Pancreatic cancer associated with obesity and diabetes: an alternative approach for its targeting

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Term Occurence Count Dictionary
obesity 39 endocrinologydiseases
type 2 diabetes mellitus 1 endocrinologydiseases
Insulin 3 endocrinologydiseasesdrugs
cysteamine 4 endocrinologydiseasesdrugs
diabetes mellitus 3 endocrinologydiseases
glucose intolerance 1 endocrinologydiseases
hyperglycemia 1 endocrinologydiseases
metformin 3 endocrinologydiseasesdrugs

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Select Drug Character Offset Drug Term Instance
Insulin 9330 and show infiltration of fat cells in the pancreas as a consequence of PC development [[37], [38]]. Insulin resistance is a hallmark of T2DM, in which insulin fails to trigger adequate glucose uptake, leading
Insulin 37126 factor for PC. In a post-prandial state, insulin maintains the levels of circulating glucose and FFAs. Insulin resistance is a condition in which the adipose and muscle tissues and to a lesser extent the pancreas,
Insulin 37295 tissues and to a lesser extent the pancreas, brain, liver and kidney are unable to respond to insulin. Insulin resistance is a hallmark of T2DM, leading to down-regulation of insulin signaling pathways (at the post-receptor
cysteamine 43489 [167]]. VNN1 is mainly responsible for the breakdown of pantetheine to pantothenic acid (vitamin B5) and cysteamine [[168]]. It is actively involved in inflammation, migration, stress, and glucose and lipid metabolism.
cysteamine 44142 compared to patients with T2DM alone [[170]]. VNN1 reduces inflammation in PCDM by altering the levels of cysteamine and glutathione. VNN1 along with cysteamine protect the pancreatic β-cells from the oxidative stress
cysteamine 44186 reduces inflammation in PCDM by altering the levels of cysteamine and glutathione. VNN1 along with cysteamine protect the pancreatic β-cells from the oxidative stress generated during streptozotocin-induced diabetes
cysteamine 44430 Enhanced γ-glutamylcysteine synthetase activity observed in vanin-1-/- deficient mice with low levels of cysteamine resulted in an accumulation of endogenous glutathione (GSH) levels [[172], [173]]. By contrast, over expression
metformin 38020 were higher risk for PC than long term diabetic population [[141]]. Pharmacological therapies like metformin (lowers blood glucose and insulin levels), sulfonylurea (promotes secretion of insulin from the pancreas)
metformin 38448 to 2008 recruited 973 PDAC patients among them 259 were diabetic. The diabetic patients who received metformin had a lower risk of PC compared to those who were not given metformin; whereas, insulin or insulin secretagogues
metformin 38518 diabetic patients who received metformin had a lower risk of PC compared to those who were not given metformin ; whereas, insulin or insulin secretagogues administered diabetic patients had a higher risk of PC [[144]].As
Select Disease Character Offset Disease Term Instance
diabetes mellitus 8753 collectively called metabolic X syndrome [[32]]. Further, obesity is a strong risk factor for type 2 diabetes mellitus (T2DM), cardiovascular diseases and even many types of cancers such as pancreatic, hematological, prostate
diabetes mellitus 39202 increase in circulatory FFAs secreted from AT causes lipotoxicity in β-cells, resulting in PC-associated diabetes mellitus (PCDM) [[145], [148], [149]]. After tumor resection, the increased survival of PC patients was associated
diabetes mellitus 39504 Association classified PCDM, which is induced by chronic pancreatitis and pancreatic surgery, as type3c diabetes mellitus [[151]]. Still, evidence describing how diabetes leads to PC or vice versa is lacking. Some of the key
glucose intolerance 8564 a multifactorial disease associated with several metabolic disorders including insulin resistance, glucose intolerance , dyslipidemia, and elevated blood pressure. All these disorders are collectively called metabolic X
hyperglycemia 47460 suggesting its role in stem cell stimulation and chemoresistance [[70]]. In case of diabetic population, hyperglycemia is a hallmark of T2DM which stimulates PC by promoting a epithelial to mesenchymal transition and expression
obesity 96 Title: Journal of Experimental & Clinical Cancer Research : CRPancreatic cancer associated with obesity and diabetes: an alternative approach for its targetingRamesh PothurajuSatyanarayana RachaganiWade M.
