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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 | Rosetta: A com- puter program for estimating soil hydraulic parameters with hierar- chical pedotransfer functions 显示文摘 | Schaap M G Leij F J Van Genuchten M Th | 2001 | Journal of Hydrology2001，251，34： | 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 | Improved prediction of unsaturated hydraulic conductivity with the Mualem--van Genuehten model显示文摘 | Schaap M G Leij F J | 2000 | Soil Science Society of America Journal2000，64，3： | 1 |
| 5 | Considerations for improving the accuracy of permittivity measurement using time domain reflectometry 显示文摘 | Robinson D Schaap M Jones S B | 2003 | Soil Science Society of America Journal2003，67，1： | 1 |
| 6 | 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 |
| 7 | Community forest management and REDD+显示文摘 | NEWTON P SCHAAP B FOURNIER M | 2015 | Forest Policy and Economics2015，56，： | 1 |
| 8 | Management of recurrent malignant pleural effusions with a chronic indwelling pleural catheter显示文摘 | van den Toorn L M Schaap E Surmont V F | 2005 | Lung Cancer2005，，50： | 1 |
| 9 | 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 |
| 10 | A modified Mualem-Van Genuchten formulation for improved description of the hydraulic conductivity near saturation 显示文摘 | Schaap M G Van Genuchten M Th | 2005 | Vadose Zone Journal2005，5，1： | 1 |
| 11 | Using neural networks to predict soil water retention and soil hydraulic conductivity显示文摘 | Schaap M G Leij F J | 1998 | Soil and Tillage Res1998，47，： | 1 |
| 12 | ROSETTA: a computer program for estimating soil hydraulic parameters with hierarchical pedotransfer methods显示文摘 | Schaap M G Leij F J van Genuchten M Th | 2001 | Journal of Hydrology2001，251，： | 1 |
| 13 | Illustrating the benefit of using hourly monitoring data on secondary inorganic aerosol and its precursors for model evaluation 显示文摘 | Schaap M Otjes R P Weijers E P | 2011 | Atmospheric Chemistry and Physics2011，11，11： | 1 |
| 14 | Forest floor water content dynamics in a Douglas fir stand 显示文摘 | Schaap M G Bouten W Verstraten J M | 1997 | Journal of Hydrology1997，201，： | 1 |
| 15 | Comparison of four culture systems for Mycobacterium tuberculosis in the Zambian National Reference Laboratory显示文摘 | Muyoyeta M Schaap JA De Haas P | 2009 | Int J Tuberc Lung Dis2009，13，4： | 1 |
| 16 | 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 |
| 17 | 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 |
| 18 | Time of harvest determines the postharvest quality of the common mushroom Agaricus bisporus显示文摘 | BRAAKSMA A SCHAAP D J SCHIPPER C M A | 1999 | Postharvest Biology and Technology1999，16，2： | 1 |
| 19 | 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 |
| 20 | Database related accuracy and uncertainty of pedotransfer functions显示文摘 | SCHAAP M G AND LEIJ F J | 1998 | Soil Science1998，163，： | 1 |
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