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| 1 | Cholangiocarcinoma, gone without the Wnt?显示文摘Cholangiocarcinoma(CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells. A recent study by Boulter et al implicates the Wnt signaling cascade in cholangiocarcinogenesis. Wnt ligands Wnt7 B and Wnt10 A were found to be highly overexpressed in human CCA tissue. Wnt7 B protein was present throughout the tumor stroma, and often co-localized with a subset of CD68+ macrophages. To address in a direct manner whether Wnt signaling is engaged in development of CCA, Boulter et al explored the Wnt signaling pathway in an experimental model that recapitulates the multi-stage progression of human CCA.Wnt ligands found to be elevated in human CCA were also upregulated during the course of CCA development following thioacetamide treatment. Wnt10 a increased during the(pre-cancerous) regenerative phase, while Wnt7 b induction paralleled tumor growth. Along with upregulation of target genes, the findings demonstrate that the canonical Wnt pathway is progressively activated during cholangio-carcinogenesis. Macrophage depletion,eliminating a major source of Wnt7 b, prevented activation of the canonical Wnt cascade, and resulted in reduced number and volume of tumors in this model. Moreover,specific inhibitors of the canonical Wnt pathway(ICG-001 and C-59) caused reduction of tumor area and number,in xenograft and thioacetamide models of CCA. The aggregated findings show that experimental, and presumably human CCA, is a Wnt-driven tumor. Modulation of Wnt signaling, alone or in combination with surgicalor chemotherapy approaches, holds promise in the management of this fatal malignancy. | Anne T R Noll Thorsten Cramer Steven W M Olde Damink Frank G Schaap | 2016 | World Journal of Hepatology2016，8，26： | 3 |
| 2 | Selective etching of semicrystalline polymers:CF4 gas plasma treatment of poly (ethylene)显示文摘 | Olde Riekerink M B Terlingen J G A Engbers G H M | 1999 | Langmuir1999，15，14： | 1 |
| 3 | Selective etching of semicrystalline polymers: CF4 gas plasma treatment of poly(ethylene) 显示文摘 | Olde Riekerink M B Terlingen J G A Engbers G H M | 1999 | Langmuir1999，15，14： | 1 |
| 4 | Intraepithelial CDS+ tumor-infiltrating lymphocytes and a high CD8+/regnlatory T cell ratio are associated with favorable prognosis in ovarian cancer显示文摘 | Sato E Olson SH Ahn J Bundy B Nishikawa H Qian F Jungbluth AA Frosina D Gnjatic S Ambrosone C Kepner J Odunsi T Ritter G Lele S Chen YT Ohtani H Old LJ Odunsi K | 2005 | Proc Natl Acad Sci USA2005，102，18： | 1 |
| 5 | Role of ammonia and inflammation in minimal hepatic encephalopathy显示文摘 | Shawcross DL Wright G Olde Damink SW | 2007 | Metab Brain Dis2007，22，1： | 1 |
| 6 | Interorgan ammonia metabolism in liver failure:the basis of current and future therapies显示文摘 | Wright G Noiret L Olde Damink SW | | 0，，02： | 1 |
| 7 | High-permittivity temperature-stable ceramic dielectrics withlow microwave loss 显示文摘 | KELL R C GREENHAM A C OLDS G C E | 1973 | J Am Ceram Soc1973，56，7： | 1 |
| 8 | High-permittivicy temperature-stable ceramic dielectrics with low microwave toss 显示文摘 | KELL R C GREEN A C OLDS G | 1973 | J Am Ceram Soc1973，56，7： | 1 |
| 9 | Role of ammonia and inflammation in minimal hepatic encephalo pathy 显示文摘 | Shawcross DL Wright G Olde Damink SW | 2007 | Metab Brain Dis2007，22，1： | 1 |
| 10 | Re-view article : pancreatic renin-angiotensin systems inhealth and disease显示文摘 | Skipworth JR Szabadkai G Olde Damink SW | 2011 | Aliment Pharmacol Ther2011，34，8： | 1 |
| 11 | The status,quality,and expansion of the NIH full-length cDNA project:the Mammalian Gene Collection(MGC)显示文摘 | Gerhard D.S Wagner L Feingold E.A Shenmen C.M Grouse L.H Schuler G Klein S.L Old S Rasooly R Good P | | 0，，： | 1 |
| 12 | The immunobiology of cancer immunosurveillance and immunoediting显示文摘 | Dunn G P Old LJ Schreiber RD | | 0，，： | 1 |
| 13 | Esomeprazole:a proton pump in-hibitor显示文摘 | Vachhani R Olds G Velanovich V | 2009 | Expert Rev Gastroenterol Hepatol2009，3，1： | 1 |
| 14 | Role of ammonia and inflammation in minimal hepatic encephaIopathy 显示文摘 | Shawcross DL Wright G Olde Damink SW | 2007 | Metab Brain Dis2007，22，1： | 1 |
| 15 | Brain cytokine flux in acute liver failure and its relation-ship with intracranial hypertension显示文摘 | Wright G Shawcross D Olde Damink SW | 2007 | Metab Brain Dis2007，22，34： | 1 |
| 16 | Observations on terrestrial ureyite and ureyitic pyroxene 显示文摘 | Harlow G E Olds E P | 1987 | American Mineralogist1987，72，1： | 1 |
| 17 | Nutrient concentrations in mire vegetation as a measure of nutrient limitation in mire eeosystems显示文摘 | WASSEN M J OLDE V H G M DE SWART E O A M | 1995 | Journal of Vegetation Science1995，6，1： | 1 |
| 18 | The three Es of cancer immunoediting显示文摘 | Dunn G P Old L J Schreiber R D | 2004 | Annu Rev Immunol2004，22，： | 1 |
| 19 | NKT cells enhance CD4 + and CD8 + T cell responses to soluble antigen in vivo through direct interaction with dendritic cells 显示文摘 | Hermans IF Silk JD Gileadi U Salio M Mathew B Ritter G Schmidt R Harris AL Old L Cerundolo V | 2003 | J Immunol2003，171，10： | 1 |
| 20 | Postsynaptic bursting is essential for 'Hebbian' induction of associative long-term potentiation at excitatory synapses in rat hippocampus显示文摘 | PIKE F G MEREDITH R M OLDING A W A | 1999 | J Physiol1999，518，： | 1 |
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