PMID- 20739958
OWN - NLM
STAT- MEDLINE
DCOM- 20110628
LR  - 20201219
IS  - 1476-5462 (Electronic)
IS  - 0969-7128 (Linking)
VI  - 18
IP  - 2
DP  - 2011 Feb
TI  - Synergistic anti-tumor effects between oncolytic vaccinia virus and paclitaxel 
      are mediated by the IFN response and HMGB1.
PG  - 164-72
LID - 10.1038/gt.2010.121 [doi]
AB  - Recent developments in the field of oncolytic or tumor-selective viruses have 
      meant that the clinical applications of these agents are now being considered in 
      more detail. Like most cancer therapies it is likely that they will be used 
      primarily in combination with other therapeutics. Although several reports have 
      shown that oncolytic viruses can synergize with chemotherapies within an infected 
      cancer cell, it would be particularly important to determine whether factors 
      released from infected cells could enhance the action of chemotherapies at a 
      distance. Here, we demonstrate in vitro synergy between oncolytic vaccinia and 
      taxanes. However, we also show, for the first time, that this synergy is at least 
      partly due to the release of factors from the infected cells that are capable of 
      sensitizing surrounding cells to chemotherapy. Several cellular factors were 
      identified as being mediators of this bystander effect, including type I 
      interferon released soon after infection and high-mobility group protein B1 
      (HMGB1) released after cell death. This represents the first description of these 
      mechanisms for beneficial interactions between viral and traditional tumor 
      therapies. These data may provide a direct basis for the design of clinical 
      trials with agents currently in the clinic, as well as providing insight into the 
      development of next generation viral vectors.
FAU - Huang, B
AU  - Huang B
AD  - Departments of Surgery and Immunology, Hillman Cancer Center, University of 
      Pittsburgh Cancer Institute, University of Pittsburgh, 5117 Centre Avenue, 
      Pittsburgh, PA 15238, USA.
FAU - Sikorski, R
AU  - Sikorski R
FAU - Kirn, D H
AU  - Kirn DH
FAU - Thorne, S H
AU  - Thorne SH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100826
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (HMGB1 Protein)
RN  - 9008-11-1 (Interferons)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/pharmacology/*therapeutic use
MH  - Cell Cycle/drug effects
MH  - Cell Death/drug effects
MH  - Cell Line, Tumor
MH  - Combined Modality Therapy
MH  - HMGB1 Protein/*metabolism
MH  - Humans
MH  - Interferons/*metabolism
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasms/*therapy
MH  - Oncolytic Virotherapy/*methods
MH  - Oncolytic Viruses/physiology
MH  - Paclitaxel/pharmacology/*therapeutic use
MH  - *Vaccinia virus/physiology
EDAT- 2010/08/27 06:00
MHDA- 2011/06/29 06:00
CRDT- 2010/08/27 06:00
PHST- 2010/08/27 06:00 [entrez]
PHST- 2010/08/27 06:00 [pubmed]
PHST- 2011/06/29 06:00 [medline]
AID - gt2010121 [pii]
AID - 10.1038/gt.2010.121 [doi]
PST - ppublish
SO  - Gene Ther. 2011 Feb;18(2):164-72. doi: 10.1038/gt.2010.121. Epub 2010 Aug 26.