review of literature on clinical pancreatology - The Pancreapedia

activator (uPA), its receptor (uPAR) and plasminogen activator inhibitor (PAI)-2, which mayplay an important role in progression <strong>of</strong> pancreatic adenocarcinoma. The overexpression <strong>of</strong>uPAR predicted short survival in PDAC patients. In one study, two different PDAC cell lineswere used to examine the effect <strong>of</strong> small interfering (si) RNAs to uPAR, uPA and PAI-2 onproliferation, apoptosis, migration and MAP kinase activation. In both pancreatic cancer celllines, siRNA to uPAR significantly inhibited cell proliferation and migration and stimulatedapoptosis, to a greater extent than uPA siRNA. When either PDAC cell line was treated withuPAR siRNA, the level <strong>of</strong> phosphorylated ERK (p-ERK) decreased substantially, whereasphosphorylated p38 (p-p38) increased when compared to non-silencing control, uPA siRNAor PAI-2 siRNA treatment. This resulted in enhancement <strong>of</strong> the p-p38/p-ERK ratio whichfavors cancer cell arrest. Interestingly, uPAR protein expression was suppressed by p-ERKinhibition and stimulated with p-p38 inhibition, suggesting the presence <strong>of</strong> a positivefeedback loop between uPAR and ERK. In summary, the data indicate that, <strong>of</strong> the uPAsystem, uPAR exerts the strongest effects on pancreatic cancer cells, by acting through theERK signaling pathway via a positive feedback loop. Disruption <strong>of</strong> this loop with uPAR siRNAor inhibitor <strong>of</strong> p-ERK, inhibits PDAC proliferation and migration and promotes apoptosis[403].Vitamin DEcological studies support the hypothesis that there is an association between vitamin D andpancreatic cancer mortality, but observational studies are somewhat conflicting. It wascontributed further data to this issue by analyzing the differences in pancreatic cancermortality across the eastern states <strong>of</strong> Australia and investigating if there is a role <strong>of</strong> vitaminD-effective ultraviolet radiation (DUVR), which is related to latitude. Mortality data from 1968to 2005 were sourced from the Australian General Record <strong>of</strong> Incidence and Mortality books.Mortality from pancreatic cancer was 10 percent higher in southern states than inQueensland, with those in Victoria recording the highest mortality risk (relative risk, 1.13; 95% confidence interval, 1.09 to 1.17). It was found a highly significant association betweenDUVR and pancreatic cancer mortality, with an estimated 1.5 percent decrease in the riskper 10 kJ/m 2 increase in yearly DUVR. These data show an association between latitude,DUVR, and pancreatic cancer mortality. Although this study cannot be used to infer causality,it supports the need for further investigations <strong>of</strong> a possible role <strong>of</strong> vitamin D in pancreaticcancer etiology [404].ProteomicsThe purpose <strong>of</strong> one <strong>review</strong> was to describe progress in the application <strong>of</strong> proteomicapproaches to advance The understanding <strong>of</strong> the biology <strong>of</strong> pancreatic cancer as well ascontribute potential protein biomarkers for this disease. It was <strong>review</strong>ed proteomic studiesrelating to pancreatic cancer that have been published in the past 12 months. It wasdescribed novel techniques for the simplification <strong>of</strong> complex protein samples, focusingparticularly on emerging methods for reducing the complexity <strong>of</strong> blood. Both the range <strong>of</strong>proteomic-based approaches and their sensitivities for the detection <strong>of</strong> low-abundanceproteins has increased. This provides promise that further research will yield insight intopancreatic cancer, including valuable information on proteins that may ultimately serve asbiomarkers for pancreatic cancer [405].Proteomics from lymph node metastasesThe aim <strong>of</strong> one study was to observe different protein pr<strong>of</strong>iles in pancreatic cancer with andwithout lymph node metastasis (LNM), and search for novel LNM-associated proteins, whichwould help to understand the metastatic mechanisms and provide targets for therapeutic