PMID- 21884739
OWN - NLM
STAT- MEDLINE
DCOM- 20120327
LR  - 20211020
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 156
IP  - 3
DP  - 2011 Dec 20
TI  - Tumour necrosis factor-alpha increases extravasation of virus particles into 
      tumour tissue by activating the Rho A/Rho kinase pathway.
PG  - 381-9
LID - 10.1016/j.jconrel.2011.08.022 [doi]
AB  - Tumour Necrosis Factor alpha (TNF) is a pleiotropic pro-inflammatory cytokine 
      with known vascular permeabilising activity. It is employed during isolated limb 
      perfusion to enhance delivery of chemotherapeutic drugs into tumour tissue. The 
      use of conditionally-replicating lytic viruses, so called 'oncolytic 
      virotherapy', provides a new approach to cancer treatment that is currently 
      limited by the low efficiency of extravasation of viral particles into tumours. 
      We report here evidence that TNF significantly enhances the delivery of virus 
      particles through the endothelial layer to allow access to tumour cells both in 
      vitro and in vivo. Intravenous administration of TNF resulted in a 3- to 6-fold 
      increase in EL4 tumour uptake of Evans Blue/Albumin, adenovirus and 
      long-circulating polymer coated adenovirus. Interestingly, endothelial 
      permeabilisation could be suppressed in vitro and in vivo by Y-27632, a Rho 
      kinase inhibitor, without inhibiting viral infection. These data indicate that 
      TNF can enhance the delivery of virus particles into tumours through a Rho A/Rho 
      kinase dependent mechanism and may be a valuable strategy for increasing the 
      delivery of oncolytic viruses and other therapeutic agents.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Seki, Takahiro
AU  - Seki T
AD  - Department of Oncology, ORCRB, University of Oxford, Old Road Campus, Headington, 
      Oxford, OX3 7DQ, UK.
FAU - Carroll, Fionnadh
AU  - Carroll F
FAU - Illingworth, Sam
AU  - Illingworth S
FAU - Green, Nicky
AU  - Green N
FAU - Cawood, Ryan
AU  - Cawood R
FAU - Bachtarzi, Houria
AU  - Bachtarzi H
FAU - Subr, Vladimir
AU  - Subr V
FAU - Fisher, Kerry D
AU  - Fisher KD
FAU - Seymour, Leonard W
AU  - Seymour LW
LA  - eng
GR  - 11339/CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110822
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
SB  - IM
MH  - Adenoviridae/*physiology
MH  - Animals
MH  - Capillary Permeability/*drug effects
MH  - Cell Line
MH  - Endothelium, Vascular/drug effects
MH  - Humans
MH  - Mice
MH  - Neoplasms/therapy
MH  - Oncolytic Virotherapy/*methods
MH  - Oncolytic Viruses/*physiology
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Virion/*physiology
MH  - rho-Associated Kinases/*metabolism
EDAT- 2011/09/03 06:00
MHDA- 2012/03/28 06:00
CRDT- 2011/09/03 06:00
PHST- 2011/05/12 00:00 [received]
PHST- 2011/08/09 00:00 [revised]
PHST- 2011/08/14 00:00 [accepted]
PHST- 2011/09/03 06:00 [entrez]
PHST- 2011/09/03 06:00 [pubmed]
PHST- 2012/03/28 06:00 [medline]
AID - S0168-3659(11)00608-0 [pii]
AID - 10.1016/j.jconrel.2011.08.022 [doi]
PST - ppublish
SO  - J Control Release. 2011 Dec 20;156(3):381-9. doi: 10.1016/j.jconrel.2011.08.022. 
      Epub 2011 Aug 22.