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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 | Endothelial function as an end-point in interventional trial: concepts, methods and current data 显示文摘 | Luscher TF Noll G | 1996 | J Hypertension1996，14，2： | 1 |
| 3 | Molecular pathways of aging and hypertension 显示文摘 | Camici GG Sudano I Noll G | 2009 | Curr Opin Nephrol Hypertens2009，18，2： | 1 |
| 4 | Genome-wide miRNA expression profiling identifies miR-9-3 and miR-193a as targets for DNA methylation in non-small cell lung cancers 显示文摘 | Heller G Weinzierl M Noll C | 2012 | Clin Cancer Res2012，18，6： | 1 |
| 5 | Broadcasting and team sports显示文摘 | NOLL ROGER G | 2007 | Scottish J Political Economy2007，54，3： | 1 |
| 6 | Endothelin receptor antagonists in congestive heart failure:a new therapeutic principle for the future显示文摘 | Noll G Ruschitzka FI | 2001 | J Am Coll Cardiol2001，37，6： | 1 |
| 7 | Endothelin receptor antagonists in congestive heart failure:a new therapeutic principle for the future显示文摘 | Spieker LE Noll G Ruschitzka FT | 2001 | Am Coll Cardiol2001，37，： | 1 |
| 8 | Combination of ACEI inhibitors and Calcium antagonists: a logical approach显示文摘 | Ruschitzlka FT Noll G Luscher TF | 1998 | J Cardiovas Pharmacol1998，31，2： | 1 |
| 9 | Current strategies and perspectives for correcting endothelial dysfunction in atherosclerosis 显示文摘 | Spieker LE Noll G | 2001 | J Cardiovasc Pharmacol2001，38，2： | 1 |
| 10 | Intervalence Charge-transfer Bands in Triphenylamine-based Polmers显示文摘 | Lambent C Noll G | 2003 | Synthetic Met2003，139，1： | 1 |
| 11 | Implementation of scalable power and area efficient high-throughput Viterbi decoders显示文摘 | Gemmeke T Gansen M Noll T G | 2002 | IEEE J Sol Sta Circ2002，37，7： | 1 |
| 12 | Working under pressure: the vascular endothelium in arterial hypertension显示文摘 | Spieker LE Noll G Ruschitzka FT | 2000 | J Hum Hypertens2000，14，1011： | 1 |
| 13 | Methods for characterization of preharvest sprouting resistance in a wheat breeding program显示文摘 | Humphreys D G Noll J | 2002 | Euphytica2002，126，： | 1 |
| 14 | 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 |
| 15 | The endothelium in coronary artery disease显示文摘 | Ruschitzka ET Noll G Luscher TF | 1997 | Caridology1997，88，3： | 1 |
| 16 | Function as an end-point in interventional triads,concepts, methods and current date 显示文摘 | Luscher TF Noll G | 1996 | J Hypertens Suppl1996，14，： | 1 |
| 17 | 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 |
| 18 | Genome-wide miRNA expression profiling identifies miR-9-3 and miR- 193a as targets for DNA methylation in non-small cell lung cancers显示文摘 | Heller G Weinzierl M Noll C | 2012 | C/in Cancer Res2012，18，6： | 1 |
| 19 | Oral treatment with tetrahydrobiopterin reverses endothelial dysfunction and oxidative stt'ess in hypcrcholesterolemia 显示文摘 | Hurlimann D Noll G Gatti CD | 2005 | Circulation2005，112，5： | 1 |
| 20 | Local regulation of the coronary circulation in health and disease: role of nitric oxide and endothelin显示文摘 | Wenzel RR Noll G | 1996 | Eur Heart J1996，16，3： | 1 |
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