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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 | A rapid dehydration leaf assay reveals stomatal response differences in grapevine genotypes显示文摘A simple and reliable way of phenotyping plant responses to dehydration was developed.Fully-developed leaves were detached and placed in a closed plastic box containing a salt solution to control the atmospheric water potential in the container.Three hours of dehydration(weight loss of the leaf)was optimal for measuring changes in stomatal response to dehydration.Application of the plant hormone abscisic acid(ABA)prior to leaf detachment decreased the amount of water loss,indicating that the assay was able to detect differences based on a stomatal response to dehydration.Five different Vitis genotypes(V.riparia,V.champinii,V.vinifera cv.Shiraz,V.vinifera cv.Grenache and V.vinifera cv.Cabernet Sauvignon)with known differences in drought tolerance were screened for their dehydration response and the results obtained corresponded to previous reports of stomatal responses in the vineyard.Significant differences in stomatal density along with differences in the amount and rate of water lost indicate differences in dehydration sensitivity among the genotypes screened.Differences in stomatal response to ABA were also detected.Shiraz had the lowest stomatal density and the highest ABA sensitivity among the genotypes screened,yet Shiraz lost the most amount of water,indicating that it was the least sensitive to dehydration.Despite having the highest stomatal density and intermediate stomatal sensitivity to ABA,V.riparia lost the smallest amount of water,indicating that it was the most sensitive to dehydration.The assay presented here represents a simple and reliable phenotyping method for plant responses to leaf dehydration. | Daniel W Hopper Ryan Ghan Grant R Cramer | 2014 | Horticulture Research2014，1，1： | 2 |
| 3 | Measuring special effects显示文摘 | Cramer W R Gabel P W | 2001 | Eu- ropean Coatings Journal2001，，78： | 1 |
| 4 | Novel tetranortriterpenoids with insect antifeeding activity from neem oil 显示文摘 | Kraus W Cramer R | 1981 | Liebigs Ann Chem1981，1981，1： | 1 |
| 5 | Introduction of 4-chloro-α-cyanocinnamic acid liquid matrices for high sensitivity UVMALDI-MS显示文摘 | TOWERS M W MCKENDRICK J E CRAMER R | 2010 | Journal of Proteome Research2010，9，4： | 1 |
| 6 | Calci- neurin controls growth, morphology, and pathogenicity in Aspergillus fumigatus 显示文摘 | Steinbach W J Cramer R A Perfect B Z | 2006 | Eukaryotic Cell2006，5，7： | 1 |
| 7 | Recent patterns and mechanisms of carbon exchange by terrestrial ecosystems显示文摘 | Schimel D S House J I Hibbard K A Bousquet P Ciais P Peylin P Braswell B H Apps M J Baker D Bondeau A Canadell J Churkina C: Cramer W Denning A S Field CB Friedlingstein P Goodale C Heimann M Houghton RA Melillo J M Moore B 3rd Murdiyarso D Noble L Pacala S W Prentice I C Raupach M R Rayner P J Scholes R J Steffen W L Wirth C | 2001 | Nature2001，414，： | 1 |
| 8 | A systematic overview of reviews for complementary and alternative therapies in the treatment of the fibromyalgia syndrome显示文摘 | Lauehe R Cramer H H/iuser W | 2015 | Evid Based Com- plement Alternat Med2015，2015，： | 1 |
| 9 | Evaluation of the CALINE-4 line source dispersion model for complex terrain application 显示文摘 | Benson P E Nokesm W Cramer R L | 1986 | Transp Res1986，，1058： | 1 |
| 10 | Predictive value of serum and follicular fluid leptin concentrations during assisted reproductive cycles in normal women and in women with the polycystic ovary syndrome显示文摘 | Mantzoros C S Cramer D W Liberman R F | 2000 | Hum Reprod2000，15，2： | 1 |
| 11 | Ecosystem service supply and vulnerability to global change in Europe显示文摘 | Schr ter D Cramer W Leemans R | 2005 | Science2005，310，： | 1 |
| 12 | Terrestrial NPP: towards a consistent data set for global model evaluation 显示文摘 | Scurlock J M O Cramer W Olson R J | 1999 | Ecological Applications1999，9，： | 1 |
| 13 | Ecosystem service supply and vulnerability to global change in Europe显示文摘 | Schroter D Cramer W Leemans R | 2005 | Science2005，310，5752： | 1 |
| 14 | ApoE directed thera- peutics rapidly clear β- amyloid and reverse deficits in AD mouse models显示文摘 | Cramer P E Cirrito J R Wesson D W | 2012 | Science2012，335，6075： | 1 |
| 15 | Terrestrial NPP toward a consistent data set for global model evalution 显示文摘 | Scurlock J M O Cramer W Olson R J | 1999 | Ecological Applications1999，9，3： | 1 |
| 16 | Gonado- tropin-releasing hormone agonist use in assisted reproduc- tion cycles:the influence of long and short regimens on pregnancy rates 显示文摘 | DANIEL W CRAMER M D DOUGLAS R | 1999 | Fertil Steril1999，72，1： | 1 |
| 17 | Infertility,fertility drugs, and ovarian cancer: a pooled analysis of casecontrol studies显示文摘 | Ness R B Cramer B W Goodman M T | 2002 | Am J Epidemiol2002，155，3： | 1 |
| 18 | A globai biome model based on plant physiology and dominance, soil properties and climate显示文摘 | Prentice I C Cramer W Harrison S P Leemans R Monserud R A Solomon A M | 1992 | Journal of Biogeography1992，19，： | 1 |
| 19 | Recent patterns and mechanisms of carbon exchange by terrestrial ecosystems显示文摘 | Schimel D S House J I Hibbard K A Bousquet P Ciais P Peylin P Braswell B H Apps M J Baker D Bondeau A Canadell J Churkina G Cramer W Denning A S Field CB Friedlingstein P Goodale C Heimann M Houghton PA Melillo J M Moore B 3rd Murdiyarso D Noble I Pacala S W Prentice I C Raupach M R Rayner P J Scholes R J Steffen W L Wirth C | 2001 | Nature2001，414，： | 1 |
| 20 | Harnessing ealcineurin as a novel anti-infective agent against invasive fungal infections显示文摘 | Steinbach W J Reedy J L Cramer R A Jr Perfect J R Heitman J | 2007 | Nat Rev Microbiol2007，5，： | 1 |
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