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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 | Automatic control of a 30 MWe SEGS VI parabolic trough plant显示文摘 | Thorsten Stuetzle Nathan Blair John W Mitchell | 2004 | Solar Energy2004，76，1： | 1 |
| 3 | Current evidence for transurethral laser therapy of non-muscle invasive bladder cancer 显示文摘 | Mario W K Thorsten B Mathias W | 2011 | World J Urol2011，29，4： | 1 |
| 4 | Economic, Demographic, and Institutional Determi- nants of Life Insurance Consumption Across Countries显示文摘 | Thorsten I W | 2003 | World Bank Economic Review2003，，17： | 1 |
| 5 | Expression of type IV collagen-ase correlates with the expression of vascular endothelial growth factor in primary non-small cell lung cancer显示文摘 | Thorsten W Cornelius K | 1997 | J Cancer Res Clin Oncol1997，123，5： | 1 |
| 6 | Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling 显示文摘 | Dietmar W H Thorsten S Iwan Z | 2001 | J Biomedical Materials Research2001，55，2： | 1 |
| 7 | A role for endothelin-2 and its receptors in breast tumor cell invasion 显示文摘 | MATTHEW J GRIMSHA W THORSTEN H | 2004 | Cancer Res2004，64，： | 1 |
| 8 | Cell tagging with clinically approved iron oxides:feasibility and effect of lipofection,particle size,and surface coating on labeling efficiency显示文摘 | Lars M Thorsten P Alexander W | 2005 | Radiology2005，235，1： | 1 |
| 9 | Experimental investigations on hull-fin interferences of the LOTTE airship显示文摘 | PETER F THORSTEN L SIEGFRIED W | 2003 | Aerospace Science and Technology2003，7，8： | 1 |
| 10 | Automatic Control of a 30 Mwe SEGS VI Parabolic Trough Plant 显示文摘 | THORSTEN DTUETZLE NATHN BLAIR JOHN W etc | 2004 | Solar Energy2004，，： | 1 |
| 11 | Nicotine Stroop and addiction memory-an ERP study 显示文摘 | Thorsten F Patrick W Manfred H | 2006 | International Journal of Psychophysiology2006，62，2： | 1 |
| 12 | Thermal desorption/pyrolysis coupled with photoionization time-of-flight mass spectrometry for the analysis of molecular organic compounds and oligomerie and polymeric fractions in urban particulate matter 显示文摘 | Thorsten S Jochen W Stefan M | 2006 | Anal Chem2006，78，： | 1 |
| 13 | Nicotine stroop and addiction memory: An ERP study 显示文摘 | Thorsten F Patrick W Manfred H | 2006 | International Journal ofPsychophysiology2006，62，2： | 1 |
| 14 | 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 |
| 15 | Determination of benzotriazole corrosion in- hibitors from aqueous environmental samples by liquid ehromatog- raphy-electrospray ionization-tandem mass spectrometry 显示文摘 | Stefan W Thorsten R | 2005 | Anal Chem2005，77，： | 1 |
| 16 | Pelvimetry revisited:analyzing cephalopelvic disproportion 显示文摘 | Miriam SL Thorsten RC J Sabine W | 2010 | Eur J Radiol2010，74，3： | 1 |
| 17 | Does Customer Demotion Jeopardize Loyalty? 显示文摘 | Tillmann W Thorsten Hennig- Thurau Thomas R | 2009 | Journal of Marketing2009，，： | 1 |
| 18 | Does customer demotion jeopardize loyalty? 显示文摘 | Tillmann W Hennig-Thurau Thorsten Thomas R | 2009 | Journal of Marketing2009，73，5： | 1 |
| 19 | Innovative pulmonay preservation of non-heart-beating donorgrafts in experimental lun transplantation 显示文摘 | Thorsten W Ulrich F W F Antonia F | 2004 | Eur J Cardiothorac Surg2004，26，1： | 1 |
| 20 | Au- tomatic control of a 30 MWe SEGS VI parabolic trough plant 显示文摘 | Thorsten Stuetzle Nathan Blair John W Mitchell | 2004 | Solar Energy2004，，76： | 1 |
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