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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 | Adhesion molecules in normal and pathological corneas显示文摘 | Vorkauf W Vorkauf M Nolle B | 1995 | Graefes Arch Clin Exp Ophthalmol1995，233，4： | 1 |
| 3 | Functional topographic mapping of the cortical ribbon in human vision with conventional MRI scanners显示文摘 | Schneider W Noll DC Cohen JD | 1993 | Nature1993，365，6442： | 1 |
| 4 | Copolymerization of norbornene and ethene with homogenous zirconoeenes/methylaluminoxane catalysts 显示文摘 | Kaminsky W Noll A | 1993 | Polymer Bull1993，，31： | 1 |
| 5 | Phylogenetic identity, growth- response time and rRNA operon copy number of soil bacteria indi- cate different stages of community succession 显示文摘 | Shrestha P M Noll M Liesack W | 2007 | Environmental Microbiology2007，9，： | 1 |
| 6 | Methods for measuring dynamic mechanical properties of rubber-like materials显示文摘 | Nolle A W | 1948 | Journal of Applied Physics1948，19，8： | 1 |
| 7 | Assembly of a homochiral,body-centered cubic network composed of vertex-shared Mg12cages:use of electrospray ionization mass spectrometry to monitor metal carboxylate nucleation显示文摘 | ROOD J A BOGGESS W C NOLL B C | 2007 | J Am Chem Soc2007，129，13： | 1 |
| 8 | Synthesis,structural characterization, gas sorption and guest-ex-change studies of the light weight,porous metal-or-ganic framework a- 显示文摘 | Rood J A Noll B C Henderson K W | 2006 | InorgChem2006，45，14： | 1 |
| 9 | Foundations of linear viscoelasticity显示文摘 | COLEMAN B D NOLL W | 1961 | Rev Mod Phys1961，33，： | 1 |
| 10 | Autophagy and the Im-mune System显示文摘 | Kuballa P Nolle W M Castoreno A B | 2012 | Annu Rev Immunol2012，30，： | 1 |
| 11 | A New regression based method for accurate measurement of coal and shale gas content显示文摘 | SHTEPANI E NOLL L A ELROD L W | 2010 | SPE Reservoir Evaluation & Engineering2010，13，2： | 1 |
| 12 | Internet banking 显示文摘 | Furst K Lang W W Nolle D E | 2002 | Journal of Financial Services Research2002，22，12： | 1 |
| 13 | How the Internet Affects Output and Performance at Community Banks 显示文摘 | DeYoung R Lang W W Nolle D L | 2007 | Journal of Banking & Finance2007，31，： | 1 |
| 14 | Disintegration of cytoskeletal structure of actin filaments in energy-depleted endothelial cellas 显示文摘 | Besselmann M Noll T | 1993 | Am J Physiol1993，263，2： | 1 |
| 15 | Hydrothermal crystallization of ammenium-saponite at 200℃ and al hogonus water pressure显示文摘 | Noll W | 1956 | Chemie Der Erde1956，10，6： | 1 |
| 16 | Synthesis, structural characterization, gas sorption and guest- exchange studies of the lightweight, porous metal- organic framework a- 显示文摘 | Rood J A Noll B C Henderson K W | 2006 | In- orgChem2006，45，14： | 1 |
| 17 | Evaluation of protein release from chitosan-alginate mierocapsules produced using external or internal gelation 显示文摘 | Vanderberg G W De La Nolle J | 2001 | J Microencapsul2001，18，4： | 1 |
| 18 | Methods of measuring dynamic mechanical properties of rubber-like materials 显示文摘 | Nolle N W | 1948 | Jour of Appl Phys1948，9，8： | 1 |
| 19 | Synthesis, struelura] characterization, gas sorption and guest-exchange studies of the lightweight, porous metal-organic framework α- 显示文摘 | Rood J A Noll B C Henderson K W | 2006 | Inorg Chem2006，45，14： | 1 |
| 20 | Disintegration of cy toskeletal structure of actin filaments in energy-depleted en dothelial cells显示文摘 | Kuhne W Besselmann M Noll T | 1993 | Am J Physiol1993，264，52： | 1 |
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