PMID- 12456339
OWN - NLM
STAT- MEDLINE
DCOM- 20040202
LR  - 20190901
IS  - 1093-9946 (Print)
IS  - 1093-4715 (Linking)
VI  - 8
DP  - 2003 Jan 1
TI  - Genetic modulation of hypoxia induced gene expression and angiogenesis: relevance 
      to brain tumors.
PG  - d100-16
AB  - Angiogenesis is required for the development and biologic progression of 
      infiltrative astrocytomas and takes the form of "microvascular hyperplasia" in 
      glioblastoma multiforme, the most malignant astrocytoma. This pathologic term 
      refers to an abnormal vascular proliferation that is often associated with 
      necrosis and likely originates in hypoxic zones. Both the physiologic response to 
      hypoxia and genetic alterations contribute to this process. The presence of 
      hypoxic regions within an expanding tumor mass leads to upregulation of 
      pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), 
      through increased activity of the transcriptional complex HIF-1 
      (hypoxia-inducible factor-1). HIF-1 mediated gene expression may be directly or 
      indirectly modulated by alterations in oncogenes/tumor suppressor genes that 
      occur during astrocytoma development, including PTEN, TP53, p16(CDKN2A), p14ARF, 
      EGFR, and PDGFR. Genetic alterations are also believed to influence the 
      HIF-independent expression of pro- and anti- angiogenic factors, such as basic 
      fibroblast growth factor (bFGF) and thrombospondin-1 (TSP-1), respectively. Thus, 
      genetic events that occur during the progression of infiltrating astrocytomas 
      promote angiogenesis, both by modulating hypoxia induced gene expression and by 
      regulating of pro- and anti- angiogenic factors.
FAU - Brat, Daniel J
AU  - Brat DJ
AD  - Department of Pathology and Laboratory Medicine and Laboratory of Molecular 
      Neuro-Oncology, Emory University School of Medicine, Atlanta, GA, USA. 
      dbrat@emory.edu
FAU - Kaur, Balveen
AU  - Kaur B
FAU - Van Meir, Erwin G
AU  - Van Meir EG
LA  - eng
GR  - CA-86335/CA/NCI NIH HHS/United States
GR  - CA-87830/CA/NCI NIH HHS/United States
GR  - NS-41403/NS/NINDS NIH HHS/United States
GR  - NS-42934/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
DEP - 20030101
PL  - United States
TA  - Front Biosci
JT  - Frontiers in bioscience : a journal and virtual library
JID - 9709506
SB  - IM
MH  - Animals
MH  - Brain Neoplasms/*blood supply/*genetics/physiopathology
MH  - Gene Expression Regulation, Neoplastic/*genetics
MH  - Humans
MH  - Hypoxia/*genetics/*physiopathology
MH  - Neovascularization, Pathologic/*genetics
RF  - 128
EDAT- 2002/11/29 04:00
MHDA- 2004/02/03 05:00
CRDT- 2002/11/29 04:00
PHST- 2002/11/29 04:00 [pubmed]
PHST- 2004/02/03 05:00 [medline]
PHST- 2002/11/29 04:00 [entrez]
AID - 10.2741/942 [doi]
PST - epublish
SO  - Front Biosci. 2003 Jan 1;8:d100-16. doi: 10.2741/942.