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      Decoy receptor 3 (DcR3) overexpression predicts the prognosis and pN2 in pancreatic head carcinoma

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          Abstract

          Background

          This study was carried out to examine decoy receptor 3 (DcR3) expression and investigate its clinical and prognostic significance in patients with pancreatic head carcinoma.

          Methods

          Tissue samples were obtained from 50 patients with pancreatic head carcinoma. DcR3 protein expression in tissues and sera was assessed by immunohistochemistry and ELISA. Correlations between DcR3 and clinicopathologic features and prognoses were analyzed statistically.

          Results

          Serum DcR3 levels were significantly elevated in patients with pancreatic head carcinoma compared with patients with cystadenoma and healthy individuals ( P < 0.01 and P < 0.01, respectively). DcR3 overexpression correlated with lymph node metastases and TNM stages ( P < 0.05 and P < 0.05, respectively). Median overall survival for the high DcR3 group was 16.3 months, compared to 21.6 months for the low DcR3 group ( P < 0.05). In the low DcR3 group, no significant difference was found in the overall survival between patients who underwent standard pancreatoduodenectomy (SPD) and those who had radical pancreatoduodenectomy (RPD) ( P > 0.05). In the high DcR3 group, the median overall survival rates were 16.8 months in the RPD group and 13.5 months in the SPD group ( P < 0.05).

          Conclusions

          We found that DcR3 was overexpressed in pancreatic head carcinoma. The patients with high DcR3 levels had higher pN2 stages than those with low DcR3 levels. Detecting serum DcR3 level preoperatively might be an additional approach for evaluating pN2 stage and guiding the range of lymphadenectomy.

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          Most cited references23

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          TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator.

          DR3 is a death domain-containing receptor that is upregulated during T cell activation and whose overexpression induces apoptosis and NF-kappaB activation in cell lines. Here we show that an endothelial cell-derived TNF-like factor, TL1A, is a ligand for DR3 and decoy receptor TR6/DcR3 and that its expression is inducible by TNF and IL-1alpha. TL1A induces NF-kappaB activation and apoptosis in DR3-expressing cell lines, while TR6-Fc protein antagonizes these signaling events. Interestingly, in T cells, TL1A acts as a costimulator that increases IL-2 responsiveness and secretion of proinflammatory cytokines both in vitro and in vivo. Our data suggest that interaction of TL1A with DR3 promotes T cell expansion during an immune response, whereas TR6 has an opposing effect.
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            Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer.

            Fas ligand (FasL) is produced by activated T cells and natural killer cells and it induces apoptosis (programmed cell death) in target cells through the death receptor Fas/Apol/CD95. One important role of FasL and Fas is to mediate immune-cytotoxic killing of cells that are potentially harmful to the organism, such as virus-infected or tumour cells. Here we report the discovery of a soluble decoy receptor, termed decoy receptor 3 (DcR3), that binds to FasL and inhibits FasL-induced apoptosis. The DcR3 gene was amplified in about half of 35 primary lung and colon tumours studied, and DcR3 messenger RNA was expressed in malignant tissue. Thus, certain tumours may escape FasL-dependent immune-cytotoxic attack by expressing a decoy receptor that blocks FasL.
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              A prospective randomized trial comparing standard pancreatoduodenectomy with pancreatoduodenectomy with extended lymphadenectomy in resectable pancreatic head adenocarcinoma.

              To compare operative morbidity, mortality, quality of life, and survival after pancreatoduodenectomy (PD) versus pancreatoduodenectomy with extended lymphadenectomy (PD/ELND) in patients with resectable pancreatic cancer. From May 1997 to July 2003 there were 132 patients with biopsy examination-proven or suspected adenocarcinoma of the pancreatic head who agreed to participate in a single-institution, prospective, randomized trial. If resectable at operation, patients then were randomized to standard PD (40 patients) or PD/ELND (39 patients). Quality of life was assessed by using the Functional Assessment of Response to Cancer Therapy specific to the pancreas. Morbidity, mortality, and survival were analyzed. Demographics and pathologic characteristics for both groups were similar. When comparing PD/ELND with standard PD, the median operating time was greater for the PD/ELND group (7.6 h vs 6.2 h, P < .01), blood transfusion more likely (44% vs 22%, P < .05), and the median number of lymph nodes resected was greater (36 vs 15 nodes, P < .01). Morbidity and mortality rates were comparable. Median durations of stay were 11 and 10.5 days (P = NS), respectively. There were no significant differences in 1-year (71% vs 82%), 3-year (25% vs 41%), 5-year (16.5% vs 16.4%), and median (19 vs 26 mo) survival (P = .32). At 4 months postoperatively, diarrhea, body appearance, and bowel control scored lower on the Functional Assessment of Response to Cancer Therapy specific to the pancreas after PD/ELND (P < .05). Although a much larger study would have more power to compare statistically the survival between groups, both the decrement in quality of life and similar studies showing no survival difference make PD/ELND unattractive for further prospective investigation.
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                Author and article information

                Contributors
                Journal
                World J Surg Oncol
                World J Surg Oncol
                World Journal of Surgical Oncology
                BioMed Central
                1477-7819
                2014
                5 March 2014
                : 12
                : 52
                Affiliations
                [1 ]Department of General Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China
                [2 ]Department of Oncology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China
                [3 ]Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China
                Article
                1477-7819-12-52
                10.1186/1477-7819-12-52
                3946126
                24597666
                a12ac688-26a4-411b-8902-3f87c3fc1f81
                Copyright © 2014 Zhou 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 permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                History
                : 16 August 2013
                : 19 February 2014
                Categories
                Research

                Surgery
                dcr3,lymphadenectomy,pancreatic head carcinoma,prognosis
                Surgery
                dcr3, lymphadenectomy, pancreatic head carcinoma, prognosis

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