Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149521 (chronic pancreatitis)
 7,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When using gene expression profiling to understand human tumors, one is often confronted with long lists of genes that need to be further categorized into meaningful data. We performed a comprehensive evaluation and comparison of gene expression profiles obtained from pancreatic cancers to determine those genes most differentially expressed and thus with the most promise for translation into clinically useful targets. cDNA was prepared from 50 samples of normal pancreas or duodenal mucosal tissues, 7 samples of chronic pancreatitis, and 39 samples of pancreas cancer tissues or cancer cell lines and hybridized to the complete Affymetrix Human Genome U133 GeneChip set (arrays U133A and U133B) for simultaneous analysis of 45,000 fragments corresponding to 33,000 known genes and 6,000 expressed sequence tags. Genes expressed at levels at least 3-fold greater in the pancreatic cancers as compared with nonneoplastic tissues were identified. Three hundred seventy-seven Affymetrix fragments were identified as having > or = 3-fold expression levels in pancreas cancer specimens as compared with nonneoplastic tissues, corresponding to 234 known genes. Serial analysis of gene expression libraries (http://www.ncbi.nlm.nih.gov/SAGE/) of two normal pancreatic ductal cell cultures (HX and H126) were used to exclude 17 genes with high expression levels in the normal duct epithelium (more than five tags/library). Of the remaining 217 known genes, 75 have been previously reported as highly expressed in pancreatic cancers, while the remaining 142 genes are novel. We used principal components analysis (PCA) to identify the genes among these 217 identified as the most differentially expressed and specific to pancreatic cancer tissues or cell lines. Among the most differentially expressed genes identified by PCA were Mesothelin, Muc4, Muc5A/C, Kallikrein 10, Transglutaminase 2, Fascin, TMPRSS3 and stratifin. The differential expression identified by PCA for these genes indicates they are among the more attractive targets for novel therapeutic targets, tumor markers, or as a means of screening pancreatic cancer samples for information regarding tumor classification or potential therapeutic responses. Our findings were also compared in detail to the previously reported findings of highly expressed genes in other studies of global gene expression in pancreatic cancers. We found that robust changes in gene expression were most often identified by more than one gene expression platform. Forty genes were identified by more than one method (U133 oligonucleotide arrays, cDNA arrays or serial analysis of gene expression), and 6 of these genes were identified by all three methods. Our findings identify a novel set of genes as highly expressed in pancreatic cancer, validate the differential expression of previously reported genes, and provide additional support for those genes most differentially expressed to be translated into clinically useful targets.
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PMID:Highly expressed genes in pancreatic ductal adenocarcinomas: a comprehensive characterization and comparison of the transcription profiles obtained from three major technologies. 1469 72

Mesothelin, a cell surface glycoprotein present on normal mesothelial cells, has been reported to be expressed in pancreatic adenocarcinomas. We conducted this study to fully characterize mesothelin expression in surgically resected, formalin-fixed, paraffin-embedded tissue specimens of 18 pancreatic adenocarcinomas, 9 adenocarcinomas of the ampulla of Vater, 12 adenocarcinomas of the common bile duct, and 17 cases of chronic pancreatitis. Mesothelin immunostaining was performed using the antimesothelin monoclonal antibody 5B2. All 18 cases (100%) of pancreatic adenocarcinomas showed mesothelin expression, as did 8 (89%) of 9 cases of ampullar adenocarcinoma and all 12 cases (100%) of common bile duct adenocarcinoma. In all cases of pancreaticobiliary adenocarcinoma, the adjacent normal pancreas did not stain for mesothelin. Of 17 specimens of chronic pancreatitis, 16 were negative for mesothelin expression, and 1 case showed weak mesothelin staining of fewer than 5% of normal pancreatic ducts. Our results demonstrated mesothelin expression in the majority of pancreaticobiliary adenocarcinomas and no expression in normal pancreatic tissues and in chronic pancreatitis.
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PMID:Mesothelin is overexpressed in pancreaticobiliary adenocarcinomas but not in normal pancreas and chronic pancreatitis. 1641 32

