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Báo cáo hóa học: MMP-1 is a (pre-)invasive factor in Barrettassociated esophageal adenocarcinomas and is associated with positive lymph node status
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Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: MMP-1 is a (pre-)invasive factor in Barrettassociated esophageal adenocarcinomas and is associated with positive lymph node status
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Báo cáo hóa học: " MMP-1 is a (pre-)invasive factor in Barrettassociated esophageal adenocarcinomas and is associated with positive lymph node status"Grimm et al. Journal of Translational Medicine 2010, 8:99http://www.translational-medicine.com/content/8/1/99 RESEARCH Open AccessMMP-1 is a (pre-)invasive factor in Barrett-associated esophageal adenocarcinomas and isassociated with positive lymph node statusMartin Grimm1†, Maria Lazariotou2†, Stefan Kircher3, Luisa Stuermer1, Christoph Reiber1, Andreas Höfelmayr1,Stefan Gattenlöhner4, Christoph Otto1, Christoph T Germer1, Burkhard HA von Rahden1* Abstract Background: Esophageal adenocarcinomas (EACs) arise due to gastroesophageal reflux, with Barrett’s esophagus (BE) regarded as precancerous lesion. Matrix metalloproteinases (MMPs) might play a role during the multistep carcinogenetic process. Methods: Expression of MMP-1 and -13 was analyzed in esophageal cancer (n = 41 EAC with BE, n = 19 EAC without BE, and n = 10 esophageal squamous-cell carcinomas, ESCC), furthermore in BE without intraepithelial neoplasia (IN) (n = 18), and the cell line OE-33. MMP-1 was co-labelled with Ki-67 (proliferation), Cdx-2 (marker for intestinal metaplasia, BE) and analyzed on mRNA level. MMP-1 staining results were correlated with clinicopatholocical parameters. Results: On protein level, MMP-1 expression was found in 39 of 41 (95%) EAC with BE, in 19 of 19 (100%) EAC without BE, in 6 of 10 (60%) ESCC, and in 10 of 18 (56%) BE without IN. No expression of MMP-13 was found in these specimens. Quantification showed 48% MMP-1 positive cells in EAC with BE, compared to 35% in adjacent BE (p < 0.05), 44% in EAC without BE, 32% in ESCC, and 4% in BE without IN. Immunofluorescence double staining experiments revealed increased MMP-1 expressing in proliferating cells (MMP-1+/Ki-67+) (r = 0.943 for BE and r = 0.811 for EAC). On mRNA-level, expression of MMP-1 was significantly higher in EAC compared to BE (p = 0.01) and confirmed immunohistochemical staining results. High MMP-1 levels were associated with lymph node metastases but not with poorer survival (p = 0.307). Conclusions: Our findings suggest that MMP-1 plays a role as preinvasive factor in BE-associated EAC. Expression of MMP-1 in proliferating BE and EAC cells suggest malignant proliferation following the clonal expansion model.Background of the esophagus, under the chronically damaging effect of gastroesophageal reflux [2,3]. Barrett’s esophagus -Esophageal Adenocarcinomas and Barrett’s EsophagusEsophageal adenocarcinoma is an entity of increasing defined as columnar lined epithelium in the distal eso-clinical importance, due to an unexplained incidence phagus, characterized by specialized intestinal mucosarise among white males in the Western world [1], and a (with goblet cells) - is regarded as precancerous lesion,dismal prognosis [2,3]. Chances for cure are still limited giving rise to these tumors. Malignant progression within Barrett’s esophagus (BE)to early, surgically resectable tumor stages, prior to sys-temic dissemination of the disease. Esophageal adeno- is regarded to follow a sequence of well-characterizedcarcinomas develop almost exclusively in the distal third histopathologic changes, from intestinal metaplasia, over low-grade and high-grade intraepithelial neoplasia towards invasive esophageal adenocarcinomas (EAC)*Correspondence: Rahden_B@chirurgie.uni-wuerzburg.de†Contributed equally [2,3]. However, not all EACs are associated with BE in1 Department of General-, Visceral-, Vascular and Pediatric Surgery, University surgical series [4,5], and only a minority of patients withof Wuerzburg Hospital, Oberduerrbacher Strasse 6, 97080 Wuerzburg,GermanyFull list of author information is available at the end of the article © 2010 Grimm et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which pe ...
