AIM: To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9) expres-sions in the development and progression of reflux es-ophagitis-Barrett’s metaplasia-dysplasia-adenocarcin...AIM: To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9) expres-sions in the development and progression of reflux es-ophagitis-Barrett’s metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.METHODS: GST and MMP-9 expressions were analyzed in 51 paraffin-embedded tissue samples by immunohisto-chemistry including patients with reflux esophagitis (n = 7), Barrett’s metaplasia (n = 14), Barrett and esophagi-tis (n = 8), Barrett and dysplasia (n = 7), esophageal adenocarcinoma (n = 8) and a control group without any histological changes (n = 7). Immunostaining was determined semiquantitatively. Statistical analysis with one-way ANOVA, LSD test and correlation analysis were performed. P value of < 0.05 was considered significant.RESULTS: GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to Barrett’s metaplasia and the other groups. No major changes were observed between Bar-rett, esophagitis, and Barrett and concomitant esophagi-tis. Barrett and concomitant dysplasia, and adenocarci-noma revealed a significant lower expression of GST and higher levels of MMP-9 compared to all other groups. Adenocarcinoma showed almost no expression of GST and significantly higher levels of MMP-9 than Barrett and concomitant dysplasia. Alterations of GST and MMP-9 were inversely correlated (r = - 0.82).CONCLUSION: Decreased GST and increased ex-pression of MMP-9 in Barrett’s metaplasia-dysplasia-adenocarcinoma sequence as compared to normal tissue suggest their association with esophageal tumorigenesis. Loss of GST and gain of MMP-9 in Barrett with dyspla-sia compared to non-dysplastic metaplasia indicate that these alterations may be early events in carcinogenesis. Quantification of these parameters in Barrett’s esopha-gus might be useful to identify patients at higher risk for progression to cancer.展开更多
AIM： To study the effect of proton pump inhibitor （PPI） treatment on patients with reflux esophagitis and its in vivo effect on apoptosis, p53- and epidermal growth factor receptor （EGFR） expression. METHODS： Af...AIM： To study the effect of proton pump inhibitor （PPI） treatment on patients with reflux esophagitis and its in vivo effect on apoptosis, p53- and epidermal growth factor receptor （EGFR） expression. METHODS： After informed consent was obtained, gastric biopsies of the antrum were taken from patients with reflux oesophagitis prior to and after 6 mo of 20 mg omeprazole （n = 24） or 40 mg esomeprazole （n = 22） therapy. Patients did not take any other medications known to affect the gastric mucosa. All patients were Helicobacter pylori negative as confirmed by rapid urease test and histology, respectively. Cell proliferation, apoptosis, EGFR, and p53 expression were measured by immunohistochemical techniques. At least 600 glandular epithelial cells were encountered and results were expressed as percentage of total cells counted. Was considered statistically significant. RESULTS： Although there was a trend towards increase of cell proliferation and EGFR expression both in omeprazole and esomeprazole treated group, the difference was not statistically significant. Neither apoptosis nor p53 expression was affected. CONCLUSION： Long-term PPI treatment does not significantly increase gastric epithelial cell proliferation and EGFR expression and has no effect on apoptosis and p53 expression.展开更多
AIM： To understand the local pathophysiological alterations and gene ontology-based functional classification of colonic biopsies into inflammatory and neoplastic diseases. METHODS： Total RNA was extracted from froz...AIM： To understand the local pathophysiological alterations and gene ontology-based functional classification of colonic biopsies into inflammatory and neoplastic diseases. METHODS： Total RNA was extracted from frozen biopsies and amplified by T7-method. Expression profile was evaluated by Atlas Glass 1K microarrays. After microarray quality control, applicable data were available from 10 adenomas, 6 colorectal adenocarcinomas （CRCs）, and 6 inflammatory bowel diseases （IBDs）. Multivariate statistical and cell functional analyses were performed. Real-time RT-PCR and immunohistochemistry were used for validation. RESULTS： Discriminant analysis of selected genes, could correctly reclassify all 22 samples using 4 parameters （heat shock transcription factor-l, bystin-like, calgranulin-A, TRAIL receptor 3）. IBD samples were characterized by overregulated chemokine （C-X-C motif） ligand 13, replication protein A1, E74-1ike factor 2 and downregu- fated TNF receptor-associated factor 6, BCL2-interacting killer genes. In adenomas upregulation of TNF receptorassociated factor 6, replication protein A1, E74-1ike factor 2 and underexpression of BCL2-associated X protein, calgranulin-A genes were found. CRC cases had significantly increased epidermal growth factor receptor, topoisomerase-1, v-jun, TNF receptor-associated factor 6 and TRAIL receptor 3, and decreased RAD51 and RAD52 DNA repair gene, protein phosphatase-2A and BCL2-interacting killer mRNA levels. Epidermal growth factor receptor RT-PCR and immunohistochemistry, topoisomerase-1 RT-PCR confirmed the chip results .CONCLUSION： Different histological alterations can be reclassified by functional, multivariate analysis using cDNA microarrays. Further studies with expanded sample number are needed for subclassification of pathological alterations.展开更多
