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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 | Schnelle multielement analyse in der stahl- schmelze mit laserinduzierter emissionsspektrometrie 显示文摘 | Noll R | 1997 | Stahl und Eisen1997，117，1： | 1 |
| 3 | Zernike polynomials and atmospheric turbulence 显示文摘 | Noll R J | 1976 | Journal of the Optical Society of America A($1520-8532)1976，66，3： | 1 |
| 4 | Hand- held miniature ion trap mass spectrometers 显示文摘 | OUYANG Z NOLL R J COOKS R G | 2009 | Analytical Chemistry2009，81，7： | 1 |
| 5 | Laser-induced breakdown spectroscopy of steel samples using multiple Q-switch Nd:YAG laser pulses 显示文摘 | SATTMANN R STURM V NOLL R | 1995 | J Phys1995，28，10： | 1 |
| 6 | 1,2,4-triazol-5-ones显示文摘 | Manchot V M Noll R | 1905 | Justus Liebig′s Annalen der Chemie1905，343，： | 1 |
| 7 | Government RS:D programs for commercializing space 显示文摘 | COHEN LINDA R NOLL ROGER G | 1986 | American Eco- nomic Review1986，76，2： | 1 |
| 8 | GM3 as a novel growth regulator for human gliomas显示文摘 | Noll E N Lin J Nakatsuji Y Miller R H Black P M | 2001 | Exp Neurol2001，168，： | 1 |
| 9 | Material ablation and plasma state for single and collinear double pulses interacting with iron samples at ambient gas pressures below 1bar 显示文摘 | PETTER L NOLL R | 2007 | Appl Pbys2007，86，1： | 1 |
| 10 | 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 |
| 11 | Characterisation of the water - holding capacity of fresh cheese samples by means of low resolution nuclear magnetic resonance 显示文摘 | Hinrichs R Gotz J Noll M | 2004 | Food Re- search International2004，37，7： | 1 |
| 12 | The Orbitrap: A New Mass Spectrometer显示文摘 | HU Qi-zhi NOLL R J LI Hong-yan | 2005 | Journal of Mass Spectrometry and Ion Physics2005，40，： | 1 |
| 13 | Barriers to implementing tradable air pollution permits:problems of regulatory interactions显示文摘 | Hahn R Noll R | 1983 | Yale Journal on Regulation1983，，1： | 1 |
| 14 | Kinetics and mechanisms of potassium release from sandy middle Atlantic coastal plain soils显示文摘 | Sadusky M C Sparks D L Noll M R | 1987 | Soil Science1987，4，： | 1 |
| 15 | Zernike polynomials and atmospheric turbulence显示文摘 | Noll R J | 1976 | J Opt Soc Am A1976，66，3： | 1 |
| 16 | Two paralogous yefM-yoeB loci from Staphylococcus equorum encode functional toxin-anti- toxin systems显示文摘 | Nolle N Schuster C F Bertram R | 2013 | Microbiology2013，159，8： | 1 |
| 17 | Zernike polynomials and atmospheric turbulence 显示文摘 | R J Noll | 1976 | J Opt Soc Am1976，66，3： | 1 |
| 18 | Administrative procedures as instruments of political control显示文摘 | McCubbins M D Noll R G Weingast B R | 1987 | Journal of Law Economics & Organization1987，，3： | 1 |
| 19 | Characterisation of different treated whey protein concentrates by means of low-resolution nuclear magnetic resonance 显示文摘 | Hinrichs R G6tz J Noll M | 2004 | International Dairy Journal2004，14，9： | 1 |
| 20 | Characterisation of thewater-holding capacity of fresh cheese samples by means of low resolution nuclear magnetic resonance显示文摘 | Hinrichs R Gotz J Noll M | | 0，，07： | 1 |
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