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Báo cáo hóa học: " MMP-1 is a (pre-)invasive factor in Barrettassociated esophageal adenocarcinomas and is associated with positive lymph node status"Grimm et al. Journal of Translational Medicine 2010, 8:99http://www.translational-medicine.com/content/8/1/99 RESEARCH Open AccessMMP-1 is a (pre-)invasive factor in Barrett-associated esophageal adenocarcinomas and isassociated with positive lymph node statusMartin Grimm1†, Maria Lazariotou2†, Stefan Kircher3, Luisa Stuermer1, Christoph Reiber1, Andreas Höfelmayr1,Stefan Gattenlöhner4, Christoph Otto1, Christoph T Germer1, Burkhard HA von Rahden1* Abstract Background: Esophageal adenocarcinomas (EACs) arise due to gastroesophageal reflux, with Barrett’s esophagus (BE) regarded as precancerous lesion. Matrix metalloproteinases (MMPs) might play a role during the multistep carcinogenetic process. Methods: Expression of MMP-1 and -13 was analyzed in esophageal cancer (n = 41 EAC with BE, n = 19 EAC without BE, and n = 10 esophageal squamous-cell carcinomas, ESCC), furthermore in BE without intraepithelial neoplasia (IN) (n = 18), and the cell line OE-33. MMP-1 was co-labelled with Ki-67 (proliferation), Cdx-2 (marker for intestinal metaplasia, BE) and analyzed on mRNA level. MMP-1 staining results were correlated with clinicopatholocical parameters. Results: On protein level, MMP-1 expression was found in 39 of 41 (95%) EAC with BE, in 19 of 19 (100%) EAC without BE, in 6 of 10 (60%) ESCC, and in 10 of 18 (56%) BE without IN. No expression of MMP-13 was found in these specimens. Quantification showed 48% MMP-1 positive cells in EAC with BE, compared to 35% in adjacent BE (p < 0.05), 44% in EAC without BE, 32% in ESCC, and 4% in BE without IN. Immunofluorescence double staining experiments revealed increased MMP-1 expressing in proliferating cells (MMP-1+/Ki-67+) (r = 0.943 for BE and r = 0.811 for EAC). On mRNA-level, expression of MMP-1 was significantly higher in EAC compared to BE (p = 0.01) and confirmed immunohistochemical staining results. High MMP-1 levels were associated with lymph node metastases but not with poorer survival (p = 0.307). Conclusions: Our findings suggest that MMP-1 plays a role as preinvasive factor in BE-associated EAC. Expression of MMP-1 in proliferating BE and EAC cells suggest malignant proliferation following the clonal expansion model.Background of the esophagus, under the chronically damaging effect of gastroesophageal reflux [2,3]. Barrett’s esophagus -Esophageal Adenocarcinomas and Barrett’s EsophagusEsophageal adenocarcinoma is an entity of increasing defined as columnar lined epithelium in the distal eso-clinical importance, due to an unexplained incidence phagus, characterized by specialized intestinal mucosarise among white males in the Western world [1], and a (with goblet cells) - is regarded as precancerous lesion,dismal prognosis [2,3]. Chances for cure are still limited giving rise to these tumors. Malignant progression within Barrett’s esophagus (BE)to early, surgically resectable tumor stages, prior to sys-temic dissemination of the disease. Esophageal adeno- is regarded to follow a sequence of well-characterizedcarcinomas develop almost exclusively in the distal third histopathologic changes, from intestinal metaplasia, over low-grade and high-grade intraepithelial neoplasia towards invasive esophageal adenocarcinomas (EAC)*Correspondence: Rahden_B@chirurgie.uni-wuerzburg.de†Contributed equally [2,3]. However, not all EACs are associated with BE in1 Department of General-, Visceral-, Vascular and Pediatric Surgery, University surgical series [4,5], and only a minority of patients withof Wuerzburg Hospital, Oberduerrbacher Strasse 6, 97080 Wuerzburg,GermanyFull list of author information is available at the end of the article © 2010 Grimm et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which pe ...
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