Oncolytic measles virus(OMV) is a promising antitumor agent. However, the presence of anti-measles neutralizing antibodies(NAbs) against the hemagglutinin(H) protein of OMV is a major barrier to the therapeutic applic...Oncolytic measles virus(OMV) is a promising antitumor agent. However, the presence of anti-measles neutralizing antibodies(NAbs) against the hemagglutinin(H) protein of OMV is a major barrier to the therapeutic application of OMV in clinical practice. In order to overcome this challenge, specific types of cells have been used as carriers for OMV.Differential loading strategies appear to result in different therapeutic outcomes; despite this, only few studies have reported practical ex vivo loading strategies required for effective treatment. To this end, we systematically evaluated the antitumor efficacy of OMV using different loading strategies; this involved varying the in vitro loading duration and loading dose of OMV. We found that improved oncolysis of carrier cells was achieved by a prolonged loading duration in the absence of NAbs. However, the enhanced oncolytic effect was abrogated in the presence of NAbs. Further, we found that the expression of H protein on the surface of carrier cells was predominantly determined by the loading duration rather than the loading dose. Finally, we showed that NAbs blocked viral transfer by targeting H protein prior to the occurrence of cell-to-cell interactions. Our results provide comprehensive information on the determinants of an effective loading strategy for carrier cell-based virotherapy; these results may be useful for guiding the application of OMV as an antitumor agent in clinical practice.展开更多
The nearly nine-year continuous GPS data collected since 1 March 1999 from the Crustal Motion Observation Network of China(CMONOC) were consistently analyzed.Most of the nonlinear movements in the cumulative position ...The nearly nine-year continuous GPS data collected since 1 March 1999 from the Crustal Motion Observation Network of China(CMONOC) were consistently analyzed.Most of the nonlinear movements in the cumulative position time series pro-duced by CMONOC data center disappeared;and more accurate vertical terms and tectonic signals were extracted.Displacements caused by atmospheric pressure loading,nontidal ocean loading,soil moisture mass loading,and snow cover mass loading using the National Centers for Environmental Prediction(NCEP) Reanalysis I/II models and Estimation of the Circulation and Climate of the Ocean(ECCO) data can explain most of the vertical annual terms at many stations,while only parts can be explained at Lhasa and southern coastal sites,indicating that there are some deformation mechanisms that are still unknown or not modeled accurately.The remarkable differences in vertical position time series for short-baseline sites reveal that GPS stations can be greatly affected by lo-cal factors;and attention should be paid when explaining observed GPS velocity vectors.展开更多
基金supported in part by the National Natural Science Foundation of China (81472820, 81773255, 81071860 and 81602702)Jiangsu Special Program for Clinical Medical Science and Technology (BL2014054)+2 种基金the Natural Science Foundation of Jiangsu Province of China (BK20160126)the Fundamental Research Funds for the Central Universities (021414380223 and 14380336/1-2)Six talent peaks project in Jiangsu Province to JW
文摘Oncolytic measles virus(OMV) is a promising antitumor agent. However, the presence of anti-measles neutralizing antibodies(NAbs) against the hemagglutinin(H) protein of OMV is a major barrier to the therapeutic application of OMV in clinical practice. In order to overcome this challenge, specific types of cells have been used as carriers for OMV.Differential loading strategies appear to result in different therapeutic outcomes; despite this, only few studies have reported practical ex vivo loading strategies required for effective treatment. To this end, we systematically evaluated the antitumor efficacy of OMV using different loading strategies; this involved varying the in vitro loading duration and loading dose of OMV. We found that improved oncolysis of carrier cells was achieved by a prolonged loading duration in the absence of NAbs. However, the enhanced oncolytic effect was abrogated in the presence of NAbs. Further, we found that the expression of H protein on the surface of carrier cells was predominantly determined by the loading duration rather than the loading dose. Finally, we showed that NAbs blocked viral transfer by targeting H protein prior to the occurrence of cell-to-cell interactions. Our results provide comprehensive information on the determinants of an effective loading strategy for carrier cell-based virotherapy; these results may be useful for guiding the application of OMV as an antitumor agent in clinical practice.
基金Supported by the Research Grant from Institute of Crustal Dynamics (No. ZDJ2010-17)
文摘The nearly nine-year continuous GPS data collected since 1 March 1999 from the Crustal Motion Observation Network of China(CMONOC) were consistently analyzed.Most of the nonlinear movements in the cumulative position time series pro-duced by CMONOC data center disappeared;and more accurate vertical terms and tectonic signals were extracted.Displacements caused by atmospheric pressure loading,nontidal ocean loading,soil moisture mass loading,and snow cover mass loading using the National Centers for Environmental Prediction(NCEP) Reanalysis I/II models and Estimation of the Circulation and Climate of the Ocean(ECCO) data can explain most of the vertical annual terms at many stations,while only parts can be explained at Lhasa and southern coastal sites,indicating that there are some deformation mechanisms that are still unknown or not modeled accurately.The remarkable differences in vertical position time series for short-baseline sites reveal that GPS stations can be greatly affected by lo-cal factors;and attention should be paid when explaining observed GPS velocity vectors.
