PMID- 17982491
OWN - NLM
STAT- MEDLINE
DCOM- 20080501
LR  - 20220914
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 27
IP  - 17
DP  - 2008 Apr 10
TI  - Virus-mediated oncolysis induces danger signal and stimulates cytotoxic 
      T-lymphocyte activity via proteasome activator upregulation.
PG  - 2375-81
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells and acquire 
      cellular antigens and danger signals from dying cells to initiate antitumor 
      immune responses via direct cell-to-cell interaction and cytokine production. The 
      optimal forms of tumor cell death for priming DCs for the release of danger 
      signals are not fully understood. OBP-301 (Telomelysin) is a telomerase-specific 
      replication-competent adenovirus that induces selective E1 expression and 
      exclusively kills human cancer cells. Here, we show that OBP-301 replication 
      produced the endogenous danger signaling molecule, uric acid, in infected human 
      tumor cells, which in turn stimulated DCs to produce interferon-gamma (IFN-gamma) 
      and interleukin 12 (IL-12). Subsequently, IFN-gamma release upregulated the 
      endogenous expression of the proteasome activator PA28 in tumor cells and 
      resulted in the induction of cytotoxic T-lymphocytes. Our data suggest that 
      virus-mediated oncolysis might be the effective stimulus for immature DCs to 
      induce specific activity against human cancer cells.
FAU - Endo, Y
AU  - Endo Y
AD  - Division of Surgical Oncology, Department of Surgery, Okayama University Graduate 
      School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
FAU - Sakai, R
AU  - Sakai R
FAU - Ouchi, M
AU  - Ouchi M
FAU - Onimatsu, H
AU  - Onimatsu H
FAU - Hioki, M
AU  - Hioki M
FAU - Kagawa, S
AU  - Kagawa S
FAU - Uno, F
AU  - Uno F
FAU - Watanabe, Y
AU  - Watanabe Y
FAU - Urata, Y
AU  - Urata Y
FAU - Tanaka, N
AU  - Tanaka N
FAU - Fujiwara, T
AU  - Fujiwara T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071105
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 268B43MJ25 (Uric Acid)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Adenoviridae/immunology/physiology
MH  - Cell Line, Tumor
MH  - Dendritic Cells/immunology
MH  - Enzyme Activation
MH  - Humans
MH  - Neoplasms/*immunology/pathology/virology
MH  - *Oncolytic Virotherapy
MH  - Proteasome Endopeptidase Complex/*metabolism
MH  - *Signal Transduction
MH  - T-Lymphocytes, Cytotoxic/*enzymology/*immunology
MH  - *Up-Regulation
MH  - Uric Acid/metabolism
EDAT- 2007/11/06 09:00
MHDA- 2008/05/02 09:00
CRDT- 2007/11/06 09:00
PHST- 2007/11/06 09:00 [pubmed]
PHST- 2008/05/02 09:00 [medline]
PHST- 2007/11/06 09:00 [entrez]
AID - 1210884 [pii]
AID - 10.1038/sj.onc.1210884 [doi]
PST - ppublish
SO  - Oncogene. 2008 Apr 10;27(17):2375-81. doi: 10.1038/sj.onc.1210884. Epub 2007 Nov 
      5.