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101.
Cornelia Cato ter Haar Ron J. G. Peters Jan Bosch Agnese Sbrollini Sophia Gripenstedt Rob Adams Eduard Bleijenberg Charles J. H. J. Kirchhof Reza Alizadeh Dehnavi Laura Burattini Robbert J. de Winter Peter W. Macfarlane Pieter G. Postema Sumche Man Roderick W. C. Scherptong Martin J. Schalij Arie C. Maan Cees A. Swenne 《Annals of noninvasive electrocardiology》2020,25(3)
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Rutger K. Balvers Zineb Belcaid Sanne K. van den Hengel Jenneke Kloezeman Jeroen de Vrij Hiroaki Wakimoto Rob C. Hoeben Reno Debets Sieger Leenstra Clemens Dirven Martine L.M. Lamfers 《Viruses》2014,6(8):3080-3096
Oncolytic adenoviral vectors are a promising alternative for the treatment of glioblastoma. Recent publications have demonstrated the advantages of shielding viral particles within cellular vehicles (CVs), which can be targeted towards the tumor microenvironment. Here, we studied T-cells, often having a natural capacity to target tumors, for their feasibility as a CV to deliver the oncolytic adenovirus, Delta24-RGD, to glioblastoma. The Jurkat T-cell line was assessed in co-culture with the glioblastoma stem cell (GSC) line, MGG8, for the optimal transfer conditions of Delta24-RGD in vitro. The effect of intraparenchymal and tail vein injections on intratumoral virus distribution and overall survival was addressed in an orthotopic glioma stem cell (GSC)-based xenograft model. Jurkat T-cells were demonstrated to facilitate the amplification and transfer of Delta24-RGD onto GSCs. Delta24-RGD dosing and incubation time were found to influence the migratory ability of T-cells towards GSCs. Injection of Delta24-RGD-loaded T-cells into the brains of GSC-bearing mice led to migration towards the tumor and dispersion of the virus within the tumor core and infiltrative zones. This occurred after injection into the ipsilateral hemisphere, as well as into the non-tumor-bearing hemisphere. We found that T-cell-mediated delivery of Delta24-RGD led to the inhibition of tumor growth compared to non-treated controls, resulting in prolonged survival (p = 0.007). Systemic administration of virus-loaded T-cells resulted in intratumoral viral delivery, albeit at low levels. Based on these findings, we conclude that T-cell-based CVs are a feasible approach to local Delta24-RGD delivery in glioblastoma, although efficient systemic targeting requires further improvement. 相似文献
105.
Morassa Mohseni Justin Cidado Sarah Croessmann Karen Cravero Ashley Cimino-Mathews Hong Yuen Wong Rob Scharpf Daniel J. Zabransky Abde M. Abukhdeir Joseph P. Garay Grace M. Wang Julia A. Beaver Rory L. Cochran Brian G. Blair D. Marc Rosen Bracha Erlanger Pedram Argani Paula J. Hurley Josh Lauring Ben Ho Park 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(49):17606-17611
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Stirling RG 《Chest》2012,141(3):825; author reply 825-825; author reply 826
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Phillips PP Gillespie SH Boeree M Heinrich N Aarnoutse R McHugh T Pletschette M Lienhardt C Hafner R Mgone C Zumla A Nunn AJ Hoelscher M 《The Journal of infectious diseases》2012,205(Z2):S250-S257
A growing number of new drugs for the treatment of tuberculosis are in clinical development. Confirmatory phase 3 trials are expensive and time-consuming and the question of whether one particular drug combination can be used to treat tuberculosis is less important from a public health perspective than the question of which are the shortest, simplest, most effective, and safest regimens. While preclinical and phase 1 studies provide some guidance in the selection of combinations for clinical evaluation, a large number of combinations will require phase 2 testing to ensure that only the best regimens advance to phase 3. The multi-arm multi-stage trial design is an example of a treatment selection-adaptive design where multiple experimental arms are each simultaneously compared with a common control and interim analyses allow for poor performing arms to be dropped early. Such designs, if designed and implemented correctly, require fewer patients, can be completed in a shorter time frame, and answer more relevant questions without any loss in statistical validity or scientific integrity. There are, however, practical issues that must be considered in applying this in tuberculosis treatment trials. More innovative trials designs should be considered to speed drug and regimen development for the treatment of tuberculosis. 相似文献
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