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Biomedical subjects

Paul Drillenburg

Publications and source records attributed to Paul Drillenburg.

6 recordsLinked to original sources
PubMed2002

Cyclooxygenase-2 expression during carcinogenesis in the human stomach.

The prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with a reduced risk of gastric cancer. The best-known target of these drugs is cyclooxygenase (COX); the COX-2 isoform is frequently up-regulated in gastric adenocarcinomas. Using the post-gastrectomy stomach as a model, the expression of COX-2 mRNA and protein has been investigated during tumour progression in the human stomach. COX-2 expression was comparable in gastric stump carcinomas and conventional gastric carcinomas and localized primarily to the cytoplasm of the neoplastic cells. COX-2 mRNA was elevated in biopsies containing intestinal metaplasia, as determined by reverse transcriptase polymerase chain reaction (RT-PCR). COX-2 immunopositivity became more frequent during progression from reactive epithelium to high-grade dysplasia, both in the epithelial and in the stromal cell compartment. Co-localization of COX-2-positive stromal cells was seen with CD68, alpha-smooth muscle actin (alpha-SMA), vimentin, and HLA-DR, but an as yet unidentified subpopulation of stromal cells remained. Co-localization with the macrophage marker CD68 was only observed in a minority of COX-2-positive cells. These data show that COX-2 expression is a relatively early event during carcinogenesis in the stomach. COX-2 expression increases during tumour progression in the stomach, suggesting a role for COX-2 expression in gastric tumourigenesis.

Adenocarcinoma↗
PubMed2002

Different pattern of allelic loss in Epstein-Barr virus-positive gastric cancer with emphasis on the p53 tumor suppressor pathway.

Both Helicobacter pylori (HP) and Epstein-Barr virus (EBV) have been implicated in carcinogenesis of the stomach. Fifty-seven gastric carcinomas were tested for microsatellite instability and allelic loss at several tumor suppressor loci using 21 polymorphic microsatellite markers. Furthermore, immunohistochemistry for p53 and DPC4/SMAD4 was performed. Results were analyzed according to HP and EBV status of the tumors, as assessed by immunohistochemistry and RNA in situ hybridization, respectively. Fractional allelic loss was lower in EBV-positive carcinomas (n = 15) when compared to EBV-negative carcinomas (P < 0.001). EBV positivity was inversely associated with allelic loss at specific markers on chromosomal arms 5q (APC), 17p (TP53), and 18q (DPC4/SMAD4). Allelic loss at the TP53 locus was not encountered in EBV-positive carcinomas, but occurred in 51% of EBV-negative carcinomas (P < 0.005). Moreover, none of the EBV-positive carcinomas showed unequivocal p53 immunopositivity in contrast to 39% of the EBV-negative carcinomas (P < 0.01). EBV-status was not related to microsatellite instability. There was no correlation between HP-status and any of the molecular alterations tested. In conclusion, EBV-positive gastric carcinomas follow a distinct pathogenesis at the molecular level, in which p53 is not, or differently inactivated.

Adolescent↗
PubMed2002

Differential susceptibility of multidrug resistance protein-1 deficient mice to DSS and TNBS-induced colitis.

The molecular mechanisms underlying inflammatory bowel diseases (IBD) are incompletely characterized. MRP-1, normally expressed in the large and small bowel epithelium, serves as a multidrug resistance protein. In this report we explored the role of MRP1 in IBD. Mrp1-deficient mice (mrp1-/-) were subjected to two different models of IBD. The mrp1-/- mice and wild-type (WT) mice showed equal induction of TNBS colitis, a hapten-induced T-cell mediated disease. However, in DSS colitis more severe disease was observed in mrp1-/- mice. In a survival study, mortality of mrp1-/- mice was higher. In nonlethal DSS colitis, the mean histological colitis score was significantly higher in mrp1-/- mice and showed particularly severe epithelial damage. Although endogenous LTB4 levels were significantly increased in mrp1-/- mice, treatment with a LTB4 antagonist did not reduce disease. We conclude that MRP-1 has an important role in the intestinal epithelial resistance to exogenous injury, but MRP-1 does not affect T-lymphocyte mediated mucosal damage.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Long-term follow-up of patients with a clinically benign extrahepatic biliary stenosis and K-ras mutation in endobiliary brush cytology.

BACKGROUND: K-ras mutations in endobiliary brush cytology are an early event in carcinogenesis and justify a suspicion of malignancy in patients with extrahepatic biliary stenosis. However, K-ras mutations have been detected in specimens obtained by brushing of clinically benign extrahepatic biliary stenosis. The aim of this study was to determine whether these findings represent an early or false-positive diagnosis of cancer. METHODS: Cytologic specimens were obtained by brushing in 312 consecutive patients with extrahepatic biliary stenosis. Mutations in the K-ras oncogene were detected by an enriched polymerase chain reaction and allele-specific oligonucleotide hybridization assay. Eight patients with a K-ras mutation and a clinically benign extrahepatic biliary stenosis were followed. RESULTS: After a median follow-up of 65 months, 6 of the 8 patients were alive without evidence of malignancy. One patient died of congestive heart failure. The other patient died 60 months after the specimen was obtained, possibly because of chronic pancreatitis, although previously there had been suspicion of malignancy. Biopsy specimens from the papilla were negative for neoplasia and the K-ras analysis harbored the same mutation as previously found in the brush specimen. CONCLUSION: Based on long-term follow-up, the K-ras mutations in all 8 patients with a clinically benign extrahepatic biliary stenosis must be considered as confirmed false-positives. Nevertheless, a false-positive result is infrequent. Therefore, patients with a positive K-ras mutation in biliary cytologic specimens obtained by brushing still require careful, continuing follow-up.

Cholestasis, Extrahepatic↗
PubMed2002

Intestinal metaplasia of the esophagus or esophagogastric junction: evidence of distinct clinical, pathologic, and histochemical staining features.

Our purpose was to evaluate the clinical, histologic, and histochemical staining characteristics of intestinal metaplasia (IM) at an endoscopically normal-appearing esophagogastric junction (IM-EGJ) compared with IM in a columnar-lined esophagus (IM-CLE). A prospective study included 253 patients referred for elective upper gastrointestinal endoscopy. Biopsy specimens were obtained from 2 cm above and immediately distal to the squamocolumnar junction, the gastric corpus, and the antrum. Any red mucosa above the EGJ was sampled. IM-CLE (prevalence, 5.5%) typically occurred in white male smokers with a long history of reflux symptoms. IM-EGJ (prevalence, 9.1%) was associated with corpus and antrum gastritis and with IM at these sites. IM-CLE usually (13/14 [93%]) was the incomplete type IM, whereas only 12 (52%) of 23 patients in the IM-EGJ group had incomplete IM. IM-EGJ and IM-CLE should be considered as separate entities. Further research is needed to evaluate whether neoplastic progression of IM-EGJ is related to its mucin profile.

Adenocarcinoma↗