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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 | Control of coccidiosis in chickens by vaccination显示文摘 | VERMEULEN A N SCHAAP D C SCHETTERS T P | | 0，，： | 1 |
| 3 | Neural network analysis for hierarchical prediction of soil hydraulic properties显示文摘 | Schaap M G Leij F J van Genuehten M T | 1998 | Soil Scienee Society of America Journal1998，62，4： | 1 |
| 4 | Standardized evaluation methodology and reference database for evaluating coronary artery centerline extraction algorithms显示文摘 | Schaap M Metz C T Walsum T | | 0，，05： | 1 |
| 5 | Coronary centerline extraction from CT coronary angiography images using a minimum cost path approach显示文摘 | Metz C T Schaap M Weustink A C | 2009 | IEEE Trans on Medical Physics2009，36，12： | 1 |
| 6 | The Theory and Practice of Branch Autonomy显示文摘 | D G Sprugel T M Hinckley W Schaap | 1991 | Annual Review of Ecology and Systematics1991，，： | 1 |
| 7 | Control of coccidio-sis in chickens by vaccine显示文摘 | Vermeuhn A N Schaap D c Schetters T P M | 2001 | Veterinary Parasitology2001，100，： | 1 |
| 8 | Familial Ebstein's anomaly显示文摘 | Rosenmann A Arad I Simcha A Schaap T | 1976 | J Med Genet1976，13，： | 1 |
| 9 | Rosetta: a computer program for estimating soil hydraulic parameters with hierarchical pedo- transfer functions显示文摘 | Schaap M G Leij F J van Genuchten M T | 2001 | Journal of Hydrology2001，251，34： | 1 |
| 10 | TDR calibration of organic forest floot media显示文摘 | Schaap M G de Lange L Heimovaara T J | 1996 | Soil Tech1996，11，2： | 1 |
| 11 | Standardized evaluation framework for evaluating coronary artery stenosis detection, steno- sis quantification and lumen segmentation algorithms in computed tomography angiography 显示文摘 | Kirili H A Schaap M Metz C T | 2013 | Medical Image Analysis2013，17，8： | 1 |
| 12 | ROSETYA:a computer program for estimating soil hydraulic parameters with hierarchical pedotransfer functions显示文摘 | Schaap M G Leij F J van Genuchten M T | 2001 | Journal of Hydrology2001，251，34： | 1 |
| 13 | Molecular phylogeny and evolution of morphology in the social amoebas 显示文摘 | Schaap P Winekler T Nelson M | 2006 | Science2006，314，5799： | 1 |
| 14 | Control of Coccidiosis in Chickens by Vaccination 显示文摘 | VERMEULEN A N SCHAAP D C SCHETTERS T P M | 2001 | Veterinary Parasitology2001，100，9： | 1 |
| 15 | Acidity and sweetness in apple and pear显示文摘 | VISSER T SCHAAP A A DE VRIES D P | 1968 | Euphytica1968，17，： | 1 |
| 16 | Control of coccidiosis in chickens by vaccination 显示文摘 | Vermeulen A N Schaap D C Schetters T P | 2001 | Vet Parasitol2001，100，12： | 1 |
| 17 | Control of coccidiosis in chickens by vaccination显示文摘 | Vermeulen A N Schaap D C Schetters T P M | 2000 | Vet Parasitol2000，100，： | 1 |
| 18 | Rosetta: a computer program for estimating soil hydraulic parameters with hierarchical pedotransfer function显示文摘 | Schaap M G Leij F J van Genuchten M T | 2001 | Journal of Hydrology2001，251，： | 1 |
| 19 | TDR calibration of organic forest floor media显示文摘 | Schaap M G de Lange L Heimovaara T J | 1996 | Soil Tech1996，11，2： | 1 |
| 20 | Control of coccidiosis in chicken by vaccination 显示文摘 | VERMEVULEN A N SCHAAP D C SCHETTERS T P M | 2001 | Vet Parasitol2001，100，： | 1 |
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