obesity 679 and radiotherapies. The risk factors associated with PC include several metabolic disorders such as obesity , insulin resistance and type 2 diabetes mellitus (T2DM). Studies have shown that obesity and T2DM are
obesity 769 disorders such as obesity, insulin resistance and type 2 diabetes mellitus (T2DM). Studies have shown that obesity and T2DM are associated with PC pathogenesis; however, their role in PC initiation and development remains
obesity 963 development remains obscure.Main bodySeveral biochemical and physiological factors associated with obesity and/or T2DM including adipokines, inflammatory mediators, and altered microbiome are involved in PC
obesity 1609 affected by metabolic alteration and pancreatic tumor progression.ConclusionsMetabolic diseases, such as obesity and T2DM, contribute PC development through altered metabolic pathways. Delineating key players in oncogenic
obesity 3248 sex (high incidence in men), gene mutations, cigarette smoking (nearly one quarter of all PC cases), obesity , chronic pancreatitis, and diabetes [[7], [8]].In PC, pancreatic stellate cells form a dense stromal
obesity 7324 consumption. Additionally, genetic factors such as mutation in the leptin pathway leads to monogenic obesity while chromosomal abnormalities results in syndromic obesity [[29]]. In the body, adipose tissue (AT)
obesity 7385 the leptin pathway leads to monogenic obesity while chromosomal abnormalities results in syndromic obesity [[29]]. In the body, adipose tissue (AT) plays an important role in the storage of triglycerides (TG),
obesity 8153 hypertrophy (increase in cell size) and hyperplasia (increase in cell number) [[30]]. Moreover, in obesity , heavy traffic of lipids inside the body leads to release of excess TG in the form of free fatty acids
obesity 8710 elevated blood pressure. All these disorders are collectively called metabolic X syndrome [[32]]. Further, obesity is a strong risk factor for type 2 diabetes mellitus (T2DM), cardiovascular diseases and even many types
obesity 8939 as pancreatic, hematological, prostate and breast cancers [[33]]. Recent studies have revealed that obesity and PC are strongly associated. For instance, a body mass index greater than 35 is one of the risk factors
obesity 9867 true (Fig. 1). In the present review, we have attempted to compress all the available literature on obesity -and diabetes-associated molecules involved in PC development. Several molecules have been characterized
obesity 9982 diabetes-associated molecules involved in PC development. Several molecules have been characterized in obesity -associated PC, whereas less is known about factors unique to diabetes-associated PC. These molecules
obesity 10218 focus for future investigations of the molecular oncology of cancer.Fig. 1A schematic representation of obesity - and diabetes-associated pancreatic cancer. High fat/caloric intake results in accumulation of excess
obesity 10371 High fat/caloric intake results in accumulation of excess fat, which further leads to development of obesity . a. In obesity, adipose tissue releases free fatty acids (FFAs), which enter circulation and accumulate
obesity 10386 intake results in accumulation of excess fat, which further leads to development of obesity. a. In obesity , adipose tissue releases free fatty acids (FFAs), which enter circulation and accumulate in the non-adipose
obesity 11153 and has a two-fold increased risk of PC incidence and mortality [[39], [42]]. However, link between obesity and PC is still not fully understood [[43]]. The current theory is that excess TG in obesity leads to
obesity 11246 between obesity and PC is still not fully understood [[43]]. The current theory is that excess TG in obesity leads to an increase in size and number of adipocytes, which results in devascularization, hypoxia,
obesity 12179 them, adiponectin and leptin are the most important and are therefore the focus here in discussing obesity -associated PC.AdiponectinAdiponectin is also referred to as AdipoQ, which acts on several tissues to
obesity 12537 monophosphate-activated protein kinase (AMPK) pathway. The expression of circulatory AdipoQ is decreased in obesity and diabetes. However, the role of circulating AdipoQ in PC remains debatable regarding its impact on
obesity 18357 decreases appetite and increases fatty acid oxidation through its receptor (OBR or LEPR). However, in obesity and diabetes, elevated circulatory levels of leptin do not drive the same appetite feedback responses
