PMID- 15326390
OWN - NLM
STAT- MEDLINE
DCOM- 20060414
LR  - 20200930
IS  - 1551-4005 (Electronic)
IS  - 1551-4005 (Linking)
VI  - 3
IP  - 9
DP  - 2004 Sep
TI  - Raising the bar: how HIF-1 helps determine tumor radiosensitivity.
PG  - 1107-10
AB  - Through a poorly understood mechanism, tumors respond to radiation by secreting 
      cytokines which inhibit endothelial cell apoptosis, thereby limiting treatment 
      response by minimizing vessel damage. We have recently discovered that this 
      pathway is governed by a major angiogenesis regulator, hypoxia-inducible factor-1 
      (HIF-1). We uncovered dual mechanisms initiated by radiation that both 
      simultaneously lead to HIF-1 activation: (1) reoxygenation-induced stabilization 
      of the HIF-1 dimer through free radical intermediates, and (2) 
      reoxygenation-mediated depolymerization of hypoxia-induced translational 
      suppressors known as stress granules. These findings have implications both for 
      understanding the basic science of hypoxic signaling in tumors, and for 
      discovering novel methods of enhancing conventional anti-tumor therapeutics in 
      the clinic. In this article, we will highlight the apparent importance of free 
      radical species in protecting tumor vasculature, stress granules in regulating 
      hypoxic gene expression, and HIF-1 in regulating tumor sensitivity to ionizing 
      radiation. The potential therapeutic utility of these findings will also be 
      explored, with emphasis placed on putative targets in these pathways which may 
      enhance tumor radiotherapy.
FAU - Moeller, Benjamin J
AU  - Moeller BJ
AD  - Department of Pathology, Duke University Medical Center, Durham, North Carolina 
      27710, USA.
FAU - Dewhirst, Mark W
AU  - Dewhirst MW
LA  - eng
GR  - 40355/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
DEP - 20040920
PL  - United States
TA  - Cell Cycle
JT  - Cell cycle (Georgetown, Tex.)
JID - 101137841
RN  - 0 (Free Radicals)
RN  - 0 (Hypoxia-Inducible Factor 1)
SB  - IM
MH  - Animals
MH  - Blood Vessels/physiopathology/*radiation effects
MH  - Cytoplasmic Granules/metabolism/radiation effects
MH  - Free Radicals/metabolism
MH  - Gene Expression Regulation, Neoplastic/physiology/radiation effects
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/metabolism/*radiation effects
MH  - Neoplasms/blood supply/physiopathology/*radiotherapy
MH  - Neovascularization, Pathologic/physiopathology/*radiotherapy
MH  - Oxidative Stress/physiology/radiation effects
MH  - Radiation Tolerance/*physiology
RF  - 45
EDAT- 2004/08/25 05:00
MHDA- 2006/04/15 09:00
CRDT- 2004/08/25 05:00
PHST- 2004/08/25 05:00 [pubmed]
PHST- 2006/04/15 09:00 [medline]
PHST- 2004/08/25 05:00 [entrez]
AID - 1099 [pii]
PST - ppublish
SO  - Cell Cycle. 2004 Sep;3(9):1107-10. Epub 2004 Sep 20.