This study was undertaken to determine whether recently identified proteins could be translated to clinical practice as markers to distinguish pancreatic adenocarcinoma from chronic pancreatitis on fine-needle aspirate (FNA) samples. Resected pancreatic tissue sections (n = 40) and FNA samples (n = 65) were stained for clusterin-beta, MUC4, survivin, and mesothelin. For each biomarker, the staining patterns in adenocarcinoma and in reactive ductal epithelium were evaluated and compared. Clusterin-beta stained reactive ductal epithelium significantly more frequently than pancreatic adenocarcinoma (P < .001). In comparison, MUC4 and mesothelin were expressed more frequently in pancreatic adenocarcinoma on tissue sections. Positive staining for MUC4 (91% vs 0%; P < .001) and mesothelin (62% vs 0%; P = .01) and absence of staining for clusterin-beta (90% vs 7%; P < .001) were noted significantly more frequently in adenocarcinoma cells than in reactive cells in FNA samples. Clusterin-beta and MUC4 can help distinguish reactive ductal epithelial cells from the cells of pancreatic adenocarcinoma in FNA samples.
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PMID:Biomarkers in Diagnosis of pancreatic carcinoma in fine-needle aspirates. 1701 94

To augment cytological diagnosis of pancreatic ductal adenocarcinoma (PDAC) in tissue samples obtained by minimally invasive endoscopic ultrasound-guided fine needle aspiration, we investigated whether a small set of molecular markers could accurately distinguish PDAC from chronic pancreatitis (CP). Expression levels of 29 genes were first determined by quantitative real-time RT-PCR in a training set of tissues in which the final diagnosis was PDAC (n=20) or CP (n=10). Using receiver operator characteristic curve analysis, we determined that the single gene with the highest diagnostic accuracy for discrimination of CP vs. PDAC in the training study was urokinase plasminogen activator receptor (UPAR; AUC value = 0.895, 95% CI=0.728-0.976). In the set of test tissues (n=14), the accuracy of UPAR decreased to 79%. However, we observed that the addition of 6 genes (EPCAM2, MAL2, CEA5, CEA6, MSLN and TRIM29; referred to as the 6-gene classifier) to UPAR resulted in high accuracy in both training and testing sets. Excluding 3 samples (out of 44; 7%) for which results of the UPAR/6-gene classifier were "undefined," the accuracy of the UPAR/6-gene classifier was 100% in training samples (n=29), 92% in 12 test samples (p=0.004 that results were randomly generated; p=0.046 that the UPAR/6-gene classifier was comparable to UPAR alone; chi2 test), 100% in 3 samples for which the initial cytological diagnosis was "suspicious" and 98% (40/41) overall. Our results provide evidence that molecular marker expression data can be used to augment cytological analysis.
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PMID:Accurate discrimination of pancreatic ductal adenocarcinoma and chronic pancreatitis using multimarker expression data and samples obtained by minimally invasive fine needle aspiration. 1719 96

Mesothelin, C-ERC/mesothelin is a 40-kDa cell surface glycoprotein that is normally present on normal mesothelial cells lining the pleura, peritoneum, and pericardium. Moreover, mesothelin has been shown to be overexpressed in several human cancers, including virtually all mesothelioma and pancreatic cancer, approximately 70% of ovarian cancer and extra bile duct cancer, and 50% of lung adenocarcinomas and gastric cancer. The full-length human mesothelin gene encodes the primary product, a 71-kDa precursor protein. The 71-kDa mesothelin precursor is cleaved into two products, 40-kDa C-terminal fragment that remains membrane-bound via glycosylphosphatidylinositol anchor, and a 31-kDa N-terminal fragment, megakaryocyte potentiating factor, which is secreted into the blood. The biological functions of mesothelin remain largely unknown. However, results of recent studies have suggested that the mesothelin may play a role of cell proliferation and migration. In pancreatic cancer, mesothelin expression was immunohistochemically observed in all cases, but absent in normal pancreas and in chronic pancreatitis. Furthermore, the expression of mesothelin was correlated with an poorer patient outcome in several human cancers. The limited mesothelin expression in normal tissues and high expression in many cancers makes it an attractive candidate for cancer therapy. The present review discusses the expression and function of mesothelin in cancer cells and the utility of mesothelin as a target of cancer therapy.
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PMID:Clinical impacts of mesothelin expression in gastrointestinal carcinomas. 2719 Jun 94