a majority of these loci. These findings highlight the importance of accurately modeling not only the human cancer characteristics in mice but also the environmental exposures of human populations.
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PMID:Genotype X diet interactions in mice predisposed to mammary cancer: II. Tumors and metastasis. 1828 25


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