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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 | Altered synaptic transmission in the hippocampus of transgenic mice with enhanced central nervous systems expression of interleukin-6显示文摘 | Nelson TE Olde Engberink A Hernandez R | 2012 | Brain behavior and immunity2012，26，6： | 1 |
| 3 | An endotoxin induced serum factor that cause necrosis of tmors显示文摘 | Carswell E A Old L J Kassel R L | 1975 | Pris Natal Acad Aci USA1975，72，： | 1 |
| 4 | Design and deployment of a satellite constellation using collaborative optimization显示文摘 | Budianto I A Olds J R | | 0，，06： | 1 |
| 5 | Vibrational spectroscopy for cancer diagnostics 显示文摘 | Old O J Fullwood L M Scott R | 2014 | Anal Meyhods2014，6，： | 1 |
| 6 | Risk factors which predispose first-time traumatic anterior shoulder dislocations to recurrent insta- bility in adults : a systematic review and meta-analysis显示文摘 | Olds M Ellis R Donaldson K | 2015 | Br J Sports Med2015，49，14： | 1 |
| 7 | The homeodomain protein Cdx2 regulates lactase gene promoter activity during enterocyte differentiation显示文摘 | Fang R Santiago NA Olds LC | 2000 | Gastroenterology2000，118，1： | 1 |
| 8 | Design and deployment of satellite constellation using collaborative optimization显示文摘 | Budianto I A Olds J R | 2004 | Journal of Spacecraft and Rockets2004，41，6： | 1 |
| 9 | Conciderations for phased array ultrasonics in a fully futomated inspertion systen显示文摘 | Kramb V A Olding R B Sebastian J R | | 0，，23： | 1 |
| 10 | High-permittivity temperature-stable ceramic dielectrics withlow microwave loss 显示文摘 | KELL R C GREENHAM A C OLDS G C E | 1973 | J Am Ceram Soc1973，56，7： | 1 |
| 11 | High-permittivicy temperature-stable ceramic dielectrics with low microwave toss 显示文摘 | KELL R C GREEN A C OLDS G | 1973 | J Am Ceram Soc1973，56，7： | 1 |
| 12 | The homeodomain protein Cdx2 regulates lactase gene promoter activity during enterocyte differentiation显示文摘 | Fang R Santiago NA Olds LC | 2000 | Gastroenterology2000，118，1： | 1 |
| 13 | An endotoxin-induced serum factor that causes necrosis of tumors显示文摘 | Carswell E A Old L J Kassel R L | | 0，，： | 1 |
| 14 | The status,quality,and expansion of the NIH full-length cDNA project:the Mammalian Gene Collection(MGC)显示文摘 | Gerhard D.S Wagner L Feingold E.A Shenmen C.M Grouse L.H Schuler G Klein S.L Old S Rasooly R Good P | | 0，，： | 1 |
| 15 | Esomeprazole:a proton pump in-hibitor显示文摘 | Vachhani R Olds G Velanovich V | 2009 | Expert Rev Gastroenterol Hepatol2009，3，1： | 1 |
| 16 | Imaging for Suspected Appondi- citis显示文摘 | Old J Dusing R Yap W Dirks J | 2005 | Am Faro Phys2005，71，： | 1 |
| 17 | Evidence of associations between bipolar disorder and the brain-derived neurotrophic factor (BDNF) gene 显示文摘 | Sears C Markie D Olds R | 2011 | Bipolar Disord2011，13，78： | 1 |
| 18 | Moderate hypothernfia in patients with acute liver failure and uncon- trolled intracranial hypertension 显示文摘 | Jalan R Olde Damink SW Deutz NE | 2004 | Gastroenterology2004，127，5： | 1 |
| 19 | Design and deplopment of a satellite constellation using collaborative optimization显示文摘 | BUDINATO I A OLDS J R | 2004 | Journal of Spacecraft and Rockets2004，41，6： | 1 |
| 20 | The three Es of cancer immunoediting显示文摘 | Dunn G P Old L J Schreiber R D | 2004 | Annu Rev Immunol2004，22，： | 1 |
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