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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 | Neural stem cells as a novel platform for tumor-specific delivery of therapeutic antibodies显示文摘 | FRANK R T EDMISTON M KENDALL S E | 2009 | PLoS One2009，4，12： | 1 |
| 3 | New constraints on the sources and behavior of neodymium and hafnium in seawater from Pacific Ocean ferromanganese crusts显示文摘 | VAN DE FLIERDT T FRANK M LEE D C | 2004 | Geochim et Cosmochim Acta2004，68，19： | 1 |
| 4 | Predictors of improved renal function after percutaneous stent-supported angioplasty of severe atherosclerotic ostial renal artery stenosis显示文摘 | Frank U Müller C | 2003 | Circulation2003，108，： | 1 |
| 5 | The magnitude of Late Paleozoic glacioeustatic fluctuations: A synthesis显示文摘 | Rygel M C Fielding C R Frank T D | 2008 | Journal of Sedimentary Research2008，78，8： | 1 |
| 6 | Building Dynamic capabilities: Innovation Driven by Individual, Finn, and Network - level Effects 显示文摘 | FRANK T ROTHAERMEL ANDREW M HESS | 2007 | Organization Science2007，18，6： | 1 |
| 7 | Caveolin-1-deficient aortic smooth muscle cells show cell autonomous abnormalities in proliferation, migration, and endothelin-based signal transduction显示文摘 | HASSAN G S WILLIAMS T M FRANK P G | 2006 | Am J Physiol Heart Circ Physiol2006，290，6： | 1 |
| 8 | Antithrombin activity of fucoidan显示文摘 | Frank C James B M Rita E T | 1989 | J Biol Chem1989，264，： | 1 |
| 9 | Nd and Pb iso tope evolution of deep water masses in the eastern Indian Ocean during the past 33 Myr 显示文摘 | Frank M Whiteley N van de Flierdt T | 2006 | Chemical Geology2006，226，3： | 1 |
| 10 | Upstream hydromagnetic-waves and their association with back-streaming ion populations-Isee-1 and 2 observations显示文摘 | Hoppe M M Russell C T Frank L A | | 0，，06： | 1 |
| 11 | Sensitivity of isolates of Sclerotium rolfsii from peanut in Georgia to Selected Fungicides显示文摘 | Franke M D Brenneman T B Stevenson K L | 1998 | Plant Disease1998，82，： | 1 |
| 12 | Genetic transformation of major wine grape cultivars of Vitis vinifera L显示文摘 | Iocco P Franks T Thomas M R | | 0，，： | 1 |
| 13 | Chimerism in grapevines:implications for eultivar identity,ancestry and genetic improvement显示文摘 | Franks T Botta R Thomas M R | 2002 | Theor Appl Genet2002，104，： | 1 |
| 14 | Tracing the history of submarine hydrothermal inputs and the significance of hydrothermal hafnium for the seawater budget--a combined Pb--Hf Nd isotope approach显示文摘 | VAN DE FLIERDT T FRANK M HALLIDAY A N | 2004 | Earth Planet Sc Lett2004，222，： | 1 |
| 15 | Model-based fault diagnosis in technical processes 显示文摘 | FRANK P M DING S X MARCU T | 2000 | Trans on Institute of Measurement and Control2000，22，1： | 1 |
| 16 | Social licence in design: constructive technology assessment within a mineral research and development institution 显示文摘 | Franks D M Cohen T | 2012 | Technological Forecasting and Social Change2012，79，7： | 1 |
| 17 | Predictors of improved renal function after percutaneous stent-supported angioplasty of severe atherosclerotic ostial renalartery stenosis显示文摘 | Zeller T Frank U Müller C | | 0，，18： | 1 |
| 18 | Rapid Detection of Herpes- Simplex Virus and Varieella-Zoster Virus Infections by Real-Time PCR 显示文摘 | Manfred W Ursula M K Frank T | 2003 | J Clin Mierobiol2003，41，4： | 1 |
| 19 | Chimerism in grapevines: implications for cultivar identity, ancestry and genetic improvement 显示文摘 | FRANKS T BOTTA R THOMAS M R | 2002 | Theoretical and Applied Genetics2002，104，： | 1 |
| 20 | Relationship of the Vibromyogram to the Surface Electromygramof the Human Rectus Femoris Muscle during Voluntary Isometric Contraction显示文摘 | ZHANG Y T FRANK C B RANGAYYAR R M | 1996 | J Rehabil Res Develop1996，33，4： | 1 |
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