obesity 20213 metastasis occur via the JAK2/STAT3/MMP13 pathway [[68]] (Fig. 2).A high fat/caloric diet leads to obesity , insulin resistance and increased leptin levels, all of which contribute to pancreatic adiposity. The
obesity 21638 signaling axis targeting has been projected as potential mediator for benefitting PC patients with obesity . Overall, the effect of AdipoQ and leptin in the progression of PC is still under investigation in obese
obesity 22036 microorganisms belonging mostly to the phyla Firmicutes and Bacteroidetes, which play an important role in obesity and other metabolic disorders [[72]]. Recent evidences suggest that diet, environmental factors and
obesity 29281 role of gut microbiota in PC tumor progression could open up new avenues in PC therapy development.In obesity , pro-inflammatory cytokines are released from AT macrophages and infiltrate into AT; however the exact
obesity 29648 promoting angiogenesis and metastasis [[93]–[95]]. Therefore, the possible common mechanism by which obesity induces inflammation in several cancers (pancreatic, lymphoma and glioblastoma) might be through TNF-α-induced
obesity 30098 TNF-α-induced IL-6 to up-regulate STAT3 signaling [[101]]. Mice with PC tumors and diet-induced or genetic obesity expressed significantly higher STAT3 in the PC tumors. The up-regulation of STAT3 can drive PC progression
obesity 32461 attention due to its mitogenic signal and its angiogenic effects on AT [[114], [115]]. In the case of obesity , HGF is released from the AT and the resulting circulatory levels contribute to pancreatic cell proliferation
obesity 33685 and migration [[121]] and may be a novel target for growth factor-induced tumor growth.HyaluronanIn obesity , TG accumulates in the pancreas along with other organs and results in inflammation, higher expression
obesity 35727 [136]]. In conclusion, inhibition of HA synthesis may be a possible therapeutic strategy against PC and obesity -associated PC. Recently, PEGPH20 has gained interest to target HA for improving intratumoral microenvironment
obesity 43758 the liver leads to development of insulin resistance and eventual T2DM. Mice exhibiting diet-induced obesity and Zucker diabetic fatty rats (model for T2DM) have more VNN1 activity in plasma as well as higher
obesity 44911 MMP9 could serve as novel pharmacological targets to treat early asymptomatic PCDM patients.Impact of obesity and diabetes on acinar, ductal and islet cellsThe pancreas islets, acinar cells, and ducts of the gland
obesity 45286 (food intake) [[175]]. Feeding chronic high fat diet to Zucker diabetic fatty rats (model for both obesity and T2DM) showed excessive fat accumulation in pancreatic acinar cells and later resulted in acinar
obesity 46236 increased pancreatic ductal cell replication is a risk factor towards pancreatitis and pancreatic cancer in obesity and or type 2 diabetes subjects [[179]].Obesity and diabetes associated PC stem cellsStudies are suggesting
obesity 46672 markers in normal pancreas might be involved in the progression of PC and resistance to drugs [[183]]. In obesity , leptin treatment affected PC progression and increased pancreatic cancer stem cell markers such as
obesity 47873 involved in metabolic diseases associated with PC stem cells.ConclusionsSeveral studies suggest that obesity and T2DM increase the risk for PC development and its pathogenesis. However, mechanistic interplay responsible
obesity 48107 and progression of pancreatic tumor remains obscure. Recent studies on key players associated with obesity and diabetes such as adipocytokines, gut microbiota, adrenomedullin, hyaluronan, vanin and matrix metalloproteinase
obesity 48345 deciphered unknown linkage present across PC as well as PCDM. These mediators play central role in promoting obesity -and diabetes-associated pancreatic cancer, however, to date studies involving therapeutic targeting
obesity 48669 that there is an urgent need to delineate biomarkers as well as therapeutic target(s) involved in the obesity and T2DM associated PC development making inroads to prevent this highly lethal malignancy
type 2 diabetes mellitus 8746 disorders are collectively called metabolic X syndrome [[32]]. Further, obesity is a strong risk factor for type 2 diabetes mellitus (T2DM), cardiovascular diseases and even many types of cancers such as pancreatic, hematological, prostate

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