文摘AIM: To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9) expres-sions in the development and progression of reflux es-ophagitis-Barrett’s metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.METHODS: GST and MMP-9 expressions were analyzed in 51 paraffin-embedded tissue samples by immunohisto-chemistry including patients with reflux esophagitis (n = 7), Barrett’s metaplasia (n = 14), Barrett and esophagi-tis (n = 8), Barrett and dysplasia (n = 7), esophageal adenocarcinoma (n = 8) and a control group without any histological changes (n = 7). Immunostaining was determined semiquantitatively. Statistical analysis with one-way ANOVA, LSD test and correlation analysis were performed. P value of < 0.05 was considered significant.RESULTS: GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to Barrett’s metaplasia and the other groups. No major changes were observed between Bar-rett, esophagitis, and Barrett and concomitant esophagi-tis. Barrett and concomitant dysplasia, and adenocarci-noma revealed a significant lower expression of GST and higher levels of MMP-9 compared to all other groups. Adenocarcinoma showed almost no expression of GST and significantly higher levels of MMP-9 than Barrett and concomitant dysplasia. Alterations of GST and MMP-9 were inversely correlated (r = - 0.82).CONCLUSION: Decreased GST and increased ex-pression of MMP-9 in Barrett’s metaplasia-dysplasia-adenocarcinoma sequence as compared to normal tissue suggest their association with esophageal tumorigenesis. Loss of GST and gain of MMP-9 in Barrett with dyspla-sia compared to non-dysplastic metaplasia indicate that these alterations may be early events in carcinogenesis. Quantification of these parameters in Barrett’s esopha-gus might be useful to identify patients at higher risk for progression to cancer.
基金Supported by the National Science Foundation (OTKA Grant No:T 034345)
文摘AIM： To study the effect of proton pump inhibitor （PPI） treatment on patients with reflux esophagitis and its in vivo effect on apoptosis, p53- and epidermal growth factor receptor （EGFR） expression. METHODS： After informed consent was obtained, gastric biopsies of the antrum were taken from patients with reflux oesophagitis prior to and after 6 mo of 20 mg omeprazole （n = 24） or 40 mg esomeprazole （n = 22） therapy. Patients did not take any other medications known to affect the gastric mucosa. All patients were Helicobacter pylori negative as confirmed by rapid urease test and histology, respectively. Cell proliferation, apoptosis, EGFR, and p53 expression were measured by immunohistochemical techniques. At least 600 glandular epithelial cells were encountered and results were expressed as percentage of total cells counted. Was considered statistically significant. RESULTS： Although there was a trend towards increase of cell proliferation and EGFR expression both in omeprazole and esomeprazole treated group, the difference was not statistically significant. Neither apoptosis nor p53 expression was affected. CONCLUSION： Long-term PPI treatment does not significantly increase gastric epithelial cell proliferation and EGFR expression and has no effect on apoptosis and p53 expression.
文摘AIM： To understand the local pathophysiological alterations and gene ontology-based functional classification of colonic biopsies into inflammatory and neoplastic diseases. METHODS： Total RNA was extracted from frozen biopsies and amplified by T7-method. Expression profile was evaluated by Atlas Glass 1K microarrays. After microarray quality control, applicable data were available from 10 adenomas, 6 colorectal adenocarcinomas （CRCs）, and 6 inflammatory bowel diseases （IBDs）. Multivariate statistical and cell functional analyses were performed. Real-time RT-PCR and immunohistochemistry were used for validation. RESULTS： Discriminant analysis of selected genes, could correctly reclassify all 22 samples using 4 parameters （heat shock transcription factor-l, bystin-like, calgranulin-A, TRAIL receptor 3）. IBD samples were characterized by overregulated chemokine （C-X-C motif） ligand 13, replication protein A1, E74-1ike factor 2 and downregu- fated TNF receptor-associated factor 6, BCL2-interacting killer genes. In adenomas upregulation of TNF receptorassociated factor 6, replication protein A1, E74-1ike factor 2 and underexpression of BCL2-associated X protein, calgranulin-A genes were found. CRC cases had significantly increased epidermal growth factor receptor, topoisomerase-1, v-jun, TNF receptor-associated factor 6 and TRAIL receptor 3, and decreased RAD51 and RAD52 DNA repair gene, protein phosphatase-2A and BCL2-interacting killer mRNA levels. Epidermal growth factor receptor RT-PCR and immunohistochemistry, topoisomerase-1 RT-PCR confirmed the chip results .CONCLUSION： Different histological alterations can be reclassified by functional, multivariate analysis using cDNA microarrays. Further studies with expanded sample number are needed for subclassification of pathological alterations.
