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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 | Displacement of Ca2+by Na+from the plasmalemms of root cells显示文摘 | Cramer G R Luchli André Polito V S | 1985 | Plant Physiol1985，79，1： | 1 |
| 3 | Displacement of Ca^2 + by Na^+ from the plasmalemma of root cells 显示文摘 | Cramer G R Lauchli A Polito V S | 1985 | Plant Physiol1985，79，： | 1 |
| 4 | Salinity-calciumn interactions on root growth and osmotic adjustment of two corn cultivars differing in salt tolerance显示文摘 | Cramer G R Abdel B R Seeman J R | 1990 | Joumal of Plant Nutrition1990，13，： | 1 |
| 5 | 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 |
| 6 | 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 |
| 7 | Displacement of Ca^2+ by Na^+ from the plasmalemma of root cells显示文摘 | CRAMER G R LAUCHLI A POLITO V S | 1985 | Plant Physiology1985，79，： | 1 |
| 8 | Rsplacement of Ca2by Na+ fromthe plasinalemma of root cells显示文摘 | Cramer G R Lauchli A Polito V S | 1985 | Plant Physiology1985，79，： | 1 |
| 9 | Salt tolerance is not associated with the sodium accumulation of two maize hybrids 显示文摘 | Cramer G R | 1994 | Aust J Plant Physiol1994，21，： | 1 |
| 10 | Displacement of Ca^2+ and Na^+ form the plasmalemms of root cells显示文摘 | Cramer G R | 1985 | Plant Physiol1985，79，： | 1 |
| 11 | Displacement of Ca2+by Na+from the plasmalemma of root cells-A primary response to salt stress显示文摘 | Cramer G R L?uchli A Polito V S | 1985 | Plant Physiology1985，79，： | 1 |
| 12 | A functional MRI study of subjects recovered from hemiparetic stroke显示文摘 | CRAMER S C NELLES G BEBSON R R | 1997 | Stroke1997，28，： | 1 |
| 13 | Kinetics of maize leaf elongation 显示文摘 | Cramer G R | 1992 | J Exp Bot1992，43，： | 1 |
| 14 | Reactive oxygen species and antioxidants:Relationships in green cells显示文摘 | ALSCHER R G DONAHUE J L CRAMER C L | 1997 | Physiol Plant1997，100，： | 1 |
| 15 | Persistent efficacy of topical eprinomectin against nematode parasites in cattle 显示文摘 | Cramer L G Pitt S R Rehbein S | 2000 | Parasitology Research2000，86，11： | 1 |
| 16 | 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 |
| 17 | Thermal sprayed titanium anode for cathcdic protection of reinforced concrete bridges显示文摘 | Cramer S D Covino B S Holcomb G R | 1999 | Journal of Thermal Spray Technology1999，8，1： | 1 |
| 18 | Effects of NaCl and CaCl2 on Ion Activities in Comple Nutrient and Root Growth of Cotton显示文摘 | Cramer G R Luchli A Epstein E | 1986 | Plant Physiol1986，81，： | 1 |
| 19 | Effects of NaC1 and CaCI2 on activities in complex of nutrient solution and root growth of cotton 显示文摘 | Cramer G R Lauchl I A Epstein E | 1986 | Plant Physiology1986，81，3： | 1 |
| 20 | Water and salinity stress in grapevines: early and late changes in transcript and metabolite profiles 显示文摘 | Cramer G R ErgiJl A Grimpletet J | 2007 | Functional & Integrative Genomics2007，7，2： | 1 |
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