Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatic cancer is a rapidly fatal disease, and there is an urgent need for early detection markers and novel therapeutic targets. The current study has used a proteomic approach of two-dimensional (2D) gel electrophoresis and mass spectrometry (MS) to identify differentially expressed proteins in six cases of pancreatic adenocarcinoma, two normal adjacent tissues, seven cases of pancreatitis, and six normal pancreatic tissues. Protein extracts of individual sample and pooled samples of each type of tissues were separated on 2D gels using two different pH ranges. Differentially expressed protein spots were in-gel digested and identified by MS. Forty proteins were identified, of which five [i.e., alpha-amylase; copper zinc superoxide dismutase; protein disulfide isomerase, pancreatic; tropomyosin 2 (TM2); and galectin-1] had been associated previously with pancreatic disease in gene expression studies. The identified proteins include antioxidant enzymes, chaperones and/or chaperone-like proteins, calcium-binding proteins, proteases, signal transduction proteins, and extracellular matrix proteins. Among these proteins, annexin A4, cyclophilin A, cathepsin D, galectin-1, 14-3-3zeta, alpha-enolase, peroxiredoxin I, TM2, and S100A8 were specifically overexpressed in tumors compared with normal and pancreatitis tissues. Differential expression of some of the identified proteins was further confirmed by Western blot analyses and/or immunohistochemical analysis. These results show the value of a proteomic approach in identifying potential markers for early diagnosis and therapeutic manipulation. The newly identified proteins in pancreatic tumors may eventually serve as diagnostic markers or therapeutic targets.
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PMID:Protein expression profiles in pancreatic adenocarcinoma compared with normal pancreatic tissue and tissue affected by pancreatitis as detected by two-dimensional gel electrophoresis and mass spectrometry. 1560 67

Leukocyte infiltration is an early and critical event in the development of acute pancreatitis. However, the mechanism of leukocyte transmigration into the pancreas and the function of leukocytes in initiating acute pancreatitis are still poorly understood. Here, we studied the role of S100A9 (MRP14), a calcium binding protein specifically released by polymorph nuclear leukocytes (PMN), in the course of acute experimental pancreatitis. Acute pancreatitis was induced by repeated supramaximal caerulein injections in S100A9 deficient or S100A9 wild-type mice. We then determined S100A9 expression, trypsinogen activation peptide (TAP) levels, serum amylase and lipase activities, and tissue myeloperoxidase (MPO) activity. Cell-cell contact dissociation was analyzed in vitro with biovolume measurements of isolated acini after incubation with purified S100A8/A9 heterodimers, and in vivo as measurement of Evans Blue extravasation after intravenous application of S100A8/A9. Pancreatitis induced increased levels of S100A9 in the pancreas. However, infiltration of leukocytes and MPO activity in the lungs and pancreas during acute pancreatitis was decreased in S100A9-deficient mice and associated with significantly lower serum amylase and lipase activities as well as reduced intrapancreatic TAP-levels. Incubation of isolated pancreatic acini with purified S100A8/A9-heterodimers resulted in a rapid dissociation of acinar cell-cell contacts which was highly calcium-dependent. Consistent with these findings, in vivo application of S100A8/A9 in mice was in itself sufficient to induce pancreatic cell-cell contract dissociation as indicated by Evans Blue extravasation. These data show that the degree of intrapancreatic trypsinogen activation is influenced by the extent of leukocyte infiltration into the pancreas which, in turn, depends on the presence of S100A9 that is secreted from PMN. S100A9 directly affects leukocyte tissue invasion and mediates cell contact dissociation via its calcium binding properties.
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PMID:The calcium binding protein S100A9 is essential for pancreatic leukocyte infiltration and induces disruption of cell-cell contacts. 1845 88

In search of novel serological protein biomarkers for human colorectal cancer (CRC), we analyzed CRC tissues using two-dimensional difference in-gel electrophoresis (2D-DIGE) on a narrow range IPG strip (pH 5.5-6.7). By comparing tumor tissues with matched normal tissues in a pairwise manner (n = 6), we identified 34 up-regulated and 17 down-regulated spots with intensity changes greater than 2-fold (Student's t-test, p < 0.05). Expression of both mRNA and protein levels of four proteins, adenosylhomocysteinase, Nm23-H1, S100A8 and S100A9, in CRC tissues was further evaluated by semiquantitative RT-PCR and Western blot analysis. The results revealed that all four proteins were elevated in the tumor tissues. We also confirmed, by immunohistochemistry, that adenosylhomocysteinase and Nm23-H1 were overexpressed in tumor cell cytoplasm and that S100A8 and S100A9 proteins were strongly expressed in tumor infiltrating immune cells. Western blot analysis with fractionated plasma samples showed that S100A8 and S100A9 were significantly increased in the plasma of CRC patients (n = 77) and colorectal adenoma patients (n = 11), compared to healthy controls (n = 21). The area under a receiver operating characteristic (ROC) curve was 0.91 for S100A8 and 0.89 for S100A9, which was superior to the established tumor marker carcinoembryonic antigen with 0.78 for the area under the ROC curve. Some patients with inflammatory diseases such as pancreatitis also showed elevated levels of the proteins. Importantly, in comparison to the control group, both proteins showed a remarkable change at the early stage of cancer. Therefore, we suggest S100A8 and S100A9 as candidates for serological biomarkers in combination with other serum markers that aid CRC diagnosis.
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PMID:Identification of S100A8 and S100A9 as serological markers for colorectal cancer. 1918 48