Browsing by Subject "Pancreatic adenocarcinoma"
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- PublicationOpen AccessElevated tissue expression of RANKL and RANK is associated with poorer survival rates in pancreatic cancer patients(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Ortega, Miguel A; Jiménez Álvarez, Laura; Fraile Martinez, Oscar; Garcia Montero, Cielo; Leon Oliva, Diego De; Toledo Lobo, M. Val; Palacios, Esther; Granado, Paula; Esteban, Alfonso; Guijarro, Luis G.; Pekarek, Leonel; Asúnsolo, Ángel; Buján, Julia; García Honduvilla, Natalio; Álvarez Mon, Melchor; Saez, Miguel A; Díaz Pedrero, Raúl; López González, LauraPancreatic cancer is a highly lethal malignancy with a growing incidence reported worldwide. Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, which is often diagnosed at advanced stages, making its prognosis and medical management difficult. The identification of histopathological biomarkers has allowed a more precise stratification of pancreatic cancer patients, providing additional information about their prognosis and offering possible therapeutic targets to be explored. The prognostic value of the receptor activator of nuclear factor-kappa B (RANK) and its ligand (RANKL) has been evaluated in breast and prostate tumors, however, their usefulness has not been assessed in pancreatic cancer. In the present work, we analyzed the relationship between the protein expression of RANK and RANKL with the survival of 41 patients with pancreatic cancer followed for 60 months, by performing immunohisto-chemistry and Kaplan-Meier curves. Our results demonstrate a direct association of high expression levels of RANK and RANKL with poorer survival of pancreatic cancer patients in comparison to those with low/medium and null expression levels of both markers. Further studies should be conducted to explore the carcinogenic role of both components in this type of tumor, as well as additional promising translational uses.
- PublicationOpen AccessExpression of the Shwachman- Bodian-Diamond syndrome -SBDS- protein in human pancreatic cancer and chronic pancreatitis(Murcia : F. Hernández, 2008) Kayed, Hany; Bekasi, Sandor; Keleg, Sehereen; Welsch, Thilo; Esposito, Irene; Shimamura, Akiko; Michalski, Christoph W.; Friess, Helmut; Kleeff, JörgBackground: The Shwachman-Bodian- Diamond syndrome (SBDS) protein is a member of a highly conserved family which influences RNA activation and is associated with pancreatic, skeletal and bone marrow deficiencies, as well as hematological malignancies. Methods: In this study, the expression and localization of SBDS were investigated in normal human pancreatic tissues, chronic pancreatitis (CP) tissues, primary and metastatic pancreatic ductal adenocarcinoma (PDAC) tissues, as well as in cultured pancreatic cancer cell lines by immunohistochemistry, immunoblotting and immunocytochemistry. Results: In the normal pancreas, SBDS was localized in the cytoplasm of islet cells and ductal cells. In CP tissues, SBDS was found in the cytoplasm of ductal cells, tubular complexes, stromal fibroblasts and in PanIN1-2 lesions. In PDAC tissues, SBDS exhibited cytoplasmic and occasionally nuclear localization in tubular complexes, PanIN1-3 lesions, cancer cells, and stromal fibroblasts. Different levels of SBDS protein were detected in cultured pancreatic cancer cell lines. Conclusion: SBDS is expressed in normal, CP, and PDAC tissues, as well as in pancreatic cancer cell lines. The different expression and localization patterns suggest a role of SBDS in the pathogenesis of, or response to, inflammatory and neoplastic pancreatic diseases.
- PublicationOpen AccessGlucose transporter-1 expression and prognostic significance in pancreatic carcinogenesis(Murcia : F. Hernández, 2009) Pizzi, Sara; Porzionato, Andrea; Pasquali, Claudio; Guidolin, Diego; Sperti, Cosino; Fogar, Paola; Macchi, Verónica; De Caro, Raffaelle; Pedrazzoli, Sergio; Parenti, AnnaThe purposes of this study were to evaluate the prognostic significance of Glut-1 expression in patients with pancreatic ductal adenocarcinoma, and to analyse its expression in pancreatic intraepithelial neoplasias (PanIN) and non invasive intraductal papillary mucinous neoplasms (IPMN). Glut-1 expression was studied by immunohistochemistry in 60 pancreatic ductal adenocarcinomas and scored on a 4- point scale (1: <25%; 2: 25-50%; 3: 50-75%; 4: >75%). Relationships between Glut-1 score, histological grade and MIB-1 score were evaluated by the Spearman rank correlation test. Significant correlations were found between Glut-1 expression and histological grade (P<0.001) and MIB-1 score (P<0.01). Significant prognostic factors by univariate analysis were stage (P<0.0001), histological grade (P<0.001) and Glut-1 expression (P<0.005). Independent prognostic factors after multivariate analysis were stage (P<0.001) and Glut-1 expression (P<0.05), stratified as <50% and >50%. The correlation of Glut-1 score with histological grade and MIB-1 score indicated a higher glucose uptake in poorly differentiated and highly proliferative pancreatic cancer cells. Glut-1 immunohistochemical expression provides a useful prognostic factor in pancreatic ductal adenocarcinoma. Glut-1 expression was not found in PanINs 1 but in 27.8% and 43.8% of PanINs 2 and 3, and was not found in IPMNs with lowand moderate-grade dysplasia but in 60% of IPMNs with high-grade dysplasia, indicating Glut-1 involvement in a relatively early phase of pancreatic carcinogenesis.
- PublicationOpen AccessPrognostic significance of AGR2 in pancreatic ductal adenocarcinoma(Murcia : F. Hernández, 2009) Riener, Marc-Oliver; Pilarsky, Christian; Gerhardt, Josefine; Grützmann, Robert; Fritzsche, F.R.; Bahra, Marcus; Weicher, Wilko; Kristiansen, GlenBackground/Aims: The human Anterior Gradient-2 (AGR2) is strongly upregulated in various human cancers, including pancreatic ductal adenocarcinomas (PDAC), but its prognostic value in PDAC has not yet been studied. Methods: We analysed 19 microdissected PDAC cases at the mRNA level, and also 148 cases at the protein level by immunohistochemistry based on tissue microarray, using a monoclonal AGR2 antibody, and statistical analyses were applied to test for prognostic associations. Results: Overexpression of AGR2 mRNA was found to be elevated in most pancreatic cell lines and in microdissected pancreatic cancer compared to microdissected normal ductal cells. AGR2 protein was expressed in 109/148 (73.7%) of PDAC, with a higher expression in female patients (p=0.040), whereas no significant associations with other clinical-pathological parameters were found. A prognostic value of AGR2 could not be demonstrated in univariate analyses. Conclusion: Although a prognostic value of AGR2 seems unlikely, further studies are warranted to investigate the biological role of AGR2 in pancreatic adenocarcinomas.