PMID- 17280792
OWN - NLM
STAT- MEDLINE
DCOM- 20070718
LR  - 20070511
IS  - 0306-9877 (Print)
IS  - 0306-9877 (Linking)
VI  - 69
IP  - 1
DP  - 2007
TI  - Cell-permeable hypoxia-inducible factor-1 (HIF-1) antagonists function as tumor 
      radiosensitizers.
PG  - 33-5
AB  - Hypoxia is a common phenomenon in human solid tumors and has been considered as 
      an important, independent negative prognostic factor for response to treatment 
      and survival of tumor patients. Hypoxia-inducible factor-1 (HIF-1) is the central 
      transcription factor which is activated by hypoxia and modulates the expression 
      of many genes involved in cell metabolism, proliferation, apoptosis, 
      angiogenesis. Recently, it has been reported that HIF-1 contributes to tumor 
      radioresistance by upregulating survivin expression under hypoxic conditions. 
      Moreover, in hypoxic tumor cells, HIF-1 dependent signal transduction pathway is 
      activated and could be further enhanced by radiation, thereby providing survival 
      signals to adjacent vascular endothelial cells by upregulation of VEGF and bFGF 
      and resulting in tumor radioresistance through vascular radioprotection. Recent 
      research revealed that the stability of HIF-1alpha, one of the two subunits of 
      HIF-1, determines the whole HIF-1 activity and the C-terminal transactivation 
      domain of HIF-1alpha could reduce HIF-1 activity when overexpressed in tumor 
      cells by disruption of the assembly of HIF-1 transcription complex. Therefore, we 
      postulate that fusion with protein transduction domains would overcome the 
      inability of C-terminal transactivation domain of HIF-1alpha to cross cellular 
      membrane. Thus the recombinant fusion proteins could serve as cell-permeable 
      HIF-1 antagonists, function as both inhibitors of tumor angiogenesis and tumor 
      radiosensitizers, and would be widely used in clinical settings to improve tumor 
      response to radiotherapy.
FAU - Shi, Mei
AU  - Shi M
AD  - Department of Radiotherapy, Xijing Hospital, The Fourth Military Medical 
      University, No.17 Changle Western Road, Xi'an 710032, China.
FAU - Guo, Xiao-Tong
AU  - Guo XT
FAU - Shu, Mao-Guo
AU  - Shu MG
FAU - Chen, Fu-Lin
AU  - Chen FL
FAU - Li, Li-Wen
AU  - Li LW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070205
PL  - United States
TA  - Med Hypotheses
JT  - Medical hypotheses
JID - 7505668
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Radiation-Sensitizing Agents)
SB  - IM
MH  - Antineoplastic Agents/*administration & dosage
MH  - Cell Hypoxia/drug effects/radiation effects
MH  - Cell Membrane Permeability
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*antagonists & inhibitors/*metabolism
MH  - Models, Biological
MH  - Neoplasms/drug therapy/*metabolism/*radiotherapy
MH  - Radiation-Sensitizing Agents/*administration & dosage
EDAT- 2007/02/07 09:00
MHDA- 2007/07/19 09:00
CRDT- 2007/02/07 09:00
PHST- 2006/10/15 00:00 [received]
PHST- 2006/10/19 00:00 [accepted]
PHST- 2007/02/07 09:00 [pubmed]
PHST- 2007/07/19 09:00 [medline]
PHST- 2007/02/07 09:00 [entrez]
AID - S0306-9877(06)00900-5 [pii]
AID - 10.1016/j.mehy.2006.10.062 [doi]
PST - ppublish
SO  - Med Hypotheses. 2007;69(1):33-5. doi: 10.1016/j.mehy.2006.10.062. Epub 2007 Feb 
      5.