Background:Axl plays multiple roles in tumourigenesis in several cancers. Here we evaluated the expression and biological function of Axl in renal cell carcinoma (RCC).Methods:Axl expression was analysed in a tissue microarray of 174 RCC samples by immunostaining and a panel of 11 normal tumour pairs of human RCC tissues by western blot, as well as in RCC cell lines by both western blot and quantitative PCR. The effects of Axl knockdown in RCC cells on cell growth and signalling were investigated. The efficacy of a humanised Axl targeting monoclonal antibody hMAb173 was tested in histoculture and tumour xenograft.Results:We have determined by immunohistochemistry (IHC) that Axl is expressed in 59% of RCC array samples with moderate to high in 20% but not expressed in normal kidney tissue. Western blot analysis of 11 pairs of tumour and adjacent normal tissue show high Axl expression in 73% of the tumours but not normal tissue. Axl is also expressed in RCC cell lines in which Axl knockdown reduces cell viability and PI3K/Akt signalling. The Axl antibody hMAb173 significantly induced RCC cell apoptosis in histoculture and inhibited the growth of RCC tumour in vivo by 78%. The hMAb173-treated tumours also had significantly reduced Axl protein levels, inhibited PI3K signalling, decreased proliferation, and induced apoptosis.Conclusions:Axl is highly expressed in RCC and critical for RCC cell survival. Targeting Axl is a potential approach for RCC treatment.
Plasma wakefield acceleration (PWFA) has demonstrated the ability to produce very high gradients to accelerate electrons and positrons. In PWFA, a drive bunch of charged particles passes through a uniform plasma, thereby generating a wakefield that accelerates a witness bunch traveling behind the drive bunch. This process works well for electrons, but much less so for positrons due to the positive charge attracting rather than repealing the plasma electrons, which leads to reduced acceleration gradient, halo formation, and emittance growth. This problem can be alleviated by having the positron beam travel through a hollow plasma channel. Presented are modeling results for producing 10-100 cm long hollow plasma channels suitable for positron PWFA. These channels are created utilizing laser-induced gas breakdown in hydrogen gas. The results show that hollow channels with plasma densities of order 10 16 cm À3 and inner channel radii of order 20 m are possible using currently available terawatt-level lasers. At these densities and radii, preliminary positron PWFA modeling indicates that longitudinal electric fields on axis can exceed 3 GV=m.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.