Imperial College London
Alternate

DrRichardPerryman

Faculty of Medicine, Department of Brain Sciences

Research Associate
 
 
 
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Contact

 

r.perryman13 Website

 
 
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Location

 

E5Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hajji:2022:10.1172/JCI142137,
author = {Hajji, N and Garcia-Revilla, J and Sarmiento, Soto M and Perryman, R and Symington, JJ and Quarles, CC and Healey, DR and Guo, Y and Orta-Vázquez, ML and Mateos-Cordero, S and Shah, K and Bomalaski, J and Anichini, G and Tzakos, AG and Crook, T and O'Neill, K and Scheck, AC and Venero, JL and Syed, N},
doi = {10.1172/JCI142137},
journal = {Journal of Clinical Investigation},
pages = {1--19},
title = {Arginine deprivation alters microglia polarity and synergises with radiation to eradicate non arginine auxotrophic glioblastoma tumors},
url = {http://dx.doi.org/10.1172/JCI142137},
volume = {132},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - New approaches for the management of glioblastoma (GBM) are an urgent and unmet clinical need. Here, we illustrate that the efficacy of radiotherapy for GBM is strikingly potentiated by concomitant therapy with the arginine depleting agent ADI-PEG20 in a non-arginine auxotrophic cellular background (Arginine Succinate Synthetase 1 positive). Moreover, this combination led to durable and complete radiological and pathological response with extended disease-free survival in an orthotopic immune competent model of GBM with no significant toxicity. ADI-PEG20 not only enhances the cellular sensitivity of Arginine succinate synthetase 1 positive GBM to ionising radiation by elevated production of nitric oxide (NO) and hence generation of cytotoxic peroxynitrites, but also promotes glioma-associated macrophages/microglia infiltration into tumors and turns their classical anti-inflammatory (pro-tumor) phenotype into a pro-inflammatory (anti-tumor) phenotype. Our results provide an effective, well-tolerated and simple strategy to improve GBM treatment which merits consideration for early evaluation in clinical trials.
AU  - Hajji,N
AU  - Garcia-Revilla,J
AU  - Sarmiento,Soto M
AU  - Perryman,R
AU  - Symington,JJ
AU  - Quarles,CC
AU  - Healey,DR
AU  - Guo,Y
AU  - Orta-Vázquez,ML
AU  - Mateos-Cordero,S
AU  - Shah,K
AU  - Bomalaski,J
AU  - Anichini,G
AU  - Tzakos,AG
AU  - Crook,T
AU  - O'Neill,K
AU  - Scheck,AC
AU  - Venero,JL
AU  - Syed,N
DO  - 10.1172/JCI142137
EP  - 19
PY  - 2022///
SN  - 0021-9738
SP  - 1
TI  - Arginine deprivation alters microglia polarity and synergises with radiation to eradicate non arginine auxotrophic glioblastoma tumors
T2  - Journal of Clinical Investigation
UR  - http://dx.doi.org/10.1172/JCI142137
UR  - https://www.jci.org/articles/view/142137
UR  - http://hdl.handle.net/10044/1/95019
VL  - 132
ER  -
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