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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 | Tissue-specific mRNA expression profiling in grape berry tissues显示文摘 | GRIMPLET J DELUC L G TILLETT R L WHEATLEY M D SCHLAUCH K A CRAMER G R CUSHMAN J C | 2007 | BMC Genomics2007，8，： | 1 |
| 3 | Eficacy and tolerability of gas? tric- retentive gabapentin for the treatment of postherpetic neural ? gia 显示文摘 | Irving G Jensen M Cramer M | 2009 | C lin J Pain2009，6，7： | 1 |
| 4 | Efficacy of vaccination at 4 and 6 weeks in the control of canine parvovirus显示文摘 | De Cramer K G Stylianides E van Vuuren M | 2011 | Vet Microbiol2011，149，12： | 1 |
| 5 | Optimization of protein extraction and solubilization for mature grape berry' clusters显示文摘 | Vincent D M D Wheatley G R Cramer | 2006 | Electrophoresis2006，27，9： | 1 |
| 6 | Efficacy and tolerability of gastric-retentive gabapentin for the treatment of postherpetic neuralgia:results of a double-blind,randomized,placebo-controlled clinical trial显示文摘 | Irving G Jensen M Cramer M | 2009 | Clini J Pain2009，25，03： | 1 |
| 7 | Estimation of toxic hazard-a decision tree approach 显示文摘 | Cramer G M Ford R A Hall R L | 1978 | Food Cosmet Toxicol1978，16，3： | 1 |
| 8 | Electronic read- out for three-channel thrombelastograph显示文摘 | Raviv G Cramer DB Epstein M | 1978 | J Med1978，9，： | 1 |
| 9 | Electronic readout for three-channel thrombelastograph 显示文摘 | Raviv G Cramer DB Epstein M | 1978 | J Med1978，9，： | 1 |
| 10 | PV System Technolo- gies:State-of-the-Art and Trends in Decentralised Elec- trification显示文摘 | G Cramer M Ibrahim W Kleinkauf | 2004 | 13(2) :38-422004，13，2： | 1 |
| 11 | The severe cardiorenal syndrome: 'Guyton revisited' 显示文摘 | BONGARTZ L G CRAMER M J DOEVENDANS P A | 2005 | Eur Heart J2005，26，： | 1 |
| 12 | Response to com- ments on ' ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models' 显示文摘 | Landreth G E Cramer P E Lakner M M | 2013 | Science2013，340，6135： | 1 |
| 13 | Efficacy and tolerability of gastric-retentive gabapentin for the treatment of postherpetic neuralgia 显示文摘 | Irving G Jensen M Cramer M | 2009 | Clin J Pain2009，25，： | 1 |
| 14 | Biological activity and modular structure of RE-1-silencing transcription factor (REST), a repressor of neuronal genes显示文摘 | THIEL G LIETZ M CRAMER M | 1998 | The Journal of Biological Chemisitry1998，273，26： | 1 |
| 15 | Optimization of protein extraction and solubilization for mature grape berry clusters 显示文摘 | VINCENT D WHEATLRY M D CRAMER G R | 2006 | Electrophoresis2006，27，9： | 1 |
| 16 | A Two - state Rural Household Demand Analysis : Microdata Evidence from Jiangsu Province 显示文摘 | Gao X M Wailes E J Cramer G L | 1996 | American Journal of Agricultural Economics1996，，3： | 1 |
| 17 | Transforming growth factor beta 1 stimulates vascular endothelial growth factor gene transcription in human cholangiocellular carcinoma cells显示文摘 | Benckert C Jonas S Cramer T Von Marschall Z Schafer G Peters M | 2003 | Cancer Res2003，63，5： | 1 |
| 18 | Recent patterns and mechanisms of carbon exchange by terrestrial ecosystems显示文摘 | Schimel D S House J I Hibbard K A Bousquet P Ciais P Peylin P Braswell B H Apps M J Baker D Bondeau A Canadell J Churkina G Cramer W Denning A S Field CB Friedlingstein P Goodale C Heimann M Houghton PA Melillo J M Moore B 3rd Murdiyarso D Noble I Pacala S W Prentice I C Raupach M R Rayner P J Scholes R J Steffen W L Wirth C | 2001 | Nature2001，414，： | 1 |
| 19 | Efficacy and tolerability of gastric-retentive gahapentin for the treatment of postherpetic neuralgia: results of a double-blind, randomized, placebo-controlled clinical trial显示文摘 | Irving G Jensen M Cramer M | 2009 | Clin J Pain2009，25，： | 1 |
| 20 | Effects of motor imagery training after chronic, complete spinal cord injury显示文摘 | CRAMER S C COHEN M J LACOURSE M G | 2007 | Exp Brain Res2007，177，2： | 1 |
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