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 role of obesity in relation to various disease processes is being increasingly studied, with reports over the last several years increasingly mentioning its association with worse outcomes in acute disease. Obesity has also gained recognition as a risk factor for severe acute pancreatitis (SAP).The mortality in SAP may be as high as 30% and is usually attributable to multi system organ failure (MSOF) earlier in the disease, and complications of necrotizing pancreatitis later [9-11]. To date there is no specific treatment for acute pancreatitis (AP) and the management is largely expectant and supportive. Obesity in general has also been associated with poor outcomes in sepsis and other pathological states including trauma and burns. With the role of unsaturated fatty acids (UFA) as propagators in SAP having recently come to light and with the recognition of acute lipotoxicity, there is now an opportunity to explore different strategies to reduce the mortality and morbidity in SAP and potentially other disease states associated with such a pathophysiology. In this review we will discuss the role of fat and implications of the consequent acute lipotoxicity on the outcomes of acute pancreatitis in lean and obese states and during acute on chronic pancreatitis.
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PMID:Role of pancreatic fat in the outcomes of pancreatitis. 2527 11

Pancreatic cancer carries a poor prognosis as most patients present with advanced disease and preferred chemotherapy regimens offer only modest effects on survival. Risk factors include smoking, obesity, heavy alcohol, and chronic pancreatitis. Pancreatic cancer has a complex relationship with diabetes, as diabetes can be both a risk factor for pancreatic cancer and a result of pancreatic cancer. Insulin, insulin-like growth factor-1 (IGF-1), and certain hormones play an important role in promoting neoplasia in diabetics. Metformin appears to reduce risk for pancreatic cancer and improve survival in diabetics with pancreatic cancer primarily by decreasing insulin/IGF signaling, disrupting mitochondrial respiration, and inhibiting the mammalian target of rapamycin (mTOR) pathway. Other potential anti-tumorigenic effects of metformin include the ability to downregulate specificity protein transcription factors and associated genes, alter microRNAs, decrease cancer stem cell proliferation, and reduce DNA damage and inflammation. Here, we review the most recent knowledge on risk factors and treatment of pancreatic cancer and the relationship between diabetes, pancreatic cancer, and metformin as a potential therapy.
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PMID:Diabetes, pancreatic cancer, and metformin therapy. 2542 78

The purpose of the review--to analyze the basic data of the role of chronic low-intensity inflammatory response as general biological process in the development and progression of chronic pancreatitis, obesity, and pancreatic cancer. Highlighted evidence from epidemiological studies showing that chronic pancreatitis and obesity are independent risk factors for pancreatic cancer, regardless of diabetes. Studied role of adipokines as Cytokines regulating of immune inflammatory response. Draws attention to the staging of pancreatic cancer in obesity.
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PMID:[Persistence of chronic inflammatory responses, role in the development of chronic pancreatitis, obesity and pancreatic cancer]. 2552 26

Pancreatic cancer (PC) will affect 48,960 persons in the United States and will result in 40,560 deaths in 2015, according to the American Cancer Society. On a global basis, at least 337,000 persons will be diagnosed with PC. The incidence of PC has increased slightly in the United States, though worldwide cases are likely to increase substantially due to the influence of cigarette smoking, rising obesity and type II diabetes. The development of PC is related to a state of chronic inflammation and insulin resistance. Well-established environmental and personal risk factors for PC include advancing age, cigarette smoking, second-hand tobacco smoke exposure, obesity, inherited familial cancer syndromes, Ashkenazi Jewish heritage, chronic pancreatitis, dietary factors, and diabetes. Other identified associations are human immunodeficiency virus infection, ABO blood group polymorphisms, hepatitis B virus, and Helicobacter pylori.
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PMID:Demographics, epidemiology, and inheritance of pancreatic ductal adenocarcinoma. 2572 48

Chronic pancreatitis (CP), a progressive inflammatory disease where acini are destroyed and replaced by fibrous tissue, increases the risk for pancreatic cancer. Risk factors include alcohol, smoking, and obesity. The effects of these risk factors are exacerbated in patients with mutations in genes that predispose to CP. The different environmental and genetic factors produce the same clinical phenotype; once CP develops, disease course is the same regardless of etiology. Critical questions still need to be answered to understand what modifies predisposition to develop CP in persons exposed to risk factors. We postulate that risk factors modulate endogenous pathways, with parathyroid hormone-related protein (PTHrP) signaling being one such pathway. In support, PTHrP levels are elevated in mice treated with alcohol, and in mouse models of cerulein- and pancreatic duct ligation-induced CP. Disrupting the Pthrp gene in acinar cells exerts protective effects (decreased edema, histological damage, amylase and cytokine release, and fibrosis) in these CP models. PTHrP levels are elevated in human CP. Currently, CP care lacks specific pharmacological interventions. Targeting PTHrP signaling may present a novel therapeutic strategy that inhibits pancreatic inflammation and fibrosis, especially since the risk of developing pancreatic cancer is strongly associated with duration of chronic inflammation.
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PMID:Role of Parathyroid Hormone-Related Protein Signaling in Chronic Pancreatitis. 2609 61

