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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 | Aluminium content of selected foods and food products 显示文摘 | Thorsten S Hasan T Hubertus B | 2011 | Environ Sci Europe2011，23，1： | 1 |
| 3 | Electronic Word-of-mouth via Consumer-opinion Platforms: What Motivates Consumers to Articulate Themselves on the Internet显示文摘 | THORSTEN H T GWINNER K P WALSH G | 2004 | Journal of Interactive Marketing2004，18，1： | 1 |
| 4 | Understandg Relinationship Marketing Outcomes: An Integration of Relational Benefits and Relationship Quality 显示文摘 | Thorsten H T Kevin P G Dwayne D G | 2002 | Journal of Service Research2002，，14： | 1 |
| 5 | Increased Blood-brain barrier permeability and brain edema after focal cerebral ischemia induced by hyperlipidemia 显示文摘 | AYMAN ELALI THORSTEN T DOEPPNER | 2011 | Stroke2011，11，： | 1 |
| 6 | Customer segmentation revisited: The case of the airline indus- try显示文摘 | Thorsten T Edlira S H Iwan W | 2008 | Transportation Research Part A2008，42，： | 1 |
| 7 | On the detection of shunts in silicon solar cells by photo-and electroluminescence imaging显示文摘 | Otwin B Jan B Thorsten T | 2008 | Progress in Photovoltaics:Research and Applications2008，16，： | 1 |
| 8 | Electro- nic Word- of-mouth Via consumer-Opinion platf-orms what motivates consumers to articulate themselves on the internet 显示文摘 | Thorsten H T Gwinner K P Walsh G | 2004 | Journal of In- teract Market2004，18，1： | 1 |
| 9 | The Impact of Customer Satisfaction and Relationship Quality on Customer Retention:a Rritical Reassessrnent and Model Development 显示文摘 | Thorsten H T | 1997 | Psychology& Marketing1997，14，8： | 1 |
| 10 | A short-term strong wind prediction model for railway application: design and verification显示文摘 | Uwe H Stefan K Thorsten T | 2002 | Journal of Wind En- gineering and Industrial Aerodynamics2002，，90： | 1 |
| 11 | The serum protein α 2-HS glycoprotein fetuin inhibits apatite formation in vitro and in mineralizing calvaris cells显示文摘 | Christian A Andreas T | 1996 | J Biol Chem1996，271，20： | 1 |
| 12 | Molecular characterization of dissolved organic matter in a north Brazilian mangrove porewater and mangrove-fringed estuaries by ultrahigh resolution fourier transform ion cyclotron resonance mass spectrometry and excitation/emission spectroscopy显示文摘 | Thorsten D Alan G M | 2007 | Marin Chemistry2007，105，： | 1 |
| 13 | The impact of customer satis- faction and relationship quality on customer retention: A critical reassessment and model development 显示文摘 | Thorsten H T Klee A | 1997 | Psychology and Marketing1997，14，8： | 1 |
| 14 | Electronic Word-of-mouth Via consumer-Opinion platforms what motivates consumers to articulate themselves on the internet显示文摘 | THORSTEN H T GWINNER K P WALSH G | | 0，，01： | 1 |
| 15 | Electronic Word- Of-Mouth Via Consumer-Opinion Platforms: What Motivates Consumers To Articulate Themselves On The lnternet显示文摘 | Thorsten H T Gwinner K P Walsh G | 2004 | Journal of Interact Market2004，18，1： | 1 |
| 16 | Beyond buffer zone protection:Acomparative study of park and buffer zone products' importance to villagers living inside Royal Chitwan National Park and to villagers living in its buffer zone显示文摘 | STEFFEN S THORSTEN T | 2006 | Journal of Environmental Management2006，78，3： | 1 |
| 17 | 17 Beta-estradiol Protects Neurons From Oxidative Stress-induced Cell Death in Vitro显示文摘 | Christian B Martina W Thorsten T | 1995 | Biochem Biophys Res Commun1995，216，： | 1 |
| 18 | Beyond buffer zone protection: a comparative study of park and buffer zone products' importance to villagers living inside Royal Chitwan National Park and to villagers living in its buffer zone显示文摘 | Steffen S Thorsten T | 2006 | Journal of Environmental Management2006，78，： | 1 |
| 19 | 17-Beta estradiol protects neurons from oxidative stress induced cell death in vitro显示文摘 | Christian B Martina W Thorsten T | 1995 | Biochem Biophys Res Commun1995，216，： | 1 |
| 20 | Electronic Word-Of-Mouth Via Consumer-Opinion Platforms What Motivates Consumers to Articulate Themselves on the Internet显示文摘 | THORSTEN H T GWINNER K P WALSH G | 2004 | Journal of Interact Market2004，18，1： | 1 |
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