Quantitative, tissue-specific analysis of cyclooxygenase gene expression in the pathogenesis of Barrett's adenocarcinoma.

Cyclooxygenase (Cox-2) is implicated in the pathogenesis of many cancers including esophageal adenocarcinoma (EAC), whereas the role of the isoform Cox-1 in carcinogenesis is not well understood. To further elucidate the role of these factors in the development of EAC, we measured the gene expressions (mRNA levels) of Cox-2 and Cox-1 by real-time quantitative polymerase chain reaction (QRT-PCR) in tissues from normal esophagus with and without erosive gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), dysplasia, adenocarcinoma, and in healthy gastric antrum. All tissues were purified by laser capture microdissection from endoscopic or surgical resection specimens. Median Cox-2 gene expression did not differ significantly among the esophageal control groups but was elevated 5-fold in BE, 8-fold in dysplasia and 16-fold in EAC compared to normal esophageal controls with no erosive GERD. Erosive GERD tissue had slightly higher median Cox-2 expression but Cox-2 expression in normal antrum was much higher than that in a normal esophagus, close to that of dysplasia. In contrast to that of Cox-2, Cox-1 expression was significantly decreased in all neoplastic tissues compared to normal controls. Cox-1 and Cox-2 expression varied over a wide range in the neoplastic tissues but over a relatively narrow range in the esophageal normal tissues. The occurrence of substantial alterations in Cox-1 and Cox-2 expression at the BE stage indicates that these are early events in the development of EAC. These results confirm the important role of Cox-2 amplification in the pathogenesis of esophageal adenocarcinoma, but the unexpected down-regulation of Cox-1 raises questions about its role in carcinogenesis.     

Acute myocardial ischemia: MR imaging with Mn-TP

Cardiac-gated magnetic resonance (MR) imaging was performed in rats to determine the effects of manganese ethylenediaminetetraphosphonate (TP). Ten normal rats received Mn-TP in a dose of 50 mumol/kg through a tail-vein injection. Spin-echo MR images were obtained before and every 10 minutes after Mn-TP injection for 1 hour. Cardiac signal intensity (SI) increased more than 70% after Mn-TP injection and remained nearly unchanged 1 hour after injection. Myocardial T1 was 517 +/- 49 msec in eight control rats and 282 +/- 61 msec (P less than .001) in six rats 81 +/- 0 minutes after injection. Nine rats underwent occlusion of the left anterior descending coronary artery prior to MR imaging. Images were obtained before and 15, 30, and 60 minutes after Mn-TP injection. In normal myocardium, SI increased up to 82% and remained elevated for 1 hour. In ischemic myocardium, SI rose 11%, leading to a marked contrast between the two tissue zones. T1 was also different in the two regions: In normal tissue, it was 206 msec +/- 54; in ischemic tissue, 338 +/- 82 (P less than .001). With T1-weighted MR imaging, Mn-TP showed a potential for delineating the jeopardized area after acute myocardial ischemia.     

Increasing cyclooxygenase-2 (cox-2) gene expression in the progression of Barrett's esophagus to adenocarcinoma correlates with that of Bcl-2

Previous studies from our laboratory and others have suggested that increased expression of cox-2 is important in the genesis of esophageal adenocarcinoma. In vitro studies suggest that cox-2 regulates expression of the anti-apoptotic protein bcl-2, thus possibly accounting for reduced apoptosis in carcinogenesis. The aim of this study was to investigate the relationship of these 2 genes in the development of Barrett's-associated adenocarcinoma. Histologic sections from endoscopic biopsies or esophagectomy specimens were classified as non-dysplastic Barrett's (n = 30), intraepithelial neoplasia (n = 12) and adenocarcinoma (n = 48). The desired tissue was isolated by laser capture microdissection and expression levels of cox-2 and bcl-2 were measured by quantitative real-time PCR (Taqman). Gene expression levels were compared to samples of the distal esophageal squamous epithelium (n = 55) and reflux-esophagitis (n = 25), without Barrett's or cancer. Expression of both bcl-2 and cox-2 were increased in non-dysplastic Barrett's (p = 0.0077, p = 0.0037), intraepithelial neoplasia (p = 0.0053, p = 0.0220) and adenocarcinoma (p < 0.0001, p < 0.0001) compared to squamous epithelium or reflux-esophagitis. Furthermore, there is a significant correlation between these two genes, especially in carcinoma (p < 0.0001).     

Detachment of man from life]

As an instrument and a weapon in the struggle for existence man has at his disposal the intellect which enables him, by means of language, to make use of conceptional thinking. But if he uses the intellect in order to manage the interactions with his equals, he unaffectedly has to observe and to manipulate the behaviour of his fellow-men as well as his own psychic processes like functions of intricate technical apparatuses, disregarding or violating the incalculable 'endothymic' part (strivings and feelings) of human being. Innate dispositions of behaviour, urges, moods, and emotions, however, constitute real life. Suppression of vital powers by the laws of rationality makes civilized people suffer.