Pancreatic cancer (PC) remains one of the worst cancers, with almost uniform lethality. PC risk is associated with westernized diet, tobacco, alcohol, obesity, chronic pancreatitis, and family history of pancreatic cancer. New targeted agents and the use of various therapeutic combinations have yet to provide adequate treatments for patients with advanced cancer. To design better preventive and/or treatment strategies against PC, knowledge of PC pathogenesis at the molecular level is vital. With the advent of genetically modified animals, significant advances have been made in understanding the molecular biology and pathogenesis of PC. Currently, several clinical trials and preclinical evaluations are underway to investigate novel agents that target signaling defects in PC. An important consideration in evaluating novel drugs is determining whether an agent can reach the target in concentrations effective to treat the disease. Recently, we have reported evidence for chemoprevention of PC. Here, we provide a comprehensive review of current updates on molecularly targeted interventions, as well as dietary, phytochemical, immunoregulatory, and microenvironment-based approaches for the development of novel therapeutic and preventive regimens. Special attention is given to prevention and treatment in preclinical genetically engineered mouse studies and human clinical studies.
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PMID:Molecular Targeted Intervention for Pancreatic Cancer. 2626 22

Pancreatic cancer is a disease with increasing incidence and high (and nearly unchanged) lethality that is caused mainly due to its late diagnosis. Risk factors for neoplastic transformation are especially chronic pancreatitis, diabetes mellitus, but also obesity and smoking. The search for suitable early markers becomes a key element of research in this area. Such markers could be microRNAs, short single-stranded RNA molecules functioning as regulators of translation. This article serves as a review of contemporary evidence of microRNA in diabetes mellitus and pancreatic cancer.
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PMID:[miRNA as a new marker of diabetes mellitus and pancreatic carcinoma progression]. 2631 Oct 27

Pancreatic cancer is an aggressive tumor with a very poor prognosis, lack of early diagnostic symptoms and highly resistant to therapy. Its incidence is approximately equal to the mortality rate. Even though in recent years progress has been made in defining the morphological and key genetic changes, it is still unclear which factors trigger its occurrence. Some risk factors are age, gender and race, genetic susceptibility, dietary factors, fever, chronic pancreatitis, diabetes and physical inactivity. Studies have shown that an increase in BMI consequently leads to an increased risk of malignancies, including pancreatic cancer. Research based on adipokines and their role in obesity and the occurrence of pancreatic cancer are the potential for a possible future therapeutic interventions.
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PMID:[CORRELATION BETWEEN OBESITY AND PANCREATIC CANCER]. 2650 75

Although the relationship between diabetes and pancreatic cancer has been studied, the effects of glycemic control on pancreatic cancer have never been evaluated. This study investigates the relationship between glycemic control and pancreatic cancer.Data from 1 million National Health Insurance beneficiaries were screened. The study cohort consisted of 46,973 diabetic patients and 652,142 nondiabetic subjects. Of the patients with diabetes, 1114 who had been admitted for hyperglycemic crisis episodes were defined as having poorly controlled diabetes. All adult beneficiaries were followed from January 1, 2005 to December 31, 2013, to determine whether pancreatic cancer was diagnosed. The Cox regression model was applied to compare the adjusted hazards for potential confounders.After controlling for age, sex, urbanization level, socioeconomic status, chronic liver disease, hypertension, coronary artery disease, hyperlipidemia, malignancies, smoking, chronic obstructive pulmonary disease, obesity, history of alcohol intoxication, chronic renal insufficiency, biliary tract disease, chronic pancreatitis, Charlson Comorbidity Index score, and high-dimensional propensity score, the adjusted hazard ratio of pancreatic cancer was 2.53 (95% confidence interval 1.96-3.26) in patients with diabetes. In diabetic patients with poor glycemic control, the hazard ratio of pancreatic cancer was significantly higher (hazard ratio 3.61, 95% confidence interval 1.34-9.78).This cohort study reveals a possible relationship between diabetes and pancreatic cancer. Moreover, poorly controlled diabetes may be associated with a higher possibility of pancreatic cancer.
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PMID:Effect of glycemic control on the risk of pancreatic cancer: A nationwide cohort study. 3126 18

Pancreatic ductal adenocarcinoma is associated with a poor prognosis and a high case-fatality rate. The reasons for poor prognosis are low rates of curative resection due to local infiltration and distant metastasis. To increase survival rates of patients with pancreatic cancer, early detection through surveillance and screening is important. However, screening could only be cost-effective in high-risk populations. Identification of significant risk factors therefore assumes significance. Risk factors could be non-modifiable or modifiable. Non-modifiable risk factors include increasing age, familial cancer syndromes, Afro-American race, hereditary and other forms of chronic pancreatitis, diabetes, and non-O blood group. Important modifiable risk factors include smoking, obesity, dietary factors such as non-vegetarian diet, and toxins. Preventive strategies at the population level and an effective screening program targeted at high-risk people may help in prevention and early detection of pancreatic ductal adenocarcinoma.
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PMID:Modifiable and non-modifiable risk factors for pancreatic cancer: A review. 2746 82


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