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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 | Imaging for Suspected Appondi- citis显示文摘 | Old J Dusing R Yap W Dirks J | 2005 | Am Faro Phys2005，71，： | 1 |
| 3 | Effects of thiazide-type and thiazide-like diuretics on cardiovascular events and mortality显示文摘 | Olde Engberink R Frenkel W van den Bogaard B | 2015 | Hypertension2015，65，5： | 1 |
| 4 | Postsynaptic bursting is essential for 'Hebbian' induction of associative long-term potentiation at excitatory synapses in rat hippocampus显示文摘 | PIKE F G MEREDITH R M OLDING A W A | 1999 | J Physiol1999，518，： | 1 |
| 5 | The sur- gical treatment of childhood moyamoya disease 显示文摘 | Olds M V Griebel R W Hoffman H J | 1987 | J Neurosurg1987，66，5： | 1 |
| 6 | Phase equilibriain hydrocarbon systems: composition of the dew-point gasof the methane-water system显示文摘 | OLDS R H SAGE B H LACEY W H | 1942 | Industrial and Engi-neering Chemistry Research1942，34，10： | 1 |
| 7 | Methane-isobutane system显示文摘 | Olds R H Sage B H Lacey W N | 1942 | Industrial & Engineering Chemistry1942，34，8： | 1 |
| 8 | Soil Washing Enhanced by Humic Substances and Biodegradable Chelating Agents显示文摘 | Nell R Hartley Daniel C W Tsang William E Olds | 2014 | Soil & Sediment contamination2014，23，6： | 1 |
| 9 | Moderate hypothermia prevents cerebral hyperemia and increase in intracranial pressure in patients undergoing liver trans- plantation for acute liver failure 显示文摘 | Jalan R Olde Damink S W Deutz N E | 2011 | Transplantation2011，75，： | 1 |
| 10 | Lipopolysaccharide treatment in vivo induces widespread tissue expression of inducible nitric oxide synthase mRNA显示文摘 | Liu S Adcock I M Old R W | 1993 | Biochem Biophys Res Commun1993，196，3： | 1 |
| 11 | Candidate epigenetic biomarkers for non-invasive prenatal diagnosis of Down syndrome显示文摘 | Old R W Crea F Puszyk W | 2007 | Reprod Biomed Online2007，15，2： | 1 |
| 12 | Gut content analysis of mosquito larvae (Diptera: Culicidae) using DAPI stain and epifluorescence microscopy显示文摘 | Walker E D Olds E J Merritt R W | 1988 | Journal of Medical Entomology1988，25，： | 1 |
| 13 | Lipopolysaccharide treatment in vivo induces widespread tissue expression of inducible nitric oxide synthase Mrna显示文摘 | Liu S Adcock I M Old R W | 1993 | Biochem Biophys Res Commun1993，196，3： | 1 |
| 14 | EB curing of maritime composite structures显示文摘 | Chappas W J Devney B G Olding R P | 1999 | Radiation Physics and Chemistry1999，56，4： | 1 |
| 15 | Candidate epigenetic biomarkers for nnn-invasive prenatal diagnosis of Down syndrome显示文摘 | Old R W Crea F Puszyk W | 2007 | Reprint Biomed Online2007，15，2： | 1 |
| 16 | Non-invasive prenatal diagnosis of Down' s syndrome显示文摘 | Hulton M A Old R W | 2007 | Lancet2007，369，： | 1 |
| 17 | Somatic Cell Count During and Between Milkings 显示文摘 | OLDE RIEKERINK R G M BARKEMA H W VEENSTRA W | 2007 | Journal of Dairy Science2007，90，8： | 1 |
| 18 | Genetic aspects of vasovagal syncope:a systematic review of current evidence显示文摘 | Olde Nordkamp L R Wieling W Zwinderman A H | 2009 | Europace2009，11，4： | 1 |
| 19 | Complementary DNA sequencing: expressed sequence tags and human genome project显示文摘 | ADAMS M D KELLEY J M GOCAYNE J D DUBNICK M POLYMEROPOULOS M H XIAO H MERRIL C R WU A OLDE B MORENO R F KERLAVAGE A R MCCOMBIE W R VENTER ] C | 1991 | Science1991，252，5013： | 1 |
| 20 | Somatic cell count during and between milkings显示文摘 | OLDE RIEKERINK R G M BARKEMA H W VEENSTRA W | 2007 | Journal of Dairy Science2007，90，8： | 1 |
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