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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 | Hepatocytes as a sourceof collagen type ⅩⅧ endostatin显示文摘 | Schuppan D Cramer T Bauer M | 1998 | Lancet1998，352，9131： | 2 |
| 3 | Hepatocytes as a source of collagen type ⅩⅧ endostatin显示文摘 | Schuppan D Cramer T Bauer M | | 0，，： | 2 |
| 4 | Modelling isotope fractionation during primary cracking of natural gas: a reation kinetic approach 显示文摘 | CRAMER B KROSS B M LITTKE R | 1998 | Chemical Geology1998，149，34： | 1 |
| 5 | Sclerosing of recurrent lymphangioma using OK-432显示文摘 | Mikhail M Kennedy R Cramer B | 1995 | J Pediatr Surg1995，30，8： | 1 |
| 6 | Modelling isotope fractionation during primary cracking of natural gas:a reaction kinetic approach显示文摘 | Cramer B Krooss B M Littke R | 1998 | Chemical Geology1998，149，： | 1 |
| 7 | Neurosecretory granules in small cell invasive carcinoma of the urinary bladder显示文摘 | CRAMER S F AIKAWA M (~I-EILLIN M | 1981 | Cancer1981，47，4： | 1 |
| 8 | Structure and functioning of cluster roots and plant response to phosphate deficiency显示文摘 | Lambers H Cramer M D Shane M W | 2003 | Plant and Soil2003，248，： | 1 |
| 9 | The severe cardiorenal syndrome : ' Guyton revisited' 显示文摘 | Bongartz LG Cramer M J Doevendans PA | 2005 | Eur Heart J2005，26，1： | 1 |
| 10 | Sex difference in loneliness:The role of masculinity and femininity显示文摘 | Neyedley K A | 1998 | Sex Roles1998，38，7： | 1 |
| 11 | 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 |
| 12 | Potential for Using Waste Glass in Portland Cement Concrete显示文摘 | Craig Polley Steven M Cramer Rodolfovdela Cruz | 1998 | Journal of Materials in Civil Engineering1998，，5： | 1 |
| 13 | Evaluation of an ultra-wideband propagation channel显示文摘 | CRAMER R J M SCHOLTZ R A WIN M Z | 2002 | IEEE Trans on Antenna and Propagation2002，50，5： | 1 |
| 14 | The impact of comorbid depression on health resource utilization in a community sample of people with epilepsy显示文摘 | Cramer JA Blum D Fanning K Reed M | 2004 | Epilepsy Behav2004，5，： | 1 |
| 15 | Modelling isotope fractionation during pri mary cracking of natural gas: a reaction kinetic approach显示文摘 | Cramer B Krooss B M Littke R | 1998 | Chemical Geology1998，149，34： | 1 |
| 16 | Reaction kinetics of stable carbon isotopes in natural gas - Insights from dry, open system pyrolysis experiments 显示文摘 | Cramer B Faber E Gerling P Krooss B M | 2001 | Energ Fuel2001，15，3： | 1 |
| 17 | The severe cardiorenal syndrome: guyton revisited显示文摘 | LBongartz LG Cramer M J Doevendans PA | 2005 | Eur Heart J2005，26，11： | 1 |
| 18 | The Madin darbycanine Kidney ( MDCK) epithelial cell monolayer as a model cel-lular transport barrier显示文摘 | Cho M J Thompson D P Cramer C T | 1989 | Pharm Res1989，6，1： | 1 |
| 19 | 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 |
| 20 | Dual mechanism of vascular endothelial growth factor upregulation by hypoxia in human hepatocellular carcinoma显示文摘 | Von Marschall Z Cramer T Hocker M | 2001 | Gut2001，48，1： | 1 |
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