Pancreatic juice prostaglandin e2 concentrations are elevated in chronic pancreatitis and improve detection of early disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Abu Dayyeh BK
PROVIDER: S-EPMC4418410 | biostudies-other | 2015
REPOSITORIES: biostudies-other
Similar Datasets
Project description:BACKGROUND: The predominance of secretory IgA (S-IgA) in intestinal secretions compared with blood is well established, but concentrations of this protein in pancreatic juice and its origin, especially in chronic pancreatitis, are unknown. AIMS: To investigate the role of S-IgA in chronic pancreatitis. PATIENTS: Twenty one patients with chronic pancreatitis (group I), three patients with proven malignancies (group II), and 12 patients without pancreatic disease (group III). METHODS: Pure human pancreatic juice was collected endoscopically in four fractions after consecutive stimulation with secretin and cholecystokinin (CCK). Samples were analysed for S-IgA, protein, trypsinogen, and proteolytic activity. RESULTS: The S-IgA level was significant increased in fraction 1 of pancreatic juice of group I (1210 (1411) ng/ml) compared with controls (33 (70) ng/ml). Protein concentrations and trypsinogen content were lower in group I than in the other groups. Proteolytic activity could be observed in 53% of all 133 pancreatic juice samples, but in 87% of fraction 1. In pancreatic tissue of three patients with chronic pancreatitis both IgA and secretory component were detected by immunohistology. Expression of the secretory component by human pancreatic epithelial cells was increased in patients with chronic pancreatitis compared with normal controls. The concentration of S-IgA in pancreatic juice did not correlate with the serum S-IgA level. In contrast, serum levels of S-IgA were decreased in patients with chronic pancreatitis. CONCLUSION: There are high levels of S-IgA in human pancreatic juice following chronic inflammation and a protective role is suggested for this immunoglobulin.
| S-EPMC1727049 | biostudies-other
Project description:OBJECTIVE: Acute pancreatitis is one the important causes of systemic inflammatory response syndrome (SIRS). SIRS results in gut barrier dysfunction that allows bacterial translocation and pancreatic infection to occur. Indomethacin has been used to reduce inflammatory process and bacterial translocation in experimental models. The purpose of this study was to determine the effect of inhibition of prostaglandin E2 (PGE2) production on pancreatic infection. MATERIALS AND METHODS: An experimental model of severe acute pancreatitis (AP) was utilized. The animals were divided into three groups: sham (surgical procedure without AP induction); pancreatitis (AP induction); and indomethacin (AP induction plus administration of 3 mg/kg of indomethacin). Serum levels of interleukin (IL)-6 and IL-10, PGE2, and tumor necrosis factor (TNF)-alpha were measured 2 h after the induction of AP. We analyzed the occurrence of pancreatic infection with bacterial cultures performed 24 h after the induction of AP. The occurrence of pancreatic infection (considered positive when the CFU/g was >105), pancreatic histologic analysis, and mortality rate were studied. RESULTS: In spite of the reduction of IL-6, IL-10, and PGE2 levels in the indomethacin group, TNF-alpha level, bacterial translocation, and pancreatic infection were not influenced by administration of indomethacin. The inhibition of PGE2 production did not reduce pancreatic infection, histologic score, or mortality rate. CONCLUSION: The inhibition of PGE2 production was not able to reduce the occurrence of pancreatic infection and does not have any beneficial effect in this experimental model. Further investigations will be necessary to discover a specific inhibitor that would make it possible to develop an anti-inflammatory therapy.
| S-EPMC2225519 | biostudies-other
Project description:Background:Periostin is a matricellular protein that induces fibrillogenesis and activates cell migration. It is overexpressed in common fibrotic diseases and is also associated with abdominal adiposity/ectopic fat phenotypes. The study aimed to investigate circulating levels of periostin in health and after an attack of pancreatitis, as well as their associations with abdominal adiposity/ectopic fat phenotypes. Methods:Blood samples were obtained from healthy controls, as well as definite chronic pancreatitis (CP) and acute pancreatitis (AP) individuals during follow-up visits. Fat depositions in the pancreas, liver, skeletal muscle, as well as visceral and subcutaneous fat volumes, were quantified with the use of magnetic resonance imaging. A series of multivariable analyses were conducted, accounting for possible confounders. Results:A total of 121 individuals were included. Periostin levels were significantly higher in the CP group compared with the other groups in both unadjusted (F = 3.211, P = 0.044) and all adjusted models (F = 4.165, P = 0.019 in the most adjusted model). Intra-pancreatic fat deposition (but not the other fat phenotypes) was significantly associated with periostin concentration in the CP group (? = 49.63, P = 0.034) and explained most of its variance (32.0%). Conclusions:Individuals with CP, but not healthy individuals or those after clinical resolution of AP, are characterized by elevated circulating levels of periostin that are positively associated with intra-pancreatic fat deposition.
| S-EPMC7430919 | biostudies-literature
Project description:Pancreatic stellate cells are source of dense fibrotic stroma, a constant pathological feature of chronic pancreatitis and pancreatic adenocarcinoma. We observed correlation between levels of cyclooxygenase 2 (COX-2) and its product prostaglandin E2 (PGE2) and the extent of pancreatic fibrosis. The aims of this study were to delineate the effects of PGE2 on immortalized human pancreatic stellate cells (HPSCs) and to identify the receptor involved.Immunohistochemistry, reverse transcription-polymerase chain reaction and quantitative reverse transcription-polymerase chain reaction were used to assess COX-2, extracellular matrix, and matrix metalloproteinase gene expression. Eicosanoid profile was determined by liquid chromatography-tandem mass spectrometry. Human pancreatic stellate cell proliferation was assessed by MTS assay, migration by Boyden chamber assay, and invasion using an invasion chamber. Transient silencing was obtained by small interfering RNA.Human pancreatic stellate cells express COX-2 and synthesize PGE2. Prostaglandin E2 stimulated HPSC proliferation, migration, and invasion and stimulated expression of both extracellular matrix and matrix metalloproteinase genes. Human pancreatic stellate cells expressed all 4 EP receptors. Only blocking the EP4 receptor resulted in abrogation of PGE2-mediated HPSC activation. Specificity of EP4 for the effects of PGE2 on stellate cells was confirmed using specific antagonists.Our data indicate that PGE2 regulates pancreatic stellate cell profibrotic activities via EP4 receptor, thus suggesting EP4 receptor as useful therapeutic target for pancreatic cancer to reduce desmoplasia.
| S-EPMC3600062 | biostudies-literature
Project description:Isolated islets of the rat labelled with myo-[3H]inositol showed decreased accumulation of total inositol phosphates (InsPs) and [3H]polyphosphoinositide hydrolysis in response to glucose after preincubation with prostaglandin E2 (PGE2). The response was concentration-dependent and specific for PGE2. PGE2 did not affect basal [3H]phosphoinositide hydrolysis or InsPs accumulation. Pertussis-toxin pretreatment antagonized the response to PGE2, whereas 8-bromo cyclic AMP was without effect. The PGE2-induced decrease in InsPs may contribute to the suppression of insulin secretion.
| S-EPMC1138660 | biostudies-other
Project description:Age-standardized incidence rates for pancreatic cancer (PC) in men have increased by 25% from 1957 to 2011 in Finland. The average age of diagnosis for PC is 69 years in Nordic males, whereas the average age of diagnosis of chronic pancreatitis (CP) is 40-50 years, but the cases overlap in age. By radiology the evaluation of a pancreatic mass, i.e. the differential diagnosis between CP and PC is often difficult. Preoperative needle biopsies are difficult to obtain and are demanding to interpret. New blood based biomarkers are needed. The accuracy of the only established biomarker for PC, CA 19-9 is rather poor in differentiating between benign and malignant mass of the pancreas. In this study, we have performed mass spectrometry HDMSE analysis of serum samples from patients with chronic pancreatitis and pancreatic cancer. We have quantified 652 proteins and performed detailed statistical analysis such as principal component analysis, orthogonal partial least square discriminant analysis and receiver operating curve analysis.
2017-06-09 | PXD005144 | Pride
Project description:Pancreatic cancer has been increasing in importance in Shanghai over the last four decades. The etiology of the disease is still unclear. Evidence suggests that the COX-2 pathway, an important component of inflammation, may be involved in the disease. We aimed to evaluate the association between urinary prostaglandin E2 metabolite (PGE-M) level and risk of pancreatic cancer. From a recent population-based case-control study in Shanghai, 200 pancreatic ductal adenocarcinoma cases and 200 gender- and age- frequency matched controls were selected for the present analysis. Urinary PGE-M was measured with a liquid chromatography/mass spectrometric assay. Adjusted unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A positive association was observed between PGE-M leve and pancreatic cancer risk: OR = 1.63 (95% CI 1.01-2.63) for the third tertile compared to the first. Though the interactions were not statistically significant, the associations tended to be stronger among subjects with diabetes history (OR = 3.32; 95% CI 1.20-9.19) and higher meat intake (OR = 2.12; 95% CI 1.10-4.06). The result suggests that higher urinary PGE-M level may be associated with increased risk of pancreatic ductal adenocarcinoma.
| S-EPMC4332509 | biostudies-literature
Project description:Purpose: The measurement of mutations in pancreatic juice samples collected from the duodenum during endoscopic ultrasound (EUS) may improve the diagnostic evaluation of patients undergoing pancreatic surveillance. Our aim was to evaluate the accuracy of using pancreatic juice mutation concentrations to predict the presence and histologic grade of neoplasia in the pancreas.Experimental Design: Digital next-generation sequencing (NGS) of pancreatic juice DNA using a targeted 12-gene panel was performed on 67 patients undergoing pancreatic evaluation during EUS, including patients with pancreatic ductal adenocarcinoma, patients who subsequently underwent pancreatic resection for precursor lesions, patients undergoing surveillance for their familial/inherited susceptibility to pancreatic cancer, and normal pancreas disease controls.Results: Patients with pancreatic cancer or high-grade dysplasia as their highest grade lesion had significantly higher pancreatic juice mutation concentrations than all other subjects (mean/SD digital NGS score; 46.6 ± 69.7 vs. 6.2 ± 11.6, P = 0.02). Pancreatic juice mutation concentrations distinguished patients with pancreatic cancer or high-grade dysplasia in their resection specimen from all other subjects with 72.2% sensitivity and 89.4% specificity [area under the curve (AUC) = 0.872]. Mutant TP53/SMAD4 concentrations could distinguish patients with pancreatic cancer or high-grade dysplasia in their resection specimen from all other subjects with 61.1% sensitivity and 95.7% specificity (AUC = 0.819). Among 31 high-risk individuals under surveillance, 2 of the 3 individuals with most abnormal pancreatic juice mutation profiles also had the most abnormalities on pancreatic imaging.Conclusions: Pancreatic juice mutation analysis using digital NGS has potential diagnostic utility in the evaluation of patients undergoing pancreatic surveillance. Clin Cancer Res; 24(12); 2963-74. ©2018 AACRSee related commentary by Lipner and Yeh, p. 2713.
| S-EPMC6435263 | biostudies-literature
Project description:Age-standardized incidence rates for pancreatic cancer (PC) in men have increased by 25% from 1957 to 2011 in Finland. The average age of diagnosis for PC is 69 years in Nordic males, whereas the average age of diagnosis of chronic pancreatitis (CP) is 40-50 years, but the cases overlap in age. By radiology the evaluation of a pancreatic mass, i.e. the differential diagnosis between CP and PC is often difficult. Preoperative needle biopsies are difficult to obtain and are demanding to interpret. New blood based biomarkers are needed. The accuracy of the only established biomarker for PC, CA 19-9 is rather poor in differentiating between benign and malignant mass of the pancreas. In this study, we have performed mass spectrometry HDMSE analysis of serum samples from patients with chronic pancreatitis and pancreatic cancer. We have quantified 652 proteins and performed detailed statistical analysis such as principal component analysis, orthogonal partial least square discriminant analysis and receiver operating curve analysis.
2018-08-31 | MSV000082883 | MassIVE
Project description:Pancreatitis is a fibro-inflammatory disorder of the pancreas that can occur acutely or chronically as a result of the activation of digestive enzymes that damage pancreatic cells, which promotes inflammation. Chronic pancreatitis with persistent fibro-inflammation of the pancreas progresses to pancreatic cancer, which is the fourth leading cause of cancer deaths across the globe. Pancreatic cancer involves cross-talk of inflammatory, proliferative, migratory, and fibrotic mechanisms. In this review, we discuss the role of cytokines in the inflammatory cell storm in pancreatitis and pancreatic cancer and their role in the activation of SDF1?/CXCR4, SOCS3, inflammasome, and NF-?B signaling. The aberrant immune reactions contribute to pathological damage of acinar and ductal cells, and the activation of pancreatic stellate cells to a myofibroblast-like phenotype. We summarize several aspects involved in the promotion of pancreatic cancer by inflammation and include a number of regulatory molecules that inhibit that process.
| S-EPMC7577953 | biostudies-literature