PMID- 9142119
OWN - NLM
STAT- MEDLINE
DCOM- 19970528
LR  - 20220129
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 3
IP  - 5
DP  - 1997 May
TI  - Targeting gene expression to hypoxic tumor cells.
PG  - 515-20
AB  - Solid tumors with areas of low oxygen tension (hypoxia) have a poor prognosis, as 
      cells in this environment often survive radiation and chemotherapy. In this 
      report we describe how this hypoxic environment can be used to activate 
      heterologous gene expression driven by a hypoxia-responsive element (HRE), which 
      interacts with the transcriptional complex hypoxia-inducible factor-1 (HIF-1). 
      Our results demonstrate that the HIF-1/HRE system of gene regulation is active in 
      hypoxic tumor cells and show the potential of exploiting tumor-specific 
      conditions for the targeted expression of diagnostic or therapeutic genes in 
      cancer therapy.
FAU - Dachs, G U
AU  - Dachs GU
AD  - Experimental Oncology Division, Medical Research Council, Harwell, UK.
FAU - Patterson, A V
AU  - Patterson AV
FAU - Firth, J D
AU  - Firth JD
FAU - Ratcliffe, P J
AU  - Ratcliffe PJ
FAU - Townsend, K M
AU  - Townsend KM
FAU - Stratford, I J
AU  - Stratford IJ
FAU - Harris, A L
AU  - Harris AL
LA  - eng
GR  - G0500366/MRC_/Medical Research Council/United Kingdom
GR  - P01-CA-55165/CA/NCI NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Prodrugs)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - 88876-88-4 (1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol)
RN  - 8FE7LTN8XE (Misonidazole)
RN  - D83282DT06 (Flucytosine)
RN  - EC 2.7.2.3 (Phosphoglycerate Kinase)
RN  - EC 3.5.4.- (Nucleoside Deaminases)
RN  - EC 3.5.4.1 (Cytosine Deaminase)
RN  - S88TT14065 (Oxygen)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Animals
MH  - Antimetabolites, Antineoplastic/pharmacology
MH  - Cell Hypoxia
MH  - Cytosine Deaminase
MH  - DNA-Binding Proteins/*physiology
MH  - Fibrosarcoma/*genetics/metabolism
MH  - Flucytosine/pharmacology
MH  - Fluorouracil/pharmacology
MH  - Gene Expression Regulation, Neoplastic/drug effects/*genetics
MH  - Genes, Reporter/genetics
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Mice
MH  - Mice, Nude
MH  - Misonidazole/analogs & derivatives/pharmacology
MH  - Neoplasm Transplantation
MH  - Nuclear Proteins/*physiology
MH  - Nucleoside Deaminases/genetics
MH  - Oxygen/*pharmacology
MH  - Phosphoglycerate Kinase/*genetics
MH  - Prodrugs/pharmacology
MH  - Promoter Regions, Genetic/genetics
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - *Transcription Factors
MH  - Tumor Cells, Cultured
EDAT- 1997/05/01 00:00
MHDA- 1997/05/01 00:01
CRDT- 1997/05/01 00:00
PHST- 1997/05/01 00:00 [pubmed]
PHST- 1997/05/01 00:01 [medline]
PHST- 1997/05/01 00:00 [entrez]
AID - 10.1038/nm0597-515 [doi]
PST - ppublish
SO  - Nat Med. 1997 May;3(5):515-20. doi: 10.1038/nm0597-515.