Mutation Profile and Fluorescence In Situ Hybridization Analyses Increase Detection of Malignancies in Biliary Strictures.

Background & Aims: It is a challenge to detect malignancies in biliary strictures. Various sampling methods are available to increase diagnostic yield, but these require additional procedure time and expertise. We evaluated the combined accuracy of fluorescence in situ hybridization (FISH) and polymerase chain reaction-based DNA mutation profiling (MP) of specimens collected using standard brush techniques.

Diagnostic and therapeutic biomarkers in pancreaticobiliary malignancy.

Pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) are two malignancies that carry significant morbidity and mortality. The poor prognoses of these cancers are strongly related to lack of effective screening modalities as well as few therapeutic options. In this review, we highlight novel biomarkers that have the potential to be used as diagnostic, prognostic and predictive markers.

Comparison of His and GST tagged versions of recombinant pancreatitis associated protein 2 in modulation of inflammatory responses.

Objective And Design: Pancreatitis associated proteins (PAP) are highly upregulated in acute pancreatitis and other inflammatory states and have been shown to possess immunomodulatory properties. However, continued study of PAP has been hampered by the ability to effectively isolate appropriate amounts of protein from pancreatic juice or efficient generation of recombinant proteins. Here we describe two different methods for generating recombinant PAP2 protein (rPAP2), using either His or GST tagged bacterial methodology with comparison of function.

Administration of anti-Reg I and anti-PAPII antibodies worsens pancreatitis.

Context: The regeneration protein family (Reg), which includes Reg I and PAPII, is expressed in pancreas acinar cells, and increases in acute pancreatitis. We have demonstrated that Reg gene knockdown worsens severity of acute pancreatitis in the rat and hypothesize that the proteins offer a protective effect in this disease.

Objective: We investigated the ability of anti-Reg and anti-PAP antibody to neutralize pancreatic Reg protein and affect pancreatitis severity.

Pancreatic regenerating protein I in chronic pancreatitis and aging: implications for new therapeutic approaches to diabetes.

Objectives: We investigated the relationship of pancreatic regenerating protein (reg) in models of acinar cell atrophy and aging, and the effect of reg I protein replacement on glucose tolerance.

Methods: Rats underwent pancreatic duct ligation (PDL) and were followed through 12 months. Aging rats were studied at 12 and 20 months.

Mutational characterization of pancreatitis-associated protein 2 domains involved in mediating cytokine secretion in macrophages and the NF-kappaB pathway.

Pancreatitis-associated protein 2 (PAP2) is a member of the Reg3 gene family and is classified as a group 7 C-type lectin-like protein. In rats, each of the three PAP isoforms has independent immunologic functional effects on macrophages. We have previously shown that PAP2 up-regulates inflammatory cytokines in macrophages in a dose-dependent manner and acts through NF-kappaB mechanisms.

Pancreatitis-associated protein 2 modulates inflammatory responses in macrophages.

Pancreatitis-associated proteins (PAP) are stress-induced secretory proteins that are implicated in immunoregulation. Previous studies have demonstrated that PAP is up-regulated in acute pancreatitis and that gene knockdown of PAP correlated with worsening severity of pancreatitis, suggesting a protective effect for PAP. In the present study, we investigated the effect of PAP2 in the regulation of macrophage physiology.

Small-interference RNA gene knockdown of pancreatitis-associated proteins in rat acute pancreatitis.

Objectives: Pancreatitis-associated proteins (PAPs) are induced in acute pancreatitis and antisense-mediated gene knockdown of PAP decreased PAP gene expression and worsened pancreatitis. Here, we investigated the effect of a more stable inhibition of PAP using small-interference RNA gene knockdown in vitro and in an in vivo model of experimental pancreatitis.

Methods: Pancreatitis-associated protein-specific siRNA was administered to AR42J cell cultures or rats induced with pancreatitis.

Use of gene expression profiles in cells of peripheral blood to identify new molecular markers of acute pancreatitis.

Hypothesis: Blood leukocytes play a major role in mediating local and systemic inflammation during acute pancreatitis. We hypothesize that peripheral blood mononuclear cells (PBMCs) in circulation exhibit unique changes in gene expression and could provide a "reporter" function that reflects the inflammatory response in the pancreas with acute pancreatitis.

Design: To determine specific changes in blood leukocytes during acute pancreatitis, we studied the gene transcription profile in PBMCs in a rat model of experimental pancreatitis (sodium taurocholate).