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      CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer

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          Abstract

          Although CD133 has been shown to be a marker for cancer stem cells in various tumours, its expression in pancreatic cancer has not yet been clinically reported. In this study, we investigated the relationship between CD133 expression and clinicopathological factors in pancreatic cancer. Pancreatic head carcinoma specimens from 80 patients who underwent surgical resection were immunohistochemically assessed for CD133, vascular endothelial growth factor (VEGF)-C, CXCR4, CD34, Ki-67, and cytokeratin (CK) expressions. Sixty percentage (48/80) of specimens were CD133-positive, with less than 15% cells per specimen expressing the marker. CD133-positive cells were found at the peripheral site of adenocarcinoma glandular structures and were negative for CK. There was a significant correlation between CD133 expression and clinicopathological factors, including histological type, lymphatic invasion, and lymph node metastasis ( P=0.0215, 0.0023, and 0.0024, respectively). Vascular endothelial growth factor-C expression was also significantly correlated with CD133 expression ( P=0.0002). Consequently, the 5-year survival rate of CD133-positive patients was significantly lower than that of CD133-negative patients ( P=0.0002) and multivariate analysis revealed that CD133 expression was an independent prognostic factor ( P=0.0103). These results suggest that CD133 expression in pancreatic cancer was significantly associated with lymphatic metastasis, VEGF-C expression, and prognosis.

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          Most cited references34

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          Identification of pancreatic cancer stem cells.

          Emerging evidence has suggested that the capability of a tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells. Although data have been provided to support this theory in human blood, brain, and breast cancers, the identity of pancreatic cancer stem cells has not been determined. Using a xenograft model in which primary human pancreatic adenocarcinomas were grown in immunocompromised mice, we identified a highly tumorigenic subpopulation of pancreatic cancer cells expressing the cell surface markers CD44, CD24, and epithelial-specific antigen (ESA). Pancreatic cancer cells with the CD44(+)CD24(+)ESA(+) phenotype (0.2-0.8% of pancreatic cancer cells) had a 100-fold increased tumorigenic potential compared with nontumorigenic cancer cells, with 50% of animals injected with as few as 100 CD44(+)CD24(+)ESA(+) cells forming tumors that were histologically indistinguishable from the human tumors from which they originated. The enhanced ability of CD44(+)CD24(+)ESA(+) pancreatic cancer cells to form tumors was confirmed in an orthotopic pancreatic tail injection model. The CD44(+)CD24(+)ESA(+) pancreatic cancer cells showed the stem cell properties of self-renewal, the ability to produce differentiated progeny, and increased expression of the developmental signaling molecule sonic hedgehog. Identification of pancreatic cancer stem cells and further elucidation of the signaling pathways that regulate their growth and survival may provide novel therapeutic approaches to treat pancreatic cancer, which is notoriously resistant to standard chemotherapy and radiation.
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            Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures.

            The use of avidin-biotin interaction in immunoenzymatic techniques provides a simple and sensitive method to localize antigens in formalin-fixed tissues. Among the several staining procedures available, the ABC method, which involves an application of biotin-labeled secondary antibody followed by the addition of avidin-biotin-peroxidase complex, gives a superior result when compared to the unlabeled antibody method. The availability of biotin-binding sites in the complex is created by the incubation of a relative excess of avidin with biotin-labeled peroxidase. During formation of the complex, avidin acts as a bridge between biotin-labeled peroxidase molecules; and biotin-labeled peroxidase molecules, which contains several biotin moieties, serve as a link between the avidin molecules. Consequently, a "lattice" complex containing several peroxidase molecules is likely formed. Binding of this complex to the biotin moieties associated with secondary antibody results in a high staining intensity.
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              Applying the principles of stem-cell biology to cancer.

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                Author and article information

                Journal
                Br J Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                18 March 2008
                15 April 2008
                22 April 2008
                : 98
                : 8
                : 1389-1397
                Affiliations
                [1 ]Department of Surgical Oncology and Digestive Surgery, Field of Oncology, Course of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Science 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
                [2 ]Frontier Science Research Center, Kagoshima University, Faculty of Medicine 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
                Author notes
                [* ]Author for correspondence: sonshin@ 123456m2.kufm.kagoshima-u.ac.jp
                [3]

                These authors contributed equally to this work.

                Article
                6604307
                10.1038/sj.bjc.6604307
                2361715
                18349830
                0cf152c8-ed77-47da-95ad-403c9f87d8d3
                Copyright 2008, Cancer Research UK
                History
                : 02 January 2008
                : 11 February 2008
                Categories
                Molecular Diagnostics

                Oncology & Radiotherapy
                pancreatic cancer,predicting factor,lymph node metastasis,cd133,vegf-c,cancer